Process for preparing purified alkali metal salts of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate without isolation of intermediates

This invention relates to a 5 step process for preparing a purified alkali metal salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate in one reaction vessel without isolation of intermediates. The steps are as follows: A) reacting an alkali metal salt of 4-hydroxybenzenesulfonic acid with a C.sub.2 to C.sub.4 carboxylic anhydride in a solvent to form an alkali metal salt of 4-acyloxybenzenesulfonic acid and a C.sub.2 to C.sub.4 carboxylic acid. B) adding an [(1-oxyalkanoyl)amino]alkanoic acid and a transesterification catalyst to the reaction product of step A) and heating at a temperature and pressure sufficient to maintain reflux of the solvent and to remove the C.sub.2 to C.sub.4 carboxylic acid from the reaction vessel to form a reaction mixture containing an alkali metal salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate. C) removing the solvent from the reaction mixture formed in step B). D) mixing the alkali metal salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate product of step C) with acetic acid. E) and finally separating the product from the acetic acid. The purified alkali metal salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate product is useful as a bleach activator in detergents.

FIELD OF THE INVENTION 
This invention relates to a five step process for preparing a purified 
alkali metal salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate. 
BACKGROUND OF THE INVENTION 
Acyloxybenzenesulfonic acid salts are used as bleach activators in 
detergents. European Patent Application No. 0 355 384 A1 discloses a 
procedure for preparing 4-acyloxybenzenesulfonic acid salts by reacting 
4-hydroxybenzenesulfonic acid salts with an anhydride and a carboxylic 
acid. An acyloxybenzenesulfonic acid salt is isolated from the reaction 
mixture. After termination of the reaction, the acyloxybenzenesulfonic 
acid salt is washed with a hydrophilic solvent such as an alcohol. Such a 
procedure should not be used to prepare an alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate because the intermediate 
[(1-oxyalkanoyl)amino]alkanoic acid can cyclize to form an acyl lactam 
which is not useful as a bleach activator and must be removed from the 
product. Additional purification steps would also reduce the yield of the 
product. 
European Patent Application No. 0 105 672 A1 discloses a one-pot method of 
preparing an acyloxybenzene sulphonate salt wherein sodium 
4-hydroxybenzenesulfonate reacts simultaneously with acetic anhydride and 
a carboxylic acid. The separation and recycling of the excess carboxylic 
acid is accomplished by washing with a hydrophobic solvent such as ether 
or hexane. A disadvantage of this procedure is that the intermediate, 
sodium 4-hydroxybenzenesulfonate, is insoluble in the hydrophobic 
solvents, and therefore, remains in the product when the reaction is 
incomplete. An acyloxybenzene sulphonate salt prepared according to 
European Patent Application No. 0 105 672 A1 does not satisfy the 
requirements of high-percent-yield and high purity. A further disadvantage 
is that the sodium 4-hydroxybenzenesulfonate has to be finely ground which 
is a tedious and cost-intensive process in order to achieve a complete 
reaction to give the acyloxybenzene sulphonate salt. Otherwise, a part of 
the intermediate product, 4-hydroxybenzenesulfonate, remains in the final 
product. Moreover, hydrophobic solvents such as ether or hexane should not 
be used to purify crude preparations of an alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate because the intermediate 
[(1-oxyalkanoyl)amino]alkanoic acid is not soluble in hydrophobic 
solvents, and thus, would remain in the product. 
Accordingly what is needed is a process to prepare high yields of a 
purified alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate in one reaction vessel 
without isolation of intermediates. Moreover, the intermediate products 
such as sodium 4-acetoxybenzenesulfonate and 
[(1-oxyalkanoyl)amino]alkanoic acid should not remain in the final 
product. In addition, it would be advantageous to accomplish isolation of 
the product by direct evaporation of reaction solvent. 
