MXPA00001771A - Process for preparing and/or purifying amido acid phenyl ester sulfonates - Google Patents

Abstract

The present invention relates to a process for the preparation of a purified salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate. The process comprises the steps of:(a) providing a source of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate;(b) admixing the source with a water-based purification system to form a purification mixture, the water-based purification system having water present at a ratio of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate to water ranging from about 1:0.05 to about 1:50, preferably from about 1:0.1 to about 1:40;(c) separating a purified salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate from the purification mixture;and (d) collecting said purified salt of 4-sulfophenyl-[(1-oxyalkanoyl)amino]alkanoate. In preferred embodiments, the purification mixture includes a processing aide such as ethyl alcohol, propyl alcohol, isopropyl alcohol, acetone and mixtures thereof.

Description

PROCEDURE FOR FILLING AND / OR PURJF1CAR FIBERUCE AMINO ACID STERSULPHONATES TECHNICAL FIELD This invention relates to a process for preparing and / or purifying phenyl estersulfonates of amino acids. More specifically, this invention relates to a process for preparing purified salts of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate.

BACKGROUND OF THE INVENTION The synthesis of ingredients for use in consumer articles of low unit price, such as laundry detergents, fabric softeners and the like, is of great interest to manufacturers. In effect, the synthesis of ingredients at low cost is usually the step that determines a reduction in tariffs, in the procedure of bringing a consumer item to the market. Due to the large number of ingredients in items such as laundry detergents, it is necessary to minimize the cost of the particular ingredients in order to maintain the accumulated cost of the products within an acceptable price range. The cost related to the manufacture of ingredients for consumer items is usually due either to the cost of the raw materials used to make those ingredients or to the complex chemical reactions and procedures required in their manufacture. Consequently, manufacturers are in a constant search for cheap raw materials or simplified reaction sequences. The phenyl estersulfonates of amino acids form a class of materials that can be used as bleach activators in laundry detergents and other types of cleaning compositions containing bleach. This type of activators has several desirable properties, such as an excellent bleaching performance with minimal damage to fabric dye, good compatibility with washing machines and a good wash profile. Although it is potentially simple to obtain these materials from cheap raw materials, the synthesis thereof has a certain degree of complexity and usually involves the use of solvents. Also, problems of development of impurities that produce color in the final product may arise. In this way, the synthesis of the phenyl estersulfonates of amino acids is not so simple and can be surprisingly problematic. Various processes are known for the preparation of phenyl estersulfonates of amino acids. U.S. Patent No. 5,466,840 describes a 5-step process for the preparation of these compounds. Other similar procedures are described in U.S. Patents 5,391,780; 5,414,099; 5,534,642; 5,153,541; 5,650,527; 5,286,879 and 5,523,434.

Accordingly, there remains a need to create a simple, inexpensive and efficient process for the production of phenyl estersulfonates of amino acids.

