Patent Publication Number: US-4058625-A

Title: Broad spectrum antimicrobial compositions containing tris-(hydroxymethyl)aminomethane and polyamines

Description:
DISCLOSURE OF THE INVENTION 
     This invention relates to antibacterial compositions. More particularly, this invention relates to compositions comprising an admixture of tris-(hydroxymethyl)-aminomethane and either individually or in combination a polyamine having the structural formula: ##STR1## where: Each A is alike or different and is substituted or unsubstituted [3.1.1] or [2.2.1] bicycloheptyl or bicycloheptenyl; 
     Each n is alike or different and is the integer 0 or 1; 
     Each R 1  is alike or different and is C 1  to C 4  alkylene; 
     Z is ##STR2##   where R 5  is hydrogen, aminoethyl, aminopropyl, C 1  to C 4  hydroxyalkyl, or C 2  to C 4  dihydroxyalkyl; and 
     R 6  is hydrogen, C 1  to C 4  hydroxyalkyl or C 2  to C 4  dihydroxyalkyl; 
     Y is either ##STR3##   or --R 2  -- where R 2  is 2-hydroxy-1,3-trimethylene, or R 1  as previously defined; 
     R 3  is hydrogen, C 1  to C 4  alkyl, C 2  to C 4  aminoalkyl or C 1  to C 4  hydroxyalkyl, or C 2  to C 4  dihydroxyalkyl, e.g., 2,3-dihydroxypropyl and 3,4-dihydroxybutyl; 
     R 4  is 2-hydroxy-1,3-trimethylene, or R 1  as previously defined; 
     Or when R 3  and R 6  taken together are ethylene, R 4  is also ethylene, and R 5  is aminoethyl, aminopropyl, or aminohydroxypropyl. 
     When A is [2.2.1] bicycloheptyl or bicycloheptenyl, it has the formula: ##STR4## where each R is alike or different and is C 1  to C 4  alkyl or hydrogen, R&#39; is alike or different and is hydrogen or C 1  to C 4  alkyl or R&#39; an adjacent carbon atoms can comprise an olefinic bond, and optionally their acid addition salts particularly the hydrochloride. 
     Generally, it is preferred that the sum of the number of carbon atoms in all the R and R&#39; groups is ten or less. In most preferred embodiments R&#39; and R are independently hydrogen or methyl and less than five of all of R&#39; and R are methyl. In the most highly preferred embodiments each A is either 3,3-dimethylnorborn-2-yl or norborn-2-yl and R 1  is ethylene. 
     When A is [3.1.1] bicycloheptyl or bicyclocheptenyl, it has the structural formula: ##STR5## where R is alike or different and is hydrogen or C 1  to C 4  alkyl and the dashed line indicates saturation or olefinic unsaturation either between the c- and d- or between the d- and e-positions, the bicyclo group being bonded to (R 1 ) n  through the c-, d- or e-position of the ring. Preferred [3.1.1] bicyclic groups include those where R is methyl or hydrogen and no more than four R groups are methyl, such for examples, as 2-, 3-, and 4-norpinanyl; 2-, 3-, and 4-(2-norpinenyl); 2-, 3-, and 4-(6,6-dimethylnorpinanyl); 2- and 4-(3,6,6-trimethyl-2-norpinenyl); 3-(2,4,6,6-tetramethyl-2-norpinenyl); 3- and 4-pinanyl; 3- and 4-(2-pinenyl); and 3- and 4 -(3-pinenyl). 
     The antibacterial composition comprises at least 0.5 part by weight of the tris-(hydroxymethyl)aminiomethane for each part by weight of the polyamine expressed as the base compound, and more preferably from 1 to 500 parts of the tris-(hydroxymethyl)aminomethane. Generally, the combination of trisamine and polyamine is combined in a suitable solvent or dispersant as a carrier. Such solvents or dispersants, for example, are usually polar and those such as water, lower alkylene glycol, or lower alkanols including amyl alcohol are especially suitable as well as in mixtures of such solvents. Such inclusion of the antibacterial combination in a suitable solvent is not required to produce the synergistic action, but is merely a convenience when using the combination as an antibacterial agent. In fact, an excess of tris-(hydroxymethyl)aminomethane can conveniently be employed as an admixture with salts of the polyamines in powders, suspensions, or solutions. 
     In formulations including the synergistic composition of this invention, it is suitable to include other antibacterial agents, suspending agents, wetting agents, antiscaling agents, corrosion inhibitors, and pH control agents such as the usual buffers commonly employed to achieve a desired pH. Therefore, alkali silicates, alkali phosphates, alkali gluconates, polyphosphates, and pyrophosphates, organic amines, polyamines, and polyamides; anionic, cationic and non-ionic wetting agents; alkali carbonates, bicarbonates, sulfates, sesquicarbonates; and the like can suitably be included in the final formulation. 
     In use, the antibacterial composition can be applied as a rinse, a drench, or if employed as a cleanser for skin can be used as a soap, a cream, or a foaming composition. If desired, the material can also be packaged in aerosol form and sprayed on surfaces where antibacterial control is desired. In addition, the material can be used to impregnate fabrics, woven or nonwoven to render them bacteriostatic. 
     One especially desirable application is its use in floor and wall cleaning formulations wherein the antibacterial composition, preferably including also pH control agents, wetting agents, and those other agents that are commonly found in floor cleaning formulations is further diluted with water and applied by mopping, swabbing or other conventional means. 
     Acid addition salts of one or more amino functions of the diazaalkane, triazaalkane or tetraazaalkane moiety of the polyamine can be employed. Suitable anions for the salt include anions derived from inorganic acids as well as those of organic acids such, for example, as halide, i.e., chloride, bromide or iodide or sulfate, nitrate, bisulfate, phosphate, acetate, propionate, maleate, succinate, laurate, palmitate, oleate, stearate, ascorbate, gluconate, citrate, carbonate, bicarbonate, benzoate, salicylate, pamoate, phthalate, furoate, picolinate, dodecylbenzenesulfonate, laurylethersulfate, nicotinate and the like. Generally, any anion derived from an acid is suitable and satisfactory when the polyamine salt anion, for example, the chloride is replaced with other anions, by well known anion exchange technigues. Most suitably, the chloride salt is passed through an anion exchange resin. 
     In a preferred embodiment of this invention, an antimicrobial composition of polyamine, e.g., 1-[1,5 -di-(3,3-dimethylnorborn-2-yl)-3-pentyl]-1,5,9-triazanonane trihydrochloride admixed with tris-(hydroxymethyl)aminomethane provides upon solution in aqueous media a concentration of 1-100 ppm of polyamine salt and 1000 -5000 ppm of tris-(hydroxymethyl)aminomethane. Whereas the polyamine salt by itself is capable of inhibiting gram negative and gram positive bacteria at such dilutions, various strains of Proteus and Serratia appear unaffected. In the present of the tris(hydroxymethyl)aminomethane they are controlled by the polyamine even at its lower concentration range. Moreover, only about one-half to one-tenth the inhibitory concentrations of polyamine is needed in combination to suppress Pseudomonas aeruginosa and Staphylococcus aureus as compared to the polyamine alone. 
    