SUMMARY OF THE INVENTION 
The present invention is directed to a process for preparing a purified 
alkali metal salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate in one 
vessel without isolation of intermediates comprising the steps of: 
(A) reacting an alkali metal salt of 4-hydroxybenzenesulfonic acid with a 
C.sub.2 to C.sub.4 carboxylic anhydride at a sufficient temperature and 
time in a solvent to form a alkali metal salt of 4-acyloxybenzenesulfonic 
acid and a C.sub.2 to C.sub.4 carboxylic acid, wherein the alkali metal 
salt of 4-hydroxybenzenesulfonic acid and C.sub.2 to C.sub.4 carboxylic 
anhydride are present in a mole ratio of 1:1 to 1:40, respectively, and 
the solvent is present in a weight ratio of 2:1 to 50:1 based on the 
weight of the alkali metal salt of 4-hydroxybenzenesulfonic acid; 
(B) adding an [(1-oxyalkanoyl)amino]alkanoic acid and at least one 
transesterification catalyst to the reaction product of Step (A) and 
heating at a temperature of 150.degree. C. to 250.degree. C. for 0.5 to 10 
hours and pressure sufficient to maintain reflux of the solvent and to 
remove the C.sub.2 to C.sub.4 carboxylic acid from the reaction vessel, to 
form a reaction mixture containing an alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate, wherein the moles of the 
[(1-oxyalkanoyl)amino]alkanoic acid added is 0.7 to 5 times the moles of 
the alkali metal salt of 4-hydroxybenzenesulfonic acid used in Step (A); 
(C) removing solvent from the reaction mixture containing the alkali metal 
salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate formed in Step (B); 
(D) mixing the alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate product of Step (C) with 
acetic acid; and 
(E) separating the alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate of Step (D) from the acetic 
acid to obtain a purified alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate and an acetic acid filtrate, 
said purified alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate has the general formula: 
##STR1## 
wherein R is selected from the group consisting of C.sub.5 -C.sub.21 
alkyl, C.sub.5 -C.sub.21 alkenyl, chlorinated C.sub.5 -C.sub.21 alkyl, and 
phenyl; R.sup.1 is selected from the group consisting of hydrogen and a 
C.sub.1 -C.sub.3 alkyl; M is selected from the group consisting of 
hydrogen, ammonium, and an alkali metal atom; and n is an integer from 1 
to 8.

DESCRIPTION OF THE INVENTION 
The process of the present invention for preparing purified alkali metal 
salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate involves five steps. 
In the first step, Step (A), an alkali metal salt of 
4-hydroxybenzenesulfonic acid is reacted with a C.sub.2 to C.sub.4 
carboxylic anhydride preferably at a temperature of 100.degree. C. to 
250.degree. C. for 0.5 to 5 hours in a solvent to form a alkali metal salt 
of 4-acyloxybenzenesulfonic acid and a C.sub.2 to C.sub.4 carboxylic acid. 
Preferably, the reaction is conducted at a temperature of 140.degree. C. 
to 170.degree. C. for 1 to 2 hours. Temperatures above 250.degree. C. are 
not recommended since desulfonation reactions forming a phenol ester 
instead of a sulfonate are more likely to occur. Preferably, the 
temperature is maintained below 200.degree. C. The alkali metal salt of 
the 4-hydroxybenzenesulfonic acid may be any alkali metal salt such as 
sodium, potassium, calcium, or magnesium. However, sodium is the preferred 
alkali metal salt. 
The C.sub.2 to C.sub.4 carboxylic anhydride is present in an amount of 1 to 
40 moles per mole of the alkali metal salt of 4-hydroxybenzenesulfonic 
acid, preferably 1 to 5 moles. Most preferably, the C.sub.2 to C.sub.4 
carboxylic anhydride is present in an amount of 1 to 1.5 moles per mole of 
the alkali metal salt of 4-hydroxybenzenesulfonic acid. Examples of 
suitable C.sub.2 to C.sub.4 carboxylic anhydrides are: acetic anhydride, 
propionic anhydride, butyric anhydride, and isobutyric anhydride. 
Preferably, the C.sub.2 to C.sub.4 carboxylic anhydride is acetic 
anhydride. 
Solvents for use in Step (A) include polar aprotic solvents such as 
N,N-dimethylacetamide; dialkyl sulfoxide wherein the alkyl group has one 
to six carbon atoms such as dimethyl sulfoxide; dimethyl ethers of 
diethylene glycol such as triglyme; cyclic or acyclic alkyl sulfones 
wherein the alkyl group has one to six carbon atoms such as 
tetrahydrothiophene-1,1-dioxide; and halogenated aromatic solvents such as 
dichlorobenzene and trichlorobenzene; and alkyl substituted aromatic 
solvents where the alkyl groups contain one to six carbon atoms such as 
triisopropylbenzene. Preferably, the solvent is 
tetrahydrothiophene-1,1-dioxide. 
The solvent is present in an amount of 2:1 to 50:1 weight ratio based on 
the weight of the alkali metal salt of 4-hydroxybenzenesulfonic acid, 
preferably 4:1 to 6:1 weight ratio. Insufficient solvent results in 
incomplete solubility of the starting materials which leads to an 
incomplete reaction and results in longer reaction times and thick pasty 
reaction mixtures which are difficult to process. Although there is no 
critical higher limit to the amount of solvent, the use of greater than 50 
times the weight of the alkali metal salt of 4-hydroxybenzenesulfonic acid 
renders the process unnecessarily expensive from the point of view of 
applying energy for heating and cooling during removal of excess solvent. 
Solvents not useful in the process of the present invention include protic 
solvents such as water, alcohols, and carboxylic acids containing 1 to 20 
carbon atoms such as acetic acid. Protic solvents such as alcohols react 
with the C.sub.2 to C.sub.4 carboxylic anhydride used in Step (A) and 
interfere with the transesterification reaction in Step (B). Carboxylic 
acids such as acetic acid may be used in Step (A), but must be removed in 
Step (B) to allow the reaction to proceed to completion. 