BRIEF DESCRIPTION OF THE INVENTION This need is addressed in the present invention characterized in that it provides an improved process for the preparation of phenyl estersulfonates of purified amino acids. This invention utilizes a water-based purification system to remove the color producing compounds and other impurities of the phenyl ester of sulfonate from amino acids. The use of this water-based purification system eliminates a greater percentage of impurities that produce color than the systems based on acetic acid used in previous techniques. The use of the water-based purification system also allows a greater degree of flexibility in the process to synthesize the salts of phenylethersulfonates of amino acids due to their ability to purify or crystallize the salt in the presence of important amounts, that is, greater than 10% and, generally, greater than between 20 and 40%, of the reaction solvent required in the synthesis and, in this way, eliminates the need for a step to remove or eliminate the solvent. Likewise, the water-based purification system increases the flexibility of the synthesis process by providing the ability to work both in a suspension and in a homogeneous solution. Accordingly, the purification process of this invention can be applied both in suspensions of crystallized salt of the product and in homogeneous solutions of salt dissolved from the product which would subsequently allow controlled recrystallization. In accordance with a first embodiment of this invention, there is provided a process for the preparation of a purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate. The procedure includes the following steps: a) provide a source of 4-sulfophenyl - [(1-oxyalkanoyl) amino] -alkanoate; b) mixing the source with a water-based purification system to form a purification mixture, and the water-based purification system should have water present at a ratio of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate with respect to water of about 1: 0.05, to about 1: 50, preferably of about 1: 0.1 to about 1: 40; c) separating a purified salt of 4-sulfophenyl [(1-oxyalkanoyl) amino] -alkanoate from the purification mixture; and d) recovering the purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] -alkanoate. Preferably, the source of 4-sulfophenyl - [(1-oxyalkanoyl) amino] -alkanoate includes a polar aprotic reaction solvent selected from a group consisting of dialkylacetamides, dialkylsulphoxides, dialkyl ethers of polyethylene glycol and cyclic or cyclic alkylsulphones, and with greater 1, 1-tetrahydric oxide rotiofen preference. The water-based purification system also preferably includes a processing aid such as that selected from a group consisting of straight or branched Ci to Ce diols or alcohols, linear or branched Ci to Ce ketones, Ci to Ce esters. cyclic or acyl cyclic or acyclic ethers, linear or branched, cyclic or acyclic Ci to C sulfoxides and sulphones and mixtures thereof. More preferably, the processing aid is chosen from a group consisting of ethyl alcohol, propyl alcohol, isopropyl alcohol, acetone and a mixture thereof. In the most preferred situations, the processing aid has a density less than or equal to 1.1, tetrahydrothiophene dioxide, and is present at a ratio of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate with respect to auxiliary processing from 1: 0.1 to about 1: 50 and most preferably from 1: 1 to around 1: 20. If convenient, the step of mixing further includes the step of heating the purification mixture to a temperature of about 30 ° C to about 100 ° C. According to a second embodiment of this invention, the process for preparing the purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate includes the steps of: a) reacting a salt of 4-hydroxybenzenesulfonic acid with an anhydride carboxylic acid in a reaction solvent to form a reaction mixture having a saHSe * 4-acyloxybenzenesulfonic acid and a carboxylic acid; b) adding a [(1-oxyalkanoyl) amino] alkanoic acid and at least one transesterification catalyst to the reaction mixture and heating to a temperature of about 120 ° C to about 220 ° C for about 0.5 to 10 hours and at a pressure sufficient to maintain the reflux of the reaction solvent to form a reaction product containing a salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate; c) mixing the reaction product with a water-based purification system to form a purification mixture, and the water-based purification system should have water present at a ratio of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate with respect to water on a scale of between 1: 0.05 to about 1: 50; d) separating a purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate from the purification mixture; and e) recovering the purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate. According to a third embodiment of this invention, a process for preparing the purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate includes the steps of: a) reacting an alkali metal salt of 4-hydroxybenzenesulfonic acid with a carboxylic anhydride of C2 to C at the temperature and for a sufficient time in a reaction solvent to form a reaction mixture with an alkali metal salt of 4-hydroxybenzenesulfonic acid and a carboxylic acid of C2 to C4, further characterized because the alkali metal salt of 4-hydroxybenzenesulfonic acid and the carboxylic anhydride of C2 to C4 are present in a molar ratio of 1: 1 to 1: 40, respectively, and the reaction solvent is present in a weight ratio of 1. : 1 to 20: 1 based on the weight of the alkali metal salt of 4-hydroxybenzenesulfonic acid, provided that the excess carboxylic anhydride is removed from the reaction vessel under a pressure n reduced; b) adding a [(1-oxyalkanoyl) amino] alkanoic acid and at least one transesterification catalyst to the reaction mixture and heating to a temperature of about 120 ° C to about 220 ° C for about 0.5 to 10 hours , at a pressure sufficient to maintain the reflux of the reaction solvent and remove the carboxylic acid from C2 to C4 of the reaction vessel, to form a reaction product containing a salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate, characterized in that the amount of moles of the added [(1-oxyalkanoyl) amino] alkanoic acid is from 0.7 to 5 times the amount of moles of the alkali metal salt of 4-hydroxybenzenesulfonic acid; c) mixing the reaction product containing a reaction solvent and a salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate with a water-based purification system to form a purification mixture, and the Water-based purification includes a processing aid with water present at a ratio of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate to water on a scale of 1: 0.05 to about 1: 50; d) separating a purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate from the remainder of the purification mixture; e) recovering the purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate; and Accordingly, one of the objects of this invention is to provide a process for preparing a purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate. Another object of this invention is to provide a process like the aforementioned one in which a water-based purification system is used to remove impurities that produce color. A further object of this invention is to provide flexibility to a process for preparing a salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate. These and other objects, features and advantages of the present invention will be apparent to persons who are familiar with the ordinary art, from the following description and from the appended claims. All percentages, ratios and proportions in this document are based on weight, unless otherwise indicated. All documents cited herein are appended by reference to this document. _ & * DETAILED DESCRIPTION OF FYAS PREFERRED MODALITIES The process of this invention for preparing purified salts of phenylethyl sulphonates of amino acids has as an important feature the inclusion of a water-based purification system. As indicated above, it is the use of the water-based purification system with or without a processing aid which leads to the benefits and advantages of this invention. The process, in general, includes providing a source of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate, mixing the source with a water-based purification system and separating the purified product. Although it is possible to obtain the source of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate by various means, the preferred source is the in situ preparation. of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate.