    
     The following examples show methods for preparing the polyamines of this invention as typical of those that can be used in applications employing the synergistic composition of this invention. 
     The compounds of this invention are preferably prepared according to the following sequence of reactions: ##STR6## where A, Z and n have their previously defined meanings, HX is a mono or polybasic organic or inorganic acid, where sufficient HX is provided to protonate at least one amino group of polyamine. 
     The preparation of polyamine I comprises the straightforward Schiff base reaction of the appropriate ketone IV and the appropriate amine V followed by hydrogenation of the Schiff base VI to form polyamine I. 
     If amine V has more than one primary amino group, it can either be symmetrical or unsymmetrical. An amine V, which is a symmetrical amine, e.g, where R 2  and R 4  are alike when R 5  and R 6  are hydrogen; or where R 2  and R 4  are ethylene, R 5  is aminoethyl, and R 6  is hydrogen; or where R 2  is trimethylene when R 5  is 3-aminopropyl and R 6  is hydrogen; forms a single Schiff base VI. This is because regardless of which terminal primary amino group of amine V reacts with ketone IV, the same product results. However, where amine V is unsymmetrical two products can result. One is Schiff base VI. The other products have, for example, the formula VI(a) when R 5  and R 6  are hydrogen; ##STR7## or, for example, the formula VI(b) when R 5  is aminoethyl or aminopropyl: ##STR8## where A, R 1-6  and n are as previously defined. Note that both products VI(a) and VI(b) come within the scope of the definition given for Schiff base VI. Where Schiff bases of formulas VI and VI(a) and VI(b) are produced they can be separated, if desired, by the usual and well known separation techniques, i.e., distillation and the like. 
     As an alternative to using an unsymmetrical amine V and obtaining a mixture of Schiff bases VI and VI(a) or VI(b), the reaction can be conducted stepwise. For example, 1,2-diaminoethane may be converted to a Schiff base with 1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentanone, catalytically reduced, then the remaining primary amino nitrogen selectively cyanoethylated with acrylonitrile, followed by catalytic hydrogenation to furnish 1-[1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentyl]-1,4,8-triazaoctane. 
     The availability and preparation of ketones IV are discussed in a later portion of this specification. Amines V are known and can conveniently be prepared. Some especially preferred methods of preparation include the condensation of acrylonitrile with ammonia followed by hydrogenation to obtain 3,3&#39;-iminobispropylamine. Also, an N-alkylated trimethylenediamine may be reacted with epichlorohydrin and the resultant product converted with alcoholic ammonia to an N-alkylated-N&#39;-(3-amino-2-hydroxypropyl)trimethylenediamine. 
     To prepare Schiff base VI, ketone IV and amine V are dissolved in a suitable inert solvent, for example, toluene, and heated to reflux, until reaction is substantially complete, 5 to 20 hours usually being sufficient for water removal by azeotropic distillation. The solvent is then removed under reduced pressure and the residue comprising the Schiff base VI is dissolved in an inert solvent preferably an alkanol, such as ethanol or isopropanol. 
     After dissolution, the Schiff base VI is catalytically or chemically reduced. 
     If reduction is catalytic, any unsaturated carbon to carbon bonds in A will also be reduced or hydrogenated, as well as the carbon to nitrogen bond of the Schiff base VI. In such catalytic reductions, hydrogen saturates an alkanol solution of Schiff base VI using agitation in the presence of the usual hydrogenation catalysts, such as transition metals and their reducible oxides. Especially effective catalysts are the noble metals and their oxides. A particularly preferred catalyst is platinum oxide. Generally, the hydrogenation reaction is carried out in a manner well known in the art. Small particles, e.g., 100-300 mesh of catalyst are admixed with the Schiff base and excess amine in alcohol and placed in a closed system pressurized with from 3-5 atmospheres of hydrogen gas. After reaction is complete, the pressure is released and the catalyst separated from the reaction mixture by filtration. The filtrate containing the bicycloheptyl polyamine I, is then further purified by usual techniques. Preferably, whatever solvent may be present is removed under reduced pressure, the residue then dissolved in diethylether, washed with water, followed by a further washing with a saturated aqueous sodium chloride solution. After drying over anhydrous sodium sulfate, the diethylether is removed by evaporation under reduced pressure giving the bicycloheptylpolyamine I usually as an oil. The bicycloheptylpolyamine may then be redissolved in loweralkanols, mixtures of loweralkanols and water diethylether, dioxane and then neutralized with an acid, e.g., hydrogen chloride, or neutralized directly with aqueous acids. 
     Acid addition salts are then isolated, if desired, by precipitation, evaporation or other usually employed techniques. 
     Suitable anions X for the salt I(a) include anions derived from inorganic acids as well as those or organic acids such for example as halide, e.g., chloride, bromide or iodide or sulfate, bisulfate, nitrate, phosphate, acetate, propionate, maleate, succinate, laurate, oleate, palmitate, stearate, ascorbate, gluconate, citrate, carbonate, bicarbonate, benzoate, salicylate, pamoate phthalate, furoate, picolinate, dodecylbenzenesulfonate, laurylethersulfate, nicotinate and the like. Generally, any anion derived from an acid is suitable and satisfactory when the polyamine salt anion X - , e.g., chloride is to be replaced with other anions by well known anion exchange techniques. 
     When preparing bicycloheptenylpolyamines, that is the product I where olefinic unsaturation in ring A is retained, a selective chemical rather than a catalytic reduction is employed to reduce Schiff base VI to product I. 
     In this chemically reductive procedure, the ketone IV is reacted with the appropriate amine as before, but the Schiff base VI is dissolved in an inert alkanol or ether-type solvent is reacted with a chemical reductant such as sodium borohydride or lithium aluminum hydride, respectively. Although as little as an equivalent of the chemical reductant can be used successfully, more satisfactory results are obtained if at least two molar excess of and preferably at least a 2.5 molar excess of the chemical reductant is employed. After any initial reaction has subsided, the reaction mixture of Schiff base VI and reductant may be heated to reflux for an hour or two, then cooled to room temperature, and afterwards concentrated under vacuum. The residue obtained is then further purified as by treatment with mineral acid or inorganic base as was described for bicycloheptylpolyamines I and the salt may thereafter be formed as previously described. 
     The bicycloheptyl and bicycloheptenyl ketones IV are prepared by four alternative methods, which are set forth below as (A) through (D). 
     A. The Condensation of Acids -- This method involves the following reaction scheme: ##STR9## 
     Acylative decarboxylation of acids VII is employed by heating the acid at elevated temperatures either with transition metals, preferably iron, transition metal oxides, alkaline earth oxides, with polyphosphoric acid or with boron trifluoride. Most suitably, acylative reaction is achieved by passage of acid vapors over catalysts such as heated thoria aerogel. 
     Condensation-decarboxylation of an acid is the preferred method for preparing ketone IV when each A-(R 1 ) n  group is alike, a mixture of products being obtained when several different acids are combined in a reaction. The preferred reaction comprises admixing carboxylic acid VII with reduced iron powder and stirring in an inert atmosphere at 195° C. to 200° C. for 1-6 hours to form an iron salt. 
     Preferably, the carboxylic acid VII and iron are agitated under an inert atmosphere of nitrogen for at least 2 hours at 195° C. to 200° C. 
     After 2 hours, the temperature is increased suitably to 290° C. to 295° C. and agitation continued for at least another 3 hour period, 4 hours usually being sufficient. The reaction mixture is allowed to cool, and then is extracted with a suitable inert solvent such as diethylether and filtered. The solvent extracts are concentrated under reduced pressure. The residual liquid is distilled under vacuum to isolate the ketone IV. 
     The carboxylic acids VII employed above are prepared by various means as well known in the art. One particularly useful technique is the addition of [2.2.1] bicycloheptenes, such for example, either camphene, isocamphodiene, β-fenchene, norbornylene, santene and the like to an aliphatic acid anhydride. 
     In this procedure, a mixture of the bicyclicheptene and a catalytic quantity, e.g., 0.2-0.3 mole for each mole of terpene of a free radical-forming catalyst, such as di-tert-butyl peroxide, is added dropwise over 3-5 hours to a 5-15 molar excess of refluxing aliphatic acid anhydride. After complete addition, the reaction is heated at reflux for 5-10 hours, concentrated under reduced pressure and the liquid residue is mixed with aqueous sodium hydroxide and stirred with heating on a steam bath for about 2-5 hours. The cooled alkaline solution is then extracted with ether, the ether layer is discarded and the aqueous solution acidified, and then extracted well with ether. The combined ether extracts are washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residual liquid or solid is distilled under vacuum to give the corresponding carboxylic acid, VII. 
     Other carboxylic acids are readily obtained, for example, by the Diels-Alder reaction of cyclopentadiene and alkyl substituted cyclopentadiene with various unsaturated carboxylic acids, as are later referred to in greater detail. 
     Another useful general procedure for this synthesis of the bicyclo [2.2.1] heptyl substituted alkanolic acid compounds utilizes the free radical catalyzed addition of methyl or ethyl alkanoate to unsaturated bicyclo [2.2.1] heptenes. The free radical catalysis is obtained with, for exmaple, di-t-butyl peroxide which predominantly abstracts a carbonyl-adjacent hydrogen from the alkyl alkanoate [D. J. Trecker and R. S. Foote, J. Org. Chem., 33, 3527-34 (1968)]. Addition of the resultant free radical to the olefinic terpene provides the corresponding esters. Usual hydrolysis procedures, e.g., dilute aqueous sodium hydroxide result in alcohol liberation. 
     B. Condensation of a Grignard and a Nitrile 
     Disubstituted bicycloheptyl or bicycloheptenyl alkanones can also be obtained according to the following reaction scheme. ##STR10## where (R 1 ) n  of each reactant may be the same or different 
     In the preparation of di-(substituted bicycloheptyl) alkanones a general procedure utilizes the reaction of a Grignard reagent prepared from a chloro- or bromosubstituted alkylbicyclo [2.2.1] heptane with a cyanosubstituted alkyl bicyclo [2.2.1] heptane. The resultant disubstituted iminoalkane salt complex is hydrolyzed with mineral acid to the corresponding ketone. 
     the Grignard reagent is obtained by reaction of the halide with magnesium metal, usually in the form of turnings or powder and catalyzed by very small concentrations of iodine or methyl iodide. Solvents which are useful include diethyl ether, dibutyl ether, tetrahydrofuran, dioxane and benzene. Usually, gentle warming sufficies to initiate the reaction and the halide is gradually added to the metal-solvent mixture. After complete addition the disappearance of practically all magnesium metal signifies the end of the reaction. A small excess of metal is used and moisture must be excluded; a nitrogen atmosphere is beneficial. The nitrile in two to three times its volume of solvent is then added to the Grignard reagent over a period of 15 minutes to 1 hour at ambient temperature. The reaction mixture may then be heated to reflux to insure complete reaction. Generally, a small excess of Grignard reagent as compared to nitrile is employed. From 1 to 10 hours at reflux is sufficient for complete conversion. The resultant imine salt is preferably decomposed to the ketone with aqueous mineral acids such as hydrochloric, sulfuric and phosphoric. The ketones are water-insoluble and may be extracted with water-immiscible solvents. Purification is preferably accomplished by fractional distillation under reduced pressure. It is feasible to use the crude ketone reaction mixture for the alkylation of polyamines as the reaction by-products are usually alcohols or hydrocarbons and do not react with amines. The reactant halides, if present in the crude product, should be removed prior to the ketone-amine alkylation process. 
     The concentrations of Grignard reagent and nitrile may be varied over wide limits for securing good yields in the process. 
     The halide and cyano, as well as carboxylic derivatives of bicycloheptanes and bicycloheptenes, are commonly available and have been derived from such bicycloheptanes and bicycloheptenes as norcamphane, apocamphane, camphane, α-fenchane, santane, camphenilane, α-fenchene, isocamphane, β-fenchane, norbornylene, apobornylene, bornylene, δ-fenchene, camphenilene, γ-fenchene, santene, ε-fenchene, norpinane, 2-norpinane,6,6-dimethylnorpinane, 6,6-dimethyl-2-norpinane, orthodene, homopinene, pinane, α-pinene, β-pinene, and the like. 
     Where these carboxylic, cyanao, or halo derivatives are not readily available they may be synthesized by known techniques. For example, the Diels-Alder condensation as reported in U.S. P. 3,595,917 and Newer Methods of Preparative Organic Chemisty, K. Alder Interscience, New York, New York, 1948, pages 381-456, e.g. ##STR11## where D is R, --(R 1 ) n  --COOH, --(R 1 ) n  --X, or --(R 1 ) n  --CN and where R 1 , R, and X have their previous meanings. Where D is R and each R is alkyl, the resulting bicycloheptene can be reacted with an aliphatic acid anhydride as previously described. 
     C. The reaction of Acid Halides and Malonic Esters 
     The third alternative method for preparing ketones IV employs the reaction scheme: ##STR12## where A, R 1 , and n have their previous meanings and R&#39; is C 1  to C 3  alkylene. 
     The bicyclo [2.2.1] heptylsubstituted malonic esters are prepared by way of example either from cyclopendtadienes and alkenyl substituted malonic esters followed by catalytic hydrogenation of the resultant heptene derivatives to heptanes or by alkylation of malonic ester with a halogen-substituted bicyclo [2.2.1] heptane, the halogen preferably chlorine or bromine attached directly to the ring or as part of an alkyl substituent. 
     The sodio derivative IX of t-butyl malonic ester is prepared by adding a slight molar excess of sodium hydride to a solution of the malonic ester VIII in an inert solvent such as anhydrous benzene. Reaction is effected by heating suitably to 60° C. to 80° C. with agitation until hydrogen gas evolution ceases, the reaction system being protected from atmospheric moisture. A soluttion of an equimolar quantity of acid halid X using sufficient anhydrous benzene to just dissolve the acid halide is added and the reaction heated at reflux for about 5-20 minutes. The mixture is cooled and any excess sodium hydride is destroyed by the addition of anhydrous p-toluene sulfonic acid. The reaction mixture is clarified by filtration and stripped of solvent under reduced pressure. The residue is dissolved in glacial acetic acid containing 0.3%-0.5% by weight anhydrous p-toluene sulfonic acid and approximately 2% by volume of acetic anhydride. The solution is heated to reflux for about an hour then cooled to room temperature. The solution is then poured over ice, neutralized with aqueous sodium hydroxide and the crude ketone IV product extracted with diethyl ether. The ether solution is washed with water, dried over anhydrous magnesium sulfate, filtered and stripped of solvent. 
     D. Condensation of a Ketone with a Ketone or Aldehyde and Subsequent Reduction 
     A fourth method of preparing ketone IV employs the condensation of a ketone and a ketone or aldehyde according to the following reaction scheme: ##STR13## where A is alike or different and A, R 1 , R and n have their previous definitions, and R* is independently methyl, ethyl or hydrogen. 
     The reaction comprises mixing the ketone XIV with a molar equivalent or slight excess of aldehyde or ketone XV with agitation and cooling in the presence of catalytic amounts of sodium methylate. The reaction mixture now is maintained at 40° C. for about 4-10 hours and then cooled at ambient temperature. The reaction mixture is acidified and after stripping the solvent under reduced pressure, the residue is extracted with diethyl ether. The ether extracts are washed with water and dried over magnesium sulfate. The solvent is then stripped under reduced pressure. 
     The residue XVI is dissolved in thiophene-free benzene and shaken under a pressure of 3-5 atmospheres of hydrogen in the presence of a noble metal catalyst on carbon at 20° C. The catalyst is then removed by filtration and the solvent removed. The residue is IV which can be further purified by the usual techniques. 
     Once the ketone IV is obtained it can then be reacted with a suitable polyamine V. Polyamines V which are exceptionally suitable for reaction with ketone IV include diethylenetriamine, triethylenetetramine, 3,3&#39;-iminobis(propylamine), 3,3&#39;-methyliminobis-(propylamine), dipropylenetriamine, N,N,&#39;-bis-(3-aminopropyl)-1,3-trimethylenediamine, N,N,&#39;-bis-(2-aminoethyl)-1,3-trimethylenediamine, N,N,&#39;-bis(3-aminopropyl)piperazine, N-(2-aminoethyl)-1,3-trimethylenediamine, spermidine, spermine, 1,4-bis-(2-aminoethyl)piperazine, tris-(2-aminoethyl)amine, 1-(2-aminoethyl)-4-(3-aminopropyl)piperazine, 1-(3-amino-2-hydroxypropyl)-4-(2-aminoethyl)piperazine, N-(3-amino-2-hydroxypropyl)-1,3-trimethylenediamine, 1-(2,3-dihydroxypropyl)-1,5,9-triazanonane, 1-(2-hydroxyethyl)-1,4,7,10-tetraazadecane, 4-(3,4-dihydroxybutyl)-1,4,8-triazaoctane, 1-(2-hydroxypropyl-5-hydroxymethyl-1,5,9-triazanonane, and tris-(3-aminopropyl)-amine, ethylenediamine, trimethylenediamine, and 1,3-diamino-2-hydroxypropane. 
     Substituted bicycloheptanes which are obtained in the several syntheses routes described herein may be in exo and endo isomer configurations and generally are mixtures of both. Many factors enter into the actual ratio of isomers formed and these can be temperature, solvents, steric effects, equilibration conditions, nature of substituents and others. However, it appears that the utility of the products of this invention is served without the necessity for strictly controlling the isomer composition. The content of a product mixture may be determined by vapor or liquid phase chromatography, NMR spectral analysis, fractional distillation and other methods, It is also possible to isolate pure isomers by selection of these and other separation techniques well known in the art. 
     The following specific examples are further illustrative of our invention, but should not be construed as any limitation on the compound presented in formula I or the appended claims. 
     EXAMPLE A 
     Preparation of 5-Norbornen-2-Butyric Acid 
     To refluxing acetic anhydride (1050 g., 10 moles), there is added dropwise over six hours a solution of 5-vinyl-2-norbornene (120 g., 1 mole) and di-tert-butyl peroxide (0.1 mole, 14.6 g.). After complete addition, the mixture is heated at reflux for 5 hours. The cooled reaction mixture is concentrated under reduced pressure to leave a yellow-orange residual oil, 750 ml. of 2.5N NaOH is added to the residue which is then heated on the steam bath for 1 hour. The cooled solution is extracted once with ether, made acidic with concentrated HCl and extracted thoroughly with ether. The dried (Na 2  SO 4 ) either extracts are concentrated under reduced pressure and the residue distilled under vacuum to give a colorless product, 35.5 g. (20%), b.p. 120° -124° C./0.2 mm. 
     Similarly, in an analogous manner, 3-(2-norbornen-5-yl)propionic acid is prepared from 5-ethylidene-2-norbornene; 1,5,5-trimethylnorborn-3-ylacetic acid from δ-fenchene; 5,5-dimethylnorborn-2- and 3-ylacetic acid from camphenilene; 2,5,5-trimethylnorborn-3-ylacetic acid from γ-fenchene; 3-(7,7-dimethylnorborn-2-yl)propionic acid from α-fenchene; 3-(3,3-dimethylnorborn-2-yl)-propionic acid from camphene; 3-(norborn-2-yl)propionic acid from norcamphene; norborn-2-ylacetic acid from norbornylene; 7,7-dimethylnorborn-2-ylacetic acid from apobornylene; 1,7,7-trimethylnorborn-3-acetic acid from bornylene; 2,3-dimethylnorborn-2-ylacetic acid from santene; 3-(5,5-dimethylnorborn-2-en-6-yl)propionic acid from isocamphodiene; 3-(2,2-dimethylnorborn-5-yl)propionic acid from β-fenchene; 2,7,7-trimethylnorborn-3-ylacetic acid from ε-fenchene; 1,2,3-trimethylnorborn-3-ylacetic acid from ε-fenchene, and 1,2,3,4,5,5,6,6,7,7-decamethyl bicyclo-[2.2.1]heptane-3-yl-acetic acid from 1,2,3,4,5,5,6,6,7,7-decamethyl bicyclo[2.2.1]hept-2-ene obtained by the Diels-Alder condensation of 1,1,2,3,4,5-hexamethylcyclopentadiene and 1,1,2,2-tetramethylethylene. 
     EXAMPLE B 
     Bicyclo[2.2.1]heptyl Substituted Alkanoic Acids 
     A solution of an alkyl alkanoate ester (15 mole), norbornene (14.1 g., 0.14 mole) and di-t-butyl peroxide (3.3 g., 2.25 × 10 -2  mole) is placed in a stainless steel 3-liter autoclave. The autoclave is purged with nitrogen and then rocked at 140° C. for 12 hours. After cooling, the contents of the autoclave are stripped free of unreacted norbornene, ester and peroxide decomposition products. The residual liquid, which constituted the reaction product is purified by fractional distillation. 
     Ethyl acetate and norbornene give ethyl norborn-2-ylacetate, b.p. 62° C./8.5 mm. in 64% yield and methyl isobutyrate and norbornene give methyl 2-methyl-2-(norborn-2-yl)propionate, b.p. 84° C./1.2 mm. in 55% yield. These esters are then hydrolyzed in aqueous hydrochloric acid giving (norborn-2-yl)acetic acid and 2-methyl-3-(norborn-2-yl)propionic acid. 
     EXAMPLE C 
     Preparation of 1,3-Di-(3,3-Dimethylnorborn-2-yl)-2-propanone 
     3,3-Dimethylnorborn-2-yl acetic acid (36.4 g., 0.20 mole) and iron (hydrogen reduced, 6.15 g., 0.11 mole) is heated for 1.5 hours at 195° C. under a nitrogen atmosphere. After that time, the temperature is increased to 290° C. and maintained at that temperature for 3 hours. The cooled reaction mass was extracted well with ether, filtered through Celite, and the ethereal extracts concentrated under vacuum. The residual reddish oil is distilled under vacuum to leave the product as a pale yellow liquid, 21.5 g., (71%), b.p. 156°-159° C./0.1 mm. 
     Similarly, in an analogous manner, 1,3-di-(norborn-2-yl)propanone is prepared from 2-norbornane acetic acid; 1,7-di-(5-norbornen-2-yl)-4-heptanone from 4-(5-norbornen-2-yl)butyric acid; 2,6-di(5-norbornen-2-yl)-4-heptanone from 3-(5-norborn-2-yl)butyric acid; 1,3-bis-(1,5,5-trimethylnorborn-3-yl)propanone from 1,5,5-trimethylnorborn-3-ylacetic acid; 1,3-bis-(5,5-dimethylnorborn-2- and 3-yl)propanones from 5,5-dimethylnorborn-2- and 3-ylacetic acids; 1,3-bis-(2,5,5-trimethylnorborn-3-yl)propanone from 2,5,5-trimethylnorborn-3-ylacetic acid; 1,5-bis-(7,7-dimethylnorborn-2-yl)pentan-3-one from 3-(7,7-dimethylnorborn-2-yl)propionic acid; 1,5-bis-(3,3-dimethylnorborn-2-yl)pentan-3-one from 3-(3,3-dimethylnorborn-2-yl)propionic acid; 1,5-bis-(norborn-2-yl)pentan-3-one from 3-(norborn-2-yl)propionic acid; 1,3-bis-(norborn-2-yl)-propanone from norborn-2-ylacetic acid; 1,3-bis-(7,7-dimethylnorborn-2-yl)propanone from 7,7-dimethylnorborn-2-ylacetic acid; 1,3-bis-(1,7,7-trimethylnorborn-2-yl)-propanone from 1,7,7-trimethylnorborn-2-ylacetic acid; 1,3-bis-(2,3-dimethylnorborn-2-yl)propanone from 2,3-dimethylnorborn-2-ylacetic acid; 1,5-bis-(5,5-dimethylnorborn-2-en-6-yl)pentan-3-one from 3-(5,5-dimethylnorborn-2-en-6-yl)propionic acid; 1,5-bis-(2,2-dimethylnorborn-5-yl)pentan-3-one from 3-(2,2-dimethylnorborn-5-yl)propionic acid; 1,3-bis-(2,7,7-trimethylnorborn-3-yl)propanone from 2,7,7-trimethylnorborn-3-ylacetic acid; 1,3-bis-(1,2,3-trimethylnorborn-3-yl)propanone from 1,2,3-trimethylnorborn-3-ylacetic acid; 1,3-bis-[1,2,4,5,6,7-hexamethyl-7-propyl[2.2.1]hept-5-en-3-yl]acetone from 1,2,4,5,6,7-hexamethyl-7-propyl[2.2.1]-hept-5-en- 3-ylacetic acid which is prepared by the Diels-Alder condensation of 1-methyl-1-propyl-2,3,4,5-tetramethylcyclopentadiene and 4-methylvinylacetic acid; bis-[1,2,2,3,4,5,6, 7,7-nonamethyl-bicyclo[2.2.1]hept-5-en-3-yl]acetone from 1,2,2,3,4,5,6,7,7-nonamethyl-bicyclo[2.2.1]hept-5-ene-3-ylacetic acid which is prepared by the Diels-Alder condensation of 1,1,2,3,4,5-hexamethylcyclopentadiene and 3,4,4-trimethyl vinyl acetic acid; 1,3-di-(2,4,6,6-tetramethyl-2-norpinen-3-yl)-2-propanone from 2,4,6,6-tetramethyl-2-norpinen-3-ylacetic acid; 1,3-di-(2-pinen-4-yl)-2-propanone from 2-pinen-4-ylacetic acid; 1,5-bis-(6,6-dimethylnorpinan-4-yl)pentan-3-one from 3-(6,6-dimethylnorpinan-4-yl)propionic acid and 1,5-bis-(norpinan-2-yl)pentan-3-one from 3-(norpinan-2-yl)propionic acid. 
     EXAMPLE D 
     Preparation of 2-Bicyclo[2.2.1]heptan-2-ylacetyl)bicyclo-[2.2.1]heptane 
     The sodio derivative of di-t-butyl bicyclo [2.2.1]heptan-2-ylmalonate is prepared by adding 0.36 g. of sodium hydride to a solution of the malonic ester, 3.1 g., in 75 ml. of anhydrous benzene. An Ascarite drying tube is attached to the reflux condenser. Reaction is effected by heating at 80° C. with stirring until hydrogen gas evolution ceases (approximately 2 1/2 hours). A solution of 16 gms. of bicyclo[2.2.1]heptan-2-ylcarboxylic acid chloride in 30 ml. of anhydrous benzene is then added and the reaction conducted at reflux for about 10 minutes. The mixture is cooled to room temperature and the excess sodium hydride destroyed by the addition of 0.9 g. of anhydrous p-toluene sulfonic acid. The mixture is clarified by filtration and the filtrate stripped of solvent under reduced pressure. The residue is dissolved in 75 ml. of glacial acetic acid containing 0.3 g. of anhydrous p-toluene sulfonic acid and 2% of acetic anhydride by volume. The solution is heated at reflux for  1 hour, cooled to room temperature, poured over crushed ice, neutralized by the addition of 5% sodium hydroxide solution and the product extracted with diethyl ether. The ether solution is washed with water dried over anhydrous magnesium sulfate, filtered and stripped of solvent. The residue is essentially pure 2-(bicyclo[2.2.1]heptan-2-ylacetyl)-bicyclo[2.2.1]heptane. 
     Under the same reaction conditions, the following ketones are obtained. 
     1-[3-methylbicyclo[22.2.1]hept-2-yl]-6-[3,3-dimethylbicyclo[2.2.1]hept-2-yl]hexan-3-one from 3-methylbicyclo[2.2.1]hept-2-ylmethylmalonic ester and 4-[3,3-dimethylbicyclo[2.2.1]hept-2-yl]butyric acid chloride and 1-[5,6-diethylbicyclo[2.2.1]hept-2-yl]-4-[1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]butan-2-one from 5,6-diethylbicyclo[2.2.1]hept-2-ylacetyl chloride and 1,7,7-trimethylbicyclo[2.2.1]hept-2-ylmethylmalonic ester. 
     EXAMPLE E 
     Preparation of 1-(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)-4-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)butan-2-one 
     20.6 gm. (0.1 mole) of 1-(1,3,3-trimethylbicyclo-[2.2.1]hept-2-yl)-1-buten-3-one and 18.3 gm. (0.12 mole) of camphor is dissolved in 25 ml. methyl alcohol. A solution of 3.4 gm. of potassium hydroxide in 20 ml. of methyl alcohol is then added over a period of 15 minutes using good agitation and external cooling. The reaction mixture is maintained at 40° C.-45° C. for 6 hours, cooled to 20° C., made slightly acid by the addition of dilute hydrochloric acid and the residue after solvent stripping under reduced pressure extracted with ether. The ether solution is washed two times with one-tenth its volume of cold water, dried over anhydrous magnesium sulfate and stripped of solvent under reduced pressure. The residual oil which contained 1-(1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene)-4-(1,3,3-trimethylbicyclo[2.2.1]hept-2-yl)but-3-en-2-one is dissolved in 100 ml. of thiophene-free benzene and shaken under 50 psi hydrogen pressure in the presence of 3 gm. 5% palladium on carbon at 25° C. until slightly more than theoretical hydrogen uptake is observed. The catalyst is removed by filtration and the solvent stripped. The residual oil is purified by fractional distillation under reduced pressure to provide the 1-(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)-4-(1,3,3-trimethylbicyclo[2.2.1hept-2-yl)butan-2-one. 
     In the same synthesis procedures the use of other aldehyde and ketone bicyclo[2.2.1]heptane derivatives provides a source of di-alicyclic alkanones: 
     