The second step, Step (B), is a transesterification step and involves 
adding an [(1-oxyalkanoyl)amino]alkanoic acid and a transesterification 
catalyst to the reaction product of Step (A) and heating at a temperature 
of 150.degree. C. to 250.degree. C. for 0.5 to 10 hours and pressure 
sufficient to maintain reflux of the solvent and to remove the C.sub.2 to 
C.sub.4 carboxylic acid from the reaction vessel, to form a reaction 
mixture containing an alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate. Preferably, the 
transesterification reaction is conducted at a temperature of 160.degree. 
C. to 180.degree. C. for 2 to 6 hours. Removal of the co-product 
carboxylic acid can be achieved via distillation or by sparging with an 
inert gas such as nitrogen. Additional solvent may be added in Step (B) to 
maintain a fluid reaction mixture provided it is the same solvent as used 
in Step (A). The moles of [(1-oxyalkanoyl)amino]alkanoic acid added is 0.7 
to 5 times the moles of the alkali metal salt of 4-hydroxybenzenesulfonic 
acid used in Step (A). 
The [(1-oxyalkanoyl)amino]alkanoic acid is prepared by amidation reactions 
known in the art which involve reacting a nitrogen containing compound 
selected from a lactam and an amino acid with a carboxylic acid or ester. 
Preferably, the [(1-oxyalkanoyl)amino]alkanoic acid is 
6-[(1-oxyoctyl)amino]hexanoic acid, 6-[(1oxynonyl)amino]hexanoic acid or 
6-[(1-oxydecyl)amino]hexanoic acid. Mixtures of 
[(1-oxyalkanoyl)amino]alkanoic acids may also be used. 
Suitable lactam monomers contain at least 3 carbon atoms per molecule, 
preferably 4 to 7 carbon atoms per molecule. Suitable lactam monomers 
include butyrolactam, valerolactam, epsilon-caprolactam, 
beta-propiolactam, delta-valerolactam, and similar lactams. These lactams 
may be substituted at the nitrogen atom by hydrocarbon radicals containing 
one to three carbon atoms. For example, methylcaprolactam may be used. 
Epsilon-caprolactam and substituted derivatives thereof are the preferred 
lactam monomers. 
The amino acid has the general formula NH.sub.2 (CR'R").sub.m COOH and is 
characterized by a basic amino group (NH.sub.2) and an acidic carboxyl 
group (COOH). The letter m in the formula is 1-26, preferably 1-10. The R' 
and R" groups are independently selected from hydrogen, unsubstituted or 
substituted straight chain or branched C.sub.1 -C.sub.20 alkyl, 
unsubstituted or substituted C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 
alkenyl, C.sub.3 -C.sub.8 alkynyl, and C.sub.6 -C.sub.14 aryl. 
The unsubstituted and substituted C.sub.3 -C.sub.8 cycloalkyl groups 
mentioned above refer to cycloaliphatic hydrocarbon groups which contain 3 
to 8 carbons in the ring, preferably 5 or 6 carbons, and these cycloalkyl 
groups substituted with one or two of C.sub.1 -C.sub.4 alkyl, C.sub.1 
-C.sub.4 alkoxy, hydroxy or C.sub.1 -C.sub.4 alkanoyloxy. 
The C.sub.3 -C.sub.8 alkenyl and C.sub.3 -C.sub.8 alkynyl groups represent 
straight or branched chain hydrocarbon radicals containing 3 to 8 carbons 
in the chain and which contain a carbon-carbon double bond or a 
carbon-carbon triple bond, respectively. 
The term "aryl" is used to include carbocyclic aryl groups containing up to 
fourteen carbons, e.g., phenyl and naphthyl, and those substituted with 
one or two groups selected from C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 
alkoxy, C.sub.1 -C.sub.4 -alkoxycarbonyl, C.sub.1 -C.sub.4 -alkanoyloxy, 
C.sub.1 -C.sub.4 -alkanoylamino, halogen, cyano, C.sub.1 -C.sub.4 
-alkylsulfonyl, C.sub.1 -C.sub.4 -alkylene-(OH).sub.n, O-C.sub.1 -C.sub.4 
-alkylene-(OH).sub.n, -S-C.sub.1 -C.sub.4 -alkylene-(OH).sub.n, -SO.sub.2 
-C.sub.1 -C.sub.4 -alkylene-(OH).sub.n, -CO.sub.2 -C.sub.1 -C.sub.4 
-alkylene-(OH).sub.n, SO.sub.2 N (R.sub.17)C.sub.1 -C.sub.4 
-alkylene-(OH).sub.n, -SO.sub.2 N(C.sub.1 -C.sub.4 -alkylene-OH).sub.2, 
-CON(R.sub.17)C.sub.1 -C.sub.4 -alkylene-(OH).sub.n, -CON(C.sub.1 -C.sub.4 
-alkylene-OH).sub.2, -N(SO.sub.2 C.sub.1 -C.sub.4 
-alkyl)-alkylene-(OH).sub.n or -N(SO.sub.2 phenyl)-C.sub.1 -C.sub.4 
-alkylene-(OH).sub.n ; wherein n is one or two. 