Preparation of 4-Sulfophenyl-f (1-oxyalkanoyl, amino-1-alkanoate The preparation of 4-sulfophenyl - [(1-oxyalkanoyl) amino] -alkanoate consists of two basic steps and is described in detail in U.S. Patent 5,466,840, which description is attached presently by reference In the first step, a salt, such as an alkali metal salt, of 4-hydroxybenzenesulfonic acid is reacted with a C2 to C4 carboxylic anhydride, preferably at a temperature of 50 ° C to 200 ° C for a time of 0.5 to 5 hours in a reaction solvent to form a reaction mixture having a salt of 4-acyloxybenzenesulfonic acid and a carboxylic acid of C2 to C4, preferably the reaction is carried out at a temperature from 110 ° C to 170 ° C for 1 to 2 hours It is preferable that the salt is an alkali metal salt and can be an alkali metal such as sodium and potassium, or alternatively another salt such as calcium, magnesium or ammonium, however, sodium is the highest The carboxylic anhydride of C2 to C4 is present in an amount of from about 1 to about 40 moles per mole of the salt of 4-hydroxybenzenesulfonic acid, preferably from about 1 to 5 moles, and more preferably from about from 1 to 1.5 moles. Among the suitable C2 to C4 carboxylic anhydrides are acetic anhydride, propionic anhydride, butyl anhydride and isobutyric anhydride, with acetic anhydride being the most preferred. Among the reaction solvents used in the reaction are the polar aprotic reaction solvents, such as N, N-dimethylacetamide; dialkyl sulfoxide, characterized in that the alkyl group has from 1 to 6 carbon atoms such as dimethyl sulfoxide, diethylene glycol dimethyl ethers such as triglyme, cyclic alkyl or acyclic sulfones characterized in that the alkyl group has from 1 to 6 carbon atoms. carbon such as 1, 1 tetrahydrothiophene dioxide; and halogenated aromatic solvents and characterized in that the alkyl groups contain from 1 to 6 carbon atoms such as triisopropylbenzene. Preferably, the reaction solvent is 1.1 tetrahydrothiophene dioxide. The reaction solvent is present in a ratio of the reaction solvent to the salt of 4-hydroxybenzenesulfonic acid of from about 1: 1 to about 20: 1, preferably with a weight ratio of about 4: 1 to around 6: 1. Upon completion of the formation of a salt of 4-acyloxybenzenesulfonic acid, a transesterification is carried out. In this step, a [(1-oxyalkanoyl) aminoalkanoic acid and transesterification catalyst is added to the reaction mixture of step 1 which includes the 4-acyloxybenzenesulfonic acid salt. The reaction mixture is heated to a temperature of about 120 ° C to about 220 ° C for about 0.5 to 10 hours at a pressure sufficient to maintain the reflux of the reaction solvent and to remove the carboxylic acid from C2 to C4 of the reaction vessel, to form a mixed product containing a salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate. Preferably, the transesterification reaction is carried out at a temperature of about 150 ° C to about 220 ° C for a time of 2 and 6 hours. It is possible to remove the co-carboxylic acid by distillation or by spraying the mixture with an inert gas such as nitrogen. More reaction solvent can be added in the transesterification step to maintain a fluid reaction mixture, provided that the same reaction solvent used during the first step is used. The moles of [(1-oxyalkanoyl) aminoalkanoic acid added are from about 0.7 to about 5 times the moles of the salt of 4-hydroxybenzenesulfonic acid used in the first step.