         ______________________________________                                    
Aldehyde or              Di-(bicycloheptyl)-                              
Ketone     Ketone        alkanone                                         
______________________________________                                    
3,3-dimethylbi-                                                           
           1-(1,3,3-trimethyl                                             
                         1-[3,3-dimethylbi-                               
cyclo[2.2.1]-                                                             
           bicyclo[2.2.1]-                                                
                         cyclo[2.2.1]hept-2-                              
hept-2-ylaldehyde                                                         
           hept-2-yl)-1-buten-                                            
                         yl]-5-(1,3,3-tri-                                
           3-one         methylbicyclo[2.2.                               
                         1]hept-2-yl)pentan-                              
                         3-one                                            
2,5-methylene-1,                                                          
           1-(1,3,3-trimethyl-                                            
                         1-[bicyclo[2.2.1]-                               
2,5,6-tetrahydro-                                                         
           bicyclo[2.2.1]-                                                
                         hept-2-yl]-5-(1,3,                               
benzaldehyde                                                              
           hept-2-yl)-1-buten-                                            
                         3-trimethylbicyclo-                              
           3-one         [2.2.1]hept-2-yl-                                
                         pentan-3-one                                     
3-methyl-2-nor-                                                           
           1-(1,3,3-trimethyl-                                            
                         1-[3-methylbicyclo-                              
bornanone  bicyclo[2.2.1]-                                                
                         [2.2.1]hept-2-yl]-                               
           hept-2-yl)-1-buten-                                            
                         4-(1,3,3-trimethyl-                              
           3-one         bicyclo[2.2.1]hept-                              
                         2-yl)butan-2-one                                 
2-bornyl n-                                                               
           2-bornyl n-propyl                                              
                         2-[2-ethyl-3-[1,7,                               
propyl ketone                                                             
           ketone        7-trimethylbicyclo-                              
                         [2.2.1]hept-2-yl]-                               
                         hexanoyl]-1,7,7-                                 
                         trimethylbicyclo-                                
                         [2.2.1]heptane                                   
3-[1,3,3-tri-                                                             
           1-(1,3,3-trimethyl-                                            
                         1,7-di-[1,3,3-tri-                               
methylbicyclo-                                                            
           bicyclo[2.2.1]hept-                                            
                         methylbicyclo[2.2.1]                             
[2.2.1]hept-2-                                                            
           2-yl)-1-butene-3-                                              
                         hept-2-yl]heptan-3-                              
yl]acrolein                                                               
           one           one                                              
______________________________________                                    
 