The term "aryl" is also used to include heterocyclic aryl groups such as a 
5 or 6-membered heterocyclic aromatic ring containing one oxygen atom, 
and/or one sulfur atom, and/or up to three nitrogen atoms, said 
heterocyclic aryl ring optionally fused to one or two phenyl rings or 
another 5 or 6-membered heteroaryl ring. Examples of such ring systems 
include thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, 
isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, 
tetrazolyl, thiatriazolyl, oxatriazolyl, pyridyl, pyrimidyl, pyrazinyl, 
pyridazinyl, thiazinyl, oxazinyl, triazinyl, thiadiazinyl, oxadiazinyl, 
dithiazinyl, dioxazinyl, oxathiazinyl, tetrazinyl, thiatriazinyl, 
oxatriazinyl, dithiadiazinyl, imidazolinyl, dihydropyrimidyl, 
tetrahydropyrimidyl, tetrazolo-[1,5-b]pyridazinyl and purinyl, 
benzoxazolyl, benzothiazolyl, benzimidazolyl, indolyl, and the like and 
those rings substituted with one or more substituents listed above in the 
definition of the term "aryl". 
In addition, the term "aryl" includes arylene groups. The term "arylene" is 
used to represent a divalent carbocyclic aryl hydrocarbon moiety 
containing up to fourteen carbons, e.g., o-, m- and p-phenylene, and those 
substituted with one or two groups selected from C.sub.1 -C.sub.4 -alkyl, 
C.sub.1 -C.sub.4 -alkoxy or halogen. 
The carboxylic acid compound is a carboxylic acid or carboxylic acid ester, 
or combination thereof, which contains an aliphatic, such as a straight or 
branched chain, or aliphatic radical, cycloaliphatic or hydroaromatic 
radical. The carboxylic acid or carboxylic acid ester has 6-26 carbon 
atoms, preferably 8-20 carbon atoms, and most preferably 8-10 carbon 
atoms. These radicals may be connected to the carboxyl group through an 
aromatic radical. The carboxylic acids and carboxylic acid esters may be 
straight or branched chain fatty acids of natural or synthetic origin 
which may be of a saturated or unsaturated nature. The carboxylic acids 
and esters can contain more than one carboxylic acid or ester group. 
Esters of carboxylic acids include, but are not limited to, the methyl, 
ethyl, propyl, and butyl ester of a carboxylic acid. The carboxylic acids 
and carboxylic acid esters may be used in pure form or else in the form of 
their mixtures as commercially available. 
Examples of carboxylic acids and carboxylic acid esters are: caprylic acid, 
methyl caprylate, pelargonic acid, methyl pelargonate, capric acid, methyl 
caprate, isopropyl caprate, undecylic acid, lauric acid, palmitic acid, 
stearic acid, oleic acid, linoleic acid, behenic acid, terephthalic acid, 
dimethyl terephthalate, phthalic acid, isophthalic acid, 
naphthalene-2,6-dicarboxylic acid, cyclohexanedicarboxylic acid, 
cyclohexanediacetic acid, diphenyl-4,4'-dicarboxylic acid, succinic acid, 
glutaric acid, adipic acid, azelaic acid, sebacic acid, and the like. 
Preferred carboxylic acids are capric and caprylic. Preferred carboxylic 
acid esters are methyl caprate and methyl caprylate. 
Tranesterification catalysts for use in Step (B) are known to those skilled 
in the art. Such transesterification catalysts include: tertiary amine 
catalysts, alkali metal salts, metallic catalysts, acidic catalysts, and 
combinations thereof. Specific examples of transesterification catalysts 
for use in the process of the present invention are: dimethyl 
aminopyridine, imidazole, sodium acetate, sodium hydroxide, and titanium 
tetraisopropoxide. The transesterification catalyst(s) is added in an 
amount of 0.01 to 0.3 moles per mole of the alkali metal salt of 
4-hydroxybenzenesulfonic acid used in Step (A). More than one 
transesterification catalyst may be used in Step (B). 