I saw "[(1-oxyalkanoyl) aminoalkanoic acid prepared by processes that are well known in the art and described for example in U.S. Patent Nos. 5,391,780, 5,414,099; 5,534,642; 5,153,541; 5,650,527; 5,286,879 and 5,523,434, the descriptions of which are hereby appended by reference.A preferred synthesis for [(1-oxyalkanoyl) aminoalkanoic acid is an amidation reaction which consists of reacting a nitrogen compound selected from a lactam and an amino acid with an acid or carboxylic ester Preferably, the [(1-oxyalkanoyl) aminoalkanoic acid is 6 - [(1-oxyoctyl) aminohexanoic acid, 6 - [(1-oxidecyl) aminohexanoic acid or mixtures of the three. Convenient lactam monomers have at least 3, but preferably between 4 and 7 carbon atoms per molecule, Among the suitable lactam monomers are butyrolactam, valerolactam, epsilon-caprolactam, beta propiolactam, lta valerolactam and similar lactams. These lactams can be substituted at the nitrogen atom by hydrocarbon radicals containing from 1 to 3 carbon atoms, for example methylcaprolactam. Preferred lactam monomers are epsilon-caprolactam and its convenient derivatives. The amino acid has the general formula NH2 (CR1R2) mCOOH and is characterized by the basic amino group (NH2) and the carboxyl acid group (COOH). m is an integer having a scale of value from 1 to about 26 and preferably from 1 to about 10. R1 and R2 are independently selected from hydrogen, branched d-C2o alkyl or with straight chain unsubstituted or substituted, unsubstituted or substituted C3-C8alkyl, C3-C8alkenyl, C3-C8alkynyl and Cß-Cw aryl. The aforementioned substituted or unsubstituted C3-C8 cycloalkyl groups refer to the cycloaliphatic hydrocarbon groups which contain between 3 and 8 carbon atoms in the ring, preferably between 5 and 6 carbon atoms, and these cycloalkyl groups substituted with 1 to 2 alkyl of C -? - C4, C1-C4 alkoxy, hydroxy or alkanoxy of C1-C4. The C3-C8 alkenyl and C3-C8 alkynyl groups represent straight or branched hydrocarbon radicals containing from 3 to and 8 carbon atoms in the chain and that have a carbon-carbon double bond or a carbon-carbon triple bond, respectively. The term "aryl" is used to include aryl carboxyl groups containing up to 14 carbon atoms, for example phenyl and naphthyl and those not substituted with 1 or 2 groups selected from C 1 -C 4 alkyl, alkoxy C1-C4, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkanoxy, C 1 -C 4 alkanoylamino, halogen, cyano, C 4 C alkylsulfonyl, C 1 -C 4 alkylene (OH) n, O-alkylene C? -C4- (OH) n, S-alkylene of C? -C4- (OH) n, SO2-alkylene of C1-C4- (OH) n, CO2-alkylene of C? -C4- (OH) n , SO2N (R3) -alkylene of CrC4- (OH) n, SO2N (alkylene of C? -C4-OH) 2, CON (R3) -alkylene of CrC4- (OH) n, CON- 20 alkylene of CrC4- ( OH) 2, N (SO 2 -alkyl of N (SO 2 -phenyl) -alkyl of C 1 -C 4) -alkylene- (OH) n, characterized in that the value of n is 1 or 2.