    
     EXAMPLE F 
     Preparation of 2-[1,7,7-trimethylbicyclo[2.2.1]hept-2-ylacetyl]bicyclo[2.2.1]heptane 
     a. Preparation of the Grignard Reagent of (Bicyclo[2.2.1]hept-2-yl Bromide) 
     The reagent is prepared in dried apparatus under nitrogen by addition of 5.0 gm. (0.029 mole) of the bromide in 20 ml. of dry ether to 1.0 gm. (0.041 gm.-atom) of magnesium under 15 ml. of ether containing a crystal of iodine. The mixture is refluxed for 1 hour. This Grignard reagent can also be prepared according to the method of H. Kwart and L. Kaplan, J. Am. Chem. Soc., 76, 1072 (1954). 
     b. Reaction of Grignard Reagent with 1,7,7-Trimethylbicyclo[2.2.1]hept-2-yl-acetonitrile 
     A solution of 3.5 gm. (0.02 mole) of 2-bornaneacetonitrile in 15 ml. of anhydrous ether is added over a 15 minute period to the well-stirred Grignard reagent from (a) above. After complete addition the reaction mixture is agitated for a total of 12 hours. It is then poured onto a mixture of 50 gm. ice and 20 ml. of concentrated hydrochloric acid. The ether is removed under reduced pressure and the residual mixture heated at reflux for 1 hour. The cooled mixture is extracted with 2-50 ml. portions of ether, the organic layer separated, washed with cold water, dried over anhydrous magnesium sulfate, filtered and the solvent removed by distillate. The residue is subjected to vacuum fractional distillation to obtain the 2-[1,7,7-trimethylbicyclo[ 2.2.1]hept-2-ylacetyl]bicyclo[2.2.1]heptane in pure state; typical IR carbonyl absorption at 5.8 microns is used to characterize the product. 
     Under the same conditions but substituting the following halides for norbornyl bromide and reaction of the corresponding Grignard reagent with 1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylacetonitrile these intermediate ketones are obtained: 
     