A by-product of the transesterification step, Step (B), in the case where 
6-[(1-oxyoctyl)amino]hexanoic acid is used as the 
[(1-oxyalkanoyl)amino]alkanoic acid is hexanoic acid, 
6-[[1-oxo-6-[(1-oxooctyl)amino]hexyl]amino]-,4-sulfophenyl ester, mono 
sodium salt. In the case where 6-[(1-oxynonyl)amino]hexanoic acid is used, 
a by-product of the transesterification is hexanoic acid, 
6-[[1-oxo-6-[(1-oxononyl)amino]hexyl]amino]-,4-sulfophenyl ester, mono 
sodium salt. In the case where 6-[(1-oxydecyl)amino]hexanoic acid is used, 
a by-product of the transesterification is hexanoic acid, 
6-[[1-oxo-6-[(1-oxodecyl)amino]hexyl]amino]-,4-sulfophenyl ester, mono 
sodium salt. Such impurities have the general formula: 
##STR2## 
In the above formula, R is a C.sub.5 -C.sub.21 alkyl, C.sub.5 -C.sub.21 
alkenyl, chlorinated C.sub.5 -C.sub.21 alkyl, or phenyl that can be 
substituted by 1 to 3 substituents from among the groups F, Cl, SO.sub.3 
M, COOM, C.sub.1 -C.sub.21 alkyl, or C.sub.2 -C.sub.20 alkenyl; R.sup.1 
independently represents hydrogen and a C.sub.1 -C.sub.3 alkyl; M 
represents hydrogen, ammonium, or an alkali metal atom such as sodium and 
potassium; and n is an integer from 1 to 8. 
The third step, Step (C), involves removing solvent from the reaction 
mixture containing alkali metal salt of 4-sulfophenyl-[(1-oxyalkanoyl) 
amino]alkanoate formed in Step (B). Removal of solvent is accomplished 
either by an evaporative process such as distillation or drying, or by 
crystallization followed by filtration. Removal of the solvent is 
conducted at low vacuum and at a temperature which vaporization of the 
solvent occurs. Preferably, the vacuum range is from 0.5 absolute to 100 
mm Hg, and the temperature range is from 140.degree. C. to 250.degree. C. 
Preferably, at least 90% of the solvent is removed by evaporation. More 
preferably, at least 95% of the solvent is removed by evaporation. It is 
important to note that crystallization from the reaction solvent can be 
problematic as a form of product isolation since solvents tend to complex 
with the alkali metal salt of 4-sulfophenyl-[(1oxyalkanoyl)amino]alkanoate 
to produce a gel. 
The fourth step, Step (D), involves adding acetic acid to the alkali metal 
salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate product of Step (C). 
The acetic acid should contain less than 5% water. Preferably, glacial 
acetic acid which is &gt;99% pure carboxylic acid is used. C.sub.1 to C.sub.4 
alcohols and acids and their corresponding esters may be used in place of 
acetic acid in the purification step with a lesser degree of performance. 
Purification of the alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate is accomplished by methods 
known in the art such as reslurry, wash, digestion and recrystallization. 
The acetic acid removes impurities formed during the process such as 
hexanoic acid, 6-[[1-oxo-6-[(1-oxooctyl)amino]hexyl]amino]-,4-sulfophenyl 
ester, mono sodium salt, hexanoic acid, 
6-[[1-oxo-6-[(1-oxononyl)amino]hexyl]amino]-,4-sulfophenyl ester, mono 
sodium salt, and hexanoic acid, 
6-[[1-oxo-6-[(1-oxodecyl)amino]hexyl]amino]-,4-sulfophenyl ester, mono 
sodium salt; residual solvent; and unreacted starting materials, from the 
reaction product. In addition, the acetic acid reduces color of the alkali 
metal salt of 4-sulfophenyl-[(1oxyalkanoyl)amino]alkanoate product which 
is recovered in the form of a solid. 
The fifth step, Step (E), involves separating the solid alkali metal salt 
of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate product from the acetic 
acid solution to obtain a purified alkali metal salt of 
4-sulfophenyl--[(1-oxyalkanoyl)amino]alkanoate and an acetic acid 
filtrate. Separation is accomplished by methods known in the art such as 
centrifugation or vacuum filtration. The filtrate from Step (E) of a 
previous preparation can be recycled and added as part of the acetic acid 
to Step (D) to minimize the loss of product. The product is dried by any 
standard drying technique such as in a ring drier, or a vacuum oven. Step 
(D) and Step (E) may be repeated until the alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate of a desired purity is 
obtained. Depending on the purity of the [(1-oxyalkanoyl)amino]alkanoic 
acid starting material, greater than 80% yield of product is obtained by 
the process of the present invention. 
The process of the present invention for preparing purified alkali metal 
salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate may be conducted 
stepwise as a batch process or as a continuous process. The purified 
alkali metal salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate product 
has the general formula: 
##STR3## 
In the above formula, R represents C.sub.5 -C.sub.21 alkyl, C.sub.5 
-C.sub.21 alkenyl, chlorinated C.sub.5 -C.sub.21 alkyl, or phenyl that can 
be substituted by 1 to 3 substituents from among the groups F, Cl, 
SO.sub.3 M, COOM, C.sub.1 -C.sub.21 alkyl, or C.sub.2 -C.sub.20 alkenyl; 
R.sup.1 represents hydrogen or a C.sub.1 -C.sub.3 alkyl; M represents 
hydrogen, ammonium, or an alkali metal atom such as sodium and potassium; 
and n is an integer from 1 to 8. Preferably, the purified alkali metal 
salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate product is sodium 
4-sulfophenyl-6-[(1-oxyoctyl)amino]hexanoate wherein R is C.sub.7 
H.sub.15, n is 5, and M is sodium; sodium 
4-Sulfophenyl-6-[(1-oxynonyl)amino]hexanoate, wherein R is C.sub.8 
H.sub.17, n is 5, and M is sodium; or sodium 
4-sulfophenyl-6-[(1-oxydecyl)amino]hexanoate wherein R is C.sub.9 
H.sub.19, n is 5, and M is sodium. The product may also be a mixture of 
these compounds. 