The term "aryl" is used to include heterocyclic aryl groups, such as a 5- or 6-membered heterocyclic aromatic ring, containing an oxygen atom and / or a sulfur atom, and / or up to 3 nitrogen atoms and the The heterocyclic aryl ring may be optionally fused to 1 or 2 phenyl rings or another 5- or 6-membered heteroaryl ring, examples of such ring systems being thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, tetrazolyl, thiatriazolyl, oxatriazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, thiazinyl, oxazinyl, triazinyl, tiadizinilo, oxadiazinyl, dithiazinyl, dioxazinyl, oxathiazinyl, tetrazinyl, thiatriazinyl, oxatriazinyl, dithiadiazinyl, imidazolinyl, dihydropyridyl, tetrahydropyridyl, tetrazolo- [1, 5b] pyridazinyl and purinyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, indolyl, and simi and substituted rings with one or more substituent atoms listed above in the definition of the term "aryl". Also, the term "aryl" includes the arylene groups. The term "arylene" is used to represent a divalent aryl carboxylic hydrocarbon portion containing up to 14 carbon atoms, for example, o-, m- and p-phenylene, and those substituted with one or more groups selected from C1 alkyl -C4, C4 alkoxy or halogen. The carboxylic acid compound is a carboxylic acid or carboxylic acid ester, or a combination of both, which contains a radical, aliphatic, as a straight or branched chain radical or aliphatic, cycloaliphatic or hydroaromatic radical. The carboxylic acid or carboxylic acid ester has from about 6 to about 12 carbon atoms, preferably from 8 to about 20 carbon atoms, and most preferably from 8 to 10 carbon atoms. These radicals can be linked to the carboxyl group by an aromatic radical. The carboxylic acids and esters of carboxylic acids may be straight or branched chains of fatty acids of natural or synthetic origin which may be saturated or unsaturated in nature. The carboxylic acids and esters may contain more than one group of carboxylic acids or esters. Esters of carboxylic acids include, but are not limited to, the methyl, ethyl, propyl and butyl esters of a carboxylic acid. The carboxylic acids and esters of carboxylic acids may be used in their pure form or in combination. Suitable carboxylic acids and esters include: caprylic acid, methylcaprylate, pelargonic acid, methylpelargonate, capric acid, methylcaprate, isopropylcaprate, undecylic acid, lauric acid, palmitic acid, stearic acid, oleic acid, linoleic acid, behenic acid, teraphthalic acid , dimethyl terephthalate, phthalic acid, isophthalic acid, naphthen-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. The preferred carboxylic acid esters are methylcaprate and methylcaprylate. The transesterification catalysts used in this invention are known in the art. Among these catalysts are the -., F * ~ f tertiary amine catalysts, alkali metal, metal catalysts, acid catalysts and mixtures thereof. Specific examples of the catalysts used in this invention are: dimethylaminopyridine, imidazole, sodium acetate, sodium hydroxide and titanium tetraisopropoxide. The transesterification catalyst is added in an amount of between 0.01 and 0.3 moles per mole of 4-hydroxybenzenesulfonic acid salt used in the previous step. Once the transesterification reaction and the formation of the salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate, it is possible to remove the reaction solvent following an optional step. The elimination of the solvent is achieved either by an evaporation process such as distillation or drying, or by crystallization followed by filtration. The elimination of the solvent is carried out at low vacuum at a temperature at which vaporization of the solvent occurs. Preferably, the vacuum scale ranges from absolute 0.5 to 100 mm Hg, and the temperature range goes from 120 ° C to around 230 ° C. Preferably, at least about 90% and, most preferably, at least about 95% of the solvent is removed. Of course, it is important to note that the removal of the solvent is entirely optional in this invention since the water-based purification system can operate in the presence of significant amounts of reaction solvent. The reaction product, including the 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate salt is mixed with a water-based purification system to produce the purified salt of this invention. The water-based purification system includes, of course, at least a minimum amount of water. However, other ingredients such as processing aids can be included in the system. The water-based purification system has a minimal amount of water, so that the ratio of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate to water is between 1: 0.05 and about 1: 50 . Most preferably, the ratio of the 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate salt to water is between about 1: 0.1 and about 1: 40. As noted above, it is not necessary to remove the reaction solvent from the reaction product of the synthesis of the 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate salt. In cases where at least about 10% remains, and preferably at least about 20% and most preferably at least about 40% of the reaction solvent, a smaller amount of water is required in the system. In those cases, the ratio of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate to water is preferably between about 1: 0.1 and about 1: 40. When the reaction solvent is optionally removed as described hereinabove, it is possible that a higher percentage of water is required in the purification system. In those cases, the ratio of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate to water is between about 1: 1 and about 1: 50. 8 Without being limited to theory, it is believed that the amount of water used affects the recovery of the salt produced and also the amount of color and impurities removed. For raw reaction products with a lot of color, more water can be used, while for less colored products, a smaller amount of water can be used. It is also possible to determine the amount of water depending on the impurities present in particular. A small amount removes specific impurities, while to remove other impurities a greater amount of water will be necessary. Also, the presence of larger amounts of reaction solvent, as defined above, allows a smaller amount of water to be used. As noted above, it is possible to add a processing aid to the water-based purification system to, among other reasons, improve separation and reduce foam formation during processing. The processing aid is chosen from a group consisting of linear or branched Ci to C6 diols or alcohols, linear or branched Ci to C-ketones, linear or branched Ci to C6 acids, straight or branched Ci to Ce esters. cyclic or acyclic, straight or branched Ci to Ce ethers, Ci to C6 sulfoxides and sulfones and mixtures thereof. Most preferably, the processing aid is chosen from a group consisting of methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, acetone, acetic acid and mixtures thereof, with isopropyl alcohol being the most preferred.