         ______________________________________                                    
Halide            Ketone                                                  
______________________________________                                    
2-[(2-bromoethyl)bicyclo-                                                 
                  1-[1,7,7-trimethylbicyclo-                              
[2.2.1]heptane    [2.2.1]hept-2-yl]-4-                                    
                  [bicyclo[2.2.1]heptan-2-                                
                  yl]butan-2-one                                          
2-(3-bromopropyl)bicyclo                                                  
                  1-[1,7,7-trimethylbicyclo-                              
[2.2.1]heptane    [2.2.1]hept-2-yl]-5-                                    
                  [bicyclo[2.2.1]hept-2-yl]-                              
                  pentan-2-one                                            
2-(3-bromopropyl)-5,6-di-                                                 
                  1-[1,7,7-trimethylbicyclo-                              
ethyl)bicyclo[2.2.1]heptane                                               
                  [2.2.1]hept-2-yl]-5-                                    
                  [(5,6-diethyl)bicyclo-                                  
                  [2.2.1]hept-2-yl]pentan-                                
                  2-one                                                   
2-chloromethyl-1,7,7-tri-                                                 
                  1,3-bis[1,7,7-trimethylbi-                              
methylbicyclo[2.2.1]heptane                                               
                  cyclo[2.2.1]hept-2-yl]-                                 
                  acetone                                                 
7-bromobicyclo[2.2.1]heptane                                              
                  7-[1,7,7-trimethylbicyclo-                              
                  [2.2.1]hept-2-ylacetyl]-                                
                  bicyclo[2.2.1]heptane                                   
______________________________________                                    
 
    
     Additional examples which are prepared according to this procedure include: 
     
         ______________________________________                                    
Halide       Nitrile       Ketone                                         
______________________________________                                    
2-(2-bromoethyl)-                                                         
             1,7,7-trimethylbi-                                           
                           1-[1,7,7-tri-                                  
bicyclo[2.2.1]-                                                           
             cyclo[2.2.1]hept-                                            
                           methylbicyclo-                                 
heptane      3-ylacetonitrile                                             
                           [2.2.1]hept-3-                                 
                           yl]-4-[bicyclo-                                
                           [2.2.1]hept-2-                                 
                           yl]butan-2-one                                 
2-(4-bromobutyl)bi-                                                       
             1-methylbicyclo-                                             
                           1-(1-methylbi-                                 
cyclo[2.2.1]heptane                                                       
             [2.2.1]hept-3-                                               
                           cyclo[2.2.1]-                                  
             ylacetonitrile                                               
                           hept-3-yl)-6-                                  
                           (bicyclo[2.2.1]-                               
                           hept-2-yl)hexan-                               
                           2-one                                          
2-(2-bromopropyl)bi-                                                      
             1,7,7-trimethylbi-                                           
                           1-(1,7,7-tri-                                  
cyclo[2.2.1]heptane                                                       
             cyclo[2.2.1]hept-                                            
                           methylbicyclo-                                 
             3-ylacetonitrile                                             
                           [2.2.1]hept-3-                                 
                           yl]-3-methyl-4-                                
                           (bicyclo[2.2.1]                                
                           hept-2-yl)butan-                               
                           2-one                                          
2-(4-bromobutyl)-5-                                                       
             3-(3-cyanopropyl)-                                           
                           1-(1-methylbi-                                 
methylbicyclo[2.2.1]                                                      
             1-methylbicyclo                                              
                           cyclo[2.2.1]-                                  
heptane      [2.2.1]heptane                                               
                           hept-3-yl)-8-                                  
                           (5-methylbicyclo-                              
                           [2.2.1]hept-2-                                 
                           yl)octan-4-one                                 
______________________________________                                    
 