The materials and testing procedures used for the results shown herein are 
as follows: 
Liquid Chromatography method for determining the purity of the alkali metal 
salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate product: A weighed 
amount of sample is diluted and injected onto a reversed-phase liquid 
chromatographic column using a water/acetonitrile mobile phase containing 
an ion-pairing reagent. An ultra-violet (UV) detector, set at 205 nm, is 
used to monitor component elution. The peak areas of the sample components 
are compared to the peak areas obtained from the injection of known 
standards to determine the concentration of each component. 
The process of the present invention will be further illustrated by a 
consideration of the following examples, which are intended to be 
exemplary of the invention. All parts and percentages in the examples are 
on a weight basis unless otherwise stated. 
EXAMPLE 1 
A one vessel synthesis of sodium 
4-sulfophenyl-6-[(1-oxyoctyl)amino]hexanoate and sodium 
4-sulfophenyl-6-[(1-oxydecyl)amino]hexanoate without a purification step. 
To 60 grams of tetrahydrothiophene-1,1-dioxide at 140.degree. C. was added 
with stirring 8.3 grams, 0.042 mole, of sodium 4-hydroxybenzenesulfonate 
and 6.4 grams, 0.063 mole, of acetic anhydride. The resulting mixture was 
allowed to stir at 140.degree. C. for 2 hours before the pressure was 
reduced to 100-160 mm of Hg for 45 minutes. The temperature of the 
reaction mixture was then increased to 170.degree. C., and 12 grams, 
approximately 0.046 mole, of a mixture of 6-[(1-oxyoctyl)amino]hexanoic 
acid and 6-[(1-oxydecyl)amino]hexanoic acid, 0.14 grams, 0.0014 mole, of 
imidazole, and 0.17 grams, 0.0020 mole, of sodium acetate was added. The 
resulting reaction mixture was allowed to stir for approximately 3 hours 
at 100 mm of Hg with a nitrogen sweep of approximately 0.5 cubic feet per 
hour. Acetic acid spontaneously evaporated from the reactor throughout the 
reaction and was not collected. After the three hour reaction time, the 
pressure was reduced to 20 mm of Hg and tetrahydrothiophene-1,1-dioxide 
was allowed to distill out of the reactor. After no further 
tetrahydrothiophene-1,1-dioxide would distill out of the reactor, the 
reaction mass, approximately 20 grams, was allowed to cool to a hard 
solid. The hard solid, 16.7 grams, was ground to a sand-like consistency 
and was placed into a vacuum oven at 70.degree. C. for approximately 70 
hours to yield 13.7 grams of dried product. HPLC data on the dried product 
is summarized in Table I. 
EXAMPLE 2 
A one vessel synthesis of sodium 
4-sulfophenyl-6-[(1-oxyoctyl)amino]hexanoate and sodium 
4-sulfophenyl-6-[(1-oxydecyl)amino]hexanoate without a purification step. 
To 172 grams of tetrahydrothiophene-1,1-dioxide at approximately 35.degree. 
C. was added with stirring 29 grams, 0.12 mole, sodium 
4-acetoxybenzenesulfonate, 34 grams of a mixture containing 51% of 
6-[(1-oxyoctyl)amino]hexanoic acid and 34% of 
6-[(1-oxydecyl)amino]hexanoic acid, 0.40 grams, 0.0060 mole, imidazole, 
and 0.49 grams, 0.0058 mole, sodium acetate. The reaction mixture was 
allowed to warm to approximately 170.degree. C. as the pressure was 
reduced to about 20 mm of Hg. [This combination of pressure and 
temperature provided a steady reflux at the top of a 15" long distillation 
column packed with 12" of stainless steel packing material.] The reaction 
mixture was allowed to reflux for approximately 1 hour before the pressure 
was reduced to allow the solvent to distill out of the reaction flask. The 
pressure was lowered in stages to about 5 mm of Hg until no further 
solvent distilled out of the reaction flask (approximately 1.7 hour 
elapsed during the distillation). The resulting pasty solid was allowed to 
cool to a hard solid, approximately 90 grams. The hard solid, 84.4 grams, 
was ground to a sand-like consistency and was placed into a vacuum oven at 
130.degree. C. and 29" of Hg for approximately 18 hours to yield 53.6 
grams of dried product. HPLC data on the dried product is summarized in 
Table I. 