In situations of great preference, the processing aid is miscible with water and has a density less than or equivalent to the preferred reaction solvent, 1,1-tetrahydrothiophene dioxide, in order to increase the density difference between the salt produced and the purification system and in this way facilitate the removal of salt. This solvent has a density of 1,216 gm / cm3. The processing aid is generally present in the purification system at a ratio of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate to the processing aid of between about 1: 0.1 and about 1: 50. and most preferably from about 1: 1 to about 1: 20. The amount of processing aid used depends mainly on the desired physical characteristics. It may be chosen to use a smaller amount to minimize foaming (although a smaller amount is also used when using a reaction solvent which also reduces foaming). It is convenient to use a larger quantity during the recovery of the product, as in the case of filtration or centrifugation. When a processing aid is used in conjunction with a water-based purification system, the yield of the recrystallization product is generally greater than 75%, most preferably 85%, and most preferably still at 90%. As described above, the water-based purification system provides greater flexibility to the above processing techniques, by allowing the recovery of the salt product either from a 2T, gv suspension or from a solu < Aéfj, .Crisgénea. That is, in a common processing the step of mixing the reaction product salt with the purification system, with or without a processing aid as described above, produces either a suspension or a homogeneous salt solution of the formed product. The purification can be carried out in this homogeneous suspension or solution at room temperature or slightly elevated to remove the impurities and the bodies that produce color. However, in optional embodiments, the mixing step may further include heating the mixture from about 30 ° C to 100 ° C to form a suspension or homogeneous solution of salt produced. This salt produced can then recover from the homogeneous solution or suspension to produce a highly purified salt. The use of a homogeneous solution or suspension provides flexibility and controlled recrystallization of the product to be able to determine various desired results. The next step of the process includes separating the purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate from the water-based purification system and removing any remaining solvent. It is possible to achieve this separation using methods well known in the art, such as centrifugation or filtration. The filtered substance from this separation step can be constituted by the reaction solvent, water and processing aids, if any, which can be recovered one by one and recycled at their respective steps. If desired, the purified salt can be dried by any conventional drying technique, such as an annular dryer or a vacuum oven. It is important to note that the purification with the water-based system and the separation of the product can be repeated as many times as possible. which are necessary to obtain a salt of 4-sulfophenyl- [(1-oxyalkanoyl) amino] alkanoate of the desired purity. Depending on the purity of the initial materials, a product yield greater than 80% and preferably about 90% in the processing of this invention can be obtained. The methods described herein can be performed in steps, either as an intermittent procedure or as a continuous one. The purified salt produced from 4-sulfofenH - [(1-oxyalkanoyl) amino] alkanoate has the general formula R4C (O) N (R5) (CH2) nC (O) -OBS where R4 represents C5-C2 alkyl ?, alkenyl of C5-C21, C5-C2 alkyl? chlorinated or phenyl which can be substituted with 1 to 3 substituent atoms of the groups F, Cl, SO3M, COOM, C2 alkyl? or C2-C2o alkenyl; R5 represents hydrogen or an alkyl of Ci to C3; M represents hydrogen, ammonium or an alkali metal atom such as sodium or potassium; n is an integer with a value between 1 and up to about 8; and -OBS is a residual group of oxybenzenesulfonate. Preferably, the purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate is sodium 4-sulfophenyl-6 - [(1-oxinonyl) amino] hexanoate, wherein R 4 is C 8 H? , n is 5 and / or sodium 4-sulfophenyl-6 - [(1-oxidyl) amino] hexanoate, where R 4 is C 9 H 19, n is 5. The product may also include mixtures of the compounds. ? «5¿r The process of the invention will be illustrated in more detail in the following examples, which will serve as samples of this invention.

EXAMPLE 1 To a solution stirred by mechanical means of 36 grams of water is added a crude reaction product containing 3 grams of crude sodium 4-sulfophenyl-6 - [(1-oxinonyl) amino] hexanoate and 6 grams of 1, 1- tetrahydrothiophene dioxide. The pH is adjusted to 5-6 using sulfuric acid and the resulting mixture is heated to 60 ° C. The solution is allowed to cool to 10 ° C for 1 to 2 hours. The mixture is filtered to obtain a solid salt and a colored filtered substance. The solid salt is washed with 10 grams of water and dried in a vacuum oven at 30 ° C (1-5 mm Hg) for 1 hour to obtain the dried product. The information regarding the product before and after the purification is summarized in table I.

EXAMPLE 2 To a stirred solution by mechanical means of 3 grams of water and 24 grams of isopropyl alcohol is added a crude reaction product containing about 3 grams of crude sodium 4-sulfophenyl-6 - [(1-oxinonyl) amino] hexanoate and 6 grams of 1, 1-tetrahydrothiophene dioxide. The pH is adjusted to 5-6 using sulfuric acid and it is measured. 'heat the resulting mixture to 90 ° C. The solution is stirred for 15 minutes and then allowed to cool to 25 ° C for a period of between 1 and 2 hours. The mixture is filtered under vacuum to obtain a solid and a colored filtered substance. The solid is washed with 10 grams of isopropyl alcohol and dried in a vacuum oven at 30 ° C (1-5 mm Hg) for 1 hour to obtain the dried product. The information regarding the product before and after the purification is summarized in table I.