    
     EXAMPLE G 
     N,N-Di-(2,3-dihydroxypropyl)trimethylenediamine 
     Bis-(2,3-dihydroxypropyl)amine (16.5 g., 0.1 mole) and acrylonitrile (6.4 g., 0.12 mole) was mixed in an ice bath and then warmed to room temperature. After standing for 2 hours, the mixture was then heated at 45° C.-55° C. for 3 hours. The excess acrylonitrile was removed by gentle warming under reduced pressure. The residue was taken up in ethyl alcohol, mixed with sponge nickel catalyst and hydrogenated under 200 psi hydrogen using good agitation. After filtration of catalyst the solvent and excess acrylonitrile was removed by stripping under reduced pressure to leave the product as an oil. 
     EXAMPLE H 
     N,N,N&#39;-Tri-(2,3-dihydroxypropyl)trimethylenediamine 
     N,N-di-(2,3-dihydroxypropyl)trimethylenediamine (11.1 g., 0.05 mole) was dissolved in 125 ml. of methanol and heated under reflux with agitation. Glycidol (3.7 g., 0.05 mole) was added dropwise over a period of 1.5 hour and the solution mixed an additional hour at 60° C.-80° C. The methyl alcohol and other volatiles were removed by stripping under reduced pressure to leave the product suitable for use in the next steps. 
     EXAMPLE I 
     1,1,5-Tri-(2,3-dihydroxypropyl)-1,5,9-triazanonane 
     An aliquot of the residual oil from Preparation H (5.9 g., 0.02 mole) was mixed with acrylonitrile (2.75 g., 0.05 mole) at room temperature and then warmed at 50° C.-60° C. for 10-15 hours. The excess acrylonitrile was removed by stripping under reduced pressure and the residual oil taken up in 50 ml. of ethanol, mixed with 2 g. of sponge nickel catalyst and shaken under a hydrogen atmosphere of 200 psi for 6 hours. The mixture was filtered free of catalyst and the solvent removed by distillation. The product could be brought to analytical purity by chromatography on a silica gel column and is an oil. 
     EXAMPLE 1 
     Preparation of 1-[1,5-Di-(3,3-dimethylnorborn-2-yl)-3-pentyl]-1,5,9-triazanonane Trihydrochloride 
     1,5-Di-(3,3-dimethylnorborn-2-yl)-3-pentanone (6.04 g., 0.02 mole) and 3,3&#39;-iminobispropylamine (13.1 g., 0.10 mole) in 150 ml. toluene is heated at reflux overnight with a Dean-Stark water separator. The cooled solution is concentrated under reduced pressure. The residue is dissolved in ethanol and hydrogenated with PtO 2  at room temperature and 40 psi hydrogen pressure. The platinum catalyst is filtered off and the ethanol removed under vacuum. The residual oil is dissolved in ether and the ether solution washed several times with water to remove the excess 3,3&#39;-iminobispropylamine. The ether extracts are dried over anhydrous sodium sulfate and concentrated under vacuum to leave the polyamine as a colorless oil (8.3 g., 100% yield). 
     The oil is dissolved in ether and hydrogen chloride gas is bubbled into the solution until no further precipitation occurs. The ether is evaporated under reduced pressure to leave the product as a solid which is digested with hot isopropyl alcohol. The solids are collected by filtration and dried under vacuum at 70° C. to give a colorless product 10.8 g., (97%), m.p. 260° C.-262° C. 
     To a stirred solution of the amine (0.0065 mole) in anhydrous ether (100 cc. total volume) is added dropwise a solution of propionic acid (1.5 cc., 0.02 mole) in ether (10 cc.) over about 10 minutes. The resultant precipitate is aged, filtered, washed well with ether and dried to give 1-[1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentyl]-1,5,9-triazanonane tripropionate, a white solid, m.p. 107.5° C.-109° C. 
     In an analogous manner regarding quantities and reaction conditions and using 1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentanone and the amines set forth below, there are prepared the following compounds of this invention: 
     
         ______________________________________                                    
Amine        Polyamine         M.P. ° C.                           
______________________________________                                    
Triethylenetetramine                                                      
             1-[1,5-Di-(3,3-dimethyl-                                     
                               266-267                                    
             norborn-2-yl)-3-pentyl)-                                     
             1,4,7,10-tetraazadecane                                      
             tetrahydrochloride                                           
N,N&#39;-Bis-(3-amino-                                                        
             1-[1,5-Di-(3,3-dimethyl-                                     
                                 262-263.5                                
propyl)-1,3-propane-                                                      
             norborn-2-yl)-3-pentyl]-                                     
diamine      1,5,9,13-tetraazatri-                                        
             decane tetrahydrochloride                                    
N,N&#39;-Bis-(2-amino-                                                        
             1-[1,5-Di-(3,3-dimethyl-                                     
                               261-262                                    
ethyl)-1,3-propane-                                                       
             norborn-2-yl)-3-pentyl]-                                     
diamine      1,4,8,11-tetraazaundecane                                    
             tetrahydrochloride                                           
N,N&#39;-Bis-(3-amino-                                                        
             1-[1,5-Di-(3,3-dimethyl-                                     
                               263-265                                    
propyl)-1,2-ethane-                                                       
             norborn-2-yl)-3-pentyl]-                                     
diamine      1,5,8,12-tetraazadodecane                                    
             tetrahydrochloride                                           
N,N&#39;-Bis-(3-amino-                                                        
             1-(3-Aminopropyl)-4-[3-[1,                                   
                               257-259                                    
propyl)piperazine                                                         
             5-di-(3,3-dimethylnorborn-                                   
             2-yl)-3-pentylamino]propyl]                                  
             piperazine tetrahydro-                                       
             chloride                                                     
N,N&#39;-Bis-(3-amino-                                                        
             1-[1,5-Di-(3,3-dimethyl                                      
                               237-238                                    
propyl)-N-methyl                                                          
             norborn-2-yl)-3-pentyl]-                                     
amine        5-methyl-1,5,9-tri-                                          
             azanonane trihydrochloride                                   
Tris-(3-aminopropyl)-                                                     
             1-[1,5-Di-(3,3-dimethyl-                                     
                               255-256                                    
amine        norborn-2-yl)-3-pentyl]-                                     
             5-(3-aminopropyl)-1,5,9-                                     
             triaazanonane tetrahydro-                                    
             chloride                                                     
______________________________________                                    
 