EXAMPLE 3 
A one vessel synthesis of sodium 
4-sulfophenyl-6-[(1-oxyoctyl)amino]hexanoate and sodium 
4-sulfophenyl-6-[(1-oxydecyl)amino]hexanoate without a purification step. 
To 172 grams of tetrahydrothiophene-1,1-dioxide at approximately 35.degree. 
C. was added with stirring 29 grams, 0.12 mole, sodium 
4-acetoxybenzenesulfonate, 34 grams of a mixture containing 51% of 
6-[(1-oxyoctyl)amino]hexanoic acid and 34% of 
6-[(1-oxydecyl)amino]hexanoic acid, 0.40 grams, 0.0060 mole, imidazole, 
and 0.49 grams, 0.0058 mole, sodium acetate. The reaction mixture was 
allowed to warm to approximately 170.degree. C. as the pressure was 
reduced to about 20 mm of Hg. [This combination of pressure and 
temperature provided a steady reflux at the top of a 15" long distillation 
column packed with 12" of stainless steel packing material.] The reaction 
mixture was allowed to reflux for approximately 1 hour before the pressure 
was reduced to allow the solvent to distill out of the reaction flask. The 
pressure was lowered in stages to about 5 mm of Hg until no further 
solvent distilled out of the reaction flask (approximately 1.7 hour 
elapsed during the distillation). The resulting pasty solid was allowed to 
cool to a hard solid, approximately 90 grams. The hard solid, 82.6 grams, 
was ground to a sand-like consistency and was placed into a vacuum oven at 
130.degree. C. and 29" of Hg for approximately 18 hours to yield 53.7 
grams of dried product. HPLC data on the dried product is summarized in 
Table I. 
EXAMPLE 4 
Purification of the product prepared in Example 3. 
To 215 grams of acetic acid was added with stirring 53.5 grams of crude 
solid product prepared in Example 3. The resulting mixture was allowed to 
warm to 70.degree. C. for 20 minutes before being allowed to cool to 
25.degree. C. The mixture was filtered to obtain 59.6 grams of acetic acid 
wet solids and 191.3 grams of dark colored filtrate. The wet solids were 
allowed to dry in a vacuum oven at 70.degree. C. and 20 inches of Hg for 
approximately 18 hours to yield 31.1 grams of dried material. HPLC data on 
the dried product is summarized in Table I. 
EXAMPLE 5 
Recycle of filtrate recovered in Example 4. 
To 189.4 grams of filtrate recovered in Example 4 was added 192.6 grams of 
glacial acetic acid and 95.0 grams of crude reaction product prepared in a 
manner analogous to that described in Example 2. The resulting mixture was 
allowed to warm to 70.degree. C. for 20 minutes before being allowed to 
cool to 25.degree. C. The mixture was filtered to obtain 139.7 grams of 
acetic acid wet solids and 319.9 grams of dark colored filtrate. The wet 
solids were allowed to dry in a vacuum oven at 70.degree. C. and 20 inches 
of Hg for approximately 18 hours to yield 65.8 grams of dried material. 
HPLC data on the dried material is summarized in Table I. 
EXAMPLE 6 
To 316.4 grams of filtrate recovered in Example 5 was added 105.6 grams of 
glacial acetic acid and 105.3 grams of crude reaction product prepared in 
a manner analogous to that described in Example 2. The resulting mixture 
was allowed to warm to 70.degree. C. for 20 minutes before being allowed 
to cool to 25.degree. C. The mixture was filtered to obtain 153.2 grams of 
acetic acid wet solids and 357.3 grams of dark colored filtrate. The wet 
solids were allowed to dry in a vacuum oven at 70.degree. and 20 inches of 
Hg for approximately 18 hours to yield 84.8 grams of dried material. HPLC 
data on the dried material is summarized in Table I. 
TABLE I 
__________________________________________________________________________ 
HPLC Analysis in Percent By Weight 
STARTING 
PRODUCT IMPURITY.sup.1 
IMPURITY.sup.2 
MATERIAL 
IMPURITY.sup.3 
Ex. 