EXAMPLE 3 To a stirred solution by mechanical means of 2 grams of water and 12 grams of isopropyl alcohol is added a crude reaction product consisting of 3 grams of crude sodium 4-sulfophenyl-6 - [(1-oxinonyl) amino] -hexanoate and 6 grams of 1, 1-tetrahydrothiophene dioxide. The pH is adjusted to 5-6 using sulfuric acid and the resulting mixture is heated to 65 ° C. The suspension is mixed for 15 minutes and then allowed to cool to 25 ° C for a period of between 1 and 2 hours. The mixture is filtered under vacuum to obtain a solid and a colored filtered substance. The solid is washed 3 times with 6 grams of isopropyl alcohol and dried in a vacuum oven at 30 ° C (1-5 mm Hg) for 1 hour to obtain the dried product. The information regarding the product before and after the purification is summarized in table I.

EXAMPLE 4 To a stirred solution by mechanical means of 20 grams of water and 120 grams of isopropyl alcohol is added a crude reaction product containing a reaction mixture consisting of 30 grams of sodium 4-sulfophenyl-6 - [(1-oxyoctyl) amino] hexanoate crude and 60 grams of 1, 1-tetrahydrothiophene dioxide. The pH is adjusted to 5-6 and the resulting mixture is heated to 70 ° C. The suspension is stirred for 1 hour, and allowed to cool to 10 ° C for a period of 3 hours. The mixture is centrifuged to obtain a solid and a colored centrifuged substance. The solid is put back into suspension in 25 grams of water and 130 grams of isopropyl alcohol. The resulting mixture is heated to 75 ° C. The solution is stirred for 30 minutes and allowed to cool to 10 ° C for a period of 2 hours. The mixture is centrifuged to obtain a solid and a colored filtered substance. The solid is dried in vacuo to obtain sodium 4-sulfophenyl-6 - [(1-oxyoctyl) amino] hexanoate.

EXAMPLE 5 In a flask equipped with a mechanical stirrer and a condenser, which contains a solution of 3 grams of water and 18 grams of acetone is added a crude reaction product consisting of 3 grams of a crude mixture of 4-sulfophenyl-6- [ Sodium (1-oxinonyl) amino] hexanoate and 6 grams of 1,1-tetraflhydrofuran-dioxide. The pH is adjusted to 5-6 using sulfuric acid and the resulting mixture is heated to 60 ° C. The solution is stirred for 15 minutes, and allowed to cool to 25 ° C for a period of between 1 and 2 hours. The mixture is filtered under vacuum to obtain a solid and a colored filtered substance. The solid is washed 3 times with 6 grams of acetone and dried in a vacuum oven at 30 ° C (1-5 mm Hg) for 1 hour to obtain a dry product. The information regarding the product before and after the purification is summarized in table I.

EXAMPLE 6 To a solution stirred by magnetic means of 6 grams of water and 40 grams of acetone is added a crude reaction product consisting of 32 grams of a crude solution of 4-sulfophenyl-6 - [(1-oxinonyl) amino] hexanoate of sodium composed of 14.5 grams of crude sodium 4-sulfophenyl-6 - [(1-oxinonyl) amino] hexanoate and 17.6 grams of 1,1-tetrahydrothiophene dioxide. The pH is adjusted to 5-6 using sulfuric acid and the resulting mixture is allowed to warm in a closed vessel at 90 ° C. The suspension is stirred for 15 minutes, and then it is allowed to cool to 25 ° C for a period of between 1 and 2 hours. The mixture is filtered under vacuum to obtain a solid and a colored filtered substance. The solid is washed with 40 grams of hot acetone and dried in a vacuum oven at 30 ° C (1-5 mm Hg) for 1 hour to obtain a dry product. The information regarding the * product before and after the purification is summarized in table I.

EXAMPLE 7 To a solution stirred by mechanical means of 27 grams of water is added a crude reaction product containing a reaction mixture consisting of 3 grams of sodium 4-sulfophenyl-6 - [(1-oxinonyl) amino] hexanoate. . The pH is adjusted to 5-6 using sulfuric acid and the resulting mixture is allowed to warm to 60 ° C. The clear solution is stirred for 15 minutes, and allowed to cool to 25 ° C for 1 to 2 hours. The mixture is filtered under vacuum to obtain a solid and a colored filtered substance. The solid is washed with 13.5 grams of water and i is dried in a vacuum oven at 30 ° C (1-5 mm Hg) for one hour to obtain the dried product. The information regarding the product before and after the purification is summarized in table I.