    
     Further is an analogous manner regarding quantities and reaction conditions but employing 1,3-di-(3,3-dimethylnorborn-2-yl)-2-propanone and respectively 3,3&#39;-iminobispropyl amine and triethylenetetramine there are prepared the hydrochlorides of 1-[1,3-di-(3,3-dimethylnorborn-2-yl)-2-propyl]-1,5,9-triazanonane and 1-[1,3-di-(3,3-dimethylnorborn-2-yl)-2-propyl]-1,4,7,10-tetraazadecane. 
     EXAMPLE 2 
     Preparation of 1-[1,5-Di-(2-norbornyl)- 3-pentyl]-1,5,9- Triazanonane Trihydrochloride 
     1,5-Di-(2-norbornyl)-3-pentanone (4.15 g., 0.015 mole) and 3,3&#39; iminobispropylamine (9.8 g., 0.075 mole) in 150 ml. ethanol is heated at reflux for 3 hours. The cooled solution is hydrogenated with PtO 2  at room temperature and 40 psi hydrogen pressure. The platinum catalyst is filtered off and the ethanol removed under vacuum. The residual oil is dissolved in ether and the ether solution is washed several times with water. The dried (anhydrous sodium sulfate) ether extracts are concentrated under vacuum to leave the polyamine as an oil 5.8 g (99%). 
     The oil is dissolved in aboslute methanol and cooled in an ice-water bath. Hydrogen chloride gas is bubbled into the solution. The methanol is evaporated under reduced pressure to leave a gummy solid which is recrystallized from isopropyl alcohol to leave the product as colorless crystals 6.0 g. (80%) m.p. 257° C.-258° C. 
     Also prepared by this method in an analogous manner regarding molar quantities and reaction conditions are 1[1,3-(2-norbornyl)-2-propyl] -1,5,9-triazanonane trihydrochloride from 1,3-di-(2-norbornyl)-2-propanone and 3,3&#39;-iminobispropylamine; 1-[1,3-di-2-norbornyl-2-propyl] -1,4,7,10-tetraazadecane tetrahydrochloride from 1,3-di-(2-norbornyl)-2-propanone and triethylenetetramine; 1-[1,7-di-(2-norbornyl)-4-heptyl]-1,5,9-triazanonane trihydrochloride from 1,7-di-2-norbornyl)-4-heptanone and 3,3&#39;-iminobispropylamine and 1-[2,6-di-(2-norbornyl)-4-heptyl] -1,5,9-triazanonane trihydrochloride from 2,6-di-(2-norbornyl)-4-heptanone and 3,3&#39;-iminobispropylamine. 
     EXAMPLE 3 
     Preparation of 1-[1,7-Di-(5-norbornen-2-yl)- 4-heptyl]-1,5,9-Triazanonane Trihydrochloride 
     1,7-Di-(5-norbornen-2-yl)- 4-heptanone (5.96 g., 0.02 mole) and 3,3&#39;-iminobispropylamine (13.1 g., 0.10 mole) in 150 ml. of toluene is heated at reflux overnight with a Dean-Stark water separator. The toluene is then removed under vacuum. The residual oil dissolved in 25 ml. isopropanol is added dropwise to sodium borohydride (1.90 g., 0.05 mole, excess) suspended in 50 ml. isopropanol. After complete addition, the reaction mixture is heated at reflux for one hour. The isopropanol is evaporated under reduced pressure, the residue treated with water and the aqueous mixture extracted well with ether. The combined ether extracts are back-washed with water, a saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated under vacuum to have the amine product as a clear oil 7.4 g. (90%). 
     The oil is dissolved in ether and the solution cooled in an ice-water bath. Hydrogen chloride gas is bubbled into the solution until no further precipitate is formed. The solid is collected by filtration, washed with a small amount of ether, and dried under vacuum to leave the amine trihydrochloride as a colorless product (96%). 
     EXAMPLE 4 
     Preparation of 1-[1,5-Di-(3,3-dimethylnorborn-2-yl)- 3-pentyl]-1,48-Triazaoctane 
     A mixture of 1,5-di-(3,3-dimethylnorborn-2-yl)-3 -pentanone (9.9 g., 0.03 mole) and 1,2-diaminoethane (12.0 g., 0.20 mole) in 250 ml. ethanol is heated at reflux overnight. The cooled reaction mixture is hydrogenated with PtO 2  at room temperature and 40 psi hydrogen pressure. The platinum catalyst is filtered off and the ethanol removed under reduced pressure. The residual oil is dissolved in ether and the ether solution washed several times with water to remove the excess diaminoethane. The ether extracts are dried over anhydrous sodium sulfate and concentrated under vacuum to leave a colorless oil, 11.2 g. (100%). 
     The oil is dissolved in 20 ml. tert-butanol and chilled to 0° C.-5° C. in an ice-water bath. Acrylonitrile (1.75 g., 2.2 ml., 0.033 mole) is added dropwise over a 5-minute period. The reaction mixture is allowed to warm up to room temperature and is then heated at 60° C. overnight. The t-butanol was removed under reduced pressure. The residual oil was dissolved in 150 ml. glacial acetic accid and hydrogenated with PtO 2  at room temperature and 40 psi hydrogen pressure. The platinum catalyst is filtered off and the acetic acid removed under vacuum. The residue is dissolved in ether and made basic with 10% sodium hydroxide. The ether solution is washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to leave a pale yellow oil (12.5 g.). The oil was chromatographed on activity III Woelm alumina. Elution with 20% methanol/chloroform gave an analytically pure product (4.35 g., 33%). 
     Thin layer chromatography on silica gel G and developing with ethanol/ammonium hydroxide (4:1) shows one spot R f  0.45. 
     In addition, the compounds of this invention set forth in the table below are prepared by the reactions set forth in the previous examples. It should be noted, however, that [3.1.1]bicycloheptenes tend to undergo rearrangement when attempts are undertaken to introduce substituents by free radical mechanisms as in Example A. Therefore, it is preferred that [3.1.1]bicyclic heptyl carboxylic acids be obtained by other means well known in the art. 
     
                                           TABLE I                                 
__________________________________________________________________________
                                     Schiff                               
Ketone                               Base Red.                            
A.sub.1      R.sub.1, R.sub.2                                             
                    n Amine          Via   Product                        
__________________________________________________________________________
2,4,6,6-tetramethyl-2-                                                    
             Ethylene                                                     
                    1 N,N&#39;-bis-(3-aminopropyl)-                           
                                     PtO.sub.2                            
                                           1-[1,5-di-(2,4,6,6-tetramethyl-
                                           9                              
norpinen-3-yl                                                             
              &#34;       1,2-ethanediamine    norpinan-3-yl)-3-]-1,5,8,12-   
                                           tetraazadodecane               
2,4,6,6-tetramethyl-2-                                                    
             Ethylene                                                     
                    1 3,3&#39;-iminobispropylamine                            
                                     NaBH.sub.4                           
                                           1-[1,5-di-(2,4,6,6-tetramethyl-
                                           .                              
norpinen-3-yl                                                             
              &#34;                            2-norpinen-3-yl)-3-pentyl]-1,5-
                                           9-triazanonane                 
2,4,6,6-tetramethyl-2-                                                    
             Ethylene                                                     
                    1 1-(2-hydroxyethyl)-1,4,7,                           
                                     PtO.sub.2                            
                                           1-[1,5-di-(2,4,6,6-tetramethyl-
norpinen-3-yl                                                             
              &#34;       10-tetraazadecane    norpinan-3-yl)-3-pentyl]-10-(2-
                                           hydroxyethyl)-1,4,7,10-tetra-  
                                           azadecane                      
3-pinanyl    Methylene                                                    
                    1 N,N-bis-(3-aminopropyl)-                            
                                     PtO.sub.2                            
                                           1-[1,4-di-(3-pinanyl)-2-butyl]-
             Ethylene 1,3-propanediamine   5-(3-aminopropyl)-1,5,9-triaza-
                                           nonane                         
4-pinanyl    Trimethyl-                                                   
                    1 tris-(2-aminoethyl)amine                            
                                     PtO.sub.2                            
                                           1-[1,7-di-(4-pinanyl)-4-heptyl]
                                           -                              
             ene                           4-(2-aminoethyl)-1,4,7-triaza- 
              &#34;                            heptane                        
2-pinen-3-yl 2-methyl-                                                    
                    1 1-hydroxymethyl-5-(2-                               
                                     NaBH.sub.4                           
                                           1-[2,6-dimethyl-1,7-di-(2-pinen
                                           -                              
             trimethyl-                                                   
                      hydroxypropyl)-1,5,9-                               
                                           3-yl)-4-heptyl]-5-(2-hydroxy-  
             ene      triazanonane         propyl)-9-hydroxymethyl-1,5,9- 
              &#34;                            triazanonane                   
2-pinen-4-yl Methylene                                                    
                    1 3,3&#39;-iminobispropylamine                            
                                     NaBH.sub.4                           
                                           1-[4-methyl-1,5-di-(2-pinen-4- 
             2-methyl-                     yl)-2-pentyl]-1,5,9-triazanonan
                                           e                              
             trimethylene                                                 
3-pinen-3-yl Ethylene                                                     
                    1 Diethylenetriamine                                  
                                     NaBH.sub.4                           
                                           1-[1,4-di-(3-pinen-3-yl)-2-    
             Methylene                     butyl]-1,4,7-triazaheptane     
3-pinen-3-yl Methylene                                                    
                    1 N,N&#39;-bis-(2-aminoethyl)-                            
                                     NaBH.sub.4                           
                                           1-[1,3-di-(3-pinen-3-yl)-2-    
             Methylene                                                    
                      1,3-propanediamine   propyl]-1,4,8,11-tetraazaundeca
                                           ne                             
2-norpinanyl Ethylene                                                     
                    1 3,3&#39;-iminobispropylamine                            
                                     PtO.sub.2                            
                                           1-[1,5-di-(2-norpinanyl)-3-pent
                                           yl]-                           
                                           1,5,9-triazanonane             
3-norpinanyl Methylene                                                    
                    1 Triethylenetetramine                                
                                     PtO.sub.2                            
                                           1-[1,3-di-(3-norpinanyl)-2-prop
                                           yl-                            
                                           1,4,7,10-tetraazadecane        
3-norpinanyl Ethylene                                                     
                    1 1,4-bis-(3-aminopropyl)-                            
                                     PtO.sub.2                            
                                           1-(3-aminopropyl)-4-[3-[1,5-di-
                      piperazine           (3-norpinanyl)-3-pentylamino]- 
                                           propyl]piperazine              
2-norpinen-2-yl                                                           
             Methylene                                                    
                    1 Tris-(3-aminopropyl)-                               
                                     NaBH.sub.4                           
                                           1-[1,4-di-(2-norpinen-2-yl)-2- 
             Ethylene amine                butyl]-5-(3-aminopropyl)-1,5,9-
                                           triazanonane                   
3-norpinen-2-yl                                                           
             Ethylene                                                     
                    1 3,3&#39;-iminobispropylamine                            
                                     NaBH.sub.4                           
                                           1-[1,5-di-(3-norpinen-2-yl)-3- 
                                           pentyl]-1,5,9-triazanonane     
6,6-dimethylnorpinan-                                                     
             Trimethyl-                                                   
                    1 1,4-di-(3-aminopropyl)-                             
                                     PtO.sub.2                            
                                           Mixture of 1-(3-aminopropyl)-4-
2-yl         ene      piperidine           [3-[1,7-di-(6,6-dimethylnorpina
                                           n-                             
                                           2-yl)-4-heptylamino)propyl]-   
                                           piperidine and                 
                                           1-[3-[1,7-di-(6,6-             
                                           dimethylnorpinan-2-yl)-4-heptyl
                                           -                              
                                           amino]propyl]-4-(3-aminopropyl)
                                           -                              
                                           piperidine                     
6,6-dimethylnorpinan-                                                     
             Trimethyl-                                                   
                    1 5-(2,3-dihydroxypropyl)-                            
                                     PtO.sub.2                            
                                           1-[1,5-di-(6,6-dimethylnorpinan
                                           -2-                            
2-yl         ene      1,5,9-triazanonane   yl)-2-pentyl]-5-(2,3-dihydroxy-
             Methylene                     propyl)-1,5,9-triazanonane     
3,6,6-trimethyl-2-                                                        
             Ethylene                                                     
                    1 N,N&#39;-bis-(2-aminoethyl)-                            
                                     NaBH.sub.4                           
                                           1-[1,5-di-(3,6,6-trimethyl-2-no
                                           r-                             
norpinen-4-yl         1,3-propanediamine   pinen-4-yl)-3-pentyl]-1,4,8,11-
                                           tetraazaundecane               
__________________________________________________________________________
 