C-10 
C-8 C-10 
C-8 C-10 
C-8 C-10 
C-8 C-10 
C-8 ABS 
SPS 
__________________________________________________________________________ 
1 25% 
45% 5% 10% 1% 0% 5% 2% 1% 1% 1% 6% 
2 27% 
44% 5% 9% 1% 1% 1% 3% 0% 1% 1% 5% 
3 28% 
48% 5% 10% 0% 0% 1% 3% 1% 2% 0% 5% 
4 37% 
53% 1% 3% 0% 0% 1% 1% 0% 1% 0% 2% 
5 34% 
52% 2% 4% 0% 0% 2% 1% 0% 1% 0% 3% 
6 32% 
51% 3% 5% 0% 0% 3% 1% 0% 1% 0% 3% 
__________________________________________________________________________ 
Product (C8) = alkali metal salt of 
4sulfophenyl-6-[(1oxyoctyl)amino]hexanoate 
Product (C10) = alkali metal salt of 
4sulfophenyl-6-[(1oxydecyl)amino]hexanoate 
Impurity.sup.1 (C8) = hexanoic acid, 
6[[1oxo-6-[(1oxooctyl)amino]hexyl]amino,4-sulfophenyl ester, mono sodium 
salt 
Impurity.sup.2 (C10) = hexanoic acid, 
6[[1oxo-6-[(1oxodecyl)amino]hexyl]amino,4-sulfophenyl ester, mono sodium 
salt 
Impurity.sup.2 (C8) = sodium 4octyloxybenzenesulfonate 
Impurity.sup.2 (C10) = sodium 4decyloxybenxenesulfonate 
Starting Material (C8) = [(1oxyoctyl)amino]hexanoic acid 
Starting Material (C10) = [(loxydecyl)amino]hexanoic acid 
Impurity.sup.3 (C8) = 6[[1oxo-6-[(1oxooctyl)amino]hexyl]amino]hexanoic 
acid 
Impurity.sup.3 (C10) = 6[(1oxo-6-[(1oxodecyl)amino]hexyl]amino]hexanoic 
acid 
ABS = sodium 4acetoxybenzene sulfonate 
SPS = sodium 4hydroxybenzenesulfonate 
The results in Table I clearly illustrate the effect of the purification 
step on a sodium 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate product. In 
Example 4, a 90% pure sodium 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate 
product was obtained by mixing with acetic acid. The acetic acid removed 
impurities, residual solvent, and unreacted starting materials from the 
product. In addition, the results for Examples 1-3 in Table I highlight 
the reproduceability of the process. 
EXAMPLES 7-9 
An equal weight of crude reaction product, obtained after Step (B) wherein 
the reaction solvent had been removed by filtration, and a purification 
solvent as shown in Table II were combined. The resulting mixture was 
stirred for 20 minutes at 25.degree. C., filtered, and the solids were 
dried. HPLC data on the dried material is summarized in Table II. 
EXAMPLE 10 
A crude reaction product obtained after Step (B) wherein the reaction 
solvent had been removed by filtration, was combined with acetic acid 
wherein the amount of acetic acid was 1.7 times the weight of the crude 
reaction product. The reaction product and acetic acid were heated and 
mixed for 10 minutes at 70.degree. C., cooled to 25.degree. C. and 
filtered. The solids were dried. HPLC data on the dried material is 
summarized in Table II. 
TABLE II 
__________________________________________________________________________ 
Percent of Components Removed During Purification Step 
PURIFICATION STARTING 
Ex. 
SOLVENT PRODUCT 
IMPURITY.sup.1 
MATERIAL 
IMPURITY.sup.3 
ABS 
__________________________________________________________________________ 
7 Acetic Acid 
1.5% 34.0% 77.4% 58.0% 47.3% 
8 Methanol 0% 4.4% 77.2% 47.1% 54.6% 
9 Methyl Acetate 
0% 0.0% 60.9% 3.4% 2.9% 
10 Acetic Acid 
7.3% 93.8% 83.1% 100.0% 94.3% 
__________________________________________________________________________ 
Product = sodium salt of 4sulfophenyl-6-[(1oxydecyl)amino]hexanoate. 
Impurity.sup.1 = hexanoic acid, 
6[[1oxo-6-[(1oxodecyl)amino]hexyl]amino,4-sulfophenyl ester, mono sodium 
salt 
Starting Material = [(1oxydecyl)amino]hexanoic acid 
Impurity.sup.3 = 6[[1oxo-6-[(1oxodecyl)amino]hexyl]amino]hexanoic acid 
ABS = sodium 4acetoxybenzene sulfonate 
The results in Table II clearly show that acetic acid removes significantly 
more impurities, residual solvent, and unreacted starting materials from 
the alkali metal salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate 
product than methanol or methyl acetate. Moreover, the acetic acid left 
the alkali metal salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate 
product essentially unaffected. 
The advantages associated with the process of the present invention are 
that a purified alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate is prepared without 
isolation of the 4-acetoxybenzenesulfonate. In addition, the purification 
is accomplished using acetic acid which is unexpected because acetic acid 
is a by-product in the transesterification reaction and would be expected 
to cause the reverse reaction. The present inventors have determined that 
the acetic acid removes impurities, residual solvent, and unreacted 
starting materials from the alkali metal salt of 
4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate product. Moreover, the 
acetic acid reduces the color of the purified product. 
In addition, direct evaporation of solvent in Step (C) avoids gel formation 
which typically occurs upon cooling of the reaction mixture when more than 
one [(1-oxyalkanoyl)amino]alkanoic acid is used. 
Many variations will suggest themselves to those skilled in this art in 
light of the above detailed description. All such obvious modifications 
are within the full intended scope of the appended claims.