EXAMPLE 8 To a stirred solution by mechanical means of 2.5 grams of water and 13 grams of isopropyl alcohol is added 3 grams of sodium 4-sulfophenyl-6 - [(1-oxinonyl) amino] hexanoate crude containing less than 5% by weight of 1, 1-tetrahydrothiophene dioxide. The pH is adjusted to 5.5 using sulfuric acid and the resulting mixture is heated to 80 ° C. The clear solution is stirred for 10 minutes and then allowed to cool to 25 ° C for 1 to 2 hours. The mixture is filtered under vacuum to obtain a solid and a colored filtered substance. The solid is washed 3 times with 5 grams of acetone and dried in a vacuum oven at 30 ° C (1-5 mm Hg) for 1 hour to obtain 4-sulfophenyl-6 - [(1-oxinonyl) amino] hexanoate of dry sodium. The information regarding the product before and after the purification is summarized in table I.

EXAMPLE 9 To a solution stirred by mechanical means of 3 grams of water and 12 grams of acetone is added 3 grams of a crude reaction product containing sodium 4-sulfophenyl-6 - [(1-oxinonyl) amino] hexanoate with less than 5% strength. % by weight of 1, 1-tetrahydrothiophene dioxide. The pH is adjusted to 5.5 using sulfuric acid and the resulting mixture is heated to 60 ° C. The clear solution is stirred for 10 minutes and allowed to cool to 25 ° C for 1 to 2 hours. The mixture is filtered under vacuum to obtain a solid and a colored filtered substance. The solid is washed 3 times with 5 grams of acetone and dried in a vacuum oven at 30 ° C (1-5mm Hg) for 1 hour to obtain 4-sulfophenyl-6 - [(1-oxinonyl) amino] hexanoate of dry sodium The information regarding the product before and after the purification is summarized in table I.

EXAMPLE 10 To a solution stirred by mechanical means of 1 gram of water and 6 grams of acetone is added a crude reaction product containing 3 grams of sodium 4-sulfophenyl-6 - [(1-oxidyl) amino] hexanoate and 6 grams of 1, 1-tetrahydrothiophene dioxide. The pH is adjusted to 5-6 using sulfuric acid and the resulting mixture is heated to 60 ° C. In this case, the suspension is stirred for about 10 minutes. The mixture is allowed to cool to room temperature over a period of between 1 and 2 hours. The mixture is filtered under vacuum to obtain a solid and a colored filtered substance. The solid is washed 3 times with 12 grams of acetone and dried in a vacuum oven at 30 ° C (1-5 mm Hg) for one hour to obtain 4-sulfophenyl-6 - [(1-oxidecyl) amino] hexanoate of purified sodium. The information regarding the product before and after the purification is summarized in table I.

EXAMPLE 11 A 3-necked flask with a 500 ml round bottom, dry, equipped with a (mechanical) stirrer on top, a condenser with a Dean Stark apparatus, an addition funnel, an argon source and an oil bath with A temperature controller is charged with 35.6 grams of 1, 1-tetrahydrothiophene dioxide and heated to 80 ° C. To the reaction flask is added 178 ml (2.16 mmol) of sodium acetate, 7.03 grams (0.036 moles) of sodium 4-hydroxybenzenesulfonate and 9.47 grams (0.035 moles) of a mixture of 6 - [(1-oxinonyl) aminohexanoic acid and 6 - [(1-Oxy-acyl) amino-hexanoic acid. The mixture is heated to 140 ° C. To the reaction (by means of an addition funnel) 4.07 ml (0.043 mol) of acetic anhydride is added over a period of 30 to 40 minutes at 140 ° C. Subsequently, the pressure is reduced to 15 mm Hg, and upon increasing the temperature to 165 ° C for a period of between 20 and 30 minutes, the low-boiling materials are subjected to flash vaporization and collected. The temperature is maintained at about 165 ° C (15 mm Hg) for 5 hours. After the reaction period of 5 hours, a crude reaction mixture is obtained which includes 4-sulfophenyl - [(1-oxinonyl) amino] hexanoate and 4-sulfophenyl - [(1-oxidyl) amino] -hexanoate. The crude reaction mixture is transferred to a stirring solution by mechanical means of 15 grams of water