    
     EXAMPLE 5 
     Preparation of 1-[1,5-Di-(2-norbornyl)-3-pentyl]-5-(2,3-dihydroxypropyl)- 1,5,9-triazanonane 
     1,5-Di-(2-norbornyl)-3-pentanone (6.7 g., 0.02 mole) and 3,3&#39;-(2,3-dihydroxypropylimino)bispropylamine (20.5 g., 0.10 mole), (obtained by the catalytic hydrogenation of dicyanoethylated glycerylamine), in 150 ml. of toluene is heated at reflux overnight with a Dean-Stark water separator. The cooled solution is concentrated under reduced pressure. The residue is dissolved in ethanol and hydrogenated with PtO 2  at room temperature and 40 psi hydrogen pressure. The platinum catalyst is filtered off and the ethanol removed under vacuum. The residual oil is dissolved in ether and the ether solution washed several times with water to remove the excess 3,3&#39;-(2,3-dihydroxypropylimino) bispropylamine. The ether extracts are dried over anhydrous sodium sulfate and concentrated to leave the polyamine product as an oil. 
     In a like manner and using analogous quantities, but employing N,N-di-(2,3-dihydroxypropyl)trimethylenediamine and 1,1,5-tri-(2,3-dihydroxypropyl)-1,5,9 -triazanonane instead of 3,3&#39;-(2,3-dihydroxypropylimino)bispropylamine there are prepared respectively N-[1,5-di-2-norbornyl)-3 -pentyl]-N&#39;-di-(2,3-dihydroxypropyl)trimethylenediamine, and 1-[1,5-di-(2-norbornyl)-3-pentyl]5-(2,3-dihydroxypropyl)-9,9-di-(2,3-dihydroxypropyl)-1,5,9-triazanonane. 
     EXAMPLE 6 
     Preparation of 1-[1,5-Di-(2-norbornyl)-3-pentyl]-5-(2,3-dihydroxypropyl)-9-(1,3-dihydroxyl-2-propyl)-1,5,9-triazanonane 
     1-[1,5-Di-(2-norbornyl)-3-pentyl]-5-(2,3-dihydroxypropyl)-1,5,9-triazanonane (5.2 g., 0.001 mole) and 1,3-dihydroxyacetone (9 g., 0.1 mole) in 100 ml. of chloroform was heated at reflux with a water separator connected until 1.8 ml. of water was collected (8-12 hours). The chloroform and excess 1,3-dihydroxyacetone were removed by distillation under reduced pressure. The residual oil was taken up in 75 ml. of ethanol, mixed with 1 gm. of platinum oxide and hydrogenated at 40 psi hydrogen pressure with shaking at room temperature. The catalyst was removed by filtration and ethyl alcohol by distillation to leave an oil. The product could be purified by column chromatography using silica gel and development with methyl alcohol containing ammonium hydroxide. 
     In an analogous manner but starting with N-[1,7-di-(3,3-dimethylnorborn-2-yl)-4-heptyl]ethylenediamine, instead of 1-[1,5-di-(2-norbornyl)-3-pentyl]-1,5,9-triazanonane there is obtained N-[1,7-di-(3,3-dimethylnorborn-2-yl)-4-heptyl]-N&#39;-(1,3-dihydroxy-2-propyl)ethylenediamine. 
     EXAMPLE 7 
     1-[1,7-Di-(2-norbornyl)-4-heptyl]-4,8,8-tri-(2,3-dihydroxypropyl)-1,4,8-triazaoctane 
     1-[1,7-Di-(2-norbornyl)-4-heptyl]-1,4,8-triazaoctane (4.1 g., 0.01 mole) was dissolved in 50 ml. of methanol and heated under reflux with agitation. Glycidol (15 g., 0.2 mole) was added dropwise over a period of 1.5 to 2 hours. After complete addition, the reaction mixture was stirred an additional 2 hours at 90° C.-100° C. The methyl alcohol was removed by stripping under reduced pressure and excess glycidol by distillation at 1 mm pressure. The residue could be further purified by conversion to the trihydrochloride salt in ethyl alcohol with dry hydrogen chloride and fractional crystallization. The free base may then be liberated from its salt by resin ion exchange or neutralization with aqueous sodium hydroxide. 
     In an analogous manner using the following dibicyclo[2.2.1]heptyl polyamines, there are obtained the following products. 
     
         ______________________________________                                    
Polyamine        Product                                                  
______________________________________                                    
1-[1,5-Di-(2-norbornyl)-3-                                                
                 1-[1,5-Di-(2-norbornyl)-3-                               
pentyl]-3,7-dihydroxy-1,5,9-                                              
                 pentyl]-3,7-dihydroxy-5-                                 
triazanonane     (2,3-dihydroxypropyl)-9,9-                               
                 di-(2,3-dihydroxypropyl)-                                
                 1,5,9-triazanonane                                       
1-[1,5-Di-(2-norbornyl)-3-                                                
                 1-[1,5-Di-(2-norbornyl)-3-                               
pentyl]-1,4,7-triazaheptane                                               
                 pentyl]-4-(2,3-dihydroxy-                                
                 propyl)-7,7-di-(2,3-dihydroxy-                           
                 propyl)-1,4,7-triazaheptane                              
1-[1,5-Di-(2-norbornyl)-3-                                                
                 N-[1,5-Di-(2-norbornyl)-3-                               
pentyl]ethylenediamine                                                    
                 pentyl]-N&#39;,N&#39;-di-(2,3-di-                                
                 hydroxypropyl)ethylenediamine                            
______________________________________                                    
 
    
     EXAMPLE 8 
     1-Amino-3-[1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentylamino]-2-propanol 
     A solution of 1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentanone (13.2 g., 0.04 mole) in 50 cc of anhydrous ethanol is added dropwise over about 20 minutes to a stirred solution of 1,3-diamino-2-hydroxypropane (25 g., 0.27 mole) in 200 cc of ethanol. The resulting mixture is then heated at reflux for about 2 hours, allowed to cool, 1.0 g. platinum oxide added, and the mixture reduced under a 40 psi hydrogen atmosphere until hydrogen uptake ceases. The mixture is then filtered from the catalyst, concentrated in vacuo to remove the ethanol, the oily residue taken up in ether (250 cc.), washed with water, dried over sodium sulfate, filtered and concentrated in vacuo to yield the product 1-amino-3-[1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentylamino]-2-propanol as a pale yellow oil. 
     Preparation of the dipropionate is carried out as for the tripropionate in Example 1 using 2 moles of propionic acid per mole of free diamine. Concentration of the ether solution yields the dipropionate as a very viscous oil. 
     Preparation of the dihydrochloride is achieved by adding to an ether solution of the free amine an excess of isopropanol saturated with anhydrous hydrogen chloride, or by bubbling into an ether-isopropanol solution of the amine dry hydrogen chloride until the solution is saturated. Excess ether is boiled away, fresh iospropanol added, boiled away to a small volume whereby an oil separates. The solvent is decanted from the oil, the oil admixed with a small amount of fresh ether, diluted with isopropanol, the volatiles boiled away until the cleaner oil separates again, and the process repeated. The oil is then rinsed with isopropanol, dissolved in ether, filtered and concentrated to an oil and allowed to solidify, m.p. 236° C.-237° C. 
     Also each of the respective ketones IV set forth in Examples C, D, E and F when reacted with each of the individual amines set forth in this specification, firstly, according to the method set forth in Example 1, and then secondly according to Example 3 produces the entire range of compounds described according to this invention as embodied in Formula I.