Abstract:
A process for separating organic compounds from a mixture by reverse-phase displacement chromatography, including providing a hydrophobic stationary phase; applying to the hydrophobic stationary phase a mixture comprising organic compounds to be separated; displacing the organic compounds from the hydrophobic stationary phase by applying thereto an aqueous composition comprising a non-surface active hydrophobic cationic displacer molecule and about 10 wt % or less of an organic solvent; and collecting a plurality of fractions eluted from the hydrophobic stationary phase containing the separated organic compounds; in which the non-surface active hydrophobic cationic displacer molecule comprises a hydrophobic cation and a counterion, CI, having the general formula A or B, as defined in the disclosure:

Description:
BACKGROUND 
       [0001]    Displacement chromatography (DC) in one of the three well-defined forms of column chromatography—elution, displacement, frontal. DC is principally a preparative method, but there are also analytical applications using “micropreparative” DC with packed “narrow-bore” or capillary columns. 
         [0002]    Displacement chromatography may be carried out using any one of four general chromatographic methods when suitable, high-purity displacer molecules are available. DC is used in (a) ion-exchange chromatography (cation-exchange, anion-exchange), (b) hydrophobic chromatography (reversed-phase, hydrophobic-interaction, hydrophobic charge-induction, thiophilic), (c) normal-phase chromatography including hydrophilic-interaction chromatography (HILIC) and (d) immobilized metal-ion affinity chromatography (IMAC). 
         [0003]    With optimized DC, one may obtain, simultaneously, high purity (high resolution), high recovery (high yield) and high column loading (high capacity)—the latter much higher than overloaded preparative elution chromatography. In most cases, these advantages more than compensate for the disadvantages of DC (slower flow-rates, longer run-times, need for high-purity displacers). 
         [0004]    Displacement chromatography is carried out by choosing (a) an applicable chromatographic method, (b) a suitable chromatography column with proper dimensions, (c) proper mobile phase conditions, (d) a suitable displacer molecule and (e) suitable operation protocols with properly configured LC equipment. Initially, a suitable “weakly displacing mobile phase” (carrier) is chosen, and the column is equilibrated at a suitable flow-rate. The carrier may contain a pH-buffering compound adjusted to a useful pH value. Optimal displacement flow-rates tend to be low, typically in the range of 35-105 cm/hr, though sometimes higher. A suitable amount of the sample solution is loaded onto the column at the sample-loading flow-rate. The sample solution contains the material to be purified in the carrier along with the proper level of an ion-pairing agent if the sample or displacer molecules are charged. Typical sample loadings are 50-80% of the operative breakthrough capacity. Next, a displacer mobile phase (displacer buffer), prepared from a suitable displacer compound at the proper concentration in the carrier solution, is pumped onto the column at the displacement flow-rate until the displacer breakthrough is observed. The purified sample comes off the column before the displacer breakthrough front. Fractions from the column are collected and separately analyzed for content and purity. Finally, the displacer is removed from column using a “displacer removal solution”, and then the column is cleaned and regenerated to its original state for storage or for subsequent use. 
         [0005]    Though different from elution chromatography, in some respects, displacement chromatography is easy to understand and easy to carry out. In DC, a sample is “displaced” from the column by the displacer, rather than “eluted” from the column by the mobile phase. When the output of the column is monitored online (e.g., via UV absorption, pH, or conductivity), a “displacement train” is obtained rather than an “elution chromatogram”. The displacement train is composed of side-by-side “displacement bands” rather than solvent-separated “elution peaks” in a chromatogram. When a displacement band is large enough to saturate the stationary phase, a trapezoidal “saturating band” is formed. When a displacement band is not large enough to saturate the stationary phase, a small, triangular “non-saturating band” is formed. The height of a saturating band is determined by the binding-isotherm at the point of operation; the area of a trapezoid-band or a triangle-band is proportional to the amount of the component. 
         [0006]    Hydrophobic chromatography depends almost exclusively on the unique solvation properties of water that result from the highly structured, self-associated, hydrogen-bonded liquid. For conventional reversed-phase chromatography stationary phases (uncharged C 18  column), binding is usually driven by entropy (+TΔS), which often must overcome unfavorable enthalpy (+ΔH). Thus, over the temperature ranges often used by chromatographers (10-70° C.), analyte-binding and displacer-binding often become stronger with increasing temperature. Another useful feature of hydrophobic chromatography is the use of additives that modify both the structure and strength of the self-hydrogen-bonding of the aqueous-based solvent. These additives include: salts (NaCl, K 2 HPO 4 , (NH 4 ) 2 SO 4 ), organic solvents (MeCN, MeOH, EtOH) and polar organic molecules (urea, oligo-ethyleneglycol) in chromatography buffers. 
         [0007]    Hydrophobic displacement chromatography can be carried out using chiral analytes, chiral displacers and chiral chromatography matrices. Under these conditions, an achiral displacer may be used, but a racemic mixture of a chiral displacer cannot be used. Racemic chiral analytes can also be purified using an achiral chromatography column and an achiral displacer. In this case, impurities, including diastereomers, are removed from the racemic compound of interest, but there is no chiral resolution of the enantiomers. With the proper choice of chiral chromatography matrix, mobile phase and achiral displacer, enantiomers are routinely preparatively resolved (separated). Depending on the specific circumstances, a good, enantiomerically pure, chiral displacer can have performance advantages over a good achiral displacer when carrying out a displacement separation of enantiomers on a chiral stationary phase. 
         [0008]    Development of useful, preparative hydrophobic displacement chromatography has been hampered by the unavailability of suitable, high-purity displacer molecules. We describe here new displacer molecules and methods to use them that have utility in various forms of hydrophobic displacement chromatography. 
         [0009]    Hydrophobic displacer molecules should possess a unique combination of chemical and physical properties in order for them to function efficiently. Some soluble, hydrophobic molecules can function as displacers, but only a limited few function well. Many of the molecules described in this document fulfill the necessary requirements for well-functioning displacers. 
         [0010]    Development of useful, reversed phase, preparative displacement chromatography has been hampered by the unavailability of suitable, high-purity displacer molecules. For example, U.S. Pat. No. 6,239,262 describes various reversed phase liquid chromatographic systems using low molecular weight surface-active compounds as displacers. U.S. Pat. No. 6,239,262 discloses an extremely wide range of possible charged moieties that may be coupled with hydrophobic moieties to form the disclosed surface active compounds used as displacers, but discloses that it is necessary to include a large proportion of organic solvent to mitigate the surface active properties of the disclosed displacers. The presence of such large proportions of organic solvents significantly alters the process, derogating from the benefits of reverse-phase hydrophobic displacement chromatography. In addition, the surface-active displacer compounds disclosed by U.S. Pat. No. 6,239,262 do not function well, resulting in relatively poor quality displacement trains in which a significant level of impurities may be present in the “purified” products. 
       SUMMARY 
       [0011]    The development of useful, preparative hydrophobic displacement chromatography has been hampered by the unavailability of suitable, high-purity displacer molecules that function well and can be easily detected. We describe here a new class of cationic displacer molecules and methods to use them that have utility in various forms of hydrophobic displacement chromatography. 
         [0012]    Many commercial, small cationic molecules simply don&#39;t bind to hydrophobic stationary phases well enough, while many large cationic molecules that do bind well enough either lack sufficient solubility or are plagued with detergency problems that lead to lower resolution, lower column capacity for the analyte and unwanted foaming. We find that many intermediate-sized cationic molecules, when properly designed, possess the unique combination of chemical and physical properties, including proper UV absorption, in order for them to function efficiently as hydrophobic displacers. It is true enough that there are some soluble, cationic hydrophobic molecules that can function as displacers, but only a limited few function well. Many of the molecules described in this document fulfill the necessary requirements for well-functioning displacers when used according to established displacement protocols. 
         [0013]    We have discovered and developed classes of charged hydrophobic organic compounds, either salts or zwitterions, that uniquely posses that combination of chemical and physical properties necessary for good displacer behavior in hydrophobic displacement chromatography. 
         [0014]    Accordingly, the present invention, in one embodiment, relates to a process for separating organic compounds from a mixture by reverse-phase displacement chromatography, comprising: 
         [0015]    providing a hydrophobic stationary phase; 
         [0016]    applying to the hydrophobic stationary phase a mixture comprising organic compounds to be separated; 
         [0017]    displacing the organic compounds from the hydrophobic stationary phase by applying thereto an aqueous composition comprising a non-surface active hydrophobic cationic displacer molecule and about 10 wt % or less of an organic solvent; and 
         [0018]    collecting a plurality of fractions eluted from the hydrophobic stationary phase containing the separated organic compounds; 
         [0019]    wherein the non-surface active hydrophobic cationic displacer molecule comprises a hydrophobic cation and a counterion, CI, having the general formula A or B: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0020]    wherein in the general formulae A and B, each CM or CM′ is an independent hydrophobic chemical moiety with a formal charge selected from: quaternary ammonium (I), quaternary phosphonium (II), sulfonium (III), sulfoxonium (IV), imidazolinium (amidinium) (V), guanidinium (VI), imidazolium (VII), 1,2,3,4-tetrahydroisoquinolinium (VIII), 1,2,3,4-tetrahydroquinolinium (IX), isoindolinium (X), indolinium (XI), benzimidazolium (XII), pyridinium (XIIIa, XIIIb, XIIIc, XIIId), quinolinium (XIV), isoquinolinium (XV), carboxylate (XVI), N-acyl-α-amino acid (XVII), sulfonate (XVIII), sulfate monoester (XIX), phosphate monoester (XX), phosphate diester (XXI), phosphonate monoester (XXII), phosphonate (XXIII), tetraaryl borate (XXIV), boronate (XXV), boronate ester (XXVI); wherein the chemical moieties (I)-(XXVI) have the following chemical structures: 
         [0000]    
       
                 
         
             
             
         
       
       
                 
         
             
             
         
       
       
                 
         
             
             
         
       
     
         [0021]    wherein in general formula B, CM and CM′ are independent charged chemical moieties having the same or opposite formal charge and are chemically attached to each other by a doubly connected chemical moiety, R*, which replaces one R 1 , R 2  (if present), R 3  (if present) or R 4  (if present) chemical moiety on CM and replaces one R 1 , R 2  (if present), R 3  (if present) or R 4  (if present) chemical moiety on CM′; 
         [0022]    wherein each of R 1 , R 2 , R 3  and R 4  is a linear or branched chemical moiety independently defined by the formula, 
         [0000]      —C x X 2x-2r -AR 1 —C u X 2u-2s -AR 2 ,
 
         [0023]    R* is a direct chemical bond or is a doubly connected, linear or branched chemical moiety defined by the formula, 
         [0000]      —C x X 2x-2r -AR 1 —C u X 2u-2s —,
 
         [0000]    and R 5  is a linear or branched chemical moiety defined by the formula, 
         [0000]      —C x X 2x-2r -AR 2 ;
 
         [0024]    wherein each AR 1  independently is a doubly connected methylene moiety (—CX 1 X 2 —, from methane), a doubly connected phenylene moiety (—C 6 G 4 -, from benzene), a doubly connected naphthylene moiety (—C 10 G 6 -, from naphthalene) or a doubly connected biphenylene moiety (—C 12 G 8 -, from biphenyl); 
         [0025]    wherein AR 2  independently is hydrogen (—H), fluorine (—F), a phenyl group (—C 6 G 5 ), a naphthyl group (—C 10 G 7 ) or a biphenyl group (—C 12 G 9 ); 
         [0026]    wherein each X, X 1  and X 2  is individually and independently —H, —F, —Cl or —OH; 
         [0027]    wherein any methylene moiety (—CX 1 X 2 —) within any —C x X 2x-2r — or within any —C u X 2u-2s — or within any —(CX 1 X 2 ) p — may be individually and independently replaced with an independent ether-oxygen atom, —O—, an independent thioether-sulfur atom, —S—, or an independent ketone-carbonyl group, —C(O)—, in such a manner that each ether-oxygen atom, each thioether-sulfur atom or each ketone-carbonyl group is bonded on each side to an aliphatic carbon atom or an aromatic carbon atom; 
         [0028]    wherein not more than two ether-oxygen atoms, not more than two thioether-sulfur atoms and not more than two ketone-carbonyl groups may be replaced into any —C x X 2x-2r — or into any —C u X 2u-2s —; 
         [0029]    wherein m x  is the total number of methylene groups in each —C x X 2x-2r — that are replaced with ether-oxygen atoms, thioether-sulfur atoms and ketone-carbonyl groups, and m u  is the total number of methylene groups in each —C u X 2u-2s — that are replaced with ether-oxygen atoms, thioether-sulfur atoms and ketone-carbonyl groups; 
         [0030]    wherein G is individually and independently any combination of —H, —F, —Cl, —CH 3 , —OH, —OCH 3 , —N(CH 3 ) 2 , —CF 3 , —CO 2 Me, —CO 2 NH 2 ; —CO 2 NHMe, —CO 2 NMe 2 ; 
         [0031]    wherein G* is individually and independently any combination of —F, —CI, —R 2 , —OH, —OR 2 , —NR 2 R 3 , —CF 3 , —CO 2 Me, —CO 2 NH 2 ; —CO 2 NHMe, —CO 2 NMe 2 ; 
         [0032]    wherein a pair of R 2 , R 3 , and R 4  may comprise a single chemical moiety such that R 2 /R 3 , R 2 /R 4 , R 3 /R 4 , R 2′ /R 3′ , R 2′ /R 4′  or R 3′ /R 4′  is individually and independently —(CX 1 X 2 ) p — with p=3, 4, 5 or 6; 
         [0033]    wherein the integer values of each of x, r, u, s, m x , m u  are independently selected for each R 1 , R 2 , R 3 , R 4 , R 5  and R*, integer values r and s are the total number of contained, isolated cis/trans olefinic (alkene) groups plus the total number of contained simple monocyclic structures and fall in the ranges 0≦r≦2 and 0≦s≦2, the numeric quantity x+u−m x −m u  falls in the range 0≦x+u−m x −m u ≦11; 
         [0034]    wherein at least one aromatic chemical moiety, heterocyclic aromatic chemical moiety, imidazoline chemical moiety, amidine chemical moiety or guanidine chemical moiety is contained within CM or CM′ of A or B; 
         [0035]    wherein a group-hydrophobic-index for each R-chemical-moiety (n) is numerically equal to the sum of the number of aliphatic carbon atoms plus the number of olefinic carbon atoms plus the number of thioether-sulfur atoms plus the number of chlorine atoms plus one-fifth the number of fluorine atoms plus one-half the number of ether-oxygen atoms plus one-half the number of ketone-carbon atoms plus one-half the number of aromatic carbon atoms beyond the number six minus the number of hydroxyl-oxygen atoms beyond the number one; 
         [0036]    wherein an overall-hydrophobic-index (N) for each [CM] or [CM-R*-CM′] is numerically equal to the sum of the number of aliphatic carbon atoms plus the number of olefinic carbon atoms plus the number of thioether-sulfur atoms plus the number of chlorine atoms plus one-fifth the number of fluorine atoms plus one-half the number of ether-oxygen atoms plus one-half the number of ketone-carbon atoms plus one-half the number of aromatic carbon atoms beyond the number six minus the number of hydroxyl-oxygen atoms beyond the number one; 
         [0037]    wherein the group-hydrophobic-indices ( 1 n and  1′ n) for R 1  and R 1′  fall in the range 4.0&lt; 1 n, 1′ n&lt;12.0, the group-hydrophobic-indices ( 2 n,  2′ n,  3 n,  3′ n,  5 n,  5′ n and *n) for R 2 , R 2′ , R 3 , R 3′ , R 5 , R 5′ , R*, when present, fall in the range 0.0≦ 2 n, 2′ n, 3 n, 3′ n  5 n, 5′ n,*n&lt;12.0 and the group-hydrophobic-indices ( 4 n and  4′ n) for R 4  and R 4′ , when present, fall in the range 0.0≦ 4 n, 4′ n≦5.0; 
         [0038]    wherein the overall-hydrophobic-index (N) divided by the value of g falls in the range 10.0≦N/g&lt;24.0; 
         [0039]    wherein in A, when the charged moiety, CM, has a formal positive charge or a formal negative charge, g=1, and in B, when CM and CM′ have formal positive charges or when CM and CM′ have formal negative charges, g=2, and in B when CM has a formal positive charge and CM′ has a formal negative charge, g=1; 
         [0040]    wherein the numeric value of the group-hydrophobic-index calculated for a cyclic chemical moiety is divided equally between the two respective R-chemical-moieties; 
         [0041]    wherein R 1  is identified as that R-chemical-moiety when only one such chemical moiety is attached to CM or CM′; wherein R 1  is identified as that R-chemical-moiety having the largest value of the group-hydrophobic-index when there are more than one such chemical moieties attached to CM or CM′; wherein R 4  is identified as that R-chemical-moiety having the smallest value of the group-hydrophobic-index when there are more than three such chemical moieties attached to CM or CM′; and 
         [0042]    wherein CI is a non-interfering, oppositely-charged counter-ion or mixture of such counter-ions, and the value of d is zero, a positive whole number or a positive fraction such that electroneutrality of the overall hydrophobic compound is maintained. 
         [0043]    In one embodiment, the aqueous composition comprising a non-surface active hydrophobic displacer molecule is free of added salt other than a pH buffer. 
         [0044]    In one embodiment, CM has a general formula I or II: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0045]    wherein in the general formula I or II, R 1  is a C 8 -C 11  hydrocarbyl moiety, R 2  and R 3  are independently a C 1 -C 4  hydrocarbyl moiety or benzyl, and R 4  is selected from benzyl, halo-substituted benzyl, 4-alkylbenzyl, 4-trifluoromethyl benzyl, 4-phenylbenzyl, 4-alkoxybenzyl, 4-acetamidobenzyl, H 2 NC(O)CH 2 —, PhHNC(O)CH 2 —, dialkyl-NC(O)CH 2 —, wherein alkyl is C 1 -C 4 , provided that no more than one benzyl group is present in the CM. 
         [0046]    In one embodiment, CM has a general formula I or II: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein in the general formula I or II, R 1  and R 2  are independently C 4 -C 8  alkyl or cyclohexyl, R 3  is C 1 -C 4  alkyl, and R 4  is phenyl, 2-, 3- or 4-halophenyl, benzyl, 2-, 3- or 4-halobenzyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dihalobenzyl, 2,4,6- or 3,4,5-trihalobenzyl, C 6 H 5 CH 2 CH 2 — or 2-, 3- or 4-trifluoromethylbenzyl. 
         [0047]    In one embodiment, CM has a general formula VIII, IX, X or XI, R 1  is C 5 -C 11  alkyl and R 2  is C 1 -C 8  alkyl. 
         [0048]    In one embodiment, CM has a general formula I or II: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein in the general formula I or II, R 1  is C 6 -C 11  alkyl, R 2  and R 3  independently are C 1 -C 4  alkyl, and R 4  is PhC(O)CH 2 —, 4-FC 6 H 4 C(O)CH 2 —, 4-CH 3 C 6 H 4 C(O)CH 2 —, 4-CF 3 C 6 H 4 C(O)CH 2 —, 4-ClC 6 H 4 C(O)CH 2 —, 4-BrC 6 H 4 C(O)CH 2 —, dl-PhC(O)CH(Ph)-, Ph(CH 2 ) 2 —, Ph(CH 2 ) 3 —, Ph(CH 2 ) 4 —, dl-PhCH 2 CH(OH)CH 2 —, t-PhCH═CHCH 2 —, 1-(CH 2 )naphthylene, 9-(CH 2 )anthracene, 2-, 3- or 4-FC 6 H 4 CH 2 — or benzyl. 
         [0049]    In one embodiment, CM has a general formula I or II: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein in the general formula I or II, R 1  is C 6 -C 11  alkyl, R 2  and R 3  together are —(CH 2 ) 4 —, and R 4  is PhC(O)CH 2 —, 4-FC 6 H 4 C(O)CH 2 —, 4-CH 3 C 6 H 4 C(O)CH 2 —, 4-CF 3 C 6 H 4 C(O)CH 2 —, 4-ClC 6 H 4 C(O)CH 2 —, 4-BrC 6 H 4 C(O)CH 2 —, dl-PhC(O)CH(Ph)-, Ph(CH 2 ) 2 —, Ph(CH 2 ) 3 —, Ph(CH 2 ) 4 —, dl-PhCH 2 CH(OH)CH 2 —, t-PhCH═CHCH 2 —, 2-, 3- or 4-FC 6 H 4 CH 2 —, benzyl, 3-ClC 6 H 4 CH 2 —, 2,6-F 2 C 6 H 3 CH 2 —, 3,5-F 2 C 6 H 3 CH 2 —, 4-CH 3 C 6 H 4 CH 2 —, 4-CH 3 CH 2 C 6 H 4 CH 2 —, 4-CH 3 OC 6 H 4 CH 2 —, (CH 3 ) 2 NC(O)CH 2 — or (CH 3 CH 2 ) 2 NC(O)CH 2 —. 
         [0050]    In one embodiment, CM has a general formula I or II: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein in the general formula I or II, R 1  is C 4 -C 6  alkyl, benzyl or 2-, 3- or 4-FC 6 H 4 CH 2 —, R 2  and R 3  independently are C 1 -C 8  alkyl, CH 3 (OCH 2 CH 2 ) 2 —, CH 3 CH 2 OCH 2 CH 2 OCH 2 CH 2 — or CH 3 CH 2 OCH 2 CH 2 —, and R 4  is Ph(CH 2 ) 4 —, 4-PhC 6 H 4 CH 2 —, 4-FC 6 H 4 CH 2 —, 4-CF 3 C 6 H 4 CH 2 —, PhC(O)CH 2 —, 4-FC 6 H 4 C(O)CH 2 —, 4-PhC 6 H 4 C(O)CH 2 —, 4-PhC 6 H 4 CH 2 —, naphthylene-1-CH 2 —, anthracene-9-CH 2 — or Ph(CH 2 ) n —, where n=5-8. 
         [0051]    In one embodiment, CM has a general formula [(R 1 R 2 R 3 NCH 2 ) 2 C 6 H 3 G] 2+ , wherein R 1  is C 4 -C 11  alkyl, R 2  and R 3  independently are C 1 -C 6  alkyl or R 2  and R 3  taken together are —(CH 2 ) 4 —, and G is H or F. 
         [0052]    In one embodiment, CM has a general formula [R 1 R 2 R 3 NCH 2 C 6 H 4 —C 6 H 4 CH 2 NR 1 R 2 R 3 ] 2+ , wherein R 1  is C 4 -C 11  alkyl, R 2  and R 3  independently are C 1 -C 6  alkyl or R 2  and R 3  taken together are —(CH 2 ) 4 —. 
         [0053]    In one embodiment, CM has a general formula III or IV: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein in the general formula III or IV, R 1  is C 8 -C 11  alkyl or 4,4′-CH 3 (CH 2 ) 4 C 6 H 4 —C 6 H 4 CH 2 —, R 2  is C 1 -C 6  alkyl or 4-FC 6 H 4 CH 2 —, and R 3  is C 1 -C 6  alkyl. 
         [0054]    In one embodiment, CM has a general formula XIV or XV: 
         [0000]    wherein in the general formula XIV or XV, R 1  is C 8 -C 11  alkyl, and each G and R 5  are as defined above. 
         [0055]    In one embodiment, CM has a general formula XIIIa, XIIIb, XIIIc, XIIId or XIIIe: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein in the general formula XIIIa, XIIIb, XIIIc, XIIId or XIIIe, R 1  is C 8 -C 11  alkyl or C 8 -C 11  4-phenyl, R 2  is H, C 1 -C 6  alkyl or alkoxy, 2-pyridyl, C 1 -C 6  alkyl substituted 2-pyridyl, or pyrrolidinyl, and each G is as defined above. 
         [0056]    In one embodiment, CM has a general formula VII: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein in the general formula VII, R 1  is C 5 -C 11  alkyl, R 2  and R 5  are independently H or C 1 -C 6  alkyl or phenyl. 
         [0057]    In one embodiment, CM has a general formula XII: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein in the general formula XII, R 1  is C 5 -C 11  alkyl, R 2  and R 5  are independently H or C 1 -C 6  alkyl or phenyl, and G is as defined above. 
         [0058]    In one embodiment, CM has a general formula XXIV or XXV: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein in the general formula XXIV, R 1  is phenyl, 4-EtC 6 H 4 —, 4- n PrC 6 H 4 —, 4- n BuC 6 H 4 —, 4-MeOC 6 H 4 —, 4-FC 6 H 4 —, 4-MeC 6 H 4 —, 4-MeOC 6 H 4 —, 4-EtC 6 H 4 —, 4-ClC 6 H 4 —, or C 6 F 5 —; and each of R2, R3 and R4 independently are phenyl, 4-FC 6 H 4 —, 4-MeC 6 H 4 —, 4-MeOC 6 H 4 —, 4-EtC 6 H 4 —, 4-ClC 6 H 4 — or C 6 F 5 —; and
 
wherein in the general formula XXV, R1 is 4-(4- n BuC 6 H 4 )C 6 H 4 — or 4-(4- n BuC 6 H 4 )—3-ClC 6 H 3 —
 
         [0059]    In one embodiment, CM has a general formula selected from 4-R 1 C 6 H 4 SO 3 H, 5-R 1 -2-HO—C 6 H 3 SO 3 H, 4-R 1 —C 6 H 4 —C 6 H 3 X-4′-SO 3 H, and 4-R 1 —C 6 H 4 —C 6 H 3 X-3′-SO 3 H, wherein R1 is CH 3 (CH 2 ) n , wherein n=4-10 and X is H or OH. 
         [0060]    In one embodiment, CM has a general formula XVIII or XXIII: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein in the general formula XVIII and in the general formula XXIII, R 1  is C 6 H 5 (CH 2 ) n —, wherein n=5-11. 
         [0061]    In one embodiment, CM has a general formula selected from 5-R 1 -2-HO—C 6 H 3 CO 2 H and R 1 C(O)NHCH(C 6 H 5 )CO 2 H, wherein R 1  is CH 3 (CH 12 ) n —, wherein n=4-10. 
         [0062]    In one embodiment, CM has a general formula 4-R 1 C 6 H 4 PO 3 H 2  wherein R 1  is CH 3 (CH 2 ) n —, wherein n=4-10. 
         [0063]    In one embodiment, CI is a non-interfering anion or mixture of non-interfering anions selected from: Cl − , Br − , I − , OH − , F − , OCH 3   − , d,l-HOCH 2 CH(OH)CO 2   − , HOCH 2 CO 2   − , HCO 2   − , CH 3 CO 2   − , CHF 2 CO 2   − , CHCl 2 CO 2   − , CHBr 2 CO 2   − , C 2 H 5 CO 2   − , C 2 F 5 CO 2   − ,  n C 3 H 7 CO 2   − ,  n C 3 F 7 CO 2   − , CF 3 CO 2   − , CCl 3 CO 2   − , CBr 3 CO 2   − , NO 3   − , ClO 4   − , BF 4   − , PF 6   − , HSO 4   − , HCO 3   − , H 2 PO 4   − , CH 3 OCO 2   − , CH 3 OSO 3   − , CH 3 SO 3   − , C 2 H 5 SO 3   − , NCS − , CF 3 SO 3   − , H 2 PO 3   − , CH 3 PO 3 H − , HPO 3   2− , CH 3 PO 3   2− , CO 3   2− , SO 4   2− , HPO 4   2− , PO 4   3− . 
         [0064]    In one embodiment, CI is a non-interfering inorganic cation or mixture of such non-interfering cations selected from the groups: alkali metal ions (Li + , Na + , K + , Rb + , Cs + ), alkaline earth metal ions (Mg 2+ , Ca 2+ , Sr 2+ , Ba 2+ ), divalent transition metal ions (Mn 2+ , Zn 2+ ) and NH 4   + ; wherein CI is a non-interfering organic cation or mixture of such non-interfering cations selected from the groups: protonated primary amines (1+), protonated secondary amines (1+), protonated tertiary amines (1+), protonated diamines (2+), quaternary ammonium ions (1+), sulfonium ions (1+), sulfoxonium ions (1+), phosphonium ions (1+), bis-quaternary ammonium ions (2+) that may contain C 1 -C 6  alkyl groups and/or C 2 -C 4  hydroxyalky groups. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0065]      FIGS. 1   b ,  2 ,  3 ,  4 ,  5 ,  6   b ( a )B and 7 are fraction analyses of the displacement data plotting fraction number (x-axis) against concentration (mg/mL) of each component in each fraction for the displacement chromatography process in accordance with exemplary embodiments of the present invention. 
           [0066]      FIG. 6   b ( a )A is a displacement trace for the purification of a crude synthetic peptide plotting time (x-axis) against relative absorbance units (y-axis) for the displacement chromatography process in accordance with an exemplary embodiment of the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0067]    As used herein, “non-surface-active”, with respect to a cationic non-surface-active displacer compound employed in accordance with the present invention, means that the compound so described has a critical micelle concentration (“CMC”) greater than the concentration of the compound employed in a displacement chromatography process in accordance with the present invention. In one embodiment, the concentration of the non-surface-active displacer compound is less than about 80% of the CMC for that compound in water in the absence of organic solvent, salt or other agent that would affect the CMC. In one embodiment, the concentration of the non-surface-active displacer compound is less than about 60% of the CMC for that compound in water in the absence of organic solvent, salt or other agent that would affect the CMC. In one embodiment, the concentration of the non-surface-active displacer compound is less than about 50% of the CMC for that compound in water in the absence of organic solvent, salt or other agent that would affect the CMC. 
         [0068]    In one embodiment, the aqueous composition comprising a non-surface-active cationic hydrophobic displacer molecule employed in accordance with the present invention does not exhibit adverse surface-active characteristics due to one or a combination of two or more of (1) the cationic non-surface active displacer compound is present at a concentration lower than its CMC; (2) the overall-hydrophobic-index (N) for each [CM] or [CM-R*-CM′] divided by the value of g falls in the range 10≦N/g&lt;24; (3) the group-hydrophobic-index ( 1 n) for each R 1  falls in the range 4&lt; 1 n&lt;12, the group-hydrophobic-index ( 2 n,  3 n,  5 n and *n) for each R 2 , R 3 , R 5  and R*, when present, falls in the range 0≦ 2 n,  3 n,  5 n,*n&lt;12, and the group-hydrophobic-index ( 4 n) for each R 4 , when present, falls in the range 0≦ 4 n≦5; (4) the composition contains greater than about 5 volume % or more of an organic solvent. 
         [0069]    As used herein, “low organic solvent content” generally refers to an organic solvent content in, e.g., an aqueous “carrier” composition comprising a cationic non-surface-active displacer compound in accordance with the present invention, of less than about 25% by volume. In one embodiment, the organic solvent content of the aqueous “carrier” composition contains less than about 20% by volume of any organic solvent. In one embodiment, the organic solvent content of the aqueous “carrier” composition contains less than about 15% by volume of any organic solvent. In one embodiment, the organic solvent content of the aqueous “carrier” composition contains less than about 10% by volume of any organic solvent. In one embodiment, the organic solvent content of the aqueous “carrier” composition contains less than about 5% by volume of any organic solvent. In one embodiment, the aqueous “carrier” composition contains no organic solvent. 
         [0070]    In one embodiment, the organic solvent is one or a mixture of two or more of methanol (CH 3 OH or MeOH), ethanol (C 2 H 5 OH or EtOH) or acetonitrile (CH 3 CN or MeCN). In one embodiment, the aqueous “carrier” composition contains a mixture of suitable organic solvents. In one embodiment, the aqueous “carrier” composition contains no organic solvent. 
         [0071]    Hydrophobic displacement chromatography can be carried out using chiral analytes, chiral displacers and chiral chromatography matrices. Under these conditions, an achiral displacer may be used, but a racemic mixture of a chiral displacer cannot be used. Racemic chiral analytes can also be purified using an achiral chromatography column and an achiral displacer. In this case, impurities, including diastereomers, are removed from the racemic compound of interest, but there is no chiral resolution of the enantiomers. 
         [0072]    Some of the cationic displacers described here have a quaternary nitrogen with four different groups attached and hence are inherently chiral; see for example racemic displacer compounds 43-45, 50-53, 58-59, 64-66 in Tables V-IX below. Furthermore, some of the cationic displacers contain a single chiral group attached to an achiral nitrogen atom; see for example racemic displacer compounds 203 and 206 as well as the enantiomerically pure displacer compound 67 that is derived from l-phenylalanine. With the proper choice of chiral chromatography matrix, mobile phase and achiral displacer, enantiomers are routinely preparatively resolved (separated). Depending on the specific circumstances, a good, enantiomerically pure, chiral displacer can have performance advantages over a good achiral displacer when carrying out a displacement separation of enantiomers on a chiral stationary phase. 
         [0000]    Useful pH Ranges—Various classes of cationic hydrophobic displacers having the general formula A or B, have different useful pH ranges depending on the chemical nature of the charged moieties. Cationic hydrophobic displacers that contain deprotonatable cationic groups should be operated at a pH of 1-2 units or more below the actual pKa values. Cationic hydrophobic displacers that contain protonatable anionic groups should be operated at a pH of 1-2 units or more above the actual pKa values.
       Onium Groups—Generally, quaternary ammonium, quaternary phosphonium, tertiary sulfonium, tertiary sulfoxonium and related cationic groups such as pyridinium, imidazolium, guanidinium have a wide useful pH range, 1-11 or greater, because they don&#39;t have deprotonatable N—H, S—H or P—H moieties under normal conditions.   Amine and Guanidine Groups—Tertiary aliphatic amines (pKa˜9.5) and related substituted quanidines (pKa˜13.5) with deprotonatable N—H moieties are useful cationic groups when operated at a pH of 1-2 units or more below the actual pKa values.       
 
       Displacer Binding-Strength 
       [0075]    The displacer should bind to the column more strongly than all of the components of the sample or at least more strongly than all of the major components of interest. A good rule-of-thumb is that no more than 1-4% of the sample mass should bind more strongly than the displacer. 
         [0076]    An optimal displacer should not bind too strongly nor too weakly to the stationary phase. The proper binding strength depends on the analyte of interest and the associated binding-isotherms. Usually, a range of displacers with a range of binding strengths is needed for a variety of different columns and analytes to be purified. If a displacer binds too strongly, poor performance is obtained such as lower resolution, lower analyte binding capacity, difficulty in displacer removal and longer cycle-times. If a displacer binds too weakly, a poor displacement train may result with too much “tailing” of the displaced analytes underneath the displacer, or there may be only partial displacement or no displacement at all. 
         [0077]    A convenient, rule-of-thumb method that helps in choosing displacers with the proper binding strength is to carry out simple gradient elution chromatography of potential displacers and analytes using similar columns and mobile phases that are to be used in the displacement experiment. As a first screen, the displacer should elute 5-15 minutes later than the analytes of interest in a 60 minute gradient. Ideally one would measure the isotherms of the single analytes and mixtures of analytes but this is time-consuming and often impractical. Because it operates early on the binding-isotherm, this rule-of-thumb method is not perfect, but provides a convenient starting point for further DC optimization. 
       Displacer Binding-Strength 
       [0078]    The displacer should bind to the column more strongly than all of the components of the sample or at least more strongly than all of the major components of interest. A good rule-of-thumb is that no more than 1-4% of the sample mass should bind more strongly than the displacer. 
         [0079]    An optimal displacer should not bind too strongly nor too weakly to the stationary phase. The proper binding strength depends on the analyte of interest and the associated binding-isotherms. Usually, a range of displacers with a range of binding strengths is needed for a variety of different columns and analytes to be purified. If a displacer binds too strongly, poor performance is obtained such as lower resolution, lower analyte binding capacity, difficulty in displacer removal and longer cycle-times. If a displacer binds too weakly, a poor displacement train may result with too much “tailing” of the displaced analytes underneath the displacer, or there may be only partial displacement or no displacement at all. 
         [0080]    A convenient, rule-of-thumb method that helps in choosing displacers with the proper binding strength is to carry out simple gradient elution chromatography of potential displacers and analytes using similar columns and mobile phases that are to be used in the displacement experiment. As a first screen, the displacer should elute 5-15 minutes later than the analytes of interest in a 60 minute gradient. Ideally one would measure the isotherms of the single analytes and mixtures of analytes but this is time-consuming and often impractical. Because it operates early on the binding-isotherm, this rule-of-thumb method is not perfect, but provides a convenient starting point for further DC optimization. 
       Usable Binding-Isotherms 
       [0081]    Apart from proper binding strength, useful hydrophobic displacers need to have binding-isotherms with certain other useful characteristics. 
         [0082]    (1) Monomodal, convex upward isotherms (Langmuir-type isotherm behavior) for displacer and analyte molecules facilitate the orderly formation of isotactic displacement trains and simplify the method optimization process. This is a useful property of many cationic displacer molecules in contrast to binding-isotherms of many other uncharged hydrophobic displacer molecules (non-zwitterions) such as aromatic alcohols (e.g., substituted phenols, naphthols, hydroxybiphenyls), fatty alcohols (e.g., 1-dodecanol, 1,2-dodecanediol) and uncharged fatty carboxylic acids (e.g., myristic acid) behave normally at lower concentrations and then become bimodal and rise again at higher concentrations (BET-type isotherm behavior). This binding behavior often arises from deposition of multiple layers of the hydrophobic displacer, each layer having different binding characteristics. This binding behavior greatly complicates the displacement process and its useful implementation. 
         [0083]    (2) Chromatographic results in DC are also complicated when displacer molecules undergo self-association in solution. As concentrations increase, problems with displacer self-association become worse. Again, the charged groups in cationic hydrophobic displacers inhibit self-association problems in aqueous solution. 
         [0084]    (3) Further complications also arise when product and/or impurity isotherms cross the displacer isotherm in the higher, non-linear binding region. This behavior leads to reversal of displacement order, broadening of overlap regions between displacement bands and problems with co-displacement. In this case, minor variations in displacer concentration can lead to large changes in the displacement train thereby making method optimization very difficult. 
         [0085]    We have found that properly designed cationic displacer molecules supplemented with the proper counter-ions and small amounts of useful organic solvents provide a family of effective hydrophobic displacers with Langmuir-type binding behavior and useful ranges of binding strengths. 
       Ion-Pairing Anions for Cationic Displacers 
       [0086]    With all of their many advantages, cationic hydrophobic displacer molecules have one extra requirement: choosing a good ion-pairing anion, CI. The ion-pairing anion significantly affects the binding-isotherm of the displacer and the functioning and utility of the displacer. The concentration of the ion-pairing agent is independently adjusted by adding appropriate amounts of K + , NH 4   + , protonated amine salts of an ion-pairing anion or Cl − /HCO 2   −  salts of an ion-pairing cation. The properties of an ion-pairing anion for a cationic hydrophobic displacer strongly affects its displacement properties. A few anions may be involved in ion-pairing in solution, and nearly all anions are involved in ion-pairing in the adsorbed state on the hydrophobic chromatography matrix. The same ion-pairing agent(s) for displacer and analyte should be used for good chromatographic resolution. Useful ion-pairing counter-ions are usually singly charged. Owing to their higher solvation energies, divalent ions (SO 4   2− ) and trivalent ions (PO 4   3− ) are generally less useful but may be used in some specialized cases. Exceptions to this general rule are multiple, singly-charged moieties spaced apart in a single organic ion such as  − O 3 S(CH 2 ) 4 SO 3   − . 
         [0087]    Anions with greater hydrophobic character tend to increase binding-strength and also decrease solubility. Furthermore, when using hydrophobic displacer salts, resolution of DC may decrease if the anion itself is either too hydrophobic or too hydrophilic. Typically, intermediate hydrophobic/hydrophilic character of the anion gives best results, but this varies depending on the molecule being purified. The optimal counter-ion for each purification should be determined experimentally. For example, a hydrophobic quaternary ammonium displacer with CH 3 CO 2   −  counter-ion gives good solubility and mediocre resolution, with CF 3 CO 2   −  gives mediocre, but acceptable, solubility and good resolution, and with CCl 3 CO 2   −  gives poor solubility and mediocre resolution. Volatile ion-pairing agents are conveniently removed under reduced pressure, while nonvolatile ones are readily removed by other means such as diafiltration, precipitation or crystallization. Table I gives a partial list of useful monovalent ion-pairing anions. When using anionic ion-pairing agents, the operating pH should be 1-2 pH units or more above the pKa of the respective acid. A notable exception to this guideline is trifluoroacetic acid that acts as both ion-pairing agent and pH buffer at the same time. 
         [0000]    
       
         
               
             
               
               
             
           
               
                 TABLE I 
               
               
                   
               
               
                 Monovalent Anions in Approximate Order of Ion-pairing Strength 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 Weak 
                 Fluoride &lt; Hydroxide &lt; Gluconate &lt; Glycerate &lt;  
               
               
                   
                 Glycolate &lt; Lactate 
               
               
                 Moderate  
                 Formate &lt; Acetate &lt; Bicarbonate &lt; Propionate &lt; Butyrate &lt; 
               
               
                   
                 Methanesulfonate &lt; Ethanesulfonate &lt; Difluoroacetate &lt;  
               
               
                   
                 Chloride 
               
               
                 Medium Strong  
                 Bromide &lt; Trifluoroacetate &lt; Dichloroacetate &lt; Nitrate 
               
               
                 Strong 
                 Triflate &lt; Iodide &lt; Dibromoacetate &lt; Thiocyanate &lt;  
               
               
                   
                 Trichloroacetate &lt; Perchlorate &lt; Hexafluoroisobutrate &lt; 
               
               
                   
                 Pentafluoropropionate &lt; Tetrafluoroborate &lt; 
               
               
                   
                 Hexafluorophosphate &lt; Tribromoacetate 
               
               
                   
               
             
          
         
       
     
         [0088]    Mixed anions often lead to loss of chromatographic resolution and are generally to be avoided. However, there is one set of conditions when mixed anions may be used; that is, when both (a) the anion of interest has significantly stronger ion-pairing properties than the other anions that are present and (b) the anion of interest is present in stoichiometric excess in the sample loading mixture and in the displacer buffer. 
         [0089]    The most commonly used ion-pairing anions are formate, acetate, chloride, bromide and trifluoroacetate. Owing to lower ion-pairing strength, formate and acetate require careful optimization in order to obtain good resolution. Bromide and trifluoroacetate seem to give the best results for peptides and small proteins. Generally, good chromatographic results can be obtained with chloride and bromide as ion-pairing anions, but two special precautions should be exercised. (1) Under acidic conditions, the chromatography solutions cannot be degassed by helium purging or by vacuum degassing owing to loss of gaseous HCl or HBr thereby changing the pH and changing the concentration of the anion. This problem is overcome by using degassed distilled water for preparing chromatography solutions and storing the solutions in closed containers to prevent reabsorption of air. (2) Chloride and bromide are potentially corrosive to stainless steel HPLC equipment, but equipment made from PEEK, Teflon, ceramic, glass and titanium is safe. The main problem is halide-catalyzed corrosion of stainless steel caused by air (oxygen) at low pH. If HPLC solutions are properly deoxygenated, halide-promoted corrosion of stainless steel is greatly reduced. 
       Solubility 
       [0090]    In “hydrophobic chromatography” or, more properly, “solvophobic chromatography”, where the principal solvent component is water, potential hydrophobic displacer molecules often have limited solubility. Hydrophobic molecules usually do not dissolve in water to any appreciable extent unless there are “hydrophillic groups” attached to the hydrophobic molecule, such as charged ionic-groups, hydrophillic counter-ions, polar groups or groups that function as hydrogen-bond donors or acceptors. Aromatic molecules interact with water in a unique fashion owing to the unique manner in which the pi-electrons act as weak hydrogen-bond acceptors. Furthermore, aromatic molecules can engage in face-to-face pi-stacking in aqueous solution. These small but important effects are reflected in the higher solubility in water of benzene (9 mM) and naphthalene (200 μM) compared with cyclohexane (˜10 μM) and trans-decalin (&lt;1 μM) and in the higher solubility of phenol (960 mM) and β-naphthol (7 mM) compared with the unhydroxylated arenes. The molecular structure of a useful displacer molecule should facilitate a reasonable solubility (10-50 mM) in water or in water with low organic content yet at the same time be sufficiently hydrophobic that it binds strongly to the stationary phase. Generally, charged displacer molecules have better solubility properties than neutral ones owing to the increased solvation energies of charged species, especially counter-ions. It requires a unique balance of physical and chemical properties for neutral zwitterionic molecules to behave as good displacers. Cationic hydrophobic displacers display unique solubility properties. 
         [0091]    It is important to note, generally speaking, that increasing the levels of the organic solvent in order to compensate for poor displacer solubility rarely leads to useful results. Best chromatographic results are obtained with 0-25% organic solvent, or more preferably, 2-15% organic solvent. Higher organic content (25-75%) of the mobile phase may be used in some cases but usually capacity and resolution often suffer badly. 
       Reduced Product-Displacer Association 
       [0092]    One potential problem with hydrophobic displacement chromatography is the possible association of a hydrophobic displacer with a hydrophobic analyte in solution. This can lead to significant loss of resolution and contamination. Displacer-analyte association in the adsorbed state on the stationary phase also can occur but is less problematic with proper amounts of suitable ion-pairing agents present. A good method to deal with this problem is to use charged analytes and charged hydrophobic displacers with the same charge. 
       Displacer Self-Association and Micelle Formation 
       [0093]    In some cases when the chemical structure and physical properties are conducive, cationic hydrophobic molecules can self-associate, forming micelles and micelle-like, self-associated structures in solution. This situation can lead to loss of resolution in DC as well as unwanted foaming of displacer solutions. The displacer in solution finds itself in various forms that are interrelated by various chemical equilibria. Furthermore, micelles can act as carriers for hydrophobic analyte molecules causing them to exist in solution in various forms. This unwanted phenomenon is concentration dependent and is effectively inhibited by the addition of small amounts of a suitable organic solvent such as methanol, ethanol or acetonitrile. Properly designed, cationic displacer molecules disenhance micelle formation and give better displacement results. Thus, keeping the group-hydrophobic-indices below 12.0 for R-groups, R 1 -R 3 , reduces the problem of unwanted detergency. 
       High Purity—Impurities in Displacers 
       [0094]    A displacer should have adequate purity. The object of preparative chromatography is to remove the impurities from a component of interest. Contamination of the desired compound by the displacer itself is rarely a problem, but contamination by “early displacing” impurities in the displacer solution may be problematic in some cases depending on the amounts of the impurities and their binding properties. Thus, a good displacer should contain little or no early displacing impurities. 
       Suitable UV Absorbance 
       [0095]    In order to track the location and amounts of displacer throughout the DC experiment, to watch displacer breakthrough curves and to follow displacer removal during column regeneration procedures, it is useful to have a displacer with moderate ultraviolet absorption. High absorption is not needed nor is it preferred owing to the high concentrations of displacer and analyte. Generally, colorless displacers are preferred with a UV spectrum that has strategically located windows of low absorbance so that the analytes can be followed at some frequencies and the displacer monitored at other frequencies. 
       Ease of Manufacturing and Cost 
       [0096]    Convenient and cost-effective methods of chemical synthesis, production and manufacturing are important in order to produce useful displacers and reasonable costs. Furthermore, practical methods of purification, especially non-chromatographic purification, are needed in order to achieve the purity requirements in a cost-effective manner. 
       Chemical Stability, Low Toxicity and Long Shelf-Life 
       [0097]    Among all its other desired chemical and physical properties, a useful displacer molecule should be chemically stable. It should be inert toward analyte molecules and chemically stable (non-reactive) toward water, common organic solvents, mild bases, mild acids and oxygen (air). It should be photo-stable and thermally stable under typical use and storage conditions and have a reasonable shelf-life. It greatly preferred that displacer molecules be visually colorless, yet have the requisite levels of UV absorbance. Useful displacer molecules also need to have low toxicity, not only to protect workers but to protect biological and drug samples that may come into contact with the displacer. 
       Suitable Chromatographic Columns: 
       [0098]    While the most common type of reversed-phase column is octadecyl coated silica, many hydrophobic stationary phases find utility in DC (see Table III). Ultimately, the best choice of stationary phase is experimentally determined for each system under study. 
         [0000]                                                                        TABLE II               Materials for Hydrophobic Stationary Phases                                Coated Porous Silica (covanently bonded silanes)                Octadecyl (C 18 )   Docecyl (C 12 )           Octyl (C 8 )   Hexyl (C 6 )           Butyl (C 4 )   Pentafluorophenylpropyl (C 6 F 5 —C 3 )           Phenylpropyl (Ph—C 3 )   Phenylhexyl (Ph—C 6 )           p-Biphenyl (Ph—Ph)   β-Naphthylethyl (Nap-C 2 )            Uncoated Porous Polystyrene/Divinylbenzene       Porous Fluorocarbon Polymer       Porous Polyoctadecylmethacrylate Polymer       Carbon-like Phases:                Porous Graphitized Carbon           Cleaned Charcoal           Carbon over Porous Zirconia           C 18  Bonded to Carbon over Porous Zircona            Organic Polymer Coatings over Inorganic Oxides       Mixed-Mode Hydrophobic Phases                C 18  with negative surface charge           C 18  with positive surface charge           C 18  with buried negative charge           C 18  with buried positive charge                    
Better results in displacement chromatography are obtained with longer, well-packed columns that give better recovery and yield. Table IV provides a guide for initial choices of column dimension and initial flow-rates.
 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE III 
               
             
             
               
                   
               
               
                 Chromatography Column Dimensions 
               
             
          
           
               
                 Particle 
                 Column 
                 Column 
                 Column 
                 Initial 
                 Sample 
               
               
                 Size 
                 Length 
                 Dia. 
                 Volume 
                 Flow 
                 Injection 
               
               
                 (μm) 
                 (mm) 
                 (mm) 
                 (mL) 
                 Rate b   
                 Method 
               
               
                   
               
             
          
           
               
                 2 
                 100 
                 2.1 
                 0.3464 
                 43.3  
                 μL/min 
                 3  
                 mL loop 
               
               
                 3 
                 150 
                 2.1 
                 0.5195 
                 43.3  
                 μL/min 
                 5  
                 mL loop 
               
               
                 3 
                 150 
                 3.0 
                 1.060 
                 88.4  
                 μL/min 
                 10  
                 mL loop 
               
               
                 3 
                 150 
                 4.6 
                 2.493 
                 208  
                 μL/min 
                 20  
                 mL loop/ 
               
               
                 Pump 
                   
                   
                   
                   
                   
                   
                 Inject. 
               
               
                 5 
                 250 
                 4.6 
                 4.155 
                 208  
                 μL/min 
                 40  
                 mL loop/ 
               
               
                 Pump 
                   
                   
                   
                   
                   
                   
                 Inject. 
               
             
          
           
               
                 5 
                 250 
                 10.0 
                 19.63 
                 982  
                 μL/min 
                 Inject. Pump 
               
               
                 5 
                 250 
                 20.0 
                 78.54 
                 3.93  
                 mL/min 
                 Inject. Pump 
               
               
                 10 
                     500 a   
                 10.0 
                 39.27 
                 982  
                 μL/min 
                 Inject. Pump 
               
               
                 10 
                     500 a   
                 20.0 
                 157.1 
                 3.93  
                 mL/min 
                 Inject. Pump 
               
               
                 10 
                     500 a   
                 30.0 
                 353.4 
                 8.84  
                 mL/min 
                 Inject. Pump 
               
               
                 10 
                     500 a   
                 50.0 
                 981.7 
                 24.5  
                 mL/min 
                 Inject. Pump 
               
               
                   
               
               
                 a) 500 mm or 2 × 250 mm 
               
               
                 b) Initial flow-rate = 75 cm/hr (12.5 mm/min); needs to be optimized 
               
             
          
         
       
     
         [0099]    Proper column length is important for good results. It should be long enough to fully sharpen the displacement train and give good resolution. Yet columns that are too long needlessly increase separation time and often lead to poorly packed beds and reduced resolution. In many cases, two well-packed columns can be attached end-to-end with good chromatographic results. Considerable experimentation with small molecules (MW&lt;3 KDa) indicates that optimal column length falls in the range 15-45 cm for 5 μm particles and 20-60 cm for 10 μm particles. Porous particles with pore sizes of 80-100 Å are suitable for traditional drugs and small peptides, 120-150 Å are suitable for medium and large oligopeptides and oligonucleotides and 300-500 Å are suitable for most proteins and DNA. Non-porous particles can be used, but loading capacity will significantly decrease. 
         [0100]    In cylindrical columns, it is important that a planar flow-front be established so that it is perpendicular to the axis of flow. Scaling up to purify larger amounts of sample is simple and straightforward in displacement chromatography once an optimized protocol has been developed on a smaller column. After the shortest acceptable column-length is found, scale-up is simply accomplished by increasing column diameter while maintaining a constant linear flow-rate. With proper modifications, displacement chromatography can be used with radial-flow columns and with axial-flow monolith columns. The principles of displacement chromatography can be applied in analytical and preparative thin-layer chromatography. 
       Running Successful Displacement Chromatography Experiments 
       [0101]    Though displacement chromatography of organic compounds, traditional drugs and peptides has been carried out for many years, mediocre-to-poor results are often obtained. Good displacers, good columns and good operational protocols lead to excellent reproducibility and remarkably good chromatographic performance. 
       Displacer and Concentration 
       [0102]    Initial evaluation is carried out using a good general purpose cationic displacer with proper binding strength. Cationic displacers can be used to purify cationic, neutral non-ionic and neutral zwitterionic analytes. The displacer should bind to the column more strongly than the material to be purified, but the displacer should not bind too strongly. Typical displacer concentrations are in the range 10-50 mM. Initially, displacer concentration is set at 10-15 mM. As needed, pH buffer and ion-pairing anion are added to the displacer solution. The displacer solution and carrier solution should have identical compositions (including pH), except for the presence of displacer and the level of the ion-pairing anion. Displacers 14, 198 and 318 (below) are examples of good general-purpose cationic displacers. During method optimization, it may be helpful to increase displacer concentration up to 20-30 mM or higher. 
         [0103]    Choosing an Ion-Pairing Agent 
         [0104]    Not using an ion-pairing agent, using an ineffective ion-pairing agent, using mixed ion-pairing agents and using insufficient levels of a good ion-pairing agent are some of the major causes of poor chromatographic performance in displacement chromatography experiments. This is not generally appreciated or understood by those who carry out hydrophobic displacement chromatography. This is amply demonstrated in Example 8 below. Table I contains lists of useful, monovalent, ion-pairing anions that are useful for hydrophobic chromatography. They are needed when the analyte or displacer is charged. For charged analytes and displacers, binding-isotherms strongly depend on the chemical properties of the counter-ion and its concentration. Those ion-pairing agents with moderate to moderately strong binding properties are usually the best to use. When starting experimentation with ion-pairing agents, try bromide or trifluoroacetate (free acid or NH 4   +  salt) as ion-pairing anions. When the analyte requires an ion-pairing anion, it usually dictates the choice of ion-pairing anion for the cationic displacer in the DC experiment. The ion-pairing anion for the analyte and the displacer should be the same. 
       Concentration of Ion-Pairing Agent 
       [0105]    As noted earlier, using insufficient levels of a good ion-pairing agent is one of the major causes of poor chromatographic performance in displacement chromatography experiments. The formula for calculating the suitable concentration of the ion-pairing agent in the sample solution (C IPS , mM)) is given by, 
         [0000]        C   IPS   =E   s   ×C   s (mM)× G   s  
 
         [0000]    where E s  is the excess factor for the sample, C s  is the concentration of the sample (mM) and G s  is the absolute value of the net charge of the sample at the operative pH. The optimal value of E s  is a parameter that needs to be determined experimentally. The formula for calculating the suitable concentration of the ion-pairing agent in the displacer solution (C IPD , mM) is given by, 
         [0000]        C   IPD   =E   d   ×C   d (mM)× G   d  
 
         [0000]    where E d  is the excess factor for the displacer, C d  is the concentration of the displacer (mM) and G d  is the absolute value of the net charge of the displacer at the operative pH. The optimal value of E d  is a parameter that needs to be determined experimentally. It is essential that at least a stoichiometric amount of the ion-pairing agent be present in the solutions (E s ≧1.0 and E d ≧1.0). In practice, it is our experience that E s  should be in the range 1.1-10.0, more preferably in the range 1.2-6.0, more preferably yet in the range 1.5-4.5. Furthermore, it is our experience that E d  should be in the range 1.1-10.0, more preferably in the range 1.2-4.0. Serious deterioration in chromatographic performance results when the ion-pairing concentrations are unoptimized or too low, that is E s &lt;1.0 and/or E d &lt;1.0. 
       Choosing a Good RP Column 
       [0106]    For initial reversed-phase work, several good quality octadecyl on silica or phenylhexyl on silica columns should be evaluated (5 μm spherical particles with dimensions 4.6×250 mm). Scaleup to larger preparative columns can come later and is relatively straightforward. A critical issue is to choose a suitable pore size. Matrices with pores that are too large or too small often lead to reduced capacity and sometimes reduced resolution. See Tables II and III above. 
       Flow-Rates 
       [0107]    Because displacement chromatography is a “quasi-equilibrium technique”, relatively slow flow-rates are often needed. The optimal flow-rate is the fastest flow-rate possible without losing resolution. Sample loading flow-rate and displacement flow-rate should be about the same, both in the range of 35-105 cm/hr. Start at 75 cm/hr for traditional drugs, oligopeptides and oligonucleotides or 40 cm/hr for proteins and DNA. Regeneration flow-rates should be 2-8 times the displacement flow-rate. When purifying drugs, peptides or oligonucleotides at elevated temperatures on reversed-phase columns, faster flow-rates might be used. 
       Temperature 
       [0108]    Because reversed-phase chromatography and other forms of hydrophobic chromatography are largely driven by +TΔS with +ΔH, higher temperature often leads to stronger binding, faster binding kinetics and distinctly different resolution. As a consequence, the temperature of the column and, to some extent, displacement buffers should be carefully regulated (+/−0.5° C.) in order to prevent band broadening. Initial work is often carried out at 25° C., and then elevated temperatures (45, 65° C.) are tried if the sample will tolerate it, and the boiling point of the organic solvent is suitable. 
       Choosing an Organic Solvent 
       [0109]    Although most water-miscible organic solvents will function, acetonitrile, methanol and ethanol are most commonly used. Some DC purifications are carried out with little or no organic solvent at all. This allows practical RPC and HIC purification of undenatured proteins with low salt and low organic solvent. Operating without organic solvent may also be helpful when there are safety issues associated with volatile, flammable solvents. When experimenting, first try acetonitrile for peptides, low molecular-weight organic drugs and small proteins or methanol for large proteins oligonucleotides and DNA. If solubility of the sample in water is acceptable, start with 3% v/v MeCN, 4% v/v EtOH or 5% v/v MeOH in the carrier buffer, the displacer buffer and sample loading solution; the organic content of these three solutions should be the same. Organic solvent content is an important parameter that needs to be optimized for each sample, column and displacer. For general purpose operation, organic solvent should be less than about 15 volume %, more preferably less than about 10 volume %, more preferably yet about 5 volume %. When Octadecyl columns are used, 2-3% acetonitrile, 3-4% ethanol or 4-5% methanol is usually needed for optimal functioning of the matrix. Phenylhexyl and Octyl columns can usually tolerate the absence of organic solvent. 
       Choice of pH and pH Buffer 
       [0110]    pH buffers are needed when there are ionizable protons in 
         [0000]    the sample, displacer, ion-pairing agent or on the stationary phase. Some samples are only stable within certain pH ranges. For some samples, chromatographic resolution is strongly pH-dependent. Generally, cationic samples are purified using cationic displacers and cationic buffers. The anions associated with the cationic buffers should be the same as the ion-pairing anion. In some cases, a different anion can be used as long as it has significantly weaker ion-pairing properties. Likewise, an anionic pH-buffer may be used if it has much weaker ion-pairing properties than the principle ion-pairing anion; thus, formic acid and acetic acid can be used as pH buffers when trifluoroacetate is the ion-pairing anion. For obvious reasons, neutral and cationic amines with low pK a  values are useful pH-buffers: N,N,N′,N′-tetramethylethylene-diamine (5.9, TMEDA), N-ethylpiperazine (5.0, NEP), N,N-dimethypiperazine (4.2, DMP), diazobicyclooctane (3.0, DABCO). 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE IV 
               
             
             
               
                   
               
               
                 Buffering Systems for 10 mM [D + ] [O 2 CF 3 ] Displacer 
               
             
          
           
               
                 pH 
                 Buffer 
                 IP Agent a   
                 Adjust pH 
               
               
                   
               
               
                 2.0 
                 12 mM CF 3 CO 2 H 
                 CF 3 CO 2   −   
                 NH 4 OH 
               
               
                 2.0 
                 18 mM H 3 PO 4  + 
                 CF 3 CO 2   −   
                 NH 4 OH 
               
               
                   
                 10 mM CF 3 CO 2 H 
                   
                   
               
               
                 3.0 
                 20 mM DABCO + 
                 CF 3 CO 2   −   
                 HCO 2 H 
               
               
                   
                 10 mM CF 3 CO 2 H 
                   
                   
               
               
                 3.5 
                 20 mM HCO 2 H + 
                 CF 3 CO 2   −   
                 NH 4 OH 
               
               
                   
                 10 mM CF 3 CO 2 H 
                   
                   
               
               
                 4.2 
                 20 mM DMP + 
                 CF 3 CO 2   −   
                 HCO 2 H 
               
               
                   
                 10 mM CF 3 CO 2 H 
                   
                   
               
               
                 4.6 
                 20 mM CH 3 CO 2 H + 
                 CF 3 CO 2   −   
                 NH 4 OH 
               
               
                   
                 10 mM CF 3 CO 2 H 
                   
                   
               
               
                 5.9 
                 20 mM TMEDA + 
                 CF 3 CO 2   −   
                 HCO 2 H 
               
               
                   
                 10 mM CF 3 CO 2 H 
               
               
                   
               
             
          
         
       
     
       Co-Displacement 
       [0111]    When working with samples that contain hundreds components and impurities, co-displacement is an almost unavoidable phenomenon because there are likely to be several minor components that co-displace with the major component of interest no matter where on the binding isotherms the DC experiments take place. Fortunately, co-displacement in displacement chromatography is a far less serious problem than co-elution in preparative elution chromatography. Co-displacement occurs under two, conditions: (1) when binding-isotherms are so similar that there is poor resolution and (2) when there is crossing of binding-isotherms near the operating region of the binding-isotherm. Fortunately, there are simple ways to deal with this issue: carry out a second DC experiment under different conditions by operating at a different point on the binding-isotherms by,
       a. changing the concentration of the displacer,   b. changing to a different displacer with different binding properties.       
 
         [0114]    Alternatively, the isotherms themselves can be changed by,
       c. changing the chromatography matrix (stationary phase),   d. changing the concentration of the organic solvent,   e. changing to a different organic solvent,   f. changing to a different ion-pairing agent,   g. changing the temperature.       
 
         [0120]    A second “orthogonal” IP-RP DC step typically gives excellent purity (˜99.5%) with excellent yield (90-95%). 
       Method of Sample Loading 
       [0121]    A sample is loaded onto the column through a sample injection valve using one of two methods. The sample should be loaded under frontal chromatography conditions at the same point on the binding-isotherm at which the DC experiment takes place. The carrier is not passed through the column after the sample is loaded. Method 1: A sample loading pump is used; Method 2: An injection loop is used. Usually, only partial loop injection is used. The sample in the loop should be driven out of the loop onto the column first by the carrier and then the displacer solution. Not more that 85-95% of the loop volume should be loaded onto the column so that sample diluted by carrier is not loaded. 
       Column Loading 
       [0122]    DC experiments are carried out at relatively high loading, typically in the range 60-80% of maximum loading capacity. The operative column loading capacity is not a fixed number; rather, it depends upon where on the binding-isotherm the DC experiment operates. 
         [0123]    Not all of the column capacity is available for use (see “Exception” below). In practice, only 90-98% of the column capacity can is usable. Once the sample has been loaded onto the column, the displacer buffer is then pumped onto the column. There are three fronts that develop each traveling at different velocities down the column: (1) the liquid front (T 1 , displacer buffer minus displacer), (2) the sample front (T 2 ) and (3) the displacer saturation front itself (T 3 ). The first front travels faster than the second and third fronts and limits the useable column capacity because the first front should exit the column before the displacement train (T 2 ) begins to exit. The actual velocities of the fronts depend directly on the displacement flow-rate. The ratio, α, of the front velocities, Vel 1 /Vel 2 , is given by the formula: 
         [0000]      α= K   m /( R×C   d )
 
         [0000]    where K m  is the displacer binding capacity of the matrix (mg displacer per mL packed matrix) at displacer concentration of C d , where C d  is the displacer concentration in the displacer buffer (mg displacer per mL displacer buffer), R is the ratio of the volume of the liquid in the column to the total volume of the column (mL liquid per mL m  bed volume). The maximum % usable column capacity is given by, 
         [0000]      (100×(α−1))/α.
 
         [0000]    In examples 1 b and 6b(a) below, the respective α-values are 22.24 and 21.49, and the respective maximum column capacities are 95.5% and 95.3%. Note that as C d  increases, K m  will also increase, but not as much if operating high on the nonlinear part of the isotherm. Thus, α will decrease and maximum % usable column capacity will decrease. 
         [0124]    Exception—If significant levels of unwanted, early-displacing impurities are present in the sample, one can increase the usable capacity of the column, even beyond 100% by overloading the column and spilling out these impurities during sample loading before the displacer flow is started. Thus, the column loading could be 105% of maximum based on the whole sample, but the column loading would be only 80% based on the amount of main product plus late-displacing impurities. 
       Concentration and Volume of Sample Solution 
       [0125]    The concentration of the load sample is an important operating parameter. The optimal sample loading concentration (mg/mL) is the same as the output concentration of the purified product from the displacement experiment—the plateau region of the displacement train. Binding-isotherms, the column binding capacities and the output concentrations are initially unknown. Simply carry out the first displacement experiment with the sample solution loaded onto the column using initial estimates as shown below: 
         [0000]    (1) Pick an initial column loading percentage at which the one wishes to work, say 75%. 
         [0000]      Sample loading time=displacer breakthrough time (T 3 −T 1 )×0.75=(586 min−270 min)×0.75=237 min (for Example 6b(a))
 
         [0000]    (2) Pick an initial concentration for the sample by one of two methods: 
         [0126]    (a) Initial sample conc. (mg/mL)=0.25×disp. conc. (mM)×formula wt. (mg/μmole)
       =0.12×10 mM×1.7466 mg/μmole=2.10 mg/mL (for Example 6b(a))       
 
         [0128]    (b) Pick an estimated column binding capacity for the sample, say 50 mg sample/mL matrix. Assume displacement flow-rate and sample loading flow-rate are the same:
       Initial sample conc. (mg/mL)=(col. binding capacity (mg/mL m )×col. volume (mL m )/((T 2 −T 1 )×sample flow-rate (mL/min))=(50 mg/mL m ×4.155 mL m )/((586 min−270 min)×0.208 mL/min)=3.16 mg/mL (for Example 6b(a))       
 
         [0130]    If the first DC experiment with loaded sample leads to overloaded conditions (&gt;100% loading), rerun the experiment at one-half the sample concentration. From the results of the first successful DC experiment while using a sample, actual loading concentration and actual column loading capacity are readily calculated, and those values are then used in adjusting sample concentration and loading for the second DC experiment. 
       Sample Preparation 
       [0131]    The loading sample solution is prepared at the concentration and amount described above. Enough excess solution is needed for overfilling the loop or filling the dead volume of a sample loading pump and delivery lines. The pH, amount of pH buffer and amount of organic solvent are the same as the carrier and displacer buffer. Dissolving the sample in the carrier changes its pH, so the pH of the sample solution will have to be re-adjusted after dissolution. However, the amount of ion-pairing agent may be different. The ion-pairing agent used in the sample solution must be the same one used in the displacer buffer. In this regard, the ion-pairing requirements of the sample dictate which ion-pairing agent is used in the sample solution and in the displacer solution. Based on the formal chemical charge at the operating pH and the concentration of the main analyte, the concentration of the concentration is the ion-pairing agent or ion-pairing salt is calculated. See “Concentration of Ion-Pairing Agent” above. 
         [0132]    The composition and history of the sample should be known. If the sample contains an anion, its chemical nature and amount (concentration) should also be known. (a) Obviously, if no anion is present, then no adjustment is made in sample preparation. (b) If the anion in the sample is the same as the ion-pairing anion used in the DC, then the amount of added ion-pairing anion to the sample solution is reduced accordingly. (c) If the anion in the sample has significantly weaker ion-pairing properties than the ion-pairing anion used in the DC, then its presence is ignored. (d) If the anion in the sample has stronger ion-pairing properties than the ion-pairing agent used in the DC, then the anion should be exchanged or removed before proceeding. 
       Collecting Fractions 
       [0133]    Displacement chromatography gives excellent chromatographic resolution, especially with optimized protocols using a good C 18 -reversed-phase column. However, the resolution is difficult to see because all of the bands come off the column together as back-to-back bands in the displacement train. Many of the small impurity triangle-bands are less than 30 seconds wide (&lt;100 μL). Thus, an experiment with a displacer breakthrough time of 250 minutes and 80% sample loading, the displacement train would be about 200 minutes wide, and more that 400 fractions would have to be taken so that chromatographic resolution is not lost during the fraction-collection process. Analyzing 400 fractions is truly enlightening and interesting but also a daunting task. This is when online real-time fraction analysis would be useful. In practice, we throw away resolution and collect only 100-130 larger fractions. Even this number of fractions represents a lot of work. 
         [0134]    In the circumstance in which a preparative DC experiment is conducted and only the purified main component is of interest, the fraction collecting process is greatly simplified. Based on the shape of the displacement train observed at various frequencies (UV), the beginning and ending of main band of interest is judged and then about 10 fractions are analyzed in both regions in order to determine which fractions to pool. Analyzing 20 fractions instead of 100-130 fractions is an easier task. 
       Displacer Removal and Column Regeneration 
       [0135]    The displacer is removed using 5-10 column volumes of 95/5 (v/v) ethanol-water or 80/10/10 (v/v/v) acetonitrile- n propanol-water without any pH buffer or ion-pairing agent. The object is to efficiently remove &gt;99.9% or more of the displacer from the column in the shortest amount of time. The flow-rate is increased (100-400 cm/hr) in order to speed up the column regeneration process if the matrix will tolerate the increased back-pressure. Observing the displacer removal near the absorption maximum of the displacer (see displacer instructions) allows the regeneration process to be carefully monitored and optimized by UV detection. 
       Effects of Added Salt 
       [0136]    Salts in aqueous solvents lead to solvents that are less hospitable to dissolved hydrophobic analytes and hydrophobic displacers resulting in stronger binding to hydrophobic chromatographic matrices. This is the principle behind hydrophobic-interaction chromatography (HIC). So long as solubility of the analyte is sufficient in the salt solution, the addition of salt is a good way to modulate analyte binding and selectivity to a hydrophobic matrix. 
         [0137]    In some cases, analyte binding to a hydrophobic matrix is so weak that added salt is needed in order to obtain sufficient analyte binding. Commonly used salt solutions are 0.5-2.5M (NH 4 ) 2 SO 4 , K 2 SO 4 , Na 2 SO 4 , NaCl, KCl. With the help of many different salts at various concentrations, HIC in displacement mode offers many options for useful chromatographic separations of proteins. 
       Instrument Protocols 
       [0138]    See example protocol for Example 1 (dual pump operation). Because residual displacer from previous experiments is a potential problem, the protocol has line purging operations, a quick column regeneration and equilibration operations in order to make sure that the HPLC system and column are completely clean and properly equilibrated just before sample loading. These steps are simply precautionary and not always necessary. The protocol includes the (a) a pre-equilibration sequence, (b) an equilibration sequence, (c) a sample loading sequence (d) a displacement sequence and (e) a regeneration sequence in a single protocol. In order to overcome problems with dead-volume in the system, all loading buffers, displacer buffers and sample solutions are purged through the system to waste just prior to pumping onto the column. This way, the column sees a sharp front of undiluted solutions immediately upon valve switching. The sample solutions should be degassed so that gas bubbles do not form in them. When injection loops are used, they need to be overfilled by about 10%. The overfill can be collected for further use. Full loop injections should not be used, only partial loop injections. Experience dictates that only 85-95% of the loop volume can be used depending on the inner diameter of the loop tubing because the sample solution mixes with the driver solution and dilutes it. The sample in the loop is driven onto the column by the loading buffer, but toward the end of the sample loading process, the driving solution is changed to the displacer buffer. This allows the displacer buffer to be purged through the system just prior to the displacer buffer itself being pumped directly onto the column. During the initial part of the regeneration process, slower flow-rates are used Thus, problems with high backpressure rarely occur. Once most of the displacer has been removed, higher flow-rates can be used. 
       Method Optimization 
       [0139]    As with all forms of preparative chromatography, optimization of the chromatographic methods and procedures is important, but it requires some effort. The benefits of displacement chromatography come with a price-time. The time-consuming factors are minimized during method optimization.
       Determine near optimal conditions for the displacement purification without regard for the time of the separation.   Increase the displacer concentration and the concentration of the sample loading solution until resolution decreases.   Increase the displacement flow-rate and the sample loading flow-rate until resolution decreases.   Shorten the pre-equilibration sequence and the displacer removal/column regeneration sequences.       
 
         [0144]    Existing protocols provide a useful starting point for method optimization, but they will need modification for the specific sample under study. A sample protocol (Example 1) is shown below that has been optimized for purity without regard to time. It is important to carry out method optimization adapted for the specific physical properties and chromatographic properties of the sample of interest. Upon optimization, longer methods (600-800 min) often can be reduced to 200-300 minutes and in some cases reduced to 100-150 minutes. 
         [0145]    Hydrophobic chromatography used in displacement mode has (a) high matrix productivity (gram of product per liter matrix over the lifetime of the matrix), (b) high volume productivity (gram of product per liter of column volume), (c) high solvent productivity (gram of product per liter of solvent used) yet (d) may have mediocre time productivity (gram of product per liter of unit time). Proper method optimization mitigates the time factor. 
       Properly Configured Instrumentation: 
       [0146]    A typical instrumental configuration for a small preparative HPLC system is given below.
       Main Pump: stainless steel, titanium, ceramic, PEEK; accurate 0.01-10 mL/min flow-rate; 3000-4500 psi pressure.   Optional Column Bypass Valve: two-position, six-port switching valve (stainless steel, PEEK); column inline or bypass column. This is a convenience option.   Required Sample Injection Valve: two-position, six-port injection valve (stainless steel, PEEK) for injection loop or sample injection pump.   Injection Loop: 20-40 mL injection loop (stainless steel, PEEK). Loop should be overloaded (˜10%). Only partial loop injection is used, typically no more than 85-95% of loop volume. Use one, either an injection loop or a sample pump.   Sample Pump: this is similar to main pump for sample injection. Sample should be compatible with flow path of pump head. Use one, either an injection loop or a sample pump. With a two-pump operation, the flow-rates of the two pumps should be calibrated so that their flows can be matched.   No Gradient Mixer: bypass or remove the gradient mixer in displacement chromatography.   UV Detector: Multiple wavelength or photo-diode-array detector, 200-400 nm frequency range, with short-path, low-volume quartz flow-cell (0.2-2.0 mm flowpath, &lt;10 μL flow-volume).   Optional Conductivity Detector: conductivity detector with flow cell, 0.1-200 mS, &lt;100 μL flow-volume after UV detector; bypass conductivity flow-cell when collecting fractions for analysis at displacement flow-rate &lt;500 μL/min.   Fraction Collector: 10 μL to 10 mL per fraction by time or by number of drops.   Column Cooler/Heater: 0-100° C.+/−0.5° C. If the column is operated at a temperature substantially different from ambient temperature, arrangements for heating or cooling the buffer solutions need to be made.       
 
       Example 1a 
     Example Protocol. Displacement Chromatography Purification of Crude Synthetic Angiotensin I 
     Equipment Configuration: 
       [0157]    Single Main Pump with 4 solvent lines, Sample Injection Valve with 40 mL Loop, Column Bypass Valve 
         [0158]    Sample Injection Valve: 6-port valve controlled by single-channel toggle logic (S3=0, bypass loop, S3=1 loop inline) 
         [0159]    Column Bypass Valve: 6-port valve controlled by single-channel toggle logic (S6=0, column inline, S6=1 bypass column) 
         [0160]    UV photodiode array detector after column (flow-cell: 0.5 mm pathlength, 10 μL volume) followed by conductivity detector (flow-cell: 170 μL volume). Conductivity cell bypassed when collecting fraction for analysis. 
         [0161]    Loading Buffer=A-Buffer (S1=1, flow on, S1=0 flow off); Displacer Buffer=B-Buffer (S2=1, flow on, S2=0 flow off); 
         [0162]    Displacer Removal Buffer=C-Buffer (S4=1, flow on, S4=0 flow off); Column Storage Buffer=D-Buffer (S5=1, flow on, S5=0 flow off) 
         [0163]    Before sequence begins, cleaned column briefly purged with A-buffer to remove column storage buffer. About 44 mL of degassed sample solution in a syringe is loaded into the sample injection loop; air is prevented from entering loop. 
         [0164]    See Example 7b for description of column, details about initial sample and contents of Loading Buffer/Displacer Buffer/Sample Solution. 
         [0165]    Displacer Removal Buffer (C-Buffer)=10% (v/v) 1-propanol, 10% (v/v) DI water in acetonitrile. 
         [0166]    Column Storage Buffer (D-Buffer)=50/50 (v/v) acetonitrile/water with formic acid (15 mM) and ammonium formate (15 mM). 
         [0000]    
       
         
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                   
               
               
                 Pump1 
                 Flow- 
                 Switch 
                   
                   
                   
               
               
                 Time 
                 Rate 
                 (S1-S6) 
                   
                   
                   
               
               
                 (min.) 
                 mL/min 
                 123456 
                 Operations-Functions 
                 Comments 
                 Volumes 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 0.00 
                 0.208 
                 100000 
                 start Buffer A 
                 Stabilize/Purge system  
                 (2 min.) 
               
               
                 1.98 
                 0.208 
                 100000 
                 continue 
                   
                   
               
               
                 2.00 
                 1.039 
                 100001 
                 set column-bypass; flow-rate = 1.039 
                 purge A-line 
                 (0.25 CV Buffer D) 
               
               
                 3.00 
                 1.039 
                 000011 
                 start storage Buffer D 
                 purge D-line 
                 (0.25 CV Buffer A) 
               
               
                 4.00 
                 1.039 
                 000101 
                 start regeneration Buffer C 
                 purge C-line 
                 (0.25 CV Buffer C) 
               
               
                 5.00 
                 1.039 
                 000100 
                 set column-inline; C-buffer 
                 Start pre-equilibration 
                 (2.0 CV Buffer C) 
               
               
                 13.00 
                 1.039 
                 100000 
                 start load buffer A 
                 equilibrate Buffer A 
                 (3.0 CV Buffer A) 
               
               
                 24.98 
                 1.039 
                 100000 
                 continue Buffer A 
                   
                   
               
               
                 25.00 
                 0.208 
                 100000 
                 flow-rate = 0.208 
                 equilibrate Buffer A 
                 (1.0 CV Buffer A) 
               
               
                 45.00* 
                 0.208 
                 101000 
                 set loop-inline; pump Buffer A into loop 
                 Start Sample load-Loop 
                 (27.04 mL Buffer A into loop) 
               
               
                 175.00 
                 0.208 
                 011000 
                 purge Buffer B into back of loop 
                 35.38/40 mL load (88.5%)  
                 (8.34 mL Buffer B into loop) 
               
               
                 215.10* 
                 0.208 
                 010000 
                 set loop-bypass; Buffer B thru column 
                 Start Displacement 
                 (18.1 CV buffer B) 
               
               
                 593.00* 
                 0.208 
                 010000 
                 continue 
                   
                   
               
               
                 593.02 
                 0.780 
                 100000 
                 start Buffer A 
                 Start regeneration 
                 (0.5 CV Buffer A) 
               
               
                 595.72 
                 0.780 
                 000010 
                 start storage Buffer D 
                   
                 (0.5 CV Buffer D) 
               
               
                 598.40 
                 0.780 
                 000100 
                 start regeneration Buffer C 
                   
                 (1.8 CV Buffer C) 
               
               
                 608.00 
                 0.780 
                 000100 
                 continue 
                   
                   
               
               
                 608.02 
                 1.039  
                 000100 
                 set flow-rate = 1.039 
                   
                 (7.5 CV Buffer C) 
               
               
                 638.00 
                 1.039  
                 000010 
                 start storage Buffer D 
                   
                 (8.5 CV Buffer D) 
               
               
                 671.96 
                 1.039  
                 000010 
                 continue storage Buffer D 
                   
                   
               
               
                 671.98 
                 0.000  
                 000010 
                 stop flow 
                   
                   
               
               
                 672.00 
                 0.000  
                 000000 
                 close all valves 
                 Stop 
               
               
                   
               
             
          
         
       
     
       Example 1b 
     Displacement Chromatography Purification of Crude Angiotensin I Using Displacer 14—Higher Loading at Lower Concentration (See FIG.  1   b —Analysis) 
     Operating Conditions: 
       [0167]    Starting Peptide: Desalted crude synthetic Angiotensin I, 82.7% purity, FW˜1.296 mg/μmole,
       charge=+4       
 
         [0169]    Column: Waters Xbridge BEH130, 5 μm, 135 Å, 4.6×250 mm SS, —C 18  on silica 
         [0170]    Flow-Rates: Loading=208 μL/min; Displacement=208 μL/min 
         [0171]    Ion-Pairing Agent: Trifluoroacetate (CF 3 CO 2   − ) 
         [0172]    Temperature: 23° C. 
         [0173]    pH: 2.0 
         [0174]    Displacer Buffer: 10.0 mM Displacer 14+12 mM CF 3 CO 2 H in DI water w/ 3% (v/v) MeCN, pH=2.0
       w/ NH 4 OH       
 
         [0176]    Loading Buffer: 12 mM TFA in water w/ 3% (v/v) MeCN, pH=2.0 w/ NH 4 OH 
         [0177]    Sample Solution: 4.38 mg/mL peptide in water with 3% (v/v) MeCN and 27 mM CF 3 CO 2   − ; pH=2.0
       w/ NH 4 OH       
 
         [0179]    Load Amount: 155.0 mg, 35.4 mL from 40 mL loop; 
         [0180]    Loading Time: 170.1 min. (2.84 hr) 
         [0181]    Fraction Size: 416 μL 
       Results: 
       [0182]      
         [0000]    
       
         
               
               
             
               
               
               
               
               
             
           
               
                   
               
             
             
               
                 Fraction 
                 Fractions diluted (20 μL sample + 40 μL loading  
               
               
                 Analysis:  
                 buffer) and analyzed (25 μL injection) by analytical  
               
               
                   
                 elution HPLC at 215 nm; calculations based on area %. 
               
               
                 Total Run  
                 8.4 hr 
               
               
                 Time: 
                   
               
               
                 Output 
                 3.29 mg/mL 
               
               
                 Concentration: 
                   
               
               
                 Column  
                 71.2% of maximum capacity 
               
               
                 Loading: 
                   
               
               
                 Column 
                 ~52.4 mg peptide/mL matrix @ 3.29 mg peptide/mL  
               
               
                 Capacity: 
                 solution ~167 μmole displacer/mL matrix @  
               
               
                   
                 10.0 μmole displacer/mL solution 
               
             
          
           
               
                 Purity %: 
                 99.1% 
                 99.0% 
                 98.8% 
                 98.6% 
               
               
                 Yield %: 
                   80% 
                   85% 
                   90% 
                   95% 
               
               
                   
               
             
          
         
       
     
       Comments: Sample Conc./Output Conc.=1.3 
       [0000]    
       
         
           
             Amount CF 3 CO 2   −  in sample=2.0 times stoichiometric. 
           
         
       
     
         [0184]    Excellent results are obtained. Good loading (37.3 g/L), good purity and good yield (&gt;99% purity @ 80% yield; &gt;98.5% purity @ 95% yield) are all obtained at the same time in this example where a small “analytical-type” column is used. This illustrates the power of optimized reversed-phase displacement chromatography. 
       Example 2 
     Displacement Chromatography Purification of Crude Angiotensin I Using Displacer 14—Lower Loading at Higher Concentration (See FIG.  2 —Analysis) 
     Operating Conditions: 
       [0185]    Starting Peptide: Desalted crude synthetic Angiotensin I, 82.7% purity, FW˜1.296 mg/μmole,
       charge=+4       
 
         [0187]    Column: Waters Xbridge BEH130, 5 μm, 135 Å, 4.6×250 mm SS, —C 18  on silica 
         [0188]    Flow-Rates: Loading=208 μL/min; Displacement=208 μL/min 
         [0189]    Ion-Pairing Agent: Trifluoroacetate (CF 3 CO 2   − ) 
         [0190]    Temperature: 23° C. 
         [0191]    pH: 2.0 
         [0192]    Displacer Buffer: 10.0 mM Displacer 14+12 mM CF 3 CO 2 H in DI water w/ 3% (v/v) MeCN, pH=2.0
       w/ NH 4 OH       
 
         [0194]    Loading Buffer: 12 mM TFA in water w/ 3% (v/v) MeCN, pH=2.0 w/ NH 4 OH 
         [0195]    Sample Solution: 24.0 mg/mL peptide in water with 3% (v/v) MeCN and 140 mM CF 3 CO 2   − ; pH=2.0
       w/ NH 4 OH       
 
         [0197]    Load Amount: 109.3 mg, 4.56 mL from 5 mL loop 
         [0198]    Loading Time: 21.9 min. (0.37 hr) 
         [0199]    Fraction Size: 458 μL 
       Results: 
       [0200]      
         [0000]    
       
         
               
               
             
               
               
               
               
               
             
           
               
                   
               
             
             
               
                 Fraction  
                 Fractions diluted (20 μL sample + 40 μL loading  
               
               
                 Analysis: 
                 buffer) and analyzed (25 μL injection) by analytical  
               
               
                   
                 elution HPLC at 215 nm; calculations based on area %. 
               
               
                 Total Run  
                 5.9 hr 
               
               
                 Time: 
                   
               
               
                 Output 
                 3.30 mg/mL 
               
               
                 Concentration: 
                   
               
               
                 Column  
                 50.1% of maximum capacity 
               
               
                 Loading: 
                   
               
               
                 Column 
                 ~52.5 mg peptide/mL matrix @ 3.30 mg  
               
               
                 Capacity: 
                 peptide/mL solution ~167 μmole displacer/mL matrix @  
               
               
                   
                 10.0 μmole displacer/mL solution 
               
             
          
           
               
                 Purity %:  
                 99.1% 
                 99.0% 
                 98.9% 
                 98.8% 
               
               
                 Yield %: 
                   80% 
                   85% 
                   90% 
                   95% 
               
               
                   
               
             
          
         
       
     
       Comments: Sample Conc./Output Conc.=7.3 
       [0000]    
       
         
           
             Amount CF 3 CO 2   −  in sample=1.9 times stoichiometric. 
           
         
       
     
         [0202]    Good results are obtained with moderate loading (26.3 g/L), good purity and good yield (&gt;99% purity @ 85% yield; &gt;98.5% purity @ 95% yield) using a small “analytical-type” column. Total run-time is shortened (5.9 hr) because sample loading time is shortened (2.84 hr to 0.37 hr). Similar results at ˜70% sample loading give inferior purities (data not shown) so loading percentage is reduced to about 50% at which point purity levels are improved. These data show that lower percent column loading can effectively compensate for reduced resolution caused by loading the sample at concentrations that are too high (7.3×). Thus, there is a tradeoff if high purity and high yield are to be maintained: (a) higher sample loading and longer time or lower sample loading and shorter time. For some samples that contain easy to remove impurities, high sample loading and shorter time can still lead to high purity and high yield. 
       Example 3 
     Displacement Chromatography Purification of Crude Angiotensin I Using Displacer 413—Different Displacer with “Lower Binding-Isotherm” (See FIG.  3 —Analysis) 
     Operating Conditions: 
       [0203]    Starting Peptide: Desalted crude synthetic Angiotensin I, 82.7% purity, FW˜1.296 mg/μmole, charge=+4 
         [0204]    Column: Waters Xbridge BEH130, 5 μm, 135 Å, 4.6×250 mm SS, —C 18  on silica 
         [0205]    Flow-Rates: Loading=208 μL/min; Displacement=208 μL/min 
         [0206]    Ion-Pairing Agent: Trifluoroacetate (CF 3 CO 2   − ) 
         [0207]    Temperature: 23° C. 
         [0208]    pH: 2.0 
         [0209]    Displacer Buffer: 10.0 mM Displacer 413+12 mM CF 3 CO 2 H in DI water w/ 3% (v/v) MeCN, pH=2.0
       w/ NH 4 OH       
 
         [0211]    Loading Buffer: 12 mM TFA in water w/ 3% (v/v) MeCN, pH=2.0 w/ NH 4 OH 
         [0212]    Sample Solution: 7.27 mg/mL peptide in water with 3% (v/v) MeCN and 43 mM CF 3 CO 2   − ; pH=2.0
       w/ NH 4 OH       
 
         [0214]    Load Amount: 160.7 mg, 22.1 mL from 30 mL loop 
         [0215]    Loading Time: 106.3 min. (1.77 hr) 
         [0216]    Fraction Size: 312 μL 
       Results: 
       [0217]      
         [0000]    
       
         
               
               
             
               
               
               
               
               
             
           
               
                   
               
             
             
               
                 Fraction  
                 Fractions diluted (10 μL sample + 40 μL loading  
               
               
                 Analysis: 
                 buffer) and analyzed (25 μL injection) by analytical  
               
               
                   
                 elution HPLC at 215 nm; calculations based on area %. 
               
               
                 Total Run  
                 5.6 hr 
               
               
                 Time: 
                   
               
               
                 Output 
                 5.38 mg/mL 
               
               
                 Concentration: 
                   
               
               
                 Column  
                 66.7% of maximum capacity 
               
               
                 Loading: 
                   
               
               
                 Column  
                 ~58.0 mg peptide/mL matrix @ 5.38 mg  
               
               
                 Capacity:  
                 peptide/mL solution ~115 μmole displacer/mL matix @  
               
               
                   
                 10.0 μmole displacer/mL solution 
               
             
          
           
               
                 Purity %: 
                 99.1% 
                 99.0% 
                 98.9% 
                 98.8% 
               
               
                 Yield %: 
                   80% 
                   85% 
                   90% 
                   95% 
               
               
                   
               
             
          
         
       
     
       Comments: Sample Conc./Output Conc.=1.3 
       [0000]    
       
         
           
             Amount CF 3 CO 2   −  in sample=1.9 times stoichiometric. 
           
         
       
     
         [0219]    Excellent results are obtained with good loading (38.7 g/L), excellent purity and excellent yield (&gt;99% purity @ 85% yield; &gt;98.5% purity @ 95% yield) using a small “analytical-type” column. Run-time is shortened (5.6 hr) because both sample loading time and displacement time are shortened owing to the higher sample loading and higher operating concentrations which are, in turn, caused by the “lower binding-isotherm” of Displacer 413. In this example, the same column and same peptide is used, but the displacer is changed (compare Example 1 b). These results show that equally good purities and yields are obtained when working higher on the binding-isotherms of the product and impurities. Because less Displacer 413 is needed to saturate the column at 10 mM (115 vs 167 μmole displacer/mL matrix), the peptide comes off the column at higher concentration (5.38 vs 3.19 mg/mL), and the experiment operates higher on the peptide binding-isotherm (58.0 vs 52.5 mg peptide/mL matrix). 
       Example 4 
     Displacement Chromatography Purification of Crude Angiotensin I Using Displacer 14—Different Reversed-Phase Column (See FIG.  4 —Analysis) 
     Operating Conditions: 
       [0220]    Starting Peptide: Desalted crude synthetic Angiotensin I, 82.7% purity, FW˜1.296 mg/μmole, charge=+4 
         [0221]    Column: Varian/Polymer Labs PLRP-S, 5 μm, 100 Å, 4.6×250 mm SS, uncoated porous
       polystyrene/divinylbenzene       
 
         [0223]    Flow-Rates: Loading=208 μL/min; Displacement=208 μL/min 
         [0224]    Ion-Pairing Agent: Trifluoroacetate (CF 3 CO 2   − ) 
         [0225]    Temperature: 23° C. 
         [0226]    pH: 2.0 
         [0227]    Displacer Buffer: 10.0 mM Displacer 14+12 mM CF 3 CO 2 H in DI water w/ 3% (v/v) 
         [0228]    MeCN, pH=2.0 w/ NH 4 OH 
         [0229]    Loading Buffer: 12 mM TFA in water w/ 3% (v/v) MeCN, pH=2.0 w/ NH 4 OH 
         [0230]    Sample Solution: 3.50 mg/mL peptide in water with 3% (v/v) MeCN and 22 mM CF 3 CO 2   − ; pH=2.0 w/ NH 4 OH 
         [0231]    Load Amount: 116.0 mg, 33.2 mL from 40 mL loop 
         [0232]    Loading Time: 159.4 min. (2.66 hr) 
         [0233]    Fraction Size: 458 μL 
       Results: 
       [0234]      
         [0000]    
       
         
               
               
             
               
               
               
               
               
             
           
               
                   
               
             
             
               
                 Fraction  
                 Fractions diluted (30 μL sample + 20 μL loading  
               
               
                 Analysis: 
                 buffer) and analyzed (25 μL injection) by analytical  
               
               
                   
                 elution HPLC at 215 nm; calculations based on area %. 
               
               
                 Total Run  
                 9.7 hr 
               
               
                 Time: 
                   
               
               
                 Output 
                 1.86 mg/mL 
               
               
                 Concentration: 
                   
               
               
                 Column  
                 73.2% of maximum capacity 
               
               
                 Loading: 
                   
               
               
                 Column  
                 ~38.1 mg peptide/mL matrix @ 1.86 mg peptide/mL 
               
               
                 Capacity: 
                 solution ~212 μmole displacer/mL matrix @  
               
               
                   
                 10.0 μmole displacer/mL solution 
               
             
          
           
               
                 Purity %:  
                 98.2% 
                 98.0% 
                 97.8% 
                 97.5% 
               
               
                 Yield %: 
                   60% 
                   75% 
                   80% 
                   90% 
               
               
                   
               
             
          
         
       
     
       Comments: Sample Conc./Output Conc.=2.0 
       [0000]    
       
         
           
             Amount CF 3 CO 2   −  in sample=2.0 times stoichiometric. 
           
         
       
     
         [0236]    Good results are obtained with low-to-moderate loading (27.9 g/L), moderate purity and reasonable yield (&gt;97.5% purity @ 90% yield) using a small “analytical-type” column. This example is designed to show a side-by-side comparison of two columns using the same peptide and same displacer (compare Example 1b). Generally speaking, the results for the polystyrene column are good, but not as good as those for the C 18 -on-silica column. Total run time is somewhat longer, column binding capacity is lower and final purity is somewhat lower (97.5% vs 98.5-99.0%). By adjusting the type of displacer, its concentration and the ion-pairing agent (data not shown), total run-times are shortened, and binding capacities are increased approaching those for the C 18 -on-silica columns. However, product purities largely remain about the same as this run on the polystyrene column. These results generally correspond to data from preparative elution chromatography that suggest that polystyrene columns give reduced chromatographic resolution compared to C 18 -on-silica columns. 
       Example 5 
     Displacement Chromatography Purification of Crude α-Melanotropin Using Displacer 318—Different Peptide and Different Displacer (See FIG.  5 —Analysis) 
     Operating Conditions: 
       [0237]    Starting Peptide: Desalted crude synthetic α-Melanotropin, 80.8% purity, FW˜1.665 mg/μmole, charge=+3 
         [0238]    Column: Waters Xbridge BEH130, 5 μm, 135 Å, 4.6×250 mm SS, —C 18  on silica 
         [0239]    Flow-Rates: Loading=208 μL/min; Displacement=208 μL/min 
         [0240]    Ion-Pairing Agent: Trifluoroacetate (CF 3 CO 2   − ) 
         [0241]    Temperature: 23° C. 
         [0242]    pH: 2.0 
         [0243]    Displacer Buffer: 10.0 mM Displacer 318+12 mM CF 3 CO 2 H in DI water w/ 3% (v/v) MeCN, pH=2.0 w/ NH 4 OH 
         [0244]    Loading Buffer: 12 mM TFA in water w/ 3% (v/v) MeCN, pH=2.0 w/ NH 4 OH 
         [0245]    Sample Solution: 9.04 mg/mL peptide in water with 3% (v/v) MeCN and 33 mM 
         [0246]    CF 3 CO 2   − ; pH=2.0 w/ NH 4 OH 
         [0247]    Load Amount: 216.2 mg, 23.9 mL from 30 mL loop 
         [0248]    Loading Time: 115.0 min. 
         [0249]    Fraction Size: 312 μL 
       Results: 
       [0250]      
         [0000]    
       
         
               
               
             
               
               
               
               
               
             
           
               
                   
               
             
             
               
                 Fraction  
                 Fractions diluted (10 μL sample + 50 μL loading  
               
               
                 Analysis: 
                 buffer) and analyzed (25 μL injection) by analytical  
               
               
                   
                 elution HPLC at 215 nm; calculations based on area %. 
               
               
                 Total Run  
                 6.2 hr 
               
               
                 Time: 
                   
               
               
                 Output 
                 6.52 mg/mL 
               
               
                 Concentration: 
                   
               
               
                 Column  
                 66.7% of maximum capacity 
               
               
                 Loading: 
                   
               
               
                 Column  
                 ~79.3 mg peptide/mL matrix @ 6.52 mg  
               
               
                 Capacity: 
                 peptide/mL solution ~129 μmole displacer/mL matrix  
               
               
                   
                 @ 10.0 μmole displacer/mL solution 
               
             
          
           
               
                 Purity %: 
                 99.1% 
                 99.0% 
                 98.9% 
                 98.8% 
               
               
                 Yield %: 
                   80% 
                   85% 
                   90% 
                   95% 
               
               
                   
               
             
          
         
       
     
       Comments: Sample Conc./Output Conc.=1.4 
       [0000]    
       
         
           
             Amount CF 3 CO 2   −  in sample=2.0 times stoichiometric amount. 
           
         
       
     
         [0252]    Excellent results are obtained with good loading (52.0 g/L), good purity and good yield (&gt;99% purity @ 85% yield; &gt;98.5% purity @ 95% yield) using small “analytical-type” column. This example is designed to show a side-by-side comparison (see Example 1 b) on the same column (C 18 -on-silica) using a different peptide and a different displacer. α-Melanotropin has a higher intrinsic binding capacity, and less Displacer 318 is needed to saturate the column (129 vs 167 μmole displacer/mL). Both of these factors together lead to a higher binding capacity for the peptide (79.3 vs 52.4 g peptide/L matrix), yet the displacement train sharpens nicely giving both high purity and high yield. 
       Example 6a 
     Example Protocol and Displacement Train. Displacement Chromatography Purification of Crude Synthetic α-Endorphin 
     Equipment Configuration: 
       [0253]    Main Pump(1) with 4 solvent lines, Sample Loading Pump(2) with 2 solvent lines, Pump Selector Valve 
         [0254]    Pump Selector Valve: 6-port valve controlled by single-channel toggle logic (S3=0, Pump1 to column-Pump2 to waste, S3=1 Pump1 to waste-Pump2 to column) 
         [0255]    UV photodiode array detector after column (flow-cell: 0.5 mm pathlength, 9 □L volume) followed by conductivity detector (flow-cell: 170 □L volume). 
         [0256]    Loading Buffer=A-Line on Pump1 (S1=1, flow on, S1=0 flow off); Displacer Buffer=B-Line on Pump 1 (S2=1, flow on, S2=0 flow off); Displacer Removal Buffer=C-Line on Pump1 (S4=1, flow on, S4=0 flow off); Column Storage Buffer=D-Line on 
         [0257]    Pump1 (S5=1, flow on, S5=0 flow off); Loading Buffer=A-Line on Pump2 (S6=1, flow on, S6=0, flow off); Sample Solution=B-Line on Pump2 (S7=1, flow on, S7=0 flow off). 
         [0258]    Before sequence begins, cleaned column briefly purged with A-buffer to remove column storage buffer. 
         [0259]    See Example 12b for description of column, details about initial sample and contents of Loading Buffer/Displacer Buffer/Sample Solution. 
         [0260]    Displacer Removal Buffer (C-Buffer)=10% (v/v) 1-propanol, 10% (v/v) DI water in acetonitrile. 
         [0261]    Column Storage Buffer (D-Buffer)=50/50 (v/v) acetonitrile/water with formic acid (15 mM) and ammonium formate (15 mM). 
         [0000]    
       
         
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                   
               
               
                   
                 Flow- 
                 Control 
                 Flow- 
                   
                   
                   
                   
               
               
                 Time 
                 Rate-1 
                 Switches 
                 Rate-2 
                 Pump 1 
                 Pump 2 
               
               
                 (min.) 
                 (mL/min) 
                 1234567 
                 (mL/min) 
                 Operations - Functions 
                 Operations - Functions 
                 Comments 
                 Volumes 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 0.00 
                 4.909 
                 1010010 
                 1.061 
                 purge Buffer A to waste 
                 Buffer A to column 
                 Purge System (A-line) 
                 1,.5 min. 
               
               
                 1.50 
                 4.909 
                 0010110 
                 1.061 
                 purge Buffer D to waste 
                   
                 purge D-line 
                 (0.37 CV Buffer D 
               
               
                   
                   
                   
                   
                   
                   
                   
                 to waste) 
               
               
                 3.00 
                 4.909 
                 0011010 
                 1.016 
                 purge Buffer C to waste 
                   
                 purge C-line 
                 (0.50 CV Buffer A 
               
               
                   
                   
                   
                   
                   
                   
                   
                 to wasste) 
               
               
                 5.00 
                 4.909 
                 0001010 
                 1.016 
                 Buffer C to column 
                 purge Buffer A to waste 
                 Start pre-equilibration 
                 (2.0 CV Buffer C 
               
               
                   
                   
                   
                   
                   
                   
                   
                 to column) 
               
               
                 5.50 
                 4.909 
                 0001010 
                 1.016 
                   
                 continue 
               
               
                 5.52 
                 4.909 
                 0001010 
                 0.000 
                   
                 flow-rate = 0.000 
               
               
                 13.00 
                 4.909 
                 1000010 
                 0.000 
                 Buffer A to column 
                   
                 equilibrate Buffer A 
                 (3.0 CV Buffer A) 
               
               
                 24.98 
                 4.909 
                 1000010 
                 0.000 
                 continue 
               
               
                 25.00 
                 0.961 
                 1000010 
                 0.000 
                 flow-rate = 0.961 
                   
                 equilibrate Buffer A 
                 (1.03 CV Buffer A) 
               
               
                 42.98 
                 0.961 
                 1000010 
                 0.000 
                   
                 continue 
               
               
                 43.00 
                 0.961 
                 1000001 
                 1.016 
                   
                 purge Sample to waste 
                 purge Sample to waste 
               
               
                 46.00 
                 0.961 
                 1010001 
                 1.016 
                 purge Buffer A to waste 
                 load Sample to column 
                 Start Sample load-Pump2 
               
               
                 46.10 
                 0.010 
                 1010001 
                 1.016 
                 set flow-rate to 0.010 
                   
                 slow purge Pump1 
               
               
                 243.98 
                 0.010 
                 1010001 
                 1.016 
               
               
                 246.80 
                 0.961 
                 0110001 
                 1.016 
                 purge Buffer B to waste 
                 purge B-line 
                   
                 (4.0 mL Buffer B) 
               
               
                 251.00 
                 0.961 
                 0100001 
                 1.016 
                 B-buffer to column 
                 purge Sample to waste 
                 Start Displacement-Pump1 
                 (17.96 CV Buffer B) 
               
               
                 251.50 
                 0.961 
                 0100010 
                 1.016 
                   
                 purge Buffer A to waste 
                 wash Pump2 
                 6.1 mL Buffer A to 
               
               
                   
                   
                   
                   
                   
                   
                   
                 waste) 
               
               
                 257.00 
                 0.961 
                 0100010 
                 1.016 
                   
                 continue 
               
               
                 257.02 
                 0.961 
                 0100010 
                 0.000 
                   
                 stopflow-Pump2 
               
               
                 257.04 
                 0.961 
                 0100000 
                 0.000 
                   
                 close valves-Pump2 
                 stop Pump2 
               
               
                 618.00 
                 0.961 
                 0100000 
                 0.000 
                 continue 
               
               
                 618.02 
                 3.682 
                 1000000 
                 0.000 
                 Buffer A to column 
                   
                 Start Reqeneration-Pump1 
                 (0.5 CV Buffer A 
               
               
                   
                   
                   
                   
                   
                   
                   
                 slow flow) 
               
               
                 620.72 
                 3.681 
                 0000100 
                 0.000 
                 Buffer D to column 
                   
                   
                 (0.5 CV Buffer D 
               
               
                   
                   
                   
                   
                   
                   
                   
                 slow flow) 
               
               
                 623.40 
                 3.682 
                 0001000 
                 0.000 
                 Buffer C to column 
                   
                   
                 (1.8 CV Buffer C 
               
               
                   
                   
                   
                   
                   
                   
                   
                 slow flow) 
               
               
                 633.00 
                 3.682 
                 0001000 
                 0.000 
                 continue 
               
               
                 633.02 
                 4.909 
                 0001000 
                 0.000 
                 flow-rate = 4.909 
                   
                   
                 (7.5 CV Buffer C 
               
               
                   
                   
                   
                   
                   
                   
                   
                 fast flow) 
               
               
                 663.00 
                 4.909 
                 0000100 
                 0.000 
                 start storage buffer D 
                   
                   
                 (8.5 CV Buffer D 
               
               
                   
                   
                   
                   
                   
                   
                   
                 fast flow) 
               
               
                 696.96 
                 4.909 
                 0000100 
                 0.000 
                 continue storage D-buffer 
               
               
                 696.98 
                 0.000 
                 0000100 
                 0.000 
                 stop flow 
               
               
                 697.00 
                 0.000 
                 0000000 
                 0.000 
                 close all valves 
                   
                 Stop Pump1 
               
               
                   
               
             
          
         
       
     
       Example 6b 
     Displacement Chromatography Purification of Crude Synthetic α-Endorphin Using Displacer 198—Larger Particles, Larger Columns and Lower Initial Purity (See FIG.  6   b ( a )A—Displacement Trace; FIG.  6   b ( a )B—Analysis) 
     Operating Conditions: 
       [0262]    Starting Peptide: Desalted crude synthetic α-Endorphin, 64.3% purity, FW˜1.746 mg/μmole, charge=+2 all on —C 18  on silica 
         [0263]    Column: 6b(a): Waters Xbridge BEH130, 5 μm, 135 Å, 10.0×250 mm SS, —C 18  on silica
       6b(b): Waters Xbridge BEH130, 10 μm, 135 Å, 10.0×250 mm SS, —C 18  on silica   6b(c): Waters Xbridge BEH130, 10 μm, 135 Å, 10.0×500 (2×250) mm SS, —C 18  on silica       
 
         [0266]    Flow-Rates: Loading=1016 μL/min; Displacement=961 μL/min for all three experiments. 
         [0267]    Ion-Pairing Agent: Trifluoroacetate (CF 3 CO 2   − ) 
         [0268]    Temperature: 23° C. 
         [0269]    pH: 2.0 
         [0270]    Displacer Buffer: 10.0 mM Displacer 198+12 mM CF 3 CO 2 H in DI water w/ 3% (v/v) MeCN, pH=2.0 
         [0271]    Loading Buffer: 12 mM TFA in water w/ 3% (v/v) MeCN, pH=2.0 w/ NH 4 OH 
         [0272]    Sample Solution:
       (a) 5.59 mg/mL peptide in water with 3% (v/v) MeCN and 26 mM CF 3 CO 2   − ; pH=2.0   (b) 5.59 mg/mL peptide in water with 3% (v/v) MeCN and 26 mM CF 3 CO 2   − ; pH=2.0   (c) 11.18 mg/mL peptide in water with 3% (v/v) MeCN and 52 mM CF 3 CO 2   − ; pH=2.0       
 
         [0276]    Load Amount:
       (a) 1164 mg, 208.3 mL from loading pump; Loading Time=205.0 min.   (b) 1164 mg, 208.3 mL from loading pump; Loading Time=205.0 min. (3.42 hr)   (c) 2329 mg, 208.3 mL from loading pump; Loading Time=205.0 min. (3.42 hr)       
 
         [0280]    Fraction Sizes: (a) 1.49 mL (b) 1.49 mL (c) 2.98 mL 
         [0000]    Results-6b(a) (see  FIGS. 6   b ( a )A and  6   b ( a )B) 
         [0000]                                                          Fraction    Fractions diluted (10 μL sample + 40 μL loading        Analysis:   buffer) and analyzed (25 μL injection) by analytical            elution HPLC at 215 nm; calculations based on area %.       Total Run    8.9 hr       Time:           Output   5.47 mg/mL       Concentration:           Column    70.5% of maximum capacity       Loading:           Column    ~84.1 mg peptide/mL matrix @ 5.47 mg        Capacity:   peptide/mL solution ~161 μmole displacer/mL matrix            @ 10.0 μmole displacer/mL solution            Purity %:   98.8%   98.7%   98.5%   98.2%       Yield %:     80%     85%     90%     95%                    
Results-6b(b) (no Figure):
 
         [0000]                                                          Fraction    Fractions diluted (10 μL sample + 40 μL loading        Analysis:   buffer) and analyzed (25 μL injection) by analytical            elution HPLC at 215 nm; calculations based on area %.       Total Run    9.1 hr       Time:           Output   5.27 mg/mL       Concentration:           Column    71.3% of maximum capacity       Loading:           Column    ~83.2 mg peptide/mL matrix @ 5.27        Capacity:   mg peptide/mL solution ~165 μmole displacer/mL            matrix @ 10.0 μmole displacer/mL solution            Purity %:    98.2%   98.1%   97.9%   97.5%       Yield %:     80%     85%     90%     95%                    
Results-6b(c) (no Figure):
 
         [0000]                                                          Fraction    Fractions diluted (10 μL sample + 40 μL loading        Analysis:   buffer) and analyzed (25 μL injection) by analytical            elution HPLC at 215 nm; calculations based on area %.       Total Run    14.5 hr       Time:           Output   5.41 mg/mL       Concentration:           Column    70.7% of maximum capacity       Loading:           Column    ~83.7 mg peptide/mL matrix @ 5.41 mg peptide/mL       Capacity:   solution ~162 μmole displacer/mL matrix            @ 10.0 μmole displacer/mL solution            Purity %:   98.8%   98.7%   98.5%   98.2%       Yield %:     80%     85%     90%     95%                    
Comments: Sample Conc./Output Conc.: 1.0 (6b(a)); 1.1 (6b(b)); 2.1 (6b(c)).
       Amount CF 3 CO 2   −  in sample=4.0 times stoichiometric amount (6b(a), 6b(c) &amp; 6b(c)).       
 
         [0282]    Excellent results are obtained from all three runs with good loading (59.2-59.3 g/L), high purities and good yields (&gt;98.5% purity @ 90% yield) using “semiprep-type” columns with both 5 μm and 10 μm particle sizes. Percent loadings (70.5-71.3%) and output concentrations (5.27-5.47 mg/mL) are uniform and reproducible. These examples illustrate power and utility of optimized preparative displacement chromatography. (1) There is little difference in preparative resolution between 4.6 mm and 10.0 mm ID columns of the same length packed with the same reversed-phase matrix. (2) At 25 cm column length, both 5 μm and 10 μm matrices give good results with the 10 μm material giving slightly inferior resolution as demonstrated by slightly reduced purity (˜0.6%). (3) At 50 cm column length, the 10 μm matrix regains full resolution; simple calculations suggest that a 30-40 cm bed length is sufficiently long. (4) Two well-packed columns properly attached end-to-end function effectively in displacement chromatography experiments. (5) The best pooled purity (98.8%) for a peptide (α-Endorphin) with 60+% initial purity is not much worse than the best pooled purity (99.1%) for a peptide (Angiotensin I, α-Melanotropin) with 80 μm initial purity. (6) In many cases, 1.5-2.0 times the stoichiometric amount of ion-pairing agent is used in the sample loading solution with good results; however, with α-Endorphin, significantly better resolution is obtained with 3.5-4.0 times the stoichiometric amount of CF 3 CO 2   − . 
       Example 7 
     Displacement Chromatography Purification of Prepurified α-Endorphin Using Displacer 198—Different Binding-Isotherms Lead to Improved Purity (See FIG.  7 —Analysis) 
     Operating Conditions: 
       [0283]    Starting Peptide: Prepurified α-Endorphin, 98.4% purity, FW˜1.746 mg/μmole, charge=+2 
         [0284]    Column: Waters Xbridge BEH130, 5 μm, 135 Å, 4.6×250 mm SS, —C 6 Ph on silica 
         [0285]    Flow-Rates: Loading=208 μL/min; Displacement=208 μL/min 
         [0286]    Ion-Pairing Agent: Trifluoroacetate (CF 3 CO 2   − ); 
         [0287]    Temperature: 23° C. 
         [0288]    pH: 2.0 
         [0289]    Displacer Buffer: 10.0 mM Displacer 198+12 mM CF 3 CO 2 H in DI water w/ 3% (v/v) MeCN, pH=2.0 w/ NH 4 OH 
         [0290]    Loading Buffer: 12 mM TFA in water w/ 3% (v/v) MeCN, pH=2.0 w/ NH 4 OH 
         [0291]    Sample Solution: 5.26 mg/mL peptide in water with 3% (v/v) MeCN and 21 mM CF 3 CO 2   − ; pH=2.0 w/ NH 4 OH 
         [0292]    Load Amount: 158.9 mg, 30.2 mL from 40 mL loop 
         [0293]    Loading Time: 145.2.0 min. 
         [0294]    Fraction Size: 437 μL 
       Results: 
       [0295]      
         [0000]    
       
         
               
               
             
               
               
               
               
               
             
           
               
                   
               
             
             
               
                 Fraction  
                 Fractions diluted (15 μL sample + 35 μL loading  
               
               
                 Analysis: 
                 buffer) and analyzed (25 μL injection) by analytical  
               
               
                   
                 elution HPLC at 215 nm; calculations based on area %. 
               
               
                 Total Run  
                 7.3 hr 
               
               
                 Time: 
                   
               
               
                 Output 
                 3.85 mg/mL 
               
               
                 Concentration: 
                   
               
               
                 Column  
                 71.1% of maximum capacity 
               
               
                 Loading: 
                   
               
               
                 Column  
                 ~53.8 mg peptide/mL matrix @ 3.85 mg  
               
               
                 Capacity: 
                 peptide/mL solution ~147 μmole displacer/mL matrix  
               
               
                   
                 @ 10.0 μmole displacer/mL solution 
               
             
          
           
               
                 Purity %: 
                 99.6% 
                 99.6% 
                 99.6% 
                 99.5% 
               
               
                 Yield %: 
                   80% 
                   85% 
                   90% 
                   95% 
               
               
                   
               
             
          
         
       
     
       Comments: Sample Conc./Output Conc.=1.3 
       [0000]    
       
         
           
             Amount CF 3 CO 2   −  in sample=3.6 times stoichiometric amount. 
           
         
       
     
         [0297]    Excellent results are obtained with good loading (38.3 g/L), excellent purity and excellent yield (&gt;99.5% purity @ 95% yield) using a small “analytical-type” column. This example is designed to show how purifying a prepurified sample under suitable conditions can efficiently lead to high purity peptides. (1) The sum of the impurities drops significantly from 1.6% to 0.4-0.5% with minimal loss (5-10%) in product. (2) The reduction in impurities is primarily caused by changes in binding-isotherms of product and impurities, not by improved resolution of the column. In the starting material, the 1.6% impurity is composed of 12 minor impurities 8 of which are effectively removed during this purification. The levels of the remaining 4 co-displacing components are somewhat reduced during the purification. (3) Because co-displacement of the 4 remaining impurity is the principal factor limiting final purity, the purity profile is nearly invariant from 60% recovery to 95% recovery. (4) The success of this purification results from the choice of a phenylhexyl column with different binding-isotherms. An attempt to carry out a similar displacement chromatography purification of the same sample on an octaadecyl (C 18 ) column failed to yield significant improvement (data not shown). This is likely the case because the octadecyl column is used to purify the sample from crude material in the first step. (5) These results show that two back-to-back displacement purifications can routinely lead to high-yield production of high-purity peptides. 
       Example 8 
     Displacement Chromatography Purification of Crude Angiotensin I Using Displacer 14—Using Different Ion-Pairing Anions, Concentrations and Mixtures 
       [0298]    All operating conditions for the seven experiments in Example 7 are the same except that the counter-ion for the displacer and the added amounts of ion-pairing anion (acid). In all cases, the operating pH is the same (pH=2.0). In order to reduce the amount of analytical work, comparative purity data is given for a pool of the center 15 fractions. Because the level of co-displacement is nearly invariant across the major displacement band for a given displacement experiment, analytical data from this method of pooling gives representative and comparable results. 
       Results: 
       [0299]      
         [0000]    
       
         
               
               
               
               
             
           
               
                   
               
               
                   
                   
                   
                 Center-cut 
               
               
                 Displacer Buffer 
                 Load Buffer 
                 Sample SoIn. 
                 Purity 
               
               
                   
               
             
             
               
                 A a  10 mM [D][CF 3 CO 2 ] + 
                 12 mM CF 3 CO 2 H 
                 27 mM CF 3 CO 2 H 
                 99.1% 
               
               
                 12 mM CF 3 CO 2 H 
                   
                   
                   
               
               
                 B 10 mM [D][Br] + 
                 12 mM HBr 
                 27 mM HBr 
                 99.0% 
               
               
                 12 mM HBr 
                   
                   
                   
               
               
                 C 10 mM [D][Cl] + 
                 12 mM HCl 
                 27 mM HCl 
                 98.6% 
               
               
                 12 mM HCl 
                   
                   
                   
               
               
                 D 10 mM [D][Br] + 
                 12 mM CF 3 CO 2 H 
                 27 mM CF 3 CO 2 H 
                 98.1% 
               
               
                 12 mM CF 3 CO 2 H 
                   
                   
                   
               
               
                 E 10 mM [D][Cl] + 
                 12 mM CF 3 CO 2 H 
                 27 mM CF 3 CO 2 H 
                 99.0% 
               
               
                 12 mM CF 3 CO 2 H 
                   
                   
                   
               
               
                 F 10 mM [D][Cl] + 
                 24 mM CF 3 CO 2 H 
                 27 mM CF 3 CO 2 H 
                 99.1% 
               
               
                 24 mM CF 3 CO 2 H 
                   
                   
                   
               
               
                 G 10 mM [D][Cl] + 
                 6 mM CF 3 CO 2 H 
                 27 mM CF 3 CO 2 H 
                 96.7% 
               
               
                 6 mM CF 3 CO 2 H 
               
               
                   
               
               
                 Note: 
               
               
                 a) Example 1 
               
             
          
         
       
     
       Comments: 
       [0300]    Generally good results are obtained under most conditions except experiment “G”. There are clear results from this study regarding types, mixtures and levels of ion-pairing anions.
       1. Trifluoroacetate-only (A) and bromide-only (B) experiments yield similar results (0.9-1.0% impurity) while those for the chloride-only (C) experiment gives higher impurity levels (1.4% inpurity). Thus, trifluoroacetate and bromide are better ion-pairing agents than chloride.   2. Mixed trifluoroacetate-chloride (E, F) experiments give about the same impurity levels as trifluoroacetate-only experiments as long as enough trifluoroacetate is present (0.9-1.0% impurity). In contrast, the mixed trifluoroacetate-bromide (D) experiment gives worse results; the impurity level increases from 0.9% to 1.9%. While trifluoroacetate-only (A) and bromide-only (B) experiments give good results, the mixture of anions does not. Apparently, a mixture of two ion-pairing anions of similar (but no the same) ion-pairing strength interfere with each other resulting in band broadening and higher impurity levels. The presence two ion-pairing anions of significantly different ion-pairing strength results in the stronger one dominating (as long there is enough of it present) and lower impurity levels result.   3. The worst results (G) are obtained when two ion-pairing agents are present (Cl − , CF 3 CO 2   − ) and the stronger one is present in substiochiometric amounts. This results in “double-banding” where the displacer and many components of the mixture come off the column as two bands, the first one as the chloride salt and the second as the trifluoroacetate salt. This leads to significant band broadening and overlap of each double-banded component thereby increasing the overall impurity level from 0.9% to 3.3%. Adding insufficient amounts of trifluoroacetate (stronger ion-pairing anion) gives worse results than having no trifluoroacetate at all (3.3% impurity vs 1.4% impurity). Adding higher levels of trifluoroacetate in excess of the stoichiometric amount causes the impurity levels to decrease again (3.3% to 0.9%).   4. Note that the above results apply only to the levels of trifluoroacetate (ion-pairing anion) in the displacer buffer. There was sufficient trifluoroacetate in the sample loading solution. When there is a deficiency of trifluoroacetate in the sample solution, impurity levels become even higher (data not shown).       
 
       Example 9 
     HPLC Analyses 
       [0305]    Methods 9a, 9b—Reversed-Phase for Cations: 
         [0306]    Analyses were carried out using Waters Corp. (Milford, Mass.) gradient HPLC equipped with a Waters 996 PDA detector in tandem with a Dionex/ESA Biosciences (Chelmsford, Mass.) Corona Plus CAD detector and a Waters Xbridge BEH130, 5 μm, 135 Å, 4.6×250 mm SS, —C 18  on silica, reversed-phase chromatography column (Chelmsford, Mass.). 
         [0307]    Sample Injection: 25 μL of ˜1 mM sample solution in A buffer 
         [0308]    UV detection: 208-220 nm depending on compounds to be analyzed 
         [0309]    Flow-Rate: 1.0 mL/min. 
         [0310]    A buffer: 5% CH 3 CN (v/v) in HPLC-grade dist. water with 0.1% (v/v) trifluoroacetic acid 
         [0311]    B buffer: 5% H 2 O (v/v) in HPLC-grade CH 3 CN with 0.1% (v/v) trifluoroacetic acid. Survey Gradient Method: 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 100% A 
                   0-2 min 
               
               
                   
                 100% A to 100% B 
                  2-62 min 
               
               
                   
                 100% B 
                 62-70 min 
               
               
                   
                   
               
             
          
         
       
     
       Analytical Gradient Method 
       [0312]      
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                  10% B 
                   0-2 min 
               
               
                   
                  10% B to 50% B  
                  2-57 min 
               
               
                   
                  50% B to 100% B 
                 57-62 min 
               
               
                   
                 100% B 
                 62-67 min 
               
               
                   
                   
               
             
          
         
       
     
         [0313]    Method 9c—Reversed-Phase for Long-Chain Alkyl Halides: 
         [0314]    Sample Injection: 25 μL of ˜1 mM sample solution in A buffer 
         [0315]    UV detection: 200-220 nm depending on compounds to be analyzed 
         [0316]    Flow-Rate: 1.0 mL/min. 
         [0317]    A buffer: 5% CH 3 CN (v/v) in HPLC-grade distilled water with 0.1% (v/v) trifluoroacetic acid. 
         [0318]    B buffer: 5% H 2 O (v/v) in HPLC-grade CH 3 CN with 0.1% (v/v) trifluoroacetic acid. Gradient Method: 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                  50% A/50% B 
                   0-2 min 
               
               
                   
                  50% A/50% B to 100% B 
                  2-62 min 
               
               
                   
                 100% B 
                 62-70 min 
               
               
                   
                   
               
             
          
         
       
     
       Example 10 
     Preparation of N-Decylpyrrolidine (fw=211.39) 
       [0319]    426.7 g Freshly distilled pyrrolidine (6.0 mole, fw=71.12, ˜500 mL) is added to 500 mL stirring acetonitrile in a 2 L 4-neck round-bottom flask that is equipped with a heating mantle, mechanical stirrer, 500 mL addition funnel, reflux condensor and teflon-coated thermocouple. The reaction is carried out under a nitrogen atmosphere with a slow N 2  purge. 442.4 g Freshly distilled 1-bromodecane (2.0 mole, fw=221.19, ˜415 mL) is added to the stirring mixture in a dropwise fashion at such a rate that the reaction exotherm maintains the reaction temperature in the range 45-55° C. Under these conditions, the bromodecane addition requires about 2 hours. After the entire bromodecane is added and the reaction temperature drops below 45° C., the stirring reaction mixture is heated to 80° C. for 1 hr and then allowed cool. The reaction mixture is periodically monitored by HPLC (Method 10g) in order to ensure that the bromodecane is entirely consumed. During the reaction, a less dense upper layer of the product begins to form that increases in volume as the reaction mixture cools to ambient temperature. Upon cooling as the reaction temperature reaches about 50° C., 100 mL distilled water is added portionwise to the stirring mixture in order to facilitate phase separation and prevent crystallization of pyrrolidine hydrobromide. When the reaction temperature is below 30° C., it is transferred to a 2 L separatory funnel and allowed to stand for about 3 hours in order to allow for full phase separation. The upper phase is retained in the funnel, 1.0 L 10% w/w NaOH in distilled water is added, the mixture is thoroughly mixed and then allowed to settle overnight. The phases are separated, the upper product phase is retained, 1.0 L 1% w/w NaOH in distilled water is added, the mixture is through mixed and then allowed again to settle overnight. The phases are separated, and the upper product phase is placed in a beaker along with 80 g anhydrous magnesium sulfate powder. The viscous mixture is manually mixed for about 15 minutes and then filtered through fine-porosity sintered-glass filter. Once, the product is filtered, the magnesium sulfate is washed with a small amount of n-pentane and then filtered. The pentane solution is combined with the filtered product and placed on a rotary evaporator. Most of the volatile components (pentane, residual acetonitrile, pyrrolidine, water) are removed under reduced pressure. Using the rotary evaporator, the viscous product is stirred and heated (70° C., glycol-water bath) under vacuum (˜10 torr) overnight (18 hr) while the volatiles are trapped at liquid N 2  temperature. Finally, the mixture is again stirred and heated overnight on a vacuum-line (0.5 torr, 100° C.) to remove the last traces of volatiles. This procedure yields 399 g (94%) of a pale yellow viscous liquid with a purity of 99.0-99.6% (GC, HPLC). This material is sufficiently pure for most applications. If needed, this material is distilled (118-122° C., 3 torr) giving a 90% distillation yield of a colorless liquid (99.8% purity). 
         [0320]    This is a clean reaction that produces pure product if the starting secondary amine and primary alkyl halide are themselves pure. Primary alkyl chlorides function quite well in this reaction, and the reaction time needs to be slightly extended for complete reaction. This reaction is also successfully carried out using various secondary amines: 50% aqueous dimethylamine, N-methylethylamine, diethylamine, di-n-propylamine, di-n-butylamine, pyrrolidine, piperidine, N-methylbenzylamine, N-ethylbenzylamine, N-methylaniline while using various  n C 5 - n C 12  alkyl halides. For the above reaction, a ratio of 1:3 is chosen to minimize the production of the didecyl pyrrolidinium bromide byproduct. The excess secondary amine can be regenerated and recycled by addition of inorganic base (NaOH pellets, 50% aqueous NaOH, LiOH, anhydrous Na 2 CO 3 , Na 3 PO 4 ) to the spent reaction mixture in order to regenerate the free amine followed by distillation to recover the amine or amine/solvent mixture. 
       Example 11 
     Preparation of N-(4-Fluorobenzyl)-N-decylpyrrolidinium Chloride (fw=355.97) 
       [0321]    380.5 g Purified N-decylpyrrolidine (1.8 mole, fw=211.39) is added to 720 mL stirring acetonitrile in a 2 L, 4-neck round-bottom flask that is equipped with a heating mantle, mechanical stirrer, 500 mL addition funnel, reflux condensor and teflon-coated thermocouple. The reaction is carried out under a nitrogen atmosphere with a slow N 2  purge. The stirring mixture is heated to 50° C., and 289.1 g freshly distilled 4-fluorobenzyl chloride (2.0 mole, fw=144.58) is added in a dropwise fashion over a period of about 60 minutes. The reaction mixture is then heated to about 80° C. for 8-12 hours and periodically monitored by HPLC (Method 10a) in order to ensure that the starting amine is entirely consumed. The reaction mixture is cooled to room temperature, filtered through sintered-glass and placed on a rotary evaporator to remove the solvent (acetonitrile). 1.0 L Methyl t-butyl ether (MTBE) is added portionwise with mechanical stirring to the sticky orange-yellow reaction residue. Once this mixture is fully suspended in the solvent, it is transferred to a clean 4 L Erlenmeyer flask, and an additional amount of MTBE (1.9 L) is slowly added with stirring. The mixture is allowed to stand at ambient temperature overnight, filtered through a large sintered-glass filter, twice washed with MTBE and then dried by passing dry N 2  through the product. Note: this crystalline substance is very hygroscopic and rapidly absorbs moisture from the air turning white crystals into a puddle of colorless liquid within a few minutes. Thus, ordinary filtrations are difficult and should be carried out in a dry-box or under a blanket of dry N 2  or dry air. The product is finally dried in a vacuum oven (55° C., 20 torr, 3 hr; 95° C., 20 torr, 15 hr), cooled and stored in a sealed container in a desiccator over P 2 O 5 . This procedure yields about 576 g (90%) of a white crystalline product (platelets) with &gt;99% purity. A sharp melting point in a glass capillary is measured at 137-138° C. when measured between 90-140° C. at the heating rate of 1.0° C./minute. This compound appears to exist in multiple polymorphic crystalline forms with different melting points. This crystallized material from acetonitrile/MTBE forms crystals that will melt at or below 120° C., recrystallize and remelt at about 137° C. Slow heating seems to promote thermal interconversion of polymorphs. If allowed to age long enough at 90° C. (several days), the material is converted to the higher melting form. Note that the apparent melting points are significantly lowered by the presence of small amounts of moisture. 
         [0322]    Recrystallization is accomplished using hot DME/MTBE. 100 g of the above product is dissolved in 450 g hot (˜75° C.) peroxide-free 1,2-dimethoxyethane (DME) and quickly filtered through a sintered glass filter into a clean 1 L filter-flask. 55 g hot DME is used to wash the filter. The arm of the filter flask is plugged, and the mixture in the flask is heated to about 75° C. and then allowed to cool to about 50° C. About 270 g MTBE is then added to the stirring mixture, and the mixture is briefly heated again to 50° C. The flask is then covered, and the warm solution is allowed to cool to room temperature undisturbed. Within three hours at ambient temperature copious amounts of large, white platelets crystallize from solution. Finally, the mixture is allowed to stand at 4° C. overnight (15-18 hr) in order to complete the crystallization. Taking proper precautions to protect from atmospheric moisture (see above), the cold mixture is filtered through a sintered-glass filter, twice washed with MTBE (ambient temperature) and dried on the filter as above. The product is again dried in a vacuum oven overnight, cooled and stored in a sealed container in a desiccator over P 2 O 5 . This procedure yields about 76 g (76%) of the white, crystalline salt (99.7-99.9% purity by HPLC). The filtrate solution contains substantial amounts of pure product. The solvent is completely removed, and the white residue is recrystallized again using the same method or combined with the next batch of product for recrystallization. Overall yield of recrystallization is 87-95%. 
       Example 12 
     Preparation of N-(4-Fluorobenzyl)-N-decylpyrrolidinium Hydroxide (fw=337.53) 
       [0323]    178 g Recrystallized N-(4-fluorobenzyl)-N-decylpyrrolidinium chloride (500 mmole, fw=355.97) is dissolved in 445 mL degassed, deionized water under a CO 2 -free, N 2  atmosphere in a polypropylene flask. 61.4 g Silver (I) oxide (265 mmole, fw=231.74) is added to the solution, and it is vigorously stirred with a mechanical polypropylene propeller at room temperature for 48 hours. The mixture is filtered through a polypropylene filter/felt in a polypropylene Buechner filter into a polypropylene receiving flask under a blanket of nitrogen gas. The water-clear solution is placed on a rotary evaporator, and the water is partially removed under vacuum over a period of 36-48 hours while the product (viscous liquid) is maintained at about 50° C. using an external heating bath. Acid-Base titration (hydroxide) and HPLC analysis (cation) show the final solution to contain about 41% of the quat hydroxide; atomic absorption shows residual Cl −  to be less than 2 ppm. The solution is stored at ambient temperature in a sealed, clean, polypropylene container. Yield is nearly quantitative. 
         [0324]    Modifications: This method is generally applicable to most quaternary ammonium chloride/bromide salts described here. Compounds that have base-sensitive groups (alcohols, amides, esters etc), of course, are often unstable as hydroxide salts. Stable quaternary ammonium salts are also converted to hydroxide salts using other methods such as ion-exchange, electrolysis or electrodialysis. 
       Example 13 
     Preparation of N-(4-Fluorobenzyl)-N-decylpyrrolidinium Trifluoroacetate (fw=433.53) 
       [0325]    Method A. 
         [0326]    35.6 g Purified and recrystallized N-(4-fluorobenzyl)-N-decylpyrrolidinium chloride (100 mmole, fw=355.97) is placed in a 100 mL separatory funnel followed by 35.6 g degassed, deionized water. The flask is shaken until a clear, viscous solution is formed (˜1.5 M solution). 17.1 g Trifluoroacetic acid (150 mmole, fw=114.02) is added to the mixture which is vigorously mixed. Immediately two phases form which fully separate after 60 minutes. The quat trifluoroacetate is contained in the lower layer, and the water, HCl and excess CF 3 CO 2 H is in the upper layer. The layers are separated, the product in the lower layer is placed on a rotary evaporator in order to remove the residual water, HCl and CF 3 CO 2 H under vacuum (bath temperature=50° C., vacuum=20 torr). This procedure yields 40.8 g (94%) of a pure, clear, viscous oil (ionic liquid). This material is suitable for use a displacer. HPLC purity of the quat cation is essentially identical to the starting material. Residual chloride content is about 1 mole % (chloride titration) and excess trifluoroacetate as free trifluoroacetic acid is 2-5 mole % (acid titration). A second extraction with equal weight of 30% (w/w) trifluoroacetic in water following the same procedure yields the same product with the same amount of residual trifluoroacetic acid but with chloride content reduced to &lt;0.1 mole %. While the solubility of the trifluoroacetate (TFA) salt (˜120 mM) in pure water is lower than the solubility of the chloride salt (2.0 M), the TFA salt is nonetheless adequately soluble for displacer use (10-50 mM). 
         [0327]    Method B. 
         [0328]    This is a modification of Method A based on the partitioning behavior in a two-phase diethyl ether-water extraction. The quat chloride salt strongly partitions into the water layer while the quat trifluoroacetate salt strongly partitions into the ether layer. 53.4 g Purified and recrystallized N-(4-fluorobenzyl)-N-decylpyrrolidinium chloride (150 mmole, fw=355.97) is placed in a 250 mL separatory funnel followed by 53.4 g degassed, deionized water. The flask is shaken until a clear, viscous solution is formed (˜1.5 M solution). 25.6 g Trifluoroacetic (225 mmole, fw=114.02) is added to the mixture which is vigorously mixed. Immediately two phases form with the product in the lower layer. 110 mL peroxide-free diether ether is added to the separatory funnel and the mixture is vigorously mixed again. After 2 hours, the phases fully separate with the product in the upper ether phase. The lower phase is discarded and the upper is retained. 55 mL 1% trifluoroacetic acid in distilled water is added, the mixture is vigorously mixed and phases are again allowed to separate. Again, the upper phase is retained, dried over anhydrous magnesium sulfate, filtered and placed on a rotary evaporator in order to remove the ether along with residual HCl, trifluoroacetic acid and water. This procedure yields 59.2 g (91%) of a pure, clear, viscous oil (ionic liquid). This material is suitable for use as a displacer. HPLC purity of the quat cation is essentially identical to the starting material. Residual chloride content is &lt;0.1 mole % (chloride titration) and excess trifluoroacetate as free trifluoroacetic acid is 1-3 mole % (acid titration). 
         [0329]    Method C. 
         [0330]    35.6 g Purified and recrystallized N-(4-fluorobenzyl)-N-decylpyrrolidinium chloride (100 mmole, fw=355.97) is dissolved in 75 mL distilled water in a 250 mL Erlenmeyer flask. 23.1 g Silver (I) trifluoroacetate (105 mmole, fw=220.88) and 100 mL peroxide-free diethyl ether are added to the solution, and it is vigorously stirred magnetically for 48 hours at room temperature. The mixture is filtered in order to remove silver salts, the two liquid phases are separated, the upper product phase is dried and then filtered again. The ether solution is placed on a rotary evaporator in order to remove the ether along with residual water. This procedure yields 41.2 g (95%) of a pure, clear, viscous oil (ionic liquid). This material is suitable for use a displacer. HPLC purity of the quat cation is essential identically to that of the starting material. Residual chloride content is &lt;0.01 mole %. 
         [0331]    Method D. 
         [0332]    84.6 g N-(4-Fluorobenzyl)-N-decylpyrrolidinium hydroxide solution (100 mmole, 39.9%, fw=337.53) is placed in a calibrated 1000 mL volumetric flask and about 800 mL CO 2 -free distilled water is added and mixed. Without delay, trifluoroacetic acid (˜11.4 g, fw=114.2) is carefully added dropwise with stirring and pH-monitoring. When 95% of the acid has been added, small droplets of the acid are added one-at-a-time until the unbuffered endpoint (pH=5-8) is attained. Additional CO 2 -free distilled water is added until the volume is exactly 1000 mL). This 100 mM stock solution is suitable for use a displacer. 
         [0333]    A wide range of salts are readily prepared using this method including, formate, acetate, bromide, nitrate, iodide, methanesulfonate, trifluoromethanesulfonate (triflate), trichloroacetate and perchlorate. 
         [0334]    Method E. 
         [0335]    84.6 g N-(4-Fluorobenzyl)-N-decylpyrrolidinium hydroxide solution (100 mmole, 39.9%, fw=337.53) and 100 mL peroxide-free diethyl ether are placed in a 250 mL Erlenmeyer flask. Without delay, the mixture is vigorously stirred magnetically, and trifluoroacetic acid (˜11.4 g, fw=114.2) is carefully added dropwise at an addition rate so that there is a minimal temperature rise. The room-temperature mixture is separated into two liquid phases, the upper product phase is dried and filtered, the ether solution is placed on a rotary evaporator in order to remove the ether along with residual trifluoroacetic acid and water. This procedure yields 42.0 g (97%) of a pure, clear, viscous oil (ionic liquid). This material is suitable for use a displacer. HPLC purity of the quat cation is essential identical to the starting material. Residual chloride content is &lt;0.01 mole %. 
         [0336]    Method F. 
         [0337]    38.1 g Purified N-decylpyrrolidine (0.18 mole, fw=211.39) is added to 75 mL stirring acetonitrile in a 250 mL 4-neck round-bottom flask that is equipped with a heating mantle, magnetic stirrer, 50 mL addition funnel and reflux condensor. The reaction is carried out under a nitrogen atmosphere. The stirring mixture is warmed to about 50° C., and 44.4 g freshly distilled 4-fluorobenzyl trifluoroacetate 4  (0.20 mole, fw=222.14) is added in a dropwise fashion over a period of about 60 minutes. The reaction mixture is then heated under refluxing conditions for about 24 hours and periodically monitored by HPLC in order to ensure that the starting amine is entirely consumed. The reaction mixture is cooled to room temperature, filtered through sintered-glass and placed on a rotary evaporator to remove the solvent (acetonitrile). 100 mL n-pentane is added portionwise with mechanical stirring to the yellow reaction residue. Once this mixture is fully mixed with the solvent, the upper layer is completely removed and discarded. To the oily product layer is added an equal volume of peroxide-free diethyl ether and thoroughly mixed. 100 mL n-Pentane is added, the mixture is thoroughly mixed and allowed to settle and the upper layer is separated and discarded. This trituration process with diethyl ether and pentane is repeated two more times in order to remove as much color and organic impurities as possible. Finally, the mixture is heated over night on a vacuum-line (0.5 torr, 80° C.) to remove the last traces of volatiles. This procedure yields about 55 g (71%) of a pale yellow, oily product with purity of 98.5-99.0% (HPLC). This oily product is easily purified using chromatography, but difficult to purify by other methods; for this reason, this method of preparation is less preferred. 
       Example 14 
     Preparation of N,N-Diheptyl-1,2,3,4-tetrahydroisoquinolinium Bromide (fw=410.49) 
       [0338]    48.0 g Freshly distilled 1,2,3,4-tetrahydroisoquinoline (360 mmole, fw=133.19) and 49.1 g diisopropylethylamine (380 mmole, fw=129.25) are added to 120 mL acetonitrile in a 500 mL, 3-neck, round-bottom flask that is equipped with a magnetic stirring bar, heating mantle, 250 mL addition funnel, reflux condenser and teflon-coated thermocouple. The reaction is carried out under a nitrogen atmosphere with a slow N 2  purge. The stirring mixture is heated to 50° C., and 143.3 g freshly distilled 1-bromoheptane (0.80 mole, fw=179.11) is added in a dropwise fashion over a period of about 60 minutes. The reaction mixture is then heated to about 80° C. for 10-12 hours and periodically monitored by HPLC in order to ensure that the starting amine is entirely consumed. The reaction mixture is cooled to room temperature, and 50% aqueous sodium hydroxide is added dropwise with strong agitation. The pH of the aqueous layer is monitored with pH paper. When the mixture becomes sufficiently basic (˜29 g NaOH), the lower aqueous phase is removed, and the organic solution is filtered and placed in a rotary evaporator in order to partially remove the volatile components (acetonitrile, water, diisopropylethylamine) under vacuum. When the product begins to crystallize from solution, about 300 mL diethyl ether is added portionwise with stirring. The mixture is allowed to stand at 4° C. overnight. The cold mixture is filtered through sintered glass, the solid is washed with diethyl ether and dried on the filter by passing dry nitrogen through it. It is finally dried in a vacuum oven (50° C., 20 torr) overnight. This crude product is recrystallized by dissolving it in a minimum amount of hot (70° C.) acetonitrile, quickly filtering the hot solution through sintered-glass and the allowing it to cool. Crystallization occurs on standing at room temperature and is completed by the addition of diethyl ether with cooling. The product is worked up as before. This procedure yields about 102 g (69%) of a white, crystalline product with &gt;99% purity (HPLC). 
       Example 15 
     Preparation of 3,5-Bis(N,N-dimethyldecylammoniummethyl)-1-fluorobenzene Dibromide (fw=652.68) 
       [0339]    77.9 g Freshly distilled N,N-dimethyldecylamine (420 mmole, fw=185.36) is added to 1 L stirring acetonitrile in a 2 L, 4-neck round-bottom flask that is equipped with a heating mantle, mechanical stirrer, 500 mL addition funnel, reflux condenser and teflon-coated thermocouple. The reaction is carried out under a nitrogen atmosphere with a slow N 2  purge. The stirring mixture is heated to 50° C., and 56.4 g freshly recrystallized 3,5-bis(bromomethyl)-1-fluorobenzene 5  (200 mmole, fw=281.96) in 200 mL acetonitrile is added in a dropwise fashion over a period of about 60 minutes; the reaction is mildly exothermic. The reaction mixture is then heated to about 80° C. for 3-5 hours and then rapidly filtered while hot through a sintered-glass filter into a 2 L clean filter-flask. On cooling to room temperature, copious amounts of white crystals form in solution. The product is allowed to crystallize from solution by standing at room temperature for about 3 hours, and then the mixture is allowed to stand at 4° C. overnight. The cold mixture is filtered through a sintered-glass filter, washed with cold acetonitrile, then n-pentane and finally dried by passing dry N 2  through the product. The product is finally dried in a vacuum oven (50° C., 20 torr) overnight, cooled and stored in a sealed container. This procedure yields about 125 g (96%) of a white, crystalline product. It is recrystallized from hot acetonitrile (9-10 g solvent per gram of product) yielding 120 g of the purified product (99.5-99.8% pure, HPLC). 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE V 
               
             
             
               
                   
               
               
                 Cationic Displacer Compounds 
               
             
          
           
               
                   
                   
                   
                   
                   
                   
                 HPLC  
               
               
                   
                   
                   
                   
                   
                   
                 Method 9a 
               
             
          
           
               
                 [R 1 R 2 R 3 R 4 N]  + [X]  −   
                   
                   
                   
                   
                   
                 Form. 
                 Ret. 
               
             
          
           
               
                 Nu. 
                 R 1   
                 R 2   
                 R 3   
                 R 4   
                 X −   
                 Amine 
                 CAS Num. 
                 Alkylating Agent 
                 CAS Num. 
                 Formula 
                 Weight 
                 Time 
               
               
                   
               
               
                  1 
                   n Decyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 100-44-7 
                 C 19 H 34 NCl 
                 311.938 
                 41.2 
               
               
                  2 
                   n Decyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 100-39-0 
                 C 19 H 34 NBr 
                 356.390 
                 41.2 
               
               
                  3 
                   n Decyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 103-83-3 
                 R 1 X 
                 112-29-8 
                 C 19 H 34 NBr 
                 356.390 
                 41.2 
               
               
                  4 
                   n Decyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 OH −   
                 — 
                 — 
                 — 
                 — 
                 C 19 H 35 NO 
                 293.493 
                 41.2 
               
               
                  5 
                   n Decyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 34 NO 2 F 3   
                 389.502 
                 41.2 
               
               
                  6 
                   n Decyl 
                 Methyl 
                 Ethyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 4788-37-8 
                 R 1 X 
                 112-29-8 
                 C 20 H 36 NBr 
                 370.417 
                 42.2 
               
               
                  7 
                   n Decyl 
                 Methyl 
                   n Propyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 2532-72-1 
                 R 1 X 
                 112-29-8 
                 C 21 H 38 NBr 
                 384.443 
                 44.2 
               
               
                  8 
                   n Decyl 
                 Methyl 
                   n Butyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 31844-65-2 
                 R 1 X 
                 112-29-8 
                 C 22 H 40 NBr 
                 398.470 
                 46.5 
               
               
                  9 
                   n Decyl 
                 Methyl 
                 Methyl 
                 2-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 345-35-7 
                 C 19 H 33 NClF 
                 329.929 
                 41.3 
               
               
                  10 
                   n Decyl 
                 Methyl 
                 Methyl 
                 3-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 456-42-8 
                 C 19 H 33 NClF 
                 329.929 
                 41.3 
               
               
                  11 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 352-11-4 
                 C 19 H 33 NClF 
                 329.929 
                 41.4 
               
               
                  12 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 23915-07-3 
                 C 19 H 33 NBrF 
                 374.380 
                 41.4 
               
               
                  13 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 OH −   
                 — 
                 — 
                 — 
                 — 
                 C 19 H 34 NOF 
                 311.484 
                 41.4 
               
               
                  14 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 33 NO 2 F 4   
                 407.492 
                 41.4 
               
               
                  15 
                   n Decyl 
                 Methyl 
                 Methyl 
                 2-ClC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 611-19-8 
                 C 19 H 33 NCl 2   
                 346.383 
                 42.8 
               
               
                  16 
                   n Decyl 
                 Methyl 
                 Methyl 
                 3-ClC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 620-20-2 
                 C 19 H 33 NCl 2   
                 346.383 
                 42.9 
               
               
                  17 
                   n Decyl 
                 Methyl 
                 Methyl 
                 3-ClC 6 H 4 CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 766-80-3 
                 C 19 H 33 NBrCl 
                 390.834 
                 42.9 
               
               
                  18 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-ClC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 104-83-6 
                 C 19 H 33 NCl 2   
                 346.383 
                 43.2 
               
               
                  19 
                   n Decyl 
                 Methyl 
                 Methyl 
                 3-BrC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 93277-4 
                 C 19 H 33 NBrCl 
                 390.834 
                 43.6 
               
               
                  20 
                   n Decyl 
                 Methyl 
                 Methyl 
                 3-BrC 6 H 4 CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 823-78-9 
                 C 19 H 33 NBr 2   
                 435.286 
                 43.6 
               
               
                  21 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-BrC 6 H 4 CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 823-78-9 
                 C 19 H 33 NBr 2   
                 435.286 
                 44.0 
               
               
                  22 
                   n Decyl 
                 Methyl 
                 Methyl 
                 2,4-F 2 C 6 H 3 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 452-07-3 
                 C 19 H 32 NClF 2   
                 347.919 
                 41.7 
               
               
                  23 
                   n Decyl 
                 Methyl 
                 Methyl 
                 2,6-F 2 C 6 H 3 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 67-73-4 
                 C 19 H 32 NClF 2   
                 347.919 
                 41.4 
               
               
                  24 
                   n Decyl 
                 Methyl 
                 Methyl 
                 3,5-F 2 C 6 H 3 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 220141-71-9 
                 C 19 H 32 NClF 2   
                 347.919 
                 42.0 
               
               
                  25 
                   n Decyl 
                 Methyl 
                 Methyl 
                 2,4,6-F 3 C 6 H 2 CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 151411-98-2 
                 C 19 H 31 NBrF 3   
                 410.361 
                 41.8 
               
               
                  26 
                   n Decyl 
                 Methyl 
                 Methyl 
                 3,4,5-F 3 C 6 H 2 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 732306-27-3 
                 C 19 H 31 NClF 3   
                 365.910 
                 42.8 
               
               
                  27 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-MeC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 104-82-5 
                 C 20 H 36 NCl 
                 325.965 
                 43.7 
               
               
                  28 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-CF 3 C 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 939-99-1 
                 C 20 H 33 NClF 3   
                 379.937 
                 44.1 
               
               
                  29 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-EtC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 1467-05-6 
                 C 21 H 38 NCl 
                 339.992 
                 45.9 
               
               
                  30 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-tuC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 19692-45-6 
                 C 23 H 42 NCl 
                 368.039 
                 48.7 
               
               
                  31 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-PhC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 1667-11-4 
                 C 25 H 38 NCl 
                 388.036 
                 47.7 
               
               
                  32 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-MeOC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 824-94-2 
                 C 20 H 36 NOCl 
                 341.965 
                 42.1 
               
               
                  33 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-AcNHC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 54777-65-0 
                 C 21 H 37 N 12 OCl 
                 368.990 
                 36.6 
               
               
                  34 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-MeO 2 CC 6 H 4 CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 2417-72-3 
                 C 21 H 36 NO 2 Br 
                 414.426 
                 40.2 
               
               
                  35 
                   n Decyl 
                 Methyl 
                 Methyl 
                 H 2 NC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 79-07-2 
                 C 14 H 31 N 2 OCl 
                 278.866 
                 32.1 
               
               
                  36 
                   n Decyl 
                 Methyl 
                 Methyl 
                 PhHNC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 587-65-5 
                 C 20 H 35 N 2 OCl 
                 354.963 
                 41.5 
               
               
                  37 
                   n Decyl 
                 Methyl 
                 Methyl 
                 Me 2 NC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 2675-89-0 
                 C 16 H 35 N 2 OCl 
                 306.915 
                 35.5 
               
               
                  38 
                   n Decyl 
                 Methyl 
                 Methyl 
                 Et 2 NC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 2315-36-8 
                 C 18 H 39 N 2 OCl 
                 334.968 
                 39.8 
               
               
                  39 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 17373-27-2 
                 R 4 X 
                 100-44-7 
                 C 18 H 32 NCl 
                 297.912 
                 38.0 
               
               
                  40 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 Br −   
                 NR 1 R 2 R 3   
                 17373-27-2 
                 R 4 X 
                 100-39-0 
                 C 18 H 32 NBr 
                 342.363 
                 38.0 
               
               
                  41 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 OH −   
                 — 
                 — 
                 — 
                 — 
                 C 18 H 33 NO 
                 279.466 
                 38.0 
               
               
                  42 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 20 H 32 NO 2 F 3   
                 375.475 
                 38.0 
               
               
                  42b 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 17373-27-2 
                 R 4 X 
                 352-11-4 
                 C 18 H 31 NClF 
                 315.904 
                 38.3 
               
               
                  42c 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 20 H 31 NO 2 F 4   
                 393.456 
                 38.3 
               
               
                  43 
                   n Nonyl 
                 Methyl 
                 Ethyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 4788-37-8 
                 R 1 X 
                 693-58-3 
                 C 19 H 34 NBr 
                 356.390 
                 39.7 
               
               
                  44 
                   n Nonyl 
                 Methyl 
                   n Propyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 2532-72-1 
                 R 1 X 
                 693-58-3 
                 C 20 H 36 NBr 
                 370.417 
                 41.7 
               
               
                  45 
                   n Nonyl 
                 Methyl 
                   n Butyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 31844-65-2 
                 R 1 X 
                 693-58-3 
                 C 21 H 38 NBr 
                 384.443 
                 44.0 
               
               
                  46 
                   n Octyl 
                 Methyl 
                 Methyl 
                 4-CH 3 C 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 7378-99-6 
                 R 4 X 
                 104-82-5 
                 C 18 H 32 NCl 
                 297.912 
                 37.7 
               
               
                  47 
                   n Octyl 
                 Methyl 
                 Methyl 
                 4-tuC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 7378-99-6 
                 R 4 X 
                 19692-45-6 
                 C 21 H 38 NCl 
                 339.986 
                 43.6 
               
               
                  47b 
                   n Octyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 7378-99-6 
                 R 4 X 
                 352-11-4 
                 C 17 H 29 NClF 
                 301.877 
                 34.9 
               
               
                  48 
                   n Octyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 7378-99-6 
                 R 4 X 
                 100-44-7 
                 C 17 H 30 NCl 
                 283.885 
                 34.7 
               
               
                  49 
                   n Octyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 19 H 30 NO 2 F 3   
                 361.448 
                 34.7 
               
               
                  49b 
                   n Octyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl 
                 NR 1 R 2 R 3   
                 7378-99-6 
                 R 4 X 
                 352-11-4 
                 C 17 H 29 NClF 
                 301.867 
                 35.2 
               
               
                  49c 
                   n Octyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 19 H 29 NO 2 F 4   
                 379.430 
                 35.2 
               
               
                  50 
                   n Octyl 
                 Methyl 
                 Ethyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 4788-37-8 
                 R 1 X 
                 111-83-1 
                 C 18 H 32 NBr 
                 342.363 
                 35.7 
               
               
                  51 
                   n Octyl 
                 Methyl 
                   n Propyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 2532-72-1 
                 R 1 X 
                 111-83-1 
                 C 19 H 34 NBr 
                 356.390 
                 37.7 
               
               
                  52 
                   n Octyl 
                 Methyl 
                   n Butyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 31844-65-2 
                 R 1 X 
                 111-83-1 
                 C 20 H 36 NBr 
                 370.417 
                 40.0 
               
               
                  53 
                   n Octyl 
                 Methyl 
                   n Pentyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 77223-58-6 
                 R 1 X 
                 111-83-1 
                 C 21 H 38 NBr 
                 384.443 
                 42.5 
               
               
                  53b 
                   n Heptyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 Cl 
                 NR 1 R 2 R 3   
                 5277-11-2 
                 R 4 X 
                 100-44-7 
                 C 16 H 28 NCl 
                 269.850 
                 31.8 
               
               
                  53c 
                   n Heptyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 18 H 28 NO 2 F 3   
                 347.413 
                 31.8 
               
               
                  53d 
                   n Heptyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl 
                 NR 1 R 2 R 3   
                 5277-11-2 
                 R 4 X 
                 352-11-4 
                 C 16 H 27 NClF 
                 287.840 
                 32.0 
               
               
                  53e 
                   n Heptyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 18 H 27 NO 2 F 4   
                 365.404 
                 32.0 
               
               
                  54 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 17373-28-3 
                 R 4 X 
                 100-44-7 
                 C 20 H 36 NCl 
                 325.965 
                 44.3 
               
               
                  55 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 Br −   
                 NR 1 R 2 R 3   
                 17373-28-3 
                 R 4 X 
                 100-39-0 
                 C 20 H 36 NBr 
                 370.417 
                 44.3 
               
               
                  56 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 OH −   
                 — 
                 — 
                 — 
                 — 
                 C 20 H 37 NO 
                 307.520 
                 44.3 
               
               
                  57 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 36 NO 2 F 3   
                 403.529 
                 44.3 
               
               
                  58 
                   n Undecyl 
                 Methyl 
                 Ethyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 4788-37-8 
                 R 1 X 
                 693-67-4 
                 C 21 H 38 NBr 
                 384.443 
                 45.3 
               
               
                  59 
                   n Undecyl 
                 Methyl 
                   n Propyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 2532-72-1 
                 R 1 X 
                 693-67-4 
                 C 22 H 40 NBr 
                 398.470 
                 47.3 
               
               
                  60 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 17373-28-3 
                 R 4 X 
                 352-11-4 
                 C 20 H 35 NClF 
                 343.956 
                 44.5 
               
               
                  61 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 17373-28-3 
                 R 4 X 
                 459-46-1 
                 C 20 H 35 NBrF 
                 388.407 
                 44.5 
               
               
                  62 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 OH −   
                 — 
                 — 
                 — 
                 — 
                 C 20 H 36 NOF 
                 325.510 
                 44.5 
               
               
                  63 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 35 NO 2 F 4   
                 421.519 
                 44.5 
               
               
                  64 
                   n Decyl 
                 Methyl 
                 Benzyl 
                 NH 2 C(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 112778-25-3 
                 R 4 X 
                 79-07-2 
                 C 20 H 35 N 2 OCl 
                 354.963 
                 36.5 
               
               
                  65 
                   n Decyl 
                 Methyl 
                 Benzyl 
                 PhNHC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 112778-25-3 
                 R 4 X 
                 587-65-5 
                 C 26 H 39 N 2 OCl 
                 431.061 
                 41.6 
               
               
                  66 
                   n Decyl 
                 Methyl 
                 Benzyl 
                 Me 2 NC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 112778-25-3 
                 R 4 X 
                 2675-89-0 
                 C 22 H 39 N 2 OCl 
                 383.017 
                 39.9 
               
               
                  67 
                   n Decyl 
                 Methyl 
                 Methyl 
                 l-Me 2 NC(O)CH(Bz)— 
                 Br −   
                 NR 2 R 3 R 4   
                 91904-44-8 r   
                 R 1 X 
                 112-29-8 
                 C 23 H 41 N 2 OBr 
                 441.488 
                 41.5 
               
               
                  67b 
                   n Decyl 
                 Methyl 
                 Methyl 
                 d-Me 2 NC(O)CH(Bz)— 
                 Br −   
                 NR 2 R 3 R 4   
                 91904-44-8 r   
                 R 1 X 
                 112-29-8 
                 C 23 H 40 N 2 OBr 
                 440.487 
                 41.5 
               
               
                  68 
                   n Decyl 
                 Methyl 
                 Benzyl 
                 Et 2 NC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 112778-25-3 
                 R 4 X 
                 2315-36-8 
                 C 24 H 43 N 2 OCl 
                 411.071 
                 44.2 
               
               
                  69 
                 Phenyl 
                 Methyl 
                   n Pentyl 
                   n Butyl 
                 Br −   
                 NR 1 R 3 R 4   
                 138374-52-4 
                 R 2 X 
                 74-83-9 
                 C 16 H 28 NBr 
                 314.309 
                 29.7 
               
               
                  70 
                 Phenyl 
                 Methyl 
                   n Pentyl 
                   n Pentyl 
                 Br −   
                 NR 1 R 3 R 4   
                 6249-76-9 
                 R 2 X 
                 74-83-9 
                 C 17 H 30 NBr 
                 328.336 
                 32.5 
               
               
                  71 
                 Phenyl 
                 Methyl 
                   n Pentyl 
                   n Hexyl 
                 Br −   
                 NR 1 R 3 R 4   
                 138374-53-5 
                 R 2 X 
                 74-83-9 
                 C 18 H 32 NBr 
                 342.363 
                 35.1 
               
               
                  72 
                 Phenyl 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 HNR 1 R 2   
                 100-61-8 
                 2xR 4 X + base 
                 111-25-1 
                 C 19 H 34 NBr 
                 356.390 
                 37.7 
               
               
                  73 
                 Phenyl 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 NR 1 R 3 R 4   
                 4430-09-5 
                 R 2 X 
                 74-83-9 
                 C 19 H 34 NBr 
                 356.390 
                 37.7 
               
               
                  74 
                 Phenyl 
                 Methyl 
                   n Heptyl 
                   n Hexyl 
                 Br −   
                 NR 1 R 3 R 4   
                 288572-97-4 
                 R 2 X 
                 74-83-9 
                 C 20 H 36 NBr 
                 370.417 
                 40.2 
               
               
                  75 
                 Phenyl 
                 Methyl 
                   n Heptyl 
                   n Heptyl 
                 Br −   
                 NR 1 R 3 R 4   
                 100-61-8 
                 R 2 X 
                 74-83-9 
                 C 21 H 38 NBr 
                 384.443 
                 42.7 
               
               
                  76 
                 Phenyl 
                 Methyl 
                   n Heptyl 
                   n Heptyl 
                 Br −   
                 NR 1 R 3 R 4   
                 16341-05-2 
                 R 2 X 
                 74-83-9 
                 C 21 H 38 NBr 
                 384.443 
                 42.7 
               
               
                  77 
                 Phenyl 
                 Methyl 
                   n Heptyl 
                   n Heptyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 38 NO 2 F 3   
                 417.555 
                 42.7 
               
               
                  78 
                 4-FC 6 H 4 — 
                 Methyl 
                   n Heptyl 
                   n Heptyl 
                 Br −   
                 HNR 1 R 2   
                 405-66-3 
                 2xR 4 X + base 
                 629-04-9 
                 C 21 H 37 N 1 BrF 
                 402.434 
                 42.9 
               
               
                  79 
                 4-FC 6 H 4 — 
                 Methyl 
                   n Heptyl 
                   n Heptyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 37 NO 2 F 4   
                 435.546 
                 42.9 
               
               
                  80 
                 Phenyl 
                 Methyl 
                   n Heptyl 
                   n Octyl 
                 Br −   
                 NR 1 R 2 R 4   
                 13063-61-1 
                 R 3 X 
                 629-04-9 
                 C 22 H 40 NBr 
                 398.470 
                 45.1 
               
               
                  81 
                 Phenyl 
                 Methyl 
                   n Octyl 
                   n Octyl 
                 Br −   
                 NR 1 R 3 R 4   
                 3007-75-8 
                 R 2 X 
                 74-83-9 
                 C 23 H 42 NBr 
                 412.497 
                 47.5 
               
             
          
           
               
                  82 
                 R 1  + R 2  = IN w   
                   n Butyl 
                   n Pentyl 
                 Br −   
                 NR 1 R 2 R 3   
                 5878-10-8 
                 R 4 X 
                 110-53-2 
                 C 17 H 28 NBr 
                 326.320 
                 29.7 
               
               
                  83 
                 R 1  + R 2  = IN w   
                   n Pentyl 
                   n Pentyl 
                 Br −   
                 NR 1 R 2 R 3   
                 496-15-1 
                 R 4 X 
                 110-53-2 
                 C 18 H 30 NBr 
                 340.347 
                 32.9 
               
               
                  84 
                 R 1  + R 2  = IN w   
                   n Hexyl 
                   n Pentyl 
                 Br −   
                 NR 1 R 2 R 3   
                 593281-15-3 
                 R 4 X 
                 110-53-2 
                 C 19 H 32 NBr 
                 354.374 
                 35.9 
               
               
                  85 
                 R 1  + R 2  = IN w   
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 HNR 1 R 2   
                 496-15-1 
                 2xR 4 X + base 
                 111-25-1 
                 C 20 H 34 NBr 
                 368.401 
                 38.7 
               
               
                  86 
                 R 1  + R 2  = IN w   
                   n Hexyl 
                   n Heptyl 
                 Br −   
                 NR 1 R 2 R 3   
                 593281-15-3 
                 R 4 X 
                 629-04-9 
                 C 21 H 36 NBr 
                 382.428 
                 41.4 
               
               
                  87 
                 R 1  + R 2  = IN w   
                   n Heptyl 
                   n Heptyl 
                 Br −   
                 NR 1 R 2 R 3   
                 496-15-1 
                 2xR 4 X + base 
                 629-04-9 
                 C 22 H 38 NBr 
                 396.448 
                 43.9 
               
               
                  88 
                 R 1  + R 2  = IN w   
                   n Heptyl 
                   n Heptyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 38 NO 2 F 3   
                 429.566 
                 43.9 
               
               
                  89 
                 R 1  + R 2  = IN w   
                   n Heptyl 
                   n Octyl 
                 Br −   
                 NR 1 R 2 R 3   
                 157363-64-9 
                 R 4 X 
                 111-83-1 
                 C 23 H 40 NBr 
                 410.481 
                 46.3 
               
               
                  90 
                 R 1  + R 2  = IN w   
                   n Octyl 
                   n Octyl 
                 Br −   
                 HNR 1 R 2   
                 496-15-1 
                 2xR 4 X + base 
                 111-83-1 
                 C 24 H 42 NBr 
                 424.508 
                 48.6 
               
               
                  91 
                 R 1  + R 2  = IN w   
                 Methyl 
                   n Nonyl 
                 Br −   
                 NR 1 R 2 R 3   
                 824-21-5 
                 R 4 X 
                 693-58-3 
                 C 18 H 30 NBr 
                 340.347 
                 36.5 
               
               
                  92 
                 R 1  + R 2  = IN w   
                 Methyl 
                   n Decyl 
                 Br −   
                 NR 1 R 2 R 3   
                 824-21-5 
                 R 4 X 
                 112-29-8 
                 C 19 H 32 NBr 
                 354.368 
                 39.9 
               
               
                  93 
                 R 1  + R 2  = IN w   
                 Methyl 
                   n Undecyl 
                 Br −   
                 NR 1 R 2 R 3   
                 824-21-5 
                 R 4 X 
                 693-67-4 
                 C 20 H 34 NBr 
                 368.395 
                 43.0 
               
               
                  94 
                 R 1  + R 2  = THQ w   
                   n Pentyl 
                   n Butyl 
                 Br −   
                 NR 1 R 2 R 3   
                 63074-60-2 
                 R 4 X 
                 109-65-9 
                 C 18 H 30 NBr 
                 340.347 
                 31.0 
               
               
                  95 
                 R 1  + R 2  = THQ w   
                   n Pentyl 
                   n Pentyl 
                 Br −   
                 NR 1 R 2 R 3   
                 635-46-1 
                 2xR 4 X + base 
                 110-53-2 
                 C 19 H 32 NBr 
                 354.374 
                 34.1 
               
               
                  96 
                 R 1  + R 2  = THQ w   
                   n Pentyl 
                   n Hexyl 
                 Br −   
                 NR 1 R 2 R 3   
                 63074-60-2 
                 R 4 X 
                 111-25-1 
                 C 20 H 34 NBr 
                 368.401 
                 37.1 
               
               
                  97 
                 R 1  + R 2  = THQ w   
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 HNR 1 R 2   
                 635-46-1 
                 2xR 4 X + base 
                 111-25-1 
                 C 21 H 36 NBr 
                 382.428 
                 39.7 
               
               
                  98 
                 R 1  + R 2  = THQ w   
                   n Hexyl 
                   n Heptyl 
                 Br −   
                 NR 1 R 2 R 3   
                 593281-16-4 
                 R 4 X 
                 629-04-9 
                 C 22 H 38 NBr 
                 396.454 
                 42.6 
               
               
                  99 
                 R 1  + R 2  = THQ w   
                   n Heptyl 
                   n Heptyl 
                 Br −   
                 NR 1 R 2 R 3   
                 635-46-1 
                 2xR 4 X + base 
                 629-04-9 
                 C 23 H 40 NBr 
                 410.481 
                 44.6 
               
               
                 100 
                 R 1  + R 2  = THQ w   
                   n Heptyl 
                   n Heptyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 25 H 40 NO 2 F 3   
                 443.593 
                 44.6 
               
               
                 101 
                 R 1  + R 2  = THQ w   
                   n Octyl 
                   n Heptyl 
                 Br −   
                 NR 1 R 2 R 3   
                 912546-48-6 
                 R 4 X 
                 629-04-9 
                 C 24 H 42 NBr 
                 424.508 
                 47.0 
               
               
                 102 
                 R 1  + R 2  = THQ w   
                   n Octyl 
                   n Octyl 
                 Br −   
                 HNR 1 R 2   
                 635-46-1 
                 2xR 4 X + base 
                 111-83-1 
                 C 25 H 44 NBr 
                 438.535 
                 49.2 
               
               
                 103 
                 R 1  + R 2  = THQ w   
                 Methyl 
                   n Nonyl 
                 Br −   
                 NR 1 R 2 R 3   
                 491-34-9 
                 R 4 X 
                 693-58-3 
                 C 19 H 32 NBr 
                 354.368 
                 37.6 
               
               
                 104 
                 R 1  + R 2  = THQ w   
                 Methyl 
                   n Decyl 
                 Br −   
                 NR 1 R 2 R 3   
                 491-34-9 
                 R 4 X 
                 112-29-8 
                 C 20 H 34 NBr 
                 368.395 
                 40.8 
               
               
                 105 
                 R 1  + R 2  = THQ w   
                 Methyl 
                   n Undecyl 
                 Br −   
                 NR 1 R 2 R 3   
                 491-34-9 
                 R 4 X 
                 693-67-4 
                 C 21 H 36 NBr 
                 382.421 
                 43.9 
               
             
          
           
               
                 106 
                 Benzyl 
                 Methyl 
                   n Pentyl 
                   n Butyl 
                 Br −   
                 NR 1 R 2 R 3   
                 77223-58-6 
                 R 4 X 
                 109-65-9 
                 C 17 H 30 NBr 
                 328.336 
                 32.0 
               
               
                 107 
                 Benzyl 
                 Methyl 
                   n Pentyl 
                   n Pentyl 
                 Br −   
                 NR 1 R 2 R 3   
                 77223-58-6 
                 R 4 X 
                 110-53-2 
                 C 18 H 32 NBr 
                 342.363 
                 34.8 
               
               
                 108 
                 Benzyl 
                 Methyl 
                   n Pentyl 
                   n Hexyl 
                 Br −   
                 NR 1 R 2 R 3   
                 77223-58-6 
                 R 4 X 
                 111-25-1 
                 C 19 H 34 NBr 
                 356.390 
                 37.4 
               
               
                 109 
                 Benzyl 
                 Methyl 
                   n Pentyl 
                   n Heptyl 
                 Br −   
                 NR 1 R 2 R 3   
                 77223-58-6 
                 R 4 X 
                 629-04-9 
                 C 20 H 36 NBr 
                 370.417 
                 40.3 
               
               
                 110 
                 Benzyl 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 HNR 1 R 2   
                 100-6108 
                 2xR 4 X + base 
                 111-25-1 
                 C 20 H 36 NBr 
                 370.417 
                 40.0 
               
               
                 111 
                 Benzyl 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 100-44-7 
                 C 20 H 36 NCl 
                 325.965 
                 40.0 
               
               
                 112 
                 Benzyl 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 36 NO 2 F 3   
                 403.529 
                 40.0 
               
               
                 113 
                 Benzyl 
                 Methyl 
                 Cyclohexyl 
                 Cyclohexyl 
                 Br −   
                 NR 2 R 3 R 4   
                 7560-83-0 
                 R 1 X 
                 100-39-0 
                 C 20 H 32 NBr 
                 366.385 
                 30.7 
               
               
                 114 
                 PhC(O)CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 532-27-4 
                 C 21 H 36 NOCl 
                 353.976 
                 41.5 
               
               
                 115 
                 2-FC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 345-35-7 
                 C 20 H 35 NClF 
                 343.956 
                 40.1 
               
               
                 116 
                 3-FC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 456-42-8 
                 C 20 H 35 NClF 
                 343.956 
                 40.1 
               
               
                 117 
                 4-FC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 352-11-4 
                 C 20 H 35 NClF 
                 343.956 
                 40.2 
               
               
                 118 
                 4-FC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 23915-07-3 
                 C 20 H 35 NBrF 
                 388.407 
                 40.2 
               
               
                 119 
                 4-FC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 OH −   
                 — 
                 — 
                 — 
                 — 
                 C 20 H 36 NOF 
                 325.510 
                 40.2 
               
               
                 120 
                 4-FC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 35 NO 2 F 4   
                 421.519 
                 40.2 
               
               
                 121 
                 2-ClC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 611-19-8 
                 C 20 H 35 NCl 2   
                 360.410 
                 41.7 
               
               
                 122 
                 3-ClC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 620-20-2 
                 C 20 H 35 NCl 2   
                 360.410 
                 41.8 
               
               
                 123 
                 3-ClC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 766-80-3 
                 C 20 H 35 NBrCl 
                 404.861 
                 41.8 
               
               
                 124 
                 4-ClC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 104-83-6 
                 C 20 H 35 NCl 2   
                 360.410 
                 42.1 
               
               
                 125 
                 4-F-2-ClC 6 H 3 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 93286-22-7 
                 C 20 H 34 NCl 2 F 
                 378.401 
                 42.3 
               
               
                 126 
                 6-F-2-ClC 6 H 3 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 55117-15-2 
                 C 20 H 34 NCl 2 F 
                 378.401 
                 41.8 
               
               
                 127 
                 2-F-3-ClC 6 H 3 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 85070-47-9 
                 C 20 H 34 NBrClF 
                 422.846 
                 42.3 
               
               
                 128 
                 4-F-3-ClC 6 H 3 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 192702-01-5 
                 C 20 H 34 NBrClF 
                 422.846 
                 42.7 
               
               
                 129 
                 2,3-F 2 C 6 H 3 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 113211-94-2 
                 C 20 H 34 NBrF 2   
                 406.398 
                 41.0 
               
               
                 130 
                 2,4-F 2 C 6 H 3 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 4 X 
                 452-07-3 
                 C 20 H 34 NClF 2   
                 361.941 
                 41.1 
               
               
                 131 
                 2,5-F 2 C 6 H 3 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 495-07-8 
                 C 20 H 34 NClF 2   
                 361.941 
                 40.8 
               
               
                 132 
                 2,6-F 2 C 6 H 3 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 697-73-4 
                 C 20 H 34 NClF 2   
                 361.941 
                 40.9 
               
               
                 133 
                 3,4-F 2 C 6 H 3 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 698-80-6 
                 C 20 H 34 NClF 2   
                 361.941 
                 41.2 
               
               
                 134 
                 3,5-F 2 C 6 H 3 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 220141-71-9 
                 C 20 H 34 NClF 2   
                 361.941 
                 41.4 
               
               
                 135 
                 2,4,6-F 3 C 6 H 2 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 151411-98-2 
                 C 20 H 33 NBrF 3   
                 424.388 
                 41.3 
               
               
                 136 
                 3,4,5-F 3 C 6 H 2 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 37615-53-5 
                 R 1 X 
                 732306-27-3 
                 C 20 H 33 NClF 3   
                 379.937 
                 42.2 
               
               
                 137 
                 3-BrC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 932-77-4 
                 C 20 H 35 NBrCl 
                 404.861 
                 42.2 
               
               
                 138 
                 3-BrC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 823-78-9 
                 C 20 H 35 NBr 2   
                 449.313 
                 42.7 
               
               
                 139 
                 4-BrC 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 589-15-1 
                 C 20 H 35 NBr 2   
                 449.313 
                 43.1 
               
               
                 140 
                 Ph(CH 2 ) 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 HNR 1 R 2   
                 589-08-2 
                 2xR 4 X + base 
                 111-25-1 
                 C 21 H 38 NBr 
                 384.443 
                 41.6 
               
               
                 141 
                 4-CF 3 C 6 H 4 CH 2 — 
                 Methyl 
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 NR 2 R 3 R 4   
                 37615-53-5 
                 R 1 X 
                 939-99-1 
                 C 21 H 35 NBrF 3   
                 438.415 
                 43.4 
               
               
                 142 
                 Benzyl 
                 Ethyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 1097732-09-6 
                 R 1 X 
                 100-44-7 
                 C 21 H 38 NCl 
                 339.992 
                 41.3 
               
               
                 143 
                 Benzyl 
                 Ethyl 
                   n Hexyl 
                   n Hexyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 38 NO 2 F 3   
                 417.555 
                 41.3 
               
               
                 144 
                 4-FC 6 H 4 CH 2 — 
                 Ethyl 
                   n Hexyl 
                   n Hexyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 1097732-09-6 
                 R 1 X 
                 352-11-4 
                 C 21 H 37 NClF 
                 357.983 
                 41.5 
               
               
                 145 
                 4-FC 6 H 4 CH 2 — 
                 Ethyl 
                   n Hexyl 
                   n Hexyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 37 NO 2 F 4   
                 435.546 
                 41.5 
               
               
                 146 
                 Benzyl 
                 Methyl 
                   n Heptyl 
                   n Pentyl 
                 Br −   
                 NR 1 R 2 R 3   
                 8140453-7 
                 R 4 X 
                 110-53-2 
                 C 20 H 36 NBr 
                 370.417 
                 40.1 
               
               
                 147 
                 Benzyl 
                 Methyl 
                   n Heptyl 
                   n Hexyl 
                 Br −   
                 NR 1 R 2 R 3   
                 8140453-7 
                 R 4 X 
                 111-25-1 
                 C 21 H 38 NBr 
                 384.443 
                 42.5 
               
               
                 147b 
                 4-FC 6 H 4 CH 2 — 
                 Methyl 
                   n Heptyl 
                   n Hexyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 8140453-7 
                 R 4 X 
                 352-11-4 
                 C 21 H 37 NClF 
                 357.985 
                 42.7 
               
               
                 148 
                 Benzyl 
                 Methyl 
                   n Heptyl 
                   n Heptyl 
                 Br −   
                 NR 1 R 2 R 3   
                 8140453-7 
                 R 4 X 
                 629-04-9 
                 C 22 H 40 NBr 
                 398.470 
                 45.0 
               
               
                 149 
                 Benzyl 
                 Methyl 
                   n Heptyl 
                   n Heptyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 40 NO 2 F 3   
                 431.582 
                 45.0 
               
               
                 150 
                 4-FC 6 H 4 CH 2 — 
                 Methyl 
                   n Heptyl 
                   n Heptyl 
                 Br −   
                 HNR 1 R 2   
                 405-66-3 
                 2xR 4 X + base 
                 629-04-9 
                 C 22 H 39 NBrF 
                 416.461 
                 45.2 
               
               
                 151 
                 4-FC 6 H 4 CH 2 — 
                 Methyl 
                   n Heptyl 
                   n Heptyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 39 NO 2 F 4   
                 449.573 
                 45.2 
               
               
                 152 
                 Benzyl 
                 Ethyl 
                   n Heptyl 
                   n Heptyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 1097732-10-9 
                 R 1 X 
                 100-44-7 
                 C 23 H 42 NCl 
                 368.046 
                 46.2 
               
               
                 153 
                 Benzyl 
                 Ethyl 
                   n Heptyl 
                   n Heptyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 25 H 42 NO 2 F 3   
                 445.609 
                 46.2 
               
               
                 154 
                 4-FC 6 H 4 CH 2 — 
                 Ethyl 
                   n Heptyl 
                   n Heptyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 1097732-10-9 
                 R 1 X 
                 352-11-4 
                 C 23 H 41 NClF 
                 386.036 
                 46.4 
               
               
                 155 
                 4-FC 6 H 4 CH 2 — 
                 Ethyl 
                   n Heptyl 
                   n Heptyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 25 H 41 NO 2 F 4   
                 463.600 
                 46.4 
               
               
                 156 
                 Benzyl 
                 Methyl 
                   n Heptyl 
                   n Octyl 
                 Br −   
                 NR 1 R 2 R 3   
                 71404-53-7 
                 R 4 X 
                 111-83-1 
                 C 23 H 42 NBr 
                 412.497 
                 47.4 
               
               
                 157 
                 Benzyl 
                 Methyl 
                   n Octyl 
                   n Octyl 
                 Br −   
                 HNR 1 R 2   
                 103-67-3 
                 2xR 4 X + base 
                 111-83-1 
                 C 24 H 44 NBr 
                 426.524 
                 49.8 
               
               
                 158 
                 Benzyl 
                 Methyl 
                   n Octyl 
                   n Octyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 4455-26-9 
                 R 1 X 
                 100-44-7 
                 C 24 H 44 NCl 
                 382.073 
                 50.0 
               
               
                 159 
                 4-FC 6 H 4 CH 2 —  
                 Methyl 
                   n Octyl 
                   n Octyl 
                 Cl −   
                 NR 2 R 3 R 4   
                 4455-26-9 
                 R 1 X 
                 352-11-4 
                 C 24 H 43 NClF 
                 400.063 
                 50.2 
               
             
          
           
               
                 160 
                 R 1  + R 2  = iIN w   
                   n Pentyl 
                   n Butyl 
                 Br −   
                 NR 1 R 2 R 3   
                 1197914-56-9 
                 R 4 X 
                 109-65-9 
                 C 17 H 28 NBr 
                 326.320 
                 30.3 
               
               
                 161 
                 R 1  + R 2  = iIN w   
                   n Pentyl 
                   n Pentyl 
                 Br −   
                 HNR 1 R 2   
                 496-12-8 
                 2xR 4 X + base 
                 110-53-2 
                 C 18 H 30 NBr 
                 340.347 
                 33.5 
               
               
                 161b 
                 R 1  + R 2  = iIN w   
                 Ph(CH 2 ) 3 — 
                 Ph(CH 2 ) 3 — 
                 Br −   
                 HNR 1 R 2   
                 496-12-8 
                 2xR 4 X + base 
                 637-59-2 
                 C 26 H 30 NBr 
                 436.427 
                 39.6 
               
               
                 161c 
                 R 1  + R 2  = iIN w   
                 Ph(CH 2 ) 3 — 
                 Ph(CH 2 ) 3 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 28 H 30 NO 2 F 3   
                 469.539 
                 39.6 
               
               
                 162 
                 R 1  + R 2  = iIN w   
                   n Pentyl 
                   n Hexyl 
                 Br −   
                 NR 1 R 2 R 3   
                 1197914-56-9 
                 R 4 X 
                 111-25-1 
                 C 19 H 32 NBr 
                 354.374 
                 36.5 
               
               
                 163 
                 R 1  + R 2  = iIN w   
                   n Pentyl 
                   n Octyl 
                 Br −   
                 HNR 3 R 4   
                 6835-13-8 
                 o-(XCH 2 ) 2 C 6 H 4  + base 
                 91-13-4 
                 C 21 H 36 NBr 
                 382.428 
                 42.1 
               
               
                 164 
                 R 1  + R 2  = iIN w   
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 HNR 1 R 2   
                 496-12-8 
                 2xR 4 X + base 
                 111-25-1 
                 C 20 H 34 NBr 
                 368.401 
                 39.3 
               
               
                 165 
                 R 1  + R 2  = iIN w   
                   n Heptyl 
                   n Hexyl 
                 Br −   
                 NR 1 R 2 R 3   
                 1197914-59-2 
                 R 4 X 
                 111-25-1 
                 C 21 H 36 NBr 
                 382.428 
                 42.0 
               
               
                 166 
                 R 1  + R 2  = iIN w   
                   n Heptyl 
                   n Heptyl 
                 Br −   
                 HNR 1 R 2   
                 496-12-8 
                 2xR 4 X + base 
                 629-04-9 
                 C 22 H 38 NBr 
                 396.454 
                 44.4 
               
               
                 167 
                 R 1  + R 2  = iIN w   
                   n Heptyl 
                   n Heptyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 38 NO 2 F 3   
                 429.566 
                 44.4 
               
               
                 168 
                 R 1  + R 2  = iIN w   
                   n Heptyl 
                   n Octyl 
                 Br −   
                 NR 1 R 2 R 3   
                 1197914-59-2 
                 R 4 X 
                 111-83-1 
                 C 23 H 40 NBr 
                 410.481 
                 46.8 
               
               
                 169 
                 R 1  + R 2  = iIN w   
                   n Heptyl 
                   n Octyl 
                 Br −   
                 HNR 3 R 4   
                 26627-77-0 
                 o-(XCH 2 ) 2 C 6 H 4  + base 
                 91-13-4 
                 C 23 H 40 NBr 
                 410.481 
                 46.8 
               
               
                 170 
                 R 1  + R 2  = iIN w   
                   n Octyl 
                   n Octyl 
                 Br −   
                 HNR 1 R 2   
                 496-12-8 
                 2xR 4 X + base 
                 111-83-1 
                 C 24 H 42 NBr 
                 424.508 
                 49.1 
               
               
                 171 
                 R 1  + R 2  = iIN w   
                 Methyl 
                   n Nonyl 
                 Br −   
                 NR 1 R 2 R 3   
                 3474-87-1 
                 R 4 X 
                 693-58-3 
                 C 18 H 30 NBr 
                 340.347 
                 37.0 
               
               
                 172 
                 R 1  + R 2  = iIN w   
                 Methyl 
                   n Nonyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 20 H 30 NO 2 F 3   
                 373.459 
                 37.0 
               
               
                 173 
                 R 1  + R 2  = iIN w   
                 Methyl 
                   n Decyl 
                 Br −   
                 NR 1 R 2 R 3   
                 3474-87-1 
                 R 4 X 
                 112-29-8 
                 C 19 H 32 NBr 
                 354.374 
                 40.4 
               
               
                 174 
                 R 1  + R 2  = iIN w   
                 Methyl 
                   n Decyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 32 NO 2 F 3   
                 387.486 
                 40.4 
               
               
                 175 
                 R 1  + R 2  = iIN w   
                 Methyl 
                   n Undecyl 
                 Br −   
                 NR 1 R 2 R 3   
                 3474-87-1 
                 R 4 X 
                 693-67-4 
                 C 20 H 34 NBr 
                 368.401 
                 43.5 
               
               
                 176 
                 R 1  + R 2  = iIN w   
                 Methyl 
                   n Undecyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 34 NO 2 F 3   
                 401.513 
                 43.5 
               
               
                 177 
                 R 1  + R 2  = THiQ w   
                   n Pentyl 
                   n Butyl 
                 Br −   
                 NR 1 R 2 R 3   
                 170964-25-7 
                 R 4 X 
                 109-65-9 
                 C 18 H 30 NBr 
                 340.347 
                 31.3 
               
               
                 178 
                 R 1  + R 2  = THiQ w   
                   n Pentyl 
                   n Pentyl 
                 Br −   
                 HNR 1 R 2   
                 91-21-4 
                 2xR 4 X + base 
                 110-53-2 
                 C 19 H 32 NBr 
                 354.374 
                 34.5 
               
               
                 179 
                 R 1  + R 2  = THiQ w   
                   n Pentyl 
                   n Hexyl 
                 Br −   
                 NR 1 R 2 R 3   
                 170964-25-7 
                 R 4 X 
                 111-25-1 
                 C 20 H 34 NBr 
                 368.401 
                 37.5 
               
               
                 180 
                 R 1  + R 2  = THiQ w   
                   n Pentyl 
                   n Octyl 
                 Br −   
                 HNR 3 R 4   
                 6835-13-8 
                 o-(XCH 2 )—C 6 H 4 —(CH 2 CH 2 X) + base 
                 38256-56-3 
                 C 22 H 38 NBr 
                 396.454 
                 42.8 
               
               
                 181 
                 R 1  + R 2  = THiQ w   
                   n Hexyl 
                   n Hexyl 
                 Br −   
                 HNR 1 R 2   
                 91-21-4 
                 2xR 4 X + base 
                 111-25-1 
                 C 21 H 36 NBr 
                 382.428 
                 40.2 
               
               
                 182 
                 R 1  + R 2  = THiQ w   
                   n Hexyl 
                   n Hexyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 36 NO 2 F 3   
                 415.542 
                 40.2 
               
               
                 182b 
                 R 1  + R 2  = THiQ w   
                 Ph(CH 2 ) 3 — 
                 Ph(CH 2 ) 3 — 
                 Br −   
                 HNR 1 R 2   
                 91-21-4 
                 2xR 4 X + base 
                 637-59-2 
                 C 27 H 32 NBr 
                 450.454 
                 40.5 
               
               
                 182c 
                 R 1  + R 2  = THiQ w   
                 Ph(CH 2 ) 3 — 
                 Ph(CH 2 ) 3 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 29 H 32 NO 2 F 3   
                 483.565 
                 40.5 
               
               
                 183 
                 R 1  + R 2  = THiQ w   
                   n Heptyl 
                   n Hexyl 
                 Br −   
                 NR 1 R 2 R 3   
                 170964-26-8 
                 R 4 X 
                 111-25-1 
                 C 22 H 38 NBr 
                 396.454 
                 42.7 
               
               
                 184 
                 R 1  + R 2  = THiQ w   
                   n Heptyl 
                   n Heptyl 
                 Br −   
                 HNR 1 R 2   
                 91-21-4 
                 2xR 4 X + base 
                 629-04-9 
                 C 23 H 40 NBr 
                 410.481 
                 45.1 
               
               
                 185 
                 R 1  + R 2  = THiQ w   
                   n Heptyl 
                   n Octyl 
                 Br −   
                 NR 1 R 2 R 3   
                 170964-26-8 
                 R 4 X 
                 111-83-1 
                 C 24 H 42 NBr 
                 424.508 
                 47.4 
               
               
                 186 
                 R 1  + R 2  = THiQ w   
                   n Heptyl 
                   n Octyl 
                 Br −   
                 HNR 3 R 4   
                 26627-77-0 
                 o-(XCH 2 )—C 6 H 4 —(CH 2 CH 2 X) + base 
                 38256-56-3 
                 C 24 H 42 NBr 
                 424.508 
                 47.4 
               
               
                 187 
                 R 1  + R 2  = THiQ w   
                   n Octyl 
                   n Octyl 
                 Br −   
                 HNR 1 R 2   
                 91-21-4 
                 2xR 4 X + base 
                 111-83-1 
                 C 25 H 44 NBr 
                 438.535 
                 49.6 
               
               
                 188 
                 R 1  + R 2  = THiQ w   
                 Methyl 
                   n Nonyl 
                 Br −   
                 NR 1 R 2 R 3   
                 1612-65-3 
                 R 4 X 
                 693-58-3 
                 C 19 H 32 NBr 
                 354.374 
                 37.9 
               
               
                 189 
                 R 1  + R 2  = THiQ w   
                 Methyl 
                   n Nonyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 32 NO 2 F 3   
                 387.486 
                 37.9 
               
               
                 190 
                 R 1  + R 2  = THiQ w   
                 Methyl 
                   n Decyl 
                 Br −   
                 NR 1 R 2 R 3   
                 1612-65-3 
                 R 4 X 
                 112-29-8 
                 C 20 H 34 NBr 
                 368.401 
                 41.2 
               
               
                 191 
                 R 1  + R 2  = THiQ w   
                 Methyl 
                   n Decyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 34 NO 2 F 3   
                 401.513 
                 41.2 
               
               
                 192 
                 R 1  + R 2  = THiQ w   
                 Methyl 
                   n Undecyl 
                 Br −   
                 NR 1 R 2 R 3   
                 1612-65-3 
                 R 4 X 
                 693-67-4 
                 C 21 H 36 NBr 
                 382.428 
                 44.3 
               
               
                 193 
                 R 1  + R 2  = THiQ w   
                 Methyl 
                   n Undecyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 36 NO 2 F 3   
                 415.540 
                 44.3 
               
             
          
           
               
                 194 
                   n Decyl 
                 Methyl 
                 Methyl 
                 PhC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 532-27-4 
                 C 20 H 34 NOCl 
                 339.943 
                 42.7 
               
               
                 195 
                   n Decyl 
                 Methyl 
                 Methyl 
                 PhC(O)CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 70-11-1 
                 C 20 H 34 NOBr 
                 384.394 
                 42.7 
               
               
                 196 
                   n Decyl 
                 Methyl 
                 Methyl 
                 PhC(O)CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 34 NO 3 F 3   
                 417.512 
                 42.7 
               
               
                 197 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 C(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 456-04-2 
                 C 20 H 33 NOClF 
                 357.939 
                 42.9 
               
               
                 198 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 C(O)CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 33 NO 3 F 4   
                 435.503 
                 42.9 
               
               
                 199 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-CH 3 C 6 H 4 C(O)CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 619-41-0 
                 C 21 H 36 NOBr 
                 398.421 
                 44.5 
               
               
                 200 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-CF 3 C 6 H 4 C(O)CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 383-53-9 
                 C 21 H 33 NOBrF 3   
                 452.398 
                 45.9 
               
               
                 201 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-ClC 6 H 4 C(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 937-20-2 
                 C 20 H 33 NOCl 2   
                 374.394 
                 45.2 
               
               
                 202 
                   n Decyl 
                 Methyl 
                 Methyl 
                 4-BrC 6 H 4 C(O)CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 99-73-0 
                 C 20 H 33 NOBr 2   
                 463.296 
                 45.7 
               
               
                 203 
                   n Decyl 
                 Methyl 
                 Methyl 
                 dl-PhC(O)CH(Ph)— 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 447-31-4 
                 C 26 H 38 NOCl 
                 416.047 
                 46.2 
               
               
                 204 
                   n Decyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 4 — 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 13633-25-5 
                 C 22 H 40 NBr 
                 398.470 
                 46.0 
               
               
                 205 
                   n Decyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 3 — 
                 Br −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 673-59-2 
                 C 21 H 38 NBr 
                 384.443 
                 44.4 
               
               
                 206 
                   n Decyl 
                 Methyl 
                 Methyl 
                 dl-PhCH 2 CH(OH)CH 2 — 
                 Cl −   
                 HNR 1 R 2 R 3 Cl 
                 10237-16-8 
                 2-benzyloxirane 
                 4436-24-2 
                 C 21 H 38 NOCl 
                 355.992 
                 40.9 
               
               
                 207 
                   n Decyl 
                 Methyl 
                 Methyl 
                 t-PhCH═CHCH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 2687-12-9 
                 C 21 H 36 NCl 
                 337.970 
                 44.9 
               
               
                 208 
                   n Decyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 2 — 
                 Br −   
                 NR 2 R 3 R 4   
                 1126-71-2 
                 R 1 X 
                 112-29-8 
                 C 20 H 36 NBr 
                 370.417 
                 42.8 
               
               
                 209 
                   n Decyl 
                 Methyl 
                 Methyl 
                 1-(CH 2 )naphthylene 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 86-52-2 
                 C 24 H 38 NCl 
                 376.018 
                 44.8 
               
               
                 210 
                   n Decyl 
                 Methyl 
                 Methyl 
                 9-(CH 2 )anthracene 
                 Cl −   
                 NR 1 R 2 R 3   
                 1120-24-7 
                 R 4 X 
                 24463-19-2 
                 C 27 H 38 NCl 
                 412.058 
                 48.2 
               
               
                 211 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 PhC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 17373-27-2 
                 R 4 X 
                 532-27-4 
                 C 19 H 32 NOCl 
                 325.922 
                 39.6 
               
               
                 212 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 PhC(O)CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 17373-27-2 
                 R 4 X 
                 70-11-1 
                 C 19 H 32 NOBr 
                 370.373 
                 39.6 
               
               
                 213 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 PhC(O)CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 32 NO 3 F 3   
                 403.485 
                 39.6 
               
               
                 214 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 C(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 17373-27-2 
                 R 4 X 
                 456-04-2 
                 C 19 H 31 NOClF 
                 343.912 
                 39.8 
               
               
                 215 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 4-FC 6 H 4 C(O)CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 31 NO 3 F 4   
                 421.476 
                 39.8 
               
               
                 216 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 4-CH 3 C 6 H 4 C(O)CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 17373-27-2 
                 R 4 X 
                 619-41-0 
                 C 20 H 34 NOBr 
                 384.400 
                 41.9 
               
               
                 217 
                   n Octyl 
                 Ethyl 
                 Ethyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 4088-37-3 
                 R 4 X 
                 100-44-7 
                 C 19 H 34 NCl 
                 311.938 
                 37.1 
               
               
                 218 
                   n Octyl 
                 Ethyl 
                 Ethyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 34 NO 2 F 3   
                 389.502 
                 37.1 
               
               
                 219 
                   n Octyl 
                 Ethyl 
                 Ethyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 4088-37-3 
                 R 4 X 
                 352-11-4 
                 C 19 H 33 NClF 
                 329.929 
                 37.3 
               
               
                 220 
                   n Octyl 
                 Ethyl 
                 Ethyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 33 NO 2 F 4   
                 407.492 
                 37.3 
               
               
                 221 
                   n Nonyl 
                 Ethyl 
                 Ethyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 45124-35-4 
                 R 4 X 
                 100-44-7 
                 C 20 H 36 NCl 
                 325.965 
                 40.1 
               
               
                 222 
                   n Nonyl 
                 Ethyl 
                 Ethyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 36 NO 2 F 3   
                 403.529 
                 40.1 
               
               
                 223 
                   n Nonyl 
                 Ethyl 
                 Ethyl 
                 Benzyl 
                 Br −   
                 NR 1 R 2 R 3   
                 45124-35-4 
                 R 4 X 
                 100-39-0 
                 C 20 H 36 NBr 
                 370.417 
                 40.1 
               
               
                 224 
                   n Nonyl 
                 Ethyl 
                 Ethyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 772-54-3 
                 R 1 X 
                 693-58-3 
                 C 20 H 36 NBr 
                 370.417 
                 40.1 
               
               
                 225 
                   n Nonyl 
                 Ethyl 
                 Ethyl 
                 PhC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 45124-35-4 
                 R 4 X 
                 532-27-4 
                 C 21 H 36 NOCl 
                 353.976 
                 41.8 
               
               
                 226 
                   n Nonyl 
                 Ethyl 
                 Ethyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 45124-35-4 
                 R 4 X 
                 352-11-4 
                 C 20 H 35 NFCl 
                 343.950 
                 40.4 
               
               
                 227 
                   n Nonyl 
                 Ethyl 
                 Ethyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 35 NO 2 F 4   
                 421.519 
                 40.4 
               
               
                 228 
                   n Decyl 
                 Ethyl 
                 Ethyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 6308-94-7 
                 R 4 X 
                 100-44-7 
                 C 21 H 38 NCl 
                 339.986 
                 43.3 
               
               
                 229 
                   n Decyl 
                 Ethyl 
                 Ethyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 38 NO 2 F 3   
                 417.549 
                 43.3 
               
               
                 230 
                   n Decyl 
                 Ethyl 
                 Ethyl 
                 Benzyl 
                 Br −   
                 NR 1 R 2 R 3   
                 6308-94-7 
                 R 4 X 
                 100-39-0 
                 C 21 H 38 NBr 
                 384.437 
                 43.3 
               
               
                 231 
                   n Decyl 
                 Ethyl 
                 Ethyl 
                 Benzyl 
                 Br −   
                 NR 2 R 3 R 4   
                 6308-94-7 
                 R 1 X 
                 100-39-0 
                 C 21 H 38 NBr 
                 384.437 
                 43.3 
               
               
                 232 
                   n Decyl 
                 Ethyl 
                 Ethyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 6308-94-7 
                 R 4 X 
                 352-11-4 
                 C 21 H 37 NClF 
                 357.983 
                 43.5 
               
               
                 233 
                   n Decyl 
                 Ethyl 
                 Ethyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 37 NO 2 F 4   
                 435.546 
                 43.5 
               
               
                 234 
                   n Undecyl 
                 Ethyl 
                 Ethyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 54334-64-4 
                 R 4 X 
                 100-44-7 
                 C 22 H 40 NCl 
                 354.019 
                 46.3 
               
               
                 235 
                   n Undecyl 
                 Ethyl 
                 Ethyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 40 NO 2 F 3   
                 431.582 
                 46.3 
               
               
                 236 
                   n Undecyl 
                 Ethyl 
                 Ethyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 54334-64-4 
                 R 4 X 
                 352-11-4 
                 C 22 H 39 NClF 
                 372.010 
                 46.5 
               
               
                 237 
                   n Undecyl 
                 Ethyl 
                 Ethyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 39 NO 2 F 4   
                 449.573 
                 46.5 
               
               
                 238 
                   n Heptyl 
                   n Propyl 
                   n Propyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 New d   
                 R 4 X 
                 100-44-7 
                 C 20 H 36 NCl 
                 325.965 
                 37.9 
               
               
                 239 
                   n Heptyl 
                   n Propyl 
                   n Propyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 36 NO 2 F 3   
                 403.529 
                 37.9 
               
               
                 240 
                   n Heptyl 
                   n Propyl 
                   n Propyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 New d   
                 R 4 X 
                 352-11-4 
                 C 20 H 35 NClF 
                 343.956 
                 38.1 
               
               
                 241 
                   n Heptyl 
                   n Propyl 
                   n Propyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 35 NO 2 F 4   
                 421.519 
                 38.1 
               
               
                 242 
                   n Octyl 
                   n Propyl 
                   n Propyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 99209-95-7 
                 R 4 X 
                 100-44-7 
                 C 21 H 38 NCl 
                 339.992 
                 41.0 
               
               
                 243 
                   n Octyl 
                   n Propyl 
                   n Propyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 38 NO 2 F 3   
                 417.555 
                 41.0 
               
               
                 244 
                   n Octyl 
                   n Propyl 
                   n Propyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 99209-95-7 
                 R 4 X 
                 352-11-4 
                 C 21 H 37 NClF 
                 357.983 
                 41.2 
               
               
                 245 
                   n Octyl 
                   n Propyl 
                   n Propyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 37 NO 2 F 4   
                 435.546 
                 41.2 
               
               
                 246 
                   n Nonyl 
                   n Propyl 
                   n Propyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 90105-55-8 
                 R 4 X 
                 100-44-7 
                 C 22 H 40 NCl 
                 354.019 
                 44.1 
               
               
                 247 
                   n Nonyl 
                   n Propyl 
                   n Propyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 40 NO 2 F 3   
                 431.582 
                 44.1 
               
               
                 248 
                   n Nonyl 
                   n Propyl 
                   n Propyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 90105-55-8 
                 R 4 X 
                 352-11-4 
                 C 22 H 39 NClF 
                 372.010 
                 44.3 
               
               
                 249 
                   n Nonyl 
                   n Propyl 
                   n Propyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 39 NO 2 F 4   
                 449.573 
                 44.3 
               
               
                 250 
                   n Decyl 
                   n Propyl 
                   n Propyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 88090-10-2 
                 R 4 X 
                 100-44-7 
                 C 23 H 42 NCl 
                 368.046 
                 47.2 
               
               
                 251 
                   n Decyl 
                   n Propyl 
                   n Propyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 25 H 42 NO 2 F 3   
                 445.609 
                 47.2 
               
               
                 252 
                   n Decyl 
                   n Propyl 
                   n Propyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 88090-10-2 
                 R 4 X 
                 352-11-4 
                 C 23 H 41 NClF 
                 386.036 
                 47.4 
               
               
                 253 
                   n Decyl 
                   n Propyl 
                   n Propyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 25 H 41 NO 2 F 4   
                 463.600 
                 47.4 
               
               
                 254 
                   n Undecyl 
                   n Propyl 
                   n Propyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 220644-99-1 
                 R 4 X 
                 100-44-7 
                 C 24 H 44 NCl 
                 382.073 
                 50.2 
               
               
                 255 
                   n Undecyl 
                   n Propyl 
                   n Propyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 26 H 44 NO 2 F 3   
                 459.636 
                 50.2 
               
               
                 256 
                   n Undecyl 
                   n Propyl 
                   n Propyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 220644-99-1 
                 R 4 X 
                 352-11-4 
                 C 24 H 43 NClF 
                 400.063 
                 50.4 
               
               
                 257 
                   n Undecyl 
                   n Propyl 
                   n Propyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 26 H 43 NO 2 F 4   
                 477.627 
                 50.4 
               
               
                 258 
                   n Hexyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 23601-43-6 
                 R 4 X 
                 100-44-7 
                 C 21 H 38 NCl 
                 339.992 
                 40.2 
               
               
                 259 
                   n Hexyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 38 NO 2 F 3   
                 417.555 
                 40.2 
               
               
                 260 
                   n Hexyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 23601-43-6 
                 R 4 X 
                 352-11-4 
                 C 21 H 37 NClF 
                 357.983 
                 40.4 
               
               
                 261 
                   n Hexyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 37 NO 2 F 4   
                 435.546 
                 40.4 
               
               
                 262 
                   n Heptyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 3553-87-5 
                 R 4 X 
                 100-44-7 
                 C 22 H 40 NCl 
                 354.019 
                 42.7 
               
               
                 263 
                   n Heptyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 40 NO 2 F 3   
                 431.582 
                 42.7 
               
               
                 264 
                   n Heptyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 3553-87-5 
                 R 4 X 
                 351-11-4 
                 C 22 H 39 NClF 
                 372.010 
                 42.9 
               
               
                 265 
                   n Heptyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 39 NO 2 F 4   
                 449.573 
                 42.9 
               
               
                 266 
                   n Octyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 41145-51-1 
                 R 4 X 
                 100-44-7 
                 C 23 H 42 NCl 
                 368.046 
                 45.6 
               
               
                 267 
                   n Octyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 25 H 42 NO 2 F 3   
                 445.609 
                 45.6 
               
               
                 268 
                   n Octyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 41145-51-1 
                 R 4 X 
                 352-11-4 
                 C 23 H 41 NClF 
                 386.036 
                 45.8 
               
               
                 269 
                   n Octyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 25 H 41 NO 2 F 4   
                 463.600 
                 45.8 
               
               
                 270 
                   n Nonyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 93658-58-3 
                 R 4 X 
                 100-44-7 
                 C 24 H 44 NCl 
                 382.073 
                 48.7 
               
               
                 271 
                   n Nonyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 26 H 44 NO 2 F 3   
                 459.636 
                 48.7 
               
               
                 272 
                   n Nonyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 93658-58-3 
                 R 4 X 
                 352-11-4 
                 C 24 H 43 NClF 
                 400.063 
                 48.9 
               
               
                 273 
                   n Nonyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 26 H 43 NO 2 F 4   
                 477.627 
                 48.9 
               
               
                 274 
                   n Decyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 13573-55-2 
                 R 4 X 
                 100-44-7 
                 C 25 H 46 NCl 
                 396.100 
                 51.8 
               
               
                 275 
                   n Decyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 27 H 46 NO 2 F 3   
                 473.663 
                 51.8 
               
               
                 276 
                   n Decyl 
                 MeO(CH 2 ) 2   
                 MeO(CH 2 ) 2   
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 New g   
                 R 4 X 
                 100-44-7 
                 C 23 H 42 NO 2 Cl 
                 400.045 
                 46.7 
               
               
                 277 
                   n Decyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 13573-55-2 
                 R 4 X 
                 352-11-4 
                 C 25 H 45 NClF 
                 414.090 
                 52.0 
               
               
                 278 
                   n Decyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 27 H 45 NO 2 F 4   
                 491.653 
                 52.0 
               
               
                 279 
                   n Undecyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 220645-00-1 
                 R 4 X 
                 100-44-7 
                 C 26 H 48 NCl 
                 410.127 
                 54.8 
               
               
                 280 
                   n Undecyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 28 H 48 NO 2 F 3   
                 487.690 
                 54.8 
               
               
                 281 
                   n Undecyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 220645-00-1 
                 R 4 X 
                 352-11-4 
                 C 26 H 47 NClF 
                 428.117 
                 60.0 
               
               
                 282 
                   n Undecyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 28 H 47 NO 2 F 4   
                 505.680 
                 60.0 
               
             
          
           
               
                 282b 
                 Ph(CH 2 ) 3 — 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 same as R 1   
                 Br −   
                 HNR 2 R 3   
                 123-75-1 
                 2xR 1 X + base 
                 637-59-2 
                 C 22 H 30 NBr 
                 388.384 
                 34.4 
               
               
                 282c 
                 Ph(CH 2 ) 3 — 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 same as R 1   
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 30 NO 2 F 3   
                 421.496 
                 34.4 
               
               
                 282d 
                 Ph(CH 2 ) 4 — 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Ph(CH 2 ) 3 — 
                 Br −   
                 NR 1 R 2 R 3   
                 163675-54-5 
                 R 4 X 
                 637-59-2 
                 C 23 H 32 NBr 
                 402.411 
                 36.7 
               
               
                 282e 
                 Ph(CH 2 ) 4 — 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Ph(CH 2 ) 3 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 25 H 32 NO 2 F 3   
                 435.522 
                 36.7 
               
               
                 282f 
                 Ph(CH 2 ) 4 — 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 same as R 1   
                 Br −   
                 HNR 2 R 3   
                 123-75-1 
                 2xR 1 X + base 
                 13633-25-5 
                 C 24 H 34 NBr 
                 416.438 
                 39.0 
               
               
                 282g 
                 Ph(CH 2 ) 4 — 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 same as R 1   
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 26 H 34 NO 2 F 3   
                 449.549 
                 39.0 
               
               
                 283 
                   n Heptyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 121409-85-6 
                 R 4 X 
                 100-44-7 
                 C 18 H 30 NCl 
                 295.887 
                 33.3 
               
               
                 283b 
                   n Heptyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 20 H 30 NO 2 F 3   
                 373.450 
                 33.3 
               
               
                 283c 
                   n Heptyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 121409-85-6 
                 R 4 X 
                 352-11-4 
                 C 18 H 29 NClF 
                 313.877 
                 33.5 
               
               
                 283d 
                   n Heptyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 20 H 29 NO 2 F 4   
                 391.441 
                 33.5 
               
               
                 284 
                   n Octyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 7335-08-2 
                 R 4 X 
                 100-44-7 
                 C 19 H 32 NCl 
                 309.923 
                 36.5 
               
               
                 284b 
                   n Octyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 32 NO 2 F 3   
                 387.486 
                 36.5 
               
               
                 285 
                   n Octyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 7335-08-2 
                 R 4 X 
                 352-11-4 
                 C 19 H 31 NClF 
                 327.913 
                 36.4 
               
               
                 286 
                   n Octyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 31 NO 2 F 4   
                 405.476 
                 36.4 
               
               
                 287 
                   n Octyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 PhC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 7335-08-2 
                 R 4 X 
                 532-27-4 
                 C 20 H 32 NOCl 
                 337.927 
                 38.1 
               
               
                 288 
                   n Octyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 PhC(O)CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 32 NO 3 F 3   
                 415.496 
                 38.1 
               
               
                 289 
                   n Octyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 C(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 7335-08-2 
                 R 4 X 
                 456-04-2 
                 C 20 H 31 NOClF 
                 355.923 
                 38.3 
               
               
                 290 
                   n Octyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 C(O)CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 31 NO 3 F 4   
                 433.487 
                 38.3 
               
               
                 291 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-25-9 
                 R 4 X 
                 100-44-7 
                 C 20 H 34 NCl 
                 323.949 
                 39.5 
               
               
                 292 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 34 NO 2 F 3   
                 401.513 
                 39.5 
               
               
                 293 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-25-9 
                 R 4 X 
                 352-11-4 
                 C 20 H 33 NClF 
                 341.940 
                 39.7 
               
               
                 294 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 33 NO 2 F 4   
                 419.503 
                 39.7 
               
               
                 294b 
                 Ph(CH 2 ) 6 — 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 New 
                 R 4 X 
                 352-11-4 
                 C 23 H 31 NClF 
                 375.950 
                 40.1 
               
               
                 294c 
                 Ph(CH 2 ) 6 — 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 25 H 31 NO 2 F 4   
                 453.513 
                 40.1 
               
               
                 295 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 5 — 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 30538-80-8 
                 R 4 X 
                 100-44-7 
                 C 21 H 36 NCl 
                 337.970 
                 41.4 
               
               
                 296 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 5 — 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 30538-80-8 
                 R 4 X 
                 352-11-4 
                 C 21 H 35 NClF 
                 355.961 
                 41.6 
               
               
                 297 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 PhC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-25-9 
                 R 4 X 
                 532-27-4 
                 C 21 H 34 NOCl 
                 351.960 
                 41.2 
               
               
                 298 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 PhC(O)CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 34 NO 3 F 3   
                 429.523 
                 41.2 
               
               
                 299 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 C(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-25-9 
                 R 4 X 
                 456-04-2 
                 C 21 H 33 NOClF 
                 369.950 
                 41.4 
               
               
                 300 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 C(O)CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 33 NO 3 F 4   
                 447.514 
                 41.4 
               
               
                 301 
                   n Undecyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-27-1 
                 R 4 X 
                 100-44-7 
                 C 22 H 38 NCl 
                 352.003 
                 45.8 
               
               
                 302 
                   n Undecyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 38 NO 2 F 3   
                 429.566 
                 45.8 
               
               
                 303 
                   n Undecyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-27-1 
                 R 4 X 
                 352-11-4 
                 C 22 H 37 NClF 
                 369.994 
                 46.0 
               
               
                 304 
                   n Undecyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 37 NO 2 F 4   
                 447.557 
                 46.0 
               
               
                 305 
                   n Undecyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 PhC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-27-1 
                 R 4 X 
                 532-27-4 
                 C 23 H 38 NOCl 
                 380.007 
                 47.4 
               
               
                 306 
                   n Undecyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 PhC(O)CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 25 H 38 NO 3 F 3   
                 457.577 
                 47.4 
               
               
                 307 
                   n Undecyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 C(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-27-1 
                 R 4 X 
                 456-04-2 
                 C 23 H 37 NOClF 
                 398.004 
                 47.6 
               
               
                 308 
                   n Undecyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 C(O)CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 25 H 37 NO 3 F 4   
                 475.567 
                 47.6 
               
               
                 309 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 100-44-7 
                 C 21 H 36 NCl 
                 337.976 
                 42.7 
               
               
                 310 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Benzyl 
                 Br −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 100-39-0 
                 C 21 H 36 NBr 
                 382.428 
                 42.7 
               
               
                 311 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Benzyl 
                 OH −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 37 NO 
                 319.531 
                 42.7 
               
               
                 312 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 36 NO 2 F 3   
                 415.540 
                 42.7 
               
               
                 313 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 2-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 345-35-7 
                 C 21 H 35 NClF 
                 355.967 
                 42.8 
               
               
                 314 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 3-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 456-42-8 
                 C 21 H 35 NClF 
                 355.967 
                 42.8 
               
               
                 315 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 352-11-4 
                 C 21 H 35 NClF 
                 355.967 
                 42.9 
               
               
                 316 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 459-46-1 
                 C 21 H 35 NBrF 
                 400.418 
                 42.9 
               
               
                 317 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 OH −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 36 NOF 
                 337.521 
                 42.9 
               
               
                 318 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 35 NO 2 F 4   
                 433.530 
                 42.9 
               
               
                 319 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 HCO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 36 NO 2 F 
                 365.532 
                 42.9 
               
               
                 320 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 CH 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 23 H 38 NO 2 F 
                 379.559 
                 42.9 
               
               
                 321 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 CH 3 SO 3   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 38 NO 3 FS 
                 415.607 
                 42.9 
               
               
                 322 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 SO 3   −   
                 — 
                 — 
                 — 
                 — 
                 C 22 H 35 NO 3 F 4 S 
                 469.578 
                 42.9 
               
               
                 323 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 3-ClC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 620-20-2 
                 C 21 H 35 NCl 2   
                 372.421 
                 44.5 
               
               
                 324 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 2,6-F 2 C 6 H 3 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 697-73-4 
                 C 21 H 34 NClF 2   
                 373.957 
                 43.2 
               
               
                 325 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 3,5-F 2 C 6 H 3 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 220141-71-9 
                 C 21 H 34 NClF 2   
                 373.957 
                 43.6 
               
               
                 326 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-MeC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 104-82-5 
                 C 22 H 38 NCl 
                 352.003 
                 45.7 
               
               
                 327 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-EtC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 1467-05-6 
                 C 23 H 40 NCl 
                 366.030 
                 47.9 
               
               
                 328 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-MeOC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 824-94-2 
                 C 22 H 38 NOCl 
                 368.003 
                 43.8 
               
               
                 329 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 PhC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 532-27-4 
                 C 22 H 36 NOCl 
                 365.987 
                 44.3 
               
               
                 330 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 PhC(O)CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 70-11-1 
                 C 22 H 36 NOBr 
                 410.438 
                 44.3 
               
               
                 331 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 PhC(O)CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 36 NO 3 F 3   
                 443.550 
                 44.3 
               
               
                 332 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 C(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 456-04-2 
                 C 22 H 35 NOClF 
                 383.977 
                 44.5 
               
               
                 333 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 4-FC 6 H 4 C(O)CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 35 NO 3 F 4   
                 461.540 
                 44.5 
               
               
                 334 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Ph(CH 2 ) 4 — 
                 Br −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 13633-25-5 
                 C 24 H 42 NBr 
                 424.508 
                 47.5 
               
               
                 335 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Ph(CH 2 ) 3 — 
                 Br −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 673-59-2 
                 C 23 H 40 NBr 
                 410.481 
                 45.9 
               
               
                 336 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Ph(CH 2 ) 2 — 
                 Br −   
                 NR 2 R 3 R 4   
                 6908-75-4 
                 R 1 X 
                 112-29-8 
                 C 22 H 38 NBr 
                 396.454 
                 45.3 
               
               
                 337 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 t-PhCH═CHCH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 2687-12-9 
                 C 23 H 38 NCl 
                 364.008 
                 46.4 
               
               
                 338 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Me 2 NC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 2675-89-0 
                 C 18 H 37 N 2 OCl 
                 332.957 
                 36.8 
               
               
                 339 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 Et 2 NC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 74673-26-0 
                 R 4 X 
                 2315-36-8 
                 C 20 H 41 N 2 OCl 
                 361.011 
                 41.5 
               
             
          
           
               
                 339b 
                 4-FC 6 H 4 CH 2 — 
                   n Propyl 
                   n Propyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 HNR 2 R 3   
                 142-84-7 
                 2xR 4 X + base 
                 352-11-4 
                 C 20 H 26 NClF 2   
                 353.877 
                 30.9 
               
               
                 340 
                   n Butyl 
                   n Butyl 
                   n Butyl 
                 Ph(CH 2 ) 4 — 
                 Br −   
                 NR 1 R 2 R 3   
                 102-82-9 
                 R 4 X 
                 13633-25-5 
                 C 22 H 40 NBr 
                 398.470 
                 40.2 
               
               
                 341 
                   n Butyl 
                   n Butyl 
                   n Butyl 
                 4-PhC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 102-82-9 
                 R 4 X 
                 1667-11-4 
                 C 25 H 38 NCl 
                 388.036 
                 43.3 
               
               
                 342 
                 Benzyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 Cl −   
                 HNR 2 R 3   
                 111-92-2 
                 2xR 4 X + base 
                 100-44-7 
                 C 22 H 32 NCl 
                 345.956 
                 36.6 
               
               
                 343 
                 Benzyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 32 NO 2 F 3   
                 423.519 
                 36.6 
               
               
                 344 
                 4-FC 6 H 4 CH 2 — 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 HNR 2 R 3   
                 111-92-2 
                 2xR 4 X + base 
                 352-11-4 
                 C 22 H 30 NClF 2   
                 381.936 
                 36.8 
               
               
                 345 
                 4-FC 6 H 4 CH 2 — 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 30 NO 2 F 5   
                 459.500 
                 36.8 
               
               
                 346 
                 Benzyl 
                   n Pentyl 
                   n Pentyl 
                 Benzyl 
                 Cl −   
                 HNR 2 R 3   
                 2050-92-2 
                 2xR 4 X + base 
                 — 
                 C 24 H 36 NCl 
                 374.009 
                 41.6 
               
               
                 347 
                 Benzyl 
                   n Pentyl 
                   n Pentyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 26 H 36 NO 2 F 3   
                 451.573 
                 41.6 
               
               
                 348 
                 4-FC 6 H 4 CH 2 — 
                   n Pentyl 
                   n Pentyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 HNR 2 R 3   
                 2050-92-2 
                 2xR 4 X + base 
                 352-11-4 
                 C 24 H 34 NClF 2   
                 409.990 
                 41.8 
               
               
                 349 
                 4-FC 6 H 4 CH 2 — 
                   n Pentyl 
                   n Pentyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 26 H 34 NO 2 F 5   
                 487.554 
                 41.8 
               
               
                 350 
                 Benzyl 
                   n Hexyl 
                   n Hexyl 
                 Benzyl 
                 Cl −   
                 HNR 2 R 3   
                 143-16-8 
                 2xR 4 X + base 
                 100-44-7 
                 C 26 H 40 NCl 
                 402.063 
                 46.6 
               
               
                 351 
                 Benzyl 
                   n Hexyl 
                   n Hexyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 28 H 40 NO 2 F 3   
                 479.626 
                 46.6 
               
               
                 352 
                 4-FC 6 H 4 CH 2 — 
                   n Hexyl 
                   n Hexyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 HNR 2 R 3   
                 143-16-8 
                 2xR 4 X + base 
                 352-11-4 
                 C 26 H 38 NClF 2   
                 438.044 
                 46.8 
               
               
                 353 
                 4-FC 6 H 4 CH 2 — 
                   n Hexyl 
                   n Hexyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 28 H 38 NO 2 F 5   
                 515.607 
                 46.8 
               
               
                 354 
                   n Butyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 102-82-9 
                 R 4 X 
                 100-44-7 
                 C 19 H 34 NCl 
                 311.938 
                 35.4 
               
               
                 355 
                   n Butyl 
                   n Butyl 
                   n Butyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 34 NO 2 F 3   
                 389.502 
                 35.4 
               
               
                 356 
                   n Butyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 102-82-9 
                 R 4 X 
                 352-11-4 
                 C 19 H 33 NClF 
                 329.929 
                 35.1 
               
               
                 357 
                   n Butyl 
                   n Butyl 
                   n Butyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 21 H 33 NO 2 F 4   
                 407.492 
                 35.1 
               
               
                 358 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 621-77-2 
                 R 4 X 
                 100-44-7 
                 C 22 H 40 NCl 
                 354.019 
                 42.8 
               
               
                 359 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 Benzyl 
                 Br −   
                 NR 1 R 2 R 3   
                 621-77-2 
                 R 4 X 
                 100-39-0 
                 C 22 H 40 NBr 
                 398.470 
                 42.8 
               
               
                 360 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 40 NO 2 F 3   
                 431.582 
                 42.8 
               
               
                 361 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 621-77-2 
                 R 4 X 
                 352-11-4 
                 C 22 H 39 NClF 
                 372.010 
                 43.0 
               
               
                 362 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 4-FC 6 H 4 CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 621-77-2 
                 R 4 X 
                 452-07-3 
                 C 22 H 39 NBrF 
                 416.461 
                 43.0 
               
               
                 363 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 24 H 39 NO 2 F 4   
                 449.573 
                 43.0 
               
               
                 364 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 4-CF 3 C 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 621-77-2 
                 R 4 X 
                 939-99-1 
                 C 23 H 39 NClF 3   
                 422.017 
                 45.0 
               
               
                 365 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 PhC(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 621-77-2 
                 R 4 X 
                 532-27-4 
                 C 23 H 40 NOCl 
                 382.029 
                 44.4 
               
               
                 366 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 4-FC 6 H 4 C(O)CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 621-77-2 
                 R 4 X 
                 456-04-2 
                 C 23 H 39 NOClF 
                 400.020 
                 44.6 
               
               
                 367 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 4-PhC 6 H 4 C(O)CH 2 — 
                 Br −   
                 NR 1 R 2 R 3   
                 621-77-2 
                 R 4 X 
                 135-73-9 
                 C 29 H 44 NOBr 
                 502.579 
                 50.9 
               
               
                 368 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 4-PhC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 621-77-2 
                 R 4 X 
                 1667-11-4 
                 C 28 H 44 NCl 
                 430.117 
                 49.9 
               
               
                 369 
                   n Butyl 
                   n Butyl 
                   n Butyl 
                 4-PhC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 102-82-9 
                 R 4 X 
                 1667-11-4 
                 C 25 H 38 NCl 
                 388.036 
                 43.2 
               
               
                 370 
                   n Hexyl 
                   n Hexyl 
                   n Hexyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 102-86-3 
                 R 4 X 
                 100-44-7 
                 C 25 H 48 NCl 
                 396.100 
                 49.5 
               
               
                 371 
                   n Hexyl 
                   n Hexyl 
                   n Hexyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 102-86-3 
                 R 4 X 
                 352-11-4 
                 C 25 H 45 NClF 
                 414.083 
                 49.7 
               
               
                 372 
                   n Hexyl 
                   n Hexyl 
                   n Hexyl 
                 naphthylene-1-CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 102-86-3 
                 R 4 X 
                 86-52-2 
                 C 29 H 48 NCl 
                 446.151 
                 52.3 
               
               
                 373 
                   n Hexyl 
                   n Hexyl 
                   n Hexyl 
                 anthracene-9-CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 102-86-3 
                 R 4 X 
                 24463-19-2 
                 C 33 H 50 NCl 
                 496.219 
                 55.4 
               
               
                 374 
                   n Hexyl 
                   n Hexyl 
                   n Hexyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 27 H 45 NO 2 F 4   
                 491.653 
                 50.0 
               
               
                 375 
                   n Hexyl 
                   n Hexyl 
                 EtOC 2   a   
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 New f   
                 R 4 X 
                 100-44-7 
                 C 23 H 42 NOCl 
                 384.045 
                 45.4 
               
               
                 376 
                   n Hexyl 
                   n Hexyl 
                 MeOC 2 OC 2   
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 New e   
                 R 4 X 
                 100-44-7 
                 C 24 H 44 NO 2 C 1   
                 414.072 
                 42.4 
               
               
                 377 
                   n Heptyl 
                   n Heptyl 
                   n Heptyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 2411-36-1 
                 — 
                 — 
                 C 30 H 52 NO 2 F 3   
                 515.744 
                 55.2 
               
               
                 378 
                   n Heptyl 
                   n Heptyl 
                   n Heptyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 2411-36-1 
                 R 4 X 
                 352-11-4 
                 C 28 H 51 NClF 
                 456.171 
                 55.4 
               
               
                 379 
                   n Heptyl 
                   n Heptyl 
                   n Heptyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 30 H 51 NO 2 F 4   
                 533.734 
                 55.4 
               
               
                 380 
                   n Octyl 
                   n Octyl 
                   n Octyl 
                 Benzyl 
                 Cl −   
                 NR 1 R 2 R 3   
                 1116-76-3 
                 — 
                 100-44-7 
                 C 31 H 58 NCl 
                 480.261 
                 60.3 
               
               
                 381 
                   n Octyl 
                   n Octyl 
                   n Octyl 
                 Benzyl 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 33 H 58 NO 2 F 3   
                 557.824 
                 60.3 
               
               
                 382 
                   n Octyl 
                   n Octyl 
                 EtOC 2 OC 2   a   
                 Benzyl 
                 Br −   
                 NR 1 R 2 R 3   
                 New b   
                 R 4 X 
                 100-39-0 
                 C 29 H 54 NO 2 Br 
                 528.649 
                 53.7 
               
               
                 383 
                   n Octyl 
                   n Octyl 
                   n Octyl 
                 4-FC 6 H 4 CH 2 — 
                 Cl −   
                 NR 1 R 2 R 3   
                 1116-76-3 
                 R 4 X 
                 352-11-4 
                 C 31 H 58 NClF 
                 499.250 
                 60.5 
               
               
                 384 
                   n Octyl 
                   n Octyl 
                   n Octyl 
                 4-FC 6 H 4 CH 2 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 33 H 58 NO 2 F 4   
                 576.813 
                 60.5 
               
               
                 385 
                   n Pentyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 5 — 
                 Br −   
                 NR 1 R 2 R 3   
                 26153-88-8 
                 R 4 X 
                 14469-83-1 
                 C 18 H 32 NBr 
                 342.363 
                 34.9 
               
               
                 386 
                   n Pentyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 6 — 
                 Br −   
                 NR 1 R 2 R 3   
                 26153-88-8 
                 R 4 X 
                 27976-27-8 
                 C 19 H 34 NBr 
                 356.385 
                 37.6 
               
               
                 387 
                   n Hexyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 5 — 
                 Br −   
                 NR 1 R 2 R 3   
                 4385-04-0 
                 R 4 X 
                 14469-83-1 
                 C 19 H 34 NBr 
                 356.385 
                 37.6 
               
               
                 388 
                   n Hexyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 6 — 
                 Br −   
                 NR 1 R 2 R 3   
                 4385-04-0 
                 R 4 X 
                 27976-27-8 
                 C 20 H 36 NBr 
                 370.417 
                 40.2 
               
               
                 389 
                   n Hexyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 7 — 
                 Br −   
                 NR 1 R 2 R 3   
                 5277-11-2 
                 R 4 X 
                 78573-85-0 
                 C 21 H 38 NBr 
                 384.443 
                 42.7 
               
               
                 390 
                   n Heptyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 6 — 
                 Br −   
                 NR 1 R 2 R 3   
                 4385-04-0 
                 R 4 X 
                 27976-27-8 
                 C 21 H 38 NBr 
                 384.443 
                 42.7 
               
               
                 391 
                   n Heptyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 7 — 
                 Br −   
                 NR 1 R 2 R 3   
                 5277-11-2 
                 R 4 X 
                 78573-85-0 
                 C 22 H 40 NBr 
                 398.470 
                 45.1 
               
               
                 392 
                   n Heptyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 6 — 
                 Br −   
                 NR 1 R 2 R 3   
                 7378-99-6 
                 R 4 X 
                 54646-75-2 
                 C 23 H 42 NBr 
                 412.497 
                 47.3 
               
               
                 393 
                   n Octyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 7 — 
                 Br −   
                 NR 1 R 2 R 3   
                 5277-11-2 
                 R 4 X 
                 78573-85-0 
                 C 23 H 42 NBr 
                 412.497 
                 47.4 
               
               
                 394 
                   n Octyl 
                 Methyl 
                 Methyl 
                 Ph(CH 2 ) 6 — 
                 Br −   
                 NR 1 R 2 R 3   
                 7378-99-6 
                 R 4 X 
                 54646-75-2 
                 C 24 H 44 NBr 
                 426.524 
                 49.5 
               
               
                 394b 
                 HOCH 2 CH 2 — 
                 Ph(CH 2 ) 3 — 
                 Ph(CH 2 ) 3 — 
                 Ph(CH 2 ) 3 — 
                 Br −   
                 H 2 NR 1   
                 141-43-5 
                 3xR 4 X + 2xbase 
                 637-59-2 
                 C 29 H 38 NOBr 
                 496.522 
                 40.4 
               
               
                 394c 
                 HOCH 2 CH 2 — 
                 Ph(CH 2 ) 3 — 
                 Ph(CH 2 ) 3 — 
                 Ph(CH 2 ) 3 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 31 H 38 NO 3 F 3   
                 529.634 
                 40.4 
               
               
                 394d 
                 MeOCH 2 CH 2 — 
                 Ph(CH 2 ) 3 — 
                 Ph(CH 2 ) 3 — 
                 Ph(CH 2 ) 3 — 
                 Br −   
                 H 2 NR 1   
                 109-85-3 
                 3xR 4 X + 2xbase 
                 637-59-2 
                 C 30 H 40 NOBr 
                 510.549 
                 43.8 
               
               
                 394e 
                 MeOCH 2 CH 2 — 
                 Ph(CH 2 ) 3 — 
                 Ph(CH 2 ) 3 — 
                 Ph(CH 2 ) 3 — 
                 CF 3 CO 2   −   
                 — 
                 — 
                 — 
                 — 
                 C 32 H 40 NO 3 F 3   
                 543.660 
                 43.8 
               
               
                   
               
               
                   a Me = CH 3 —, Et = C 2 H 5 , Pr = C 7 H 7 —, Bu = C 4 H 9 —, Ph = C 6 H 5 —, Bz = C 6 H 5 CH 2 —, Ac = CH 3 C(O)—, MeOC 2  = CH 3 OCH 2 CH 2 —, EtOC 2  = EtOCH 2 CH 2 —, MeOC 2 OC 2  = Me(OCH 2 CH 2 ) 2 —, EtOC 2 OC 2  = EtOCH 2 CH 2 OCH 2 CH 2 — 
               
               
                   b New compound; prepared by method in Example 1 from di-n-octylamine [1120-48-5] and slight excess (1.1X) of 2-(2-ethoxyethoxy)ethyl bromide [54550-36-6] in the presence of excess (1.5X) base (N-ethyl-di-isopropylamine). 
               
               
                   c Chemical names and chemical structures associated with abbreviations are given below. 
               
               
                   d New compound; prepared pure in good yield by method in Example 1 from 1-bromoheptane [629-04-9] and excess (3X) di-n-propylamine [142-84-7] . 
               
               
                   e New compound; prepared by method in Example 1 from di-n-hexylamine [143-16-8] and slight excess (1.1X) of 2-(2-methoxyethoxy)ethyl bromide [54149-17-6] in the presence of excess (1.5X) base (N-ethyl-di-isopropylamine). 
               
               
                   f New compound; prepared by method in Example 1 from di-n-hexylamine [143-16-8] and slight excess (1.1X) of 2-ethoxyethyl bromide [592-55-2] in the presence of excess (2.0X) base (N-ethyl-di-isopropylamine). The tertiary amine product is not isolated but allowed to react in a second step with benzyl bromide. 
               
               
                   g New compound; prepared by method in Example 1 from bis(2-methoxyethyl)amine [111-95-5] and slight excess (1.1X) of 1-bromodecane [112-28-9] in the presence of excess (1.5X) base (N-ethyl-di-isopropylamine). 
               
               
                   r CAS number for racemic amine. Pure enantiomers of N,N-dimethylphenylalanine N,N-dimethylamide are prepared from N,N-dimethylphenylalanine methylester (CAS# l-enantiomer, 27720-05-4; CAS# d-enantiomer, 1268357-63-6) and dimethylamine. 
               
               
                   s Limited solubility. 
               
               
                   t Undergoes slow transalkylation reactions at elevated temperature. 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE VI 
               
               
                   
               
               
                 [(R 1 R 2 R 3 NCH 2 ) 2 C 6 H 3 G] 2+  2[X] −  (G = H, F) and 
               
               
                 [R 1 R 2 R 3 NCH 2 C 6 H 4 —C 6 H 4 CH 2 NR 1 R 2 R 3 ] 2+  2[X] −   
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 Nu. 
                 R 1   
                 R 2   
                 R 3   
                 C 6 H 3 G or C 6 H 4 —C 6 H 4   
                 X −   
                 Amine 
               
               
                   
               
               
                 395 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 1,2-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 396 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 1,2-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 397 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 1,2-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 398 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 1,3-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 399 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 1,3-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 400 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 1,3-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 401 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 1,4-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 402 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 1,4-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 403 
                   n Undecyl 
                 Methyl 
                 Methyl 
                 1,4-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 404 
                   n Decyl 
                 Methyl 
                 Methyl 
                 1,2-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 405 
                   n Decyl 
                 Methyl 
                 Methyl 
                 1,2-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 406 
                   n Decyl 
                 Methyl 
                 Methyl 
                 1,2-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 407 
                   n Decyl 
                 Methyl 
                 Methyl 
                 1,3-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 408 
                   n Decyl 
                 Methyl 
                 Methyl 
                 1,3-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 409 
                   n Decyl 
                 Methyl 
                 Methyl 
                 1,3-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 410 
                   n Decyl 
                 Methyl 
                 Methyl 
                 2-F-1,3-C 6 H 3   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 411 
                   n Decyl 
                 Methyl 
                 Methyl 
                 2-F-1,3-C 6 H 3   
                 CF 3 CO 2   −   
                 — 
               
               
                 412 
                   n Decyl 
                 Methyl 
                 Methyl 
                 5-F-1,3-C 6 H 3   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 413 
                   n Decyl 
                 Methyl 
                 Methyl 
                 5-F-1,3-C 6 H 3   
                 CF 3 CO 2   −   
                 — 
               
               
                 414 
                   n Decyl 
                 Methyl 
                 Methyl 
                 1,4-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 415 
                   n Decyl 
                 Methyl 
                 Methyl 
                 1,4-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 416 
                   n Decyl 
                 Methyl 
                 Methyl 
                 1,4-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
             
          
           
               
                 417 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 1,2-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 418 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 1,3-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 419 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 1,3-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 420 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 1,3-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 421 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 2-F-1,3-C 6 H 3   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 422 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 2-F-1,3-C 6 H 3   
                 CF 3 CO 2   −   
                 — 
               
               
                 423 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 5-F-1,3-C 6 H 3   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 424 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 5-F-1,3-C 6 H 3   
                 CF 3 CO 2   −   
                 — 
               
               
                 425 
                   n Decyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 1,4-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
             
          
           
               
                 426 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 1,2-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 427 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 1,2-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 428 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 1,2-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 429 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 1,3-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 430 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 1,3-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 431 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 1,3-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 432 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 5-F-1,3-C 6 H 3   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 433 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 5-F-1,3-C 6 H 3   
                 CF 3 CO 2   −   
                 — 
               
             
          
           
               
                 434 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 1,3-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 435 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 1,3-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 436 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 1,3-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 437 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 2-F-1,3-C 6 H 3   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 438 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 2-F-1,3-C 6 H 3   
                 CF 3 CO 2   −   
                 — 
               
               
                 439 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 5-F-1,3-C 6 H 3   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 440 
                   n Nonyl 
                 R 2  + R 3  = —(CH 2 ) 4 — 
                 5-F-1,3-C 6 H 3   
                 CF 3 CO 2   −   
                 — 
               
             
          
           
               
                 441 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 1,4-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 442 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 1,4-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 443 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 1,4-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 444 
                   n Octyl 
                 Methyl 
                 Methyl 
                 1,2-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 445 
                   n Octyl 
                 Methyl 
                 Methyl 
                 1,2-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 446 
                   n Octyl 
                 Methyl 
                 Methyl 
                 1,2-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 447 
                   n Octyl 
                 Methyl 
                 Methyl 
                 1,3-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 448 
                   n Octyl 
                 Methyl 
                 Methyl 
                 1,3-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 449 
                   n Octyl 
                 Methyl 
                 Methyl 
                 1,3-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 450 
                   n Octyl 
                 Methyl 
                 Methyl 
                 1,4-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 451 
                   n Octyl 
                 Methyl 
                 Methyl 
                 1,4-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 452 
                   n Octyl 
                 Methyl 
                 Methyl 
                 1,4-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 453 
                   n Hexyl 
                   n Hexyl 
                 Methyl 
                 1,3-C 6 H 4   
                 Cl −   
                 2xNR 1 R 2 R 3   
               
               
                 454 
                   n Hexyl 
                   n Hexyl 
                 Methyl 
                 1,3-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 455 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 1,2-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 456 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 1,3-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 457 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 1,3-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 458 
                   n Pentyl 
                   n Pentyl 
                   n Pentyl 
                 1,4-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 459 
                   n Butyl 
                   n Butyl 
                   n Butyl 
                 1,3-C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 460 
                   n Butyl 
                   n Butyl 
                   n Butyl 
                 1,3-C 6 H 4   
                 CF 3 CO 2   −   
                 — 
               
               
                 461 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 4,4′-C 6 H 4 —C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 462 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 3,3′-C 6 H 4 —C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                 463 
                   n Nonyl 
                 Methyl 
                 Methyl 
                 2,2′-C 6 H 4 —C 6 H 4   
                 Br −   
                 2xNR 1 R 2 R 3   
               
               
                   
               
             
          
           
               
                   
                 Alkyating 
                 HPLC Method 9a 
               
             
          
           
               
                 Nu. 
                 CAS Num. 
                 Agent 
                 CAS Num. 
                 Formula 
                 Weight 
                 Time 
               
               
                   
               
               
                 395 
                 17373-28-3 
                 o-(XCH 2 ) 2 C 6 H 4   
                 612-12-4 
                 C 34 H 66 N 2 Cl 2   
                 573.817 
                 48.6 
               
               
                 396 
                 17373-28-3 
                 o-(XCH 2 ) 2 C 6 H 4   
                 91-13-4 
                 C 34 H 66 N 2 Br 2   
                 662.720 
                 48.6 
               
               
                 397 
                 — 
                 — 
                 — 
                 C 38 H 66 N 2 O 4 F 6   
                 728.944 
                 48.6 
               
               
                 398 
                 17373-28-3 
                 m-(XCH 2 ) 2 C 6 H 4   
                 626-16-4 
                 C 34 H 66 N 2 Cl 2   
                 573.817 
                 47.3 
               
               
                 399 
                 17373-28-3 
                 m-(XCH 2 ) 2 C 6 H 4   
                 626-15-3 
                 C 34 H 66 N 2 Br 2   
                 662.720 
                 47.3 
               
               
                 400 
                 — 
                 — 
                 — 
                 C 38 H 66 N 2 O 4 F 6   
                 728.944 
                 47.3 
               
               
                 401 
                 17373-28-3 
                 p-(XCH 2 ) 2 C 6 H 4   
                 623-25-6 
                 C 34 H 66 N 2 Cl 2   
                 573.817 
                 46.7 
               
               
                 402 
                 17373-28-3 
                 p-(XCH 2 ) 2 C 6 H 4   
                 623-24-5 
                 C 34 H 66 N 2 Br 2   
                 662.720 
                 46.7 
               
               
                 403 
                 — 
                 — 
                 — 
                 C 38 H 66 N 2 O 4 F 6   
                 728.944 
                 46.7 
               
               
                 404 
                 1120-24-7 
                 o-(XCH 2 ) 2 C 6 H 4   
                 612-12-4 
                 C 32 H 62 N 2 Cl 2   
                 545.763 
                 44.4 
               
               
                 405 
                 1120-24-7 
                 o-(XCH 2 ) 2 C 6 H 4   
                 91-13-4 
                 C 32 H 62 N 2 Br 2   
                 634.666 
                 44.4 
               
               
                 406 
                 — 
                 — 
                 — 
                 C 36 H 62 N 2 O 4 F 6   
                 700.890 
                 44.4 
               
               
                 407 
                 1120-24-7 
                 m-(XCH 2 ) 2 C 6 H 4   
                 626-16-4 
                 C 32 H 62 N 2 Cl 2   
                 545.763 
                 43.4 
               
               
                 408 
                 1120-24-7 
                 m-(XCH 2 ) 2 C 6 H 4   
                 626-15-3 
                 C 32 H 62 N 2 Br 2   
                 634.666 
                 43.5 
               
               
                 409 
                 — 
                 — 
                 — 
                 C 36 H 62 N 2 O 4 F 6   
                 700.890 
                 43.4 
               
               
                 410 
                 1120-24-7 
                 2-F-1,3-(XCH 2 ) 2 C 6 H 3   
                 25006-86-4 
                 C 32 H 61 N 2 Br 2 F 
                 652.656 
                 43.5 
               
               
                 411 
                 — 
                 — 
                 — 
                 C 36 H 61 N 2 O 4 F 7   
                 718.880 
                 43.5 
               
               
                 412 
                 1120-24-7 
                 5-F-1,3-(XCH 2 ) 2 C 6 H 3   
                 19252-80-9 
                 C 32 H 61 N 2 Br 2 F 
                 652.656 
                 43.6 
               
               
                 413 
                 — 
                 — 
                 — 
                 C 36 H 61 N 2 O 4 F 7   
                 718.880 
                 43.6 
               
               
                 414 
                 1120-24-7 
                 p-(XCH 2 ) 2 C 6 H 4   
                 623-25-6 
                 C 32 H 62 N 2 Cl 2   
                 545.763 
                 42.9 
               
               
                 415 
                 1120-24-7 
                 p-(XCH 2 ) 2 C 6 H 4   
                 626-15-3 
                 C 32 H 62 N 2 Br 2   
                 634.666 
                 42.9 
               
               
                 416 
                 — 
                 — 
                 — 
                 C 36 H 62 N 2 O 4 F 6   
                 700.890 
                 42.9 
               
               
                 417 
                 74673-26-0 
                 p-(XCH 2 ) 2 C 6 H 4   
                 612-12-4 
                 C 36 H 66 N 2 Cl 2   
                 597.839 
                 45.9 
               
               
                 418 
                 74673-26-0 
                 p-(XCH 2 ) 2 C 6 H 4   
                 626-16-4 
                 C 36 H 66 N 2 Cl 2   
                 597.839 
                 44.9 
               
               
                 419 
                 74673-26-0 
                 p-(XCH 2 ) 2 C 6 H 4   
                 626-15-3 
                 C 36 H 66 N 2 Br 2   
                 686.742 
                 44.9 
               
               
                 420 
                 — 
                 — 
                 — 
                 C 40 H 66 N 2 O 4 F 6   
                 752.966 
                 44.9 
               
               
                 421 
                 74673-26-0 
                 2-F-1,3-(XCH 2 ) 2 C 6 H 3   
                 25006-86-4 
                 C 36 H 65 N 2 Br 2 F 
                 704.732 
                 45.0 
               
               
                 422 
                 — 
                 — 
                 — 
                 C 40 H 65 N 2 O 4 F 7   
                 770.956 
                 45.0 
               
               
                 423 
                 74673-26-0 
                 5-F-1,3-(XCH 2 ) 2 C 6 H 3   
                 19252-80-9 
                 C 36 H 65 N 2 Br 2 F 
                 704.732 
                 45.1 
               
               
                 424 
                 — 
                 — 
                 — 
                 C 40 H 65 N 2 O 4 F 7   
                 770.956 
                 45.1 
               
               
                 425 
                 74673-26-0 
                 p-(XCH 2 ) 2 C 6 H 4   
                 623-25-6 
                 C 36 H 66 N 2 Cl 2   
                 597.839 
                 44.4 
               
               
                 426 
                 17373-27-2 
                 o-(XCH 2 ) 2 C 6 H 4   
                 612-12-4 
                 C 30 H 58 N 2 Cl 2   
                 517.709 
                 40.1 
               
               
                 427 
                 17373-27-2 
                 o-(XCH 2 ) 2 C 6 H 4   
                 91-13-4 
                 C 30 H 58 N 2 Br 2   
                 606.612 
                 40.1 
               
               
                 428 
                 — 
                 — 
                 — 
                 C 34 H 58 N 2 O 4 F 6   
                 672.836 
                 40.1 
               
               
                 429 
                 17373-27-2 
                 m-(XCH 2 ) 2 C 6 H 4   
                 626-16-4 
                 C 30 H 58 N 2 Cl 2   
                 517.709 
                 39.3 
               
               
                 430 
                 17373-27-2 
                 m-(XCH 2 ) 2 C 6 H 4   
                 626-15-3 
                 C 30 H 58 N 2 Br 2   
                 606.612 
                 39.2 
               
               
                 431 
                 — 
                 — 
                 — 
                 C 34 H 58 N 2 O 4 F 6   
                 672.836 
                 39.3 
               
               
                 432 
                 17373-27-2 
                 5-F-1,3-(XCH 2 ) 2 C 6 H 3   
                 19252-80-9 
                 C 32 H 57 N 2 Br 2 F 
                 624.602 
                 39.5 
               
               
                 433 
                 — 
                 — 
                 — 
                 C 36 H 57 N 2 O 4 F 7   
                 714.838 
                 39.5 
               
               
                 434 
                 74673-25-9 
                 p-(XCH 2 ) 2 C 6 H 4   
                 626-16-4 
                 C 34 H 62 N 2 Cl 2   
                 569.785 
                 40.8 
               
               
                 435 
                 74673-25-9 
                 p-(XCH 2 ) 2 C 6 H 4   
                 626-15-3 
                 C 34 H 62 N 2 Br 2   
                 658.688 
                 40.8 
               
               
                 436 
                 — 
                 — 
                 — 
                 C 38 H 62 N 2 O 4 F 6   
                 724.912 
                 40.8 
               
               
                 437 
                 74673-25-9 
                 2-F-1,3-(XCH 2 ) 2 C 6 H 3   
                 25006-86-4 
                 C 34 H 61 N 2 Br 2 F 
                 676.678 
                 40.9 
               
               
                 438 
                 — 
                 — 
                 — 
                 C 38 H 61 N 2 O 4 F 7   
                 742.902 
                 40.9 
               
               
                 439 
                 74673-25-9 
                 5-F-1,3-(XCH 2 ) 2 C 6 H 3   
                 19252-80-9 
                 C 34 H 61 N 2 Br 2 F 
                 676.678 
                 41.0 
               
               
                 440 
                 — 
                 — 
                 — 
                 C 38 H 61 N 2 O 4 F 7   
                 742.902 
                 41.0 
               
               
                 441 
                 17373-27-2 
                 p-(XCH 2 ) 2 C 6 H 4   
                 623-25-6 
                 C 30 H 58 N 2 Cl 2   
                 517.709 
                 39.0 
               
               
                 442 
                 17373-27-2 
                 p-(XCH 2 ) 2 C 6 H 4   
                 624-24-5 
                 C 30 H 58 N 2 Br 2   
                 606.612 
                 39.0 
               
               
                 443 
                 — 
                 — 
                 — 
                 C 34 H 58 N 2 O 4 F 6   
                 672.836 
                 39.0 
               
               
                 444 
                 7378-99-6 
                 o-(XCH 2 ) 2 C 6 H 4   
                 612-12-4 
                 C 28 H5 4 N 2 Cl 2   
                 489.656 
                 35.8 
               
               
                 445 
                 7378-99-6 
                 o-(XCH 2 ) 2 C 6 H 4   
                 91-13-4 
                 C 28 H 54 N 2 Br 2   
                 578.558 
                 35.8 
               
               
                 446 
                 — 
                 — 
                 — 
                 C 32 H 54 N 2 O 4 F 6   
                 644.782 
                 35.8 
               
               
                 447 
                 7378-99-6 
                 m-(XCH 2 ) 2 C 6 H 4   
                 626-16-4 
                 C 28 H 54 N 2 Cl 2   
                 489.656 
                 35.3 
               
               
                 448 
                 7378-99-6 
                 m-(XCH 2 ) 2 C 6 H 4   
                 626-15-3 
                 C 28 H 54 N 2 Br 2   
                 578.558 
                 35.3 
               
               
                 449 
                 — 
                 — 
                 — 
                 C 32 H 54 N 2 O 4 F 6   
                 644.782 
                 35.3 
               
               
                 450 
                 7378-99-6 
                 p-(XCH 2 ) 2 C 6 H 4   
                 623-25-6 
                 C 28 H 54 N 2 Cl 2   
                 489.656 
                 35.1 
               
               
                 451 
                 7378-99-6 
                 p-(XCH 2 ) 2 C 6 H 4   
                 624-24-5 
                 C 28 H 54 N 2 Br 2   
                 578.558 
                 35.1 
               
               
                 452 
                 — 
                 — 
                 — 
                 C 32 H 54 N 2 O 4 F 6   
                 644.782 
                 35.1 
               
               
                 453 
                 37615 
                 m-(XCH 2 ) 2 C 6 H 4   
                 626-16-4 
                 C 34 H 66 N 2 Cl 2   
                 573.817 
                 40.0 
               
               
                 454 
                 37615 
                 m-(XCH 2 ) 2 C 6 H 4   
                 626-15-3 
                 C 34 H 66 N 2 Br 2   
                 662.720 
                 40.0 
               
               
                 455 
                 621-77-2 
                 o-(XCH 2 ) 2 C 6 H 4   
                 91-13-4 
                 C 38 H 74 N 2 Br 2   
                 718.827 
                 42.3 
               
               
                 456 
                 621-77-2 
                 o-(XCH 2 ) 2 C 6 H 4   
                 626-15-3 
                 C 38 H 74 N 2 Br 2   
                 718.827 
                 42.6 
               
               
                 457 
                 — 
                 — 
                 — 
                 C 42 H 74 N 2 O 4 F 6   
                 785.051 
                 42.6 
               
               
                 458 
                 621-77-2 
                 o-(XCH 2 ) 2 C 6 H 4   
                 624-24-5 
                 C 38 H 74 N 2 Br 2   
                 718.827 
                 42.2 
               
               
                 459 
                 102-82-9 
                 o-(XCH 2 ) 2 C 6 H 4   
                 626-15-3 
                 C 32 H 62 N 2 Br 2   
                 634.666 
                 32.7 
               
               
                 460 
                 — 
                 — 
                 — 
                 C 36 H 62 N 2 O 4 F 6   
                 700.879 
                 32.7 
               
               
                 461 
                 17373-27-2 
                 4,4′-(XCH 2 C 6 H 4 ) 2   
                 20248-86-6 
                 C 36 H 62 N 2 Br 2   
                 682.713 
                 42.7 
               
               
                 462 
                 17373-27-2 
                 3,3′-(XCH 2 C 6 H 4 ) 2   
                 24656-53-9 
                 C 36 H 62 N 2 Br 2   
                 682.713 
                 43.0 
               
               
                 463 
                 17373-27-2 
                 2,2′-(XCH 2 C 6 H 4 ) 2   
                 38274-15-5 
                 C 36 H 62 N 2 Br 2   
                 682.713 
                 42.4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE VII 
               
               
                   
               
               
                 [R 1 R 2 R 3 R 4 P] + [X] −  and [R 1 R 2 R 3 S] + [X] −  and [R 1 R 2 R 3 S═O] + [X] −   
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 Nu. 
                 Salt Type 
                 R 1   
                 R 2   
                 R 3   
                 R 4   
                 X −   
                 Phosphine 
               
               
                   
               
               
                 464 
                 Phosphonium 
                   n Pentyl 
                   n Pentyl 
                 Phenyl 
                 Methyl 
                 Cl −   
                 PR 2 R 2 R 3   
               
               
                 465 
                 Phosphonium 
                   n Pentyl 
                   n Pentyl 
                 Phenyl 
                 Methyl 
                 CF 3 CO 2   −   
                 — 
               
               
                 466 
                 Phosphonium 
                   n Hexyl 
                   n Hexyl 
                 Phenyl 
                 Methyl 
                 Cl −   
                 PR 1 R 2 R 3   
               
               
                 467 
                 Phosphonium 
                   n Hexyl 
                   n Hexyl 
                 Phenyl 
                 Methyl 
                 CF 3 CO 2   −   
                 — 
               
               
                 468 
                 Phosphonium 
                   n Heptyl 
                   n Heptyl 
                 Phenyl 
                 Methyl 
                 Cl −   
                 PR 1 R 2 R 3   
               
               
                 469 
                 Phosphonium 
                   n Heptyl 
                   n Heptyl 
                 Phenyl 
                 Methyl 
                 CF 3 CO 2   −   
                 — 
               
               
                 470 
                 Phosphonium 
                   n Octyl 
                   n Octyl 
                 Phenyl 
                 Methyl 
                 Cl −   
                 PR 1 R 2 R 3   
               
               
                 471 
                 Phosphonium 
                   n Nonyl 
                 Methyl 
                 Phenyl 
                 Methyl 
                 Cl −   
                 PR 2 R 3 R 4   
               
               
                 472 
                 Phosphonium 
                   n Nonyl 
                 Methyl 
                 Phenyl 
                 Methyl 
                 CF 3 CO 2   −   
                 — 
               
               
                 473 
                 Phosphonium 
                   n Nonyl 
                 Methyl 
                 4-FC 6 H 4 — 
                 Methyl 
                 Cl −   
                 PR 2 R 3 R 4   
               
               
                 474 
                 Phosphonium 
                   n Nonyl 
                 Methyl 
                 4-FC 6 H 4 — 
                 Methyl 
                 CF 3 CO 2   −   
                 — 
               
               
                 475 
                 Phosphonium 
                   n Decyl 
                 Methyl 
                 Phenyl 
                 Methyl 
                 Cl −   
                 PR 2 R 3 R 4   
               
               
                 476 
                 Phosphonium 
                   n Decyl 
                 Methyl 
                 Phenyl 
                 Methyl 
                 CF 3 CO 2   −   
                 — 
               
               
                 477 
                 Phosphonium 
                   n Decyl 
                 Methyl 
                 4-FC 6 H 4 — 
                 Methyl 
                 Cl −   
                 PR 2 R 3 R 4   
               
               
                 478 
                 Phosphonium 
                   n Decyl 
                 Methyl 
                 4-FC 6 H 4 — 
                 Methyl 
                 CF 3 CO 2   −   
                 — 
               
               
                 479 
                 Phosphonium 
                   n Undecyl 
                 Methyl 
                 Phenyl 
                 Methyl 
                 Cl −   
                 PR 2 R 3 R 4   
               
               
                 480 
                 Phosphonium 
                   n Undecyl 
                 Methyl 
                 Phenyl 
                 Methyl 
                 CF 3 CO 2   −   
                 — 
               
               
                 481 
                 Phosphonium 
                   n Undecyl 
                 Methyl 
                 4-FC 6 H 4 — 
                 Methyl 
                 Cl −   
                 PR 2 R 3 R 4   
               
               
                 482 
                 Phosphonium 
                   n Undecyl 
                 Methyl 
                 4-FC 6 H 4 — 
                 Methyl 
                 CF 3 CO 2   −   
                 — 
               
               
                 483 
                 Sulfonium 
                 Ph(CH 2 ) 10 — 
                 Methyl 
                 Methyl 
                 — 
                 Br −   
                 SR 2 R 3   
               
               
                 484 
                 Sulfonium 
                   n Decyl 
                 4-FC 6 H 4 CH 2 — 
                 Methyl 
                 — 
                 Br −   
                 SR 1 R 3   
               
               
                 485 
                 Sulfonium 
                   n Decyl 
                 4-FC 6 H 4 — 
                 Methyl 
                 — 
                 Br −   
                 SR 1 R 2   
               
               
                 486 
                 Sulfonium 
                   n Decyl 
                 4-FC 6 H 4 — 
                 Methyl 
                 — 
                 CF 3 CO 2   −   
                 — 
               
               
                 487 
                 Sulfonium 
                 Q  a   
                 Methyl 
                 Methyl 
                 — 
                 Br −   
                 SR 2 R 3   
               
               
                 488 
                 Sulfoxonium 
                   n Decyl 
                 4-FC 6 H 4 CH 2 — 
                 Methyl 
                 — 
                 Br −   
                 O═SR 1 R 3   
               
               
                 489 
                 Sulfoxonium 
                 Q  a   
                 Methyl 
                 Methyl 
                 — 
                 Br −   
                 O═SR 2 R 3   
               
               
                   
               
             
          
           
               
                   
                 Alkylating 
                 HPLC Method 9a 
               
             
          
           
               
                   
                 Nu. 
                 CAS Num. 
                 Agent 
                 CAS Num. 
                 Formula 
                 Weight 
                 Time 
               
               
                   
                   
               
               
                   
                 464 
                 71501-08-1 
                 R 4 X 
                 74-87-3 
                 C 17 H 30 PCl 
                 300.852 
                 32.7 
               
               
                   
                 465 
                 — 
                 — 
                 — 
                 C 19 H 30 O 2 F 3 P 
                 378.415 
                 32.7 
               
               
                   
                 466 
                 18297-98-8 
                 R 4 X 
                 74-87-3 
                 C 19 H 34 PCl 
                 328.905 
                 37.9 
               
               
                   
                 467 
                 — 
                 — 
                 — 
                 C 21 H 34 O 2 F 3 P 
                 406.469 
                 37.6 
               
               
                   
                 468 
                 109706-36-7 
                 R 4 X 
                 74-87-3 
                 C 21 H 38 PCl 
                 356.959 
                 42.9 
               
               
                   
                 469 
                 — 
                 — 
                 — 
                 C 23 H 38 O 2 F 3 P 
                 434.522 
                 42.9 
               
               
                   
                 470 
                 14086-46-5 
                 R 4 X 
                 74-87-3 
                 C 23 H 42 PCl 
                 385.013 
                 47.7 
               
               
                   
                 471 
                 672-66-2 
                 R 1 X 
                 2473-01-0 
                 C 17 H 30 PCl 
                 300.852 
                 36.0 
               
               
                   
                 472 
                 — 
                 — 
                 — 
                 C 19 H 30 O 2 F 3 P 
                 378.415 
                 36.0 
               
               
                   
                 473 
                 7217-34-7 
                 R 1 X 
                 2473-01-0 
                 C 17 H 29 FPCl 
                 318.842 
                 36.2 
               
               
                   
                 474 
                 — 
                 — 
                 — 
                 C 19 H 29 O 2 F 4 P 
                 396.405 
                 36.2 
               
               
                   
                 475 
                 672-66-2 
                 R 1 X 
                 1002-69-3 
                 C 18 H 32 PCl 
                 314.879 
                 39.1 
               
               
                   
                 476 
                 — 
                 — 
                 — 
                 C 20 H 32 O 2 F 3 P 
                 392.442 
                 39.1 
               
               
                   
                 477 
                 7217-34-7 
                 R 1 X 
                 1002-69-3 
                 C 18 H 31 FPCl 
                 332.869 
                 39.3 
               
               
                   
                 478 
                 — 
                 — 
                 — 
                 C 20 H 31 O 2 F 4 P 
                 410.432 
                 39.3 
               
               
                   
                 479 
                 672-66-2 
                 R 1 X 
                 2473-03-2 
                 C 19 H 34 PCl 
                 328.905 
                 42.2 
               
               
                   
                 480 
                 — 
                 — 
                 — 
                 C 21 H 34 O 2 F 3 P 
                 406.469 
                 42.2 
               
               
                   
                 481 
                 7217-34-7 
                 R 1 X 
                 2473-03-2 
                 C 19 H 33 FPCl 
                 346.896 
                 42.4 
               
               
                   
                 482 
                 — 
                 — 
                 — 
                 C 21 H 33 O 2 F 4 P 
                 424.459 
                 42.4 
               
               
                   
                 483 
                 75-18-3 
                 R 1 X 
                 7757-83-7 
                 C 18 H 31 SBr 
                 359.416 
                 40.3 
               
               
                   
                 484 
                 22438-39-2 
                 R 2 X 
                 459-46-1 
                 C 18 H 30 FSBr 
                 377.406 
                 40.6 
               
               
                   
                 485 
                 61671-40-7 
                 R 3 X 
                 74-83-9 
                 C 17 H 28 FSBr 
                 363.379 
                 38.5 
               
               
                   
                 486 
                 — 
                 — 
                 — 
                 C 19 H 28 O 2 F 4 S 
                 396.492 
                 38.5 
               
               
                   
                 487 
                 75-18-3 
                 R 1 X 
                 80563-37-7 
                 C 20 H 27 SBr 
                 379.406 
                 34.9 
               
               
                   
                 488 
                 3079-28-5 
                 R 2 X 
                 459-46-1 
                 C 18 H 30 OFSBr 
                 393.406 
                 39.5 
               
               
                   
                 489 
                 67-68-5 
                 R 1 X 
                 80563-37-7 
                 C 20 H 27 OSBr 
                 395.406 
                 33.8 
               
               
                   
                   
               
               
                   
                   a  Q = 4,4′-CH 3 (CH 2 ) 4 C 6 H 4 —C 6 H 4 CH 2 — 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE VIII 
               
               
                   
               
               
                 [N—R 1 Z] +  [X] −  and [N,N′—R 1 Z~Z′R 1 ] 2+  2[X] −   
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 Nu. 
                 Z or Z~Z′ 
                 R 1   
                 CAS# known product 
                 X −   
                 N-Base 
                 CAS Num. 
               
               
                   
               
               
                 490 
                 4-Picolinium 
                   n Undecyl 
                 New 
                 Br −   
                 4-picoline 
                 108-89-4 
               
               
                 491 
                 4-Picolinium 
                   n Undecyl 
                 New 
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 492 
                 4-Picolinium 
                   n Decyl 
                 [70850-62-3] 
                 Br −   
                 4-picoline 
                 108-89-4 
               
               
                 493 
                 4-Picolinium 
                   n Decyl 
                 New 
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 494 
                 4-Picolinium 
                   n Nonyl 
                 New 
                 Br −   
                 4-picoline 
                 108-89-4 
               
               
                 495 
                 4-Picolinium 
                   n Nonyl 
                 New 
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 496 
                 Quinolinium 
                   n Undecyl 
                   
                 Br −   
                 4-picoline 
                 91-22-5 
               
               
                 497 
                 Quinolinium 
                   n Undecyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 498 
                 Quinolinium 
                   n Decyl 
                 [15001-43-1] 
                 Br −   
                 quinoline 
                 91-22-5 
               
               
                 499 
                 Quinolinium 
                   n Decyl 
                 New 
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 500 
                 Quinolinium 
                   n Nonyl 
                 New 
                 Br −   
                 quinoline 
                 91-22-5 
               
               
                 501 
                 Quinolinium 
                   n Nonyl 
                 New 
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 502 
                 Quinolinium 
                   n Octyl 
                   
                 Br −   
                 quinoline 
                 91-22-5 
               
               
                 503 
                 Quinolinium 
                   n Octyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 504 
                 Isoquinolinium 
                   n Undecyl 
                   
                 Br −   
                 isoquinoline 
                 119-65-3 
               
               
                 505 
                 Isoquinolinium 
                   n Undecyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 506 
                 Isoquinolinium 
                   n Decyl 
                 [51808-86-7] 
                 Br −   
                 isoquinoline 
                 119-65-3 
               
               
                 507 
                 Isoquinolinium 
                   n Decyl 
                 New 
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 508 
                 Isoquinolinium 
                   n Nonyl 
                 New 
                 Br −   
                 isoquinoline 
                 119-65-3 
               
               
                 509 
                 Isoquinolinium 
                   n Nonyl 
                 New 
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 510 
                 Isoquinolinium 
                   n Octyl 
                   
                 Br −   
                 isoquinoline 
                 119-65-3 
               
               
                 511 
                 Isoquinolinium 
                   n Octyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 512 
                 1,2-Me 2 imidazolium 
                   n Undecyl 
                   
                 Br −   
                 DMIm c   
                 1739-84-0 
               
               
                 513 
                 1,2-Me 2 imidazolium 
                   n Undecyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 514 
                 1,2-Me 2 imidazolium 
                   n Decyl 
                   
                 Br −   
                 DMIm c   
                 1739-84-0 
               
               
                 515 
                 1,2-Me 2 imidazolium 
                   n Decyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 516 
                 1,2-Me 2 imidazolium 
                   n Nonyl 
                   
                 Br −   
                 DMIm c   
                 1739-84-0 
               
               
                 517 
                 1,2-Me 2 imidazolium 
                   n Nonyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 518 
                 1,2-Me 2 -benzimidazolium 
                   n Undecyl 
                   
                 Br −   
                 DMBIm c   
                 2876-08-6 
               
               
                 519 
                 1,2-Me 2 -benzimidazolium 
                   n Undecyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 520 
                 1,2-Me 2 -benzimidazolium 
                   n Decyl 
                   
                 Br −   
                 DMBIm c   
                 2876-08-6 
               
               
                 521 
                 1,2-Me 2 -benzimidazolium 
                   n Decyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 522 
                 1,2-Me 2 -benzimidazolium 
                   n Nonyl 
                   
                 Br −   
                 DMBIm c   
                 2876-08-6 
               
               
                 523 
                 1,2-Me 2 -benzimidazolium 
                   n Nonyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 524 
                 1,2-Me 2 -benzimidazolium 
                   n Octyl 
                   
                 Br −   
                 DMBIm c   
                 2876-08-6 
               
               
                 525 
                 1,2-Me 2 -benzimidazolium 
                   n Octyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 526 
                 1-R 1 -2-Me-imidazolium 
                   n Octyl 
                   
                 Br −   
                 MIm c   
                 693-98-1 
               
               
                 527 
                 1-R 1 -2-Me-imidazolium 
                   n Octyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 528 
                 1-R 1 -2-Me-imidazolium 
                   n Heptyl 
                   
                 Br −   
                 MIm c   
                 693-98-1 
               
               
                 529 
                 1-R 1 -2-Me-imidazolium 
                   n Heptyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 530 
                 1-R 1 -2-Me-imidazolium 
                   n Hexyl 
                   
                 Br −   
                 MIm c   
                 693-98-1 
               
               
                 531 
                 1-R 1 -2-Me-imidazolium 
                   n Hexyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 532 
                 1-R 1 -2-Ph-imidazolium 
                   n Octyl 
                   
                 Br −   
                 PIm c   
                 670-96-2 
               
               
                 533 
                 1-R 1 -2-Ph-imidazolium 
                   n Heptyl 
                   
                 Br −   
                 PIm c   
                 670-96-2 
               
               
                 534 
                 1-R 1 -2-Ph-imidazolium 
                   n Hexyl 
                   
                 Br −   
                 PIm c   
                 670-96-2 
               
               
                 535 
                 1-R 1 -2-Ph-imidazolium 
                   n Pentyl 
                   
                 Br −   
                 PIm c   
                 670-96-2 
               
               
                 536 
                 1-R 1 -2-Me-benzimidazolium 
                   n Octyl 
                   
                 Br −   
                 MBIm c   
                 615-15-6 
               
               
                 537 
                 1-R 1 -2-Me-benzimidazolium 
                   n Heptyl 
                   
                 Br −   
                 MBIm c   
                 615-15-6 
               
               
                 537b 
                 1-R 1 -2-Me-benzimidazolium 
                 Ph(CH 2 ) 3 — 
                   
                 Br −   
                 MBIm c   
                 615-15-6 
               
               
                 537c 
                 1-R 1 -2-Me-benzimidazolium 
                 Ph(CH 2 ) 3 — 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 538 
                 1-R 1 -2-Me-benzimidazolium 
                   n Hexyl 
                   
                 Br −   
                 MBIm c   
                 615-15-6 
               
               
                 539 
                 1-R 1 -2-Me-benzimidazolium 
                   n Pentyl 
                   
                 Br −   
                 MBIm c   
                 615-15-6 
               
               
                 540 
                 1-R 1 -2-Me-imidazolinium 
                   n Octyl 
                   
                 Br −   
                 MImN c   
                 534-26-9 
               
               
                 541 
                 1-R 1 -2-Me-imidazolinium 
                   n Octyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 542 
                 1-R 1 -2-Me-imidazolinium 
                   n Heptyl 
                   
                 Br −   
                 MImN c   
                 534-26-9 
               
               
                 543 
                 1-R 1 -2-Me-imidazolinium 
                   n Heptyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 544 
                 1-R 1 -2-Me-imidazolinium 
                   n Hexyl 
                   
                 Br −   
                 MImN c   
                 534-26-9 
               
               
                 545 
                 1-R 1 -2-Me-imidazolinium 
                   n Hexyl 
                   
                 CF 3 CO 2   −   
                 — 
                 — 
               
               
                 546 
                 1-R 1 -2-Ph-imidazolinium 
                   n Octyl 
                   
                 Br −   
                 PImN c   
                 936-49-2 
               
               
                 547 
                 1-R 1 -2-Ph-imidazolinium 
                   n Heptyl 
                   
                 Br −   
                 PImN c   
                 936-49-2 
               
               
                 548 
                 1-R 1 -2-Ph-imidazolinium 
                   n Hexyl 
                   
                 Br −   
                 PImN c   
                 936-49-2 
               
               
                 549 
                 1-R 1 -2-Ph-imidazolinium 
                   n Pentyl 
                   
                 Br −   
                 PImN c   
                 936-49-2 
               
               
                 550 
                 5,5′-Me2-3,3′-bipyridinium 
                 nUndecyl 
                   
                 Br− 
                 5,5′-Me2-3,3′- 
                 856796-70-8 
               
               
                   
                   
                   
                   
                   
                 bipyc 
               
               
                 551 
                 3,3′-bipyridinium 
                   n Undecyl 
                   
                 Br −   
                 3,3′-bipy c   
                 581-46-4 
               
               
                 552 
                 4-Me 2 N-pyridinium d   
                   n Nonyl 
                   
                 Br −   
                 DMAP c   
                 1122-58-3 
               
               
                 553 
                 4-Me 2 N-pyridinium d   
                   n Undecyl 
                   
                 Br −   
                 DMAP c   
                 1122-58-3 
               
               
                 554 
                 4-(1-Pyrrolidino)pyridinium d   
                   n Nonyl 
                   
                 Br −   
                 PyP c   
                 2456-81-7 
               
               
                 555 
                 4-(1-Pyrrolidino)pyridinium d   
                   n Undecyl 
                   
                 Br −   
                 PyP c   
                 2456-81-7 
               
               
                 556 
                 4-(4- n Heptylphenyl)pyridinium 
                 Methyl 
                 New 
                 Br −   
                 HePP c   
                 153855-56-2 
               
               
                   
               
             
          
           
               
                   
                 Alkylating 
                 HPLC Method 9a 
               
             
          
           
               
                   
                 Nu. 
                 Agent 
                 CAS Num. 
                 Formula 
                 Weight 
                 Time 
               
               
                   
                   
               
               
                   
                 490 
                 R n X 
                 693-67-4 
                 C 17 H 30 NBr 
                 328.336 
                 40.3 
               
               
                   
                 491 
                 — 
                 — 
                 C 19 H 30 NO 2 F 3   
                 375.449 
                 40.3 
               
               
                   
                 492 
                 R 1 X 
                 112-29-8 
                 C 16 H 28 NBr 
                 314.309 
                 37.0 
               
               
                   
                 493 
                 — 
                 — 
                 C 18 H 28 NO 2 F 3   
                 347.421 
                 37.0 
               
               
                   
                 494 
                 R 1 X 
                 693-58-3 
                 C 15 H 26 NBr 
                 300.282 
                 33.5 
               
               
                   
                 495 
                 — 
                 — 
                 C 17 H 26 NO 2 F 3   
                 333.394 
                 33.5 
               
               
                   
                 496 
                 R 1 X 
                 693-67-4 
                 C 20 H 30 NBr 
                 364.371 
                 43.0 
               
               
                   
                 497 
                 — 
                 — 
                 C 2 2H 30 NO 2 F 3   
                 397.483 
                 43.0 
               
               
                   
                 498 
                 R 1 X 
                 112-29-8 
                 C 19 H 28 NBr 
                 350.342 
                 39.8 
               
               
                   
                 499 
                 — 
                 — 
                 C 21 H 28 NO 2 F 3   
                 383.454 
                 39.8 
               
               
                   
                 500 
                 R 1 X 
                 693-58-3 
                 C 18 H 26 NBr 
                 336.315 
                 36.5 
               
               
                   
                 501 
                 — 
                 — 
                 C 20 H 26 NO 2 F 3   
                 369.427 
                 36.5 
               
               
                   
                 502 
                 R 1 X 
                 111-83-1 
                 C 17 H 24 NBr 
                 322.290 
                 33.1 
               
               
                   
                 503 
                 — 
                 — 
                 C 19 H 24 NO 2 F 3   
                 355.402 
                 33.1 
               
               
                   
                 504 
                 R 1 X 
                 693-67-4 
                 C 20 H 30 NBr 
                 364.371 
                 43.0 
               
               
                   
                 505 
                 — 
                 — 
                 C 22 H 30 NO 2 F 3   
                 397.483 
                 43.0 
               
               
                   
                 506 
                 R 1 X 
                 112-29-8 
                 C 19 H 28 NBr 
                 350.342 
                 39.9 
               
               
                   
                 507 
                 — 
                 — 
                 C 21 H 28 NO 2 F 3   
                 383.454 
                 39.9 
               
               
                   
                 508 
                 R 1 X 
                 693-58-3 
                 C 18 H 26 NBr 
                 336.315 
                 36.7 
               
               
                   
                 509 
                 — 
                 — 
                 C 20 H 26 NO 2 F 3   
                 369.427 
                 36.7 
               
               
                   
                 510 
                 R 1 X 
                 111-83-1 
                 C 17 H 24 NBr 
                 322.290 
                 33.4 
               
               
                   
                 511 
                 — 
                 — 
                 C 19 H 24 NO 2 F 3   
                 355.402 
                 33.4 
               
               
                   
                 512 
                 R 1 X 
                 693-67-4 
                 C 16 H 31 N 2 Br 
                 331.340 
                 40.9 
               
               
                   
                 513 
                 — 
                 — 
                 C 18 H 31 N 2 O 2 F 3   
                 364.452 
                 40.9 
               
               
                   
                 514 
                 R 1 X 
                 112-29-8 
                 C 15 H 29 N 2 Br 
                 317.313 
                 37.6 
               
               
                   
                 515 
                 — 
                 — 
                 C 17 H 29 N 2 O 2 F 3   
                 350.425 
                 37.6 
               
               
                   
                 516 
                 R 1 X 
                 693-58-3 
                 C 14 H 27 N 2 Br 
                 303.286 
                 34.2 
               
               
                   
                 517 
                 — 
                 — 
                 C 16 H 27 N 2 O 2 F 3   
                 336.398 
                 34.2 
               
               
                   
                 518 
                 R 1 X 
                 693-67-4 
                 C 20 H 33 N 2 Br 
                 381.402 
                 44.7 
               
               
                   
                 519 
                 — 
                 — 
                 C 22 H 33 N 2 O 2 F 3   
                 414.514 
                 44.7 
               
               
                   
                 520 
                 R 1 X 
                 112-29-8 
                 C 19 H 31 N 2 Br 
                 367.375 
                 41.6 
               
               
                   
                 521 
                 — 
                 — 
                 C 21 H 31 N 2 O 2 F 3   
                 400.487 
                 41.6 
               
               
                   
                 522 
                 R 1 X 
                 693-58-3 
                 C 18 H 29 N 2 Br 
                 353.348 
                 38.5 
               
               
                   
                 523 
                 — 
                 — 
                 C 20 H 29 N 2 O 2 F 3   
                 386.460 
                 38.5 
               
               
                   
                 524 
                 R 1 X 
                 111-83-1 
                 C 17 H 27 N 2 Br 
                 339.321 
                 35.3 
               
               
                   
                 525 
                 — 
                 — 
                 C 19 H 27 N 2 O 2 F 3   
                 372.433 
                 35.3 
               
               
                   
                 526 
                 2xR 1 X + base 
                 111-83-1 
                 C 20 H 39 N 2 Br 
                 387.447 
                 47.1 
               
               
                   
                 527 
                 — 
                 — 
                 C 22 H 39 N 2 O 2 F 3   
                 420.559 
                 47.1 
               
               
                   
                 528 
                 2xR 1 X + base 
                 629-04-9 
                 C 18 H 35 N 2 Br 
                 359.393 
                 42.0 
               
               
                   
                 529 
                 — 
                 — 
                 C 20 H 35 N 2 O 2 F 3   
                 392.505 
                 42.0 
               
               
                   
                 530 
                 2xR 3 X + base 
                 111-25-1 
                 C 16 H 31 N 2 Br 
                 331.340 
                 36.5 
               
               
                   
                 531 
                 — 
                 — 
                 C 18 H 31 N 2 O 2 F 3   
                 364.452 
                 36.5 
               
               
                   
                 532 
                 2xR 1 X + base 
                 111-83-1 
                 C 25 H 41 N 2 Br 
                 449.518 
                 51.9 
               
               
                   
                 533 
                 2xR 1 X + base 
                 629-04-9 
                 C 23 H 37 N 2 Br 
                 421.464 
                 47.3 
               
               
                   
                 534 
                 2xR 1 X + base 
                 111-25-1 
                 C 21 H 33 N 2 Br 
                 393.411 
                 42.9 
               
               
                   
                 535 
                 2xR 1 X + base 
                 110-53-2 
                 C 19 H 29 N 2 Br 
                 365.357 
                 37.5 
               
               
                   
                 536 
                 2xR 1 X + base 
                 111-83-1 
                 C 24 H 41 N 2 Br 
                 437.509 
                 50.7 
               
               
                   
                 537 
                 2xR 1 X + base 
                 629-04-9 
                 C 22 H 37 N 2 Br 
                 409.456 
                 45.9 
               
               
                   
                 537b 
                 2xR 1 X + base 
                 637-59-2 
                 C 26 H 29 N 2 Br 
                 449.426 
                 41.0 
               
               
                   
                 537c 
                 — 
                 — 
                 C 28 H 29 N 2 O 2 F 3   
                 482.537 
                 41.0 
               
               
                   
                 538 
                 2xR 1 X + base 
                 111-25-1 
                 C 20 H 33 N 2 Br 
                 381.402 
                 40.6 
               
               
                   
                 539 
                 2xR 1 X + base 
                 110-53-2 
                 C 18 H 29 N 2 Br 
                 353.348 
                 36.1 
               
               
                   
                 540 
                 2xR 1 X + base 
                 111-83-1 
                 C 20 H 41 N 2 Br 
                 389.457 
                 47.8 
               
               
                   
                 541 
                 — 
                 — 
                 C 22 H 41 N 2 O 2 F 3   
                 422.568 
                 47.8 
               
               
                   
                 542 
                 2xR 1 X + base 
                 629-04-9 
                 C 18 H 37 N 2 Br 
                 361.404 
                 42.7 
               
               
                   
                 543 
                 2xR 1 X + base 
                 — 
                 C 20 H 37 N 2 O 2 F 3   
                 394.515 
                 42.7 
               
               
                   
                 544 
                 2xR 1 X + base 
                 111-25-1 
                 C 16 H 33 N 2 Br 
                 333.351 
                 37.2 
               
               
                   
                 545 
                 — 
                 — 
                 C 18 H 33 N 2 O 2 F 3   
                 366.462 
                 37.2 
               
               
                   
                 546 
                 2xR 1 X + base 
                 111-83-1 
                 C 25 H 43 N 2 Br 
                 451.526 
                 52.8 
               
               
                   
                 547 
                 2xR 1 X + base 
                 629-04-9 
                 C 23 H 39 N 2 Br 
                 423.473 
                 48.1 
               
               
                   
                 548 
                 2xR 1 X + base 
                 111-25-1 
                 C 21 H 35 N 2 Br 
                 395.420 
                 43.2 
               
               
                   
                 549 
                 2xR 1 X + base 
                 110-53-2 
                 C 19 H 31 N 2 Br 
                 367.367 
                 38.1 
               
               
                   
                 550 
                 2xR1X 
                 693-67-4 
                 C34H58N2Br2 
                 654.659 
                 46.4 
               
               
                   
                 551 
                 2xR 1 X 
                 693-67-4 
                 C 32 H 54 N 2 Br 2   
                 626.593 
                 43.8 
               
               
                   
                 552 
                 R 1 X 
                 693-58-3 
                 C 16 H 29 N 2 Br 
                 329.325 
                 37.2 
               
               
                   
                 553 
                 R 1 X 
                 693-67-4 
                 C 18 H 33 N 2 Br 
                 357.379 
                 43.5 
               
               
                   
                 554 
                 R 1 X 
                 693-58-3 
                 C 18 H 31 N 2 Br 
                 355.363 
                 39.9 
               
               
                   
                 555 
                 R 1 X 
                 693-67-4 
                 C 20 H 35 N 2 Br 
                 383.417 
                 46.2 
               
               
                   
                 556 
                 R 1 X 
                 74-83-9 
                 C 19 H 26 NBr 
                 348.328 
                 37.3 
               
               
                   
                   
               
               
                   
                   c MIm = 2-methylimidazole, DMIm = 1,2-dimethylimidazole, PIm = 2-phenylimidazole, MImN = 2-methylimidazoline, PImN = 2-phenylimidazoline, MBIm = 1-methylbenzimidazole, DMBIm = 1,2-Dimethylbenzimidazole, DMAP = 4-(dimethylamino)pyridine, PyP = 4-(1-pyrrolidino)pyridine, HePP = 4-(4- n heptylphenyl)pyridine, bipy = bipyridine, 
               
               
                   
                   d alkylation at pyridine nitrogen. 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE IX 
               
             
             
               
                   
               
               
                 Derivatives of Benzo-18-Crown-6•M + Cl −   
               
               
                 M +  = Na + , K + , NH 4   + , CH 3 NH 3   +   
               
               
                 A 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 B 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 HPLC Method 
               
               
                   
                   
                   
                 CAS  
                   
                   
                   
                 CAS  
                   
                 CAS  
                   
                 9a 
               
             
          
           
               
                 Nu. 
                 R 1   
                 R 2   
                 Num. 
                 Cation 
                 Comment 
                 Reactant 
                 Num. 
                 Reactant 
                 Num. 
                 Formula b   
                 Weight b   
                 Time 
               
               
                   
               
               
                 770 
                 4′-H— 
                 5′-H— 
                 14098- 
                 K +   
                 (A)Benzo 
                 Catechol 
                 120- 
                 Pentaethylene- 
                 57602- 
                 C 16 H 24 O 6   
                 312.356 
                 25.8 
               
               
                   
                   
                   
                 24-9 
                   
                   
                   
                 80-9 
                 glycol dibromide 
                 02-5 
                   
                   
                   
               
               
                 771 
                 4′-Br— 
                 5′-H— 
                 75460- 
                 K +   
                 (A) 
                 Benzo-18- 
                 14098- 
                 NBS 
                 128-08- 
                 C 16 H 23 O 6 Br 
                 391.252 
                 32.7 
               
               
                   
                   
                   
                 28-5 
                   
                   
                 Crown-6 
                 24-9 
                   
                 5 
                   
                   
                   
               
               
                 772 
                 4′Br— 
                 5′-Br— 
                 108695- 
                 K +   
                 (A) 
                 Benzo-18- 
                 14098- 
                 NBS 
                 128-08- 
                 C 16 H 22 O 6 Br 2   
                 470.148 
                 37.4 
               
               
                   
                   
                   
                 32-2 
                   
                   
                 Crown-6 
                 24-9 
                   
                 5 
                   
                   
                   
               
               
                 773 
                 R 1  + R 2  =  
                   
                 17454- 
                 K +   
                 2,3- 
                 2,3- 
                 92-44- 
                 Pentaethylene- 
                 57602- 
                 C 20 H 26 O 6   
                 362.414 
                 35.4 
               
               
                   
                 4′,5′-C 4 H 4 — 
                   
                 52-3 
                   
                 Nathpho 
                 Naphthalenediol 
                 4 
                 glycol dibromide 
                 02-5 
                   
                   
                   
               
               
                 774 
                 4′-C 6 H 5 — 
                 5′-H— 
                 New 
                 K +   
                 (A) 
                 4′-Br-Benzo-18- 
                 75460- 
                 C 6 H 5 B(OH) 2   
                 98-80-6 
                 C 22 H 28 O 6   
                 388.451 
                 38.6 
               
               
                   
                   
                   
                   
                   
                   
                 C-6 
                 28-5 
                   
                   
                   
                   
                   
               
               
                 775 
                 4′-(4- 
                 5′-H— 
                 85420- 
                 K +   
                 (A) 
                 4′-Br-Benzo-18- 
                 75460- 
                 p- 
                 5720- 
                 C 23 H 30 O 6   
                 402.477 
                 41.7 
               
               
                   
                 CH 3 C 6 H 4 )— 
                   
                 09-5 
                   
                   
                 C-6 
                 28-5 
                 MeC 6 H 4 B(OH) 2   
                 05-8 
                   
                   
                   
               
               
                 776 
                 4′-(4- 
                 5′-H— 
                 New 
                 — 
                 (B) 
                 4′-Me-3,4- 
                 New 
                 2 x 
                 54149- 
                 C 23 H 32 O 6   
                 404.493 
                 40.5 
               
               
                   
                 CH 3 C 6 H 4 )— 
                   
                   
                   
                   
                 (OH) 2 -biphenyl 
                   
                 MeOC 2 H 4 O— 
                 17-6 
                   
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 C 2 H 4 Br 
                   
                   
                   
                   
               
               
                 777 
                 4′-(4- 
                 5′-H— 
                 New 
                 K +   
                 (A) 
                 4′-Br-Benzo-18- 
                 75460- 
                 p-EtC 6 H 4 B(OH) 2   
                 63139- 
                 C 24 H 32 O 6   
                 416.504 
                 44.8 
               
               
                   
                 C 2 H 5 C 6 H 4 )— 
                   
                   
                   
                   
                 C-6 
                 28-5 
                   
                 21-9 
                   
                   
                   
               
               
                 778 
                 4′-(4- 
                 5′-H— 
                 New 
                 K +   
                 (A) 
                 4′-Br-Benzo-18- 
                 75460- 
                 p- 
                 134150- 
                 C 25 H 34 O 6   
                 430.530 
                 47.9 
               
               
                   
                   n C 3 H 7 C 6 H 4 )— 
                   
                   
                   
                   
                 C-6 
                 28-5 
                   n PrC 6 H 4 B(OH) 2   
                 01-9 
                   
                   
                   
               
               
                 779 
                 4′-(4- 
                 5′-H— 
                 New 
                 K +   
                 (A) 
                 4′-Br-Benzo-18- 
                 75460- 
                 p- 
                 145240- 
                 C 26 H 36 O 6   
                 444.557 
                 51.0 
               
               
                   
                   n C 4 H 9 C 6 H 4 )— 
                   
                   
                   
                   
                 C-6 
                 28-5 
                   n BuC 6 H 4 B(OH) 2   
                 28-4 
                   
                   
                   
               
               
                 780 
                 4′-(4- 
                 5′-H— 
                 New 
                 K +   
                 (A) 
                 4′-Br-Benzo-18- 
                 75460- 
                 p- n C 5 H 11 — 
                 121219- 
                 C 27 H 38 O 6   
                 458.583 
                 54.0 
               
               
                   
                   n C 5 H 11 C 6 H 4 )— 
                   
                   
                   
                   
                 C-6 
                 28-5 
                 C 6 H 4 B(OH) 2   
                 12-3 
               
               
                   
               
               
                   b cation-free crown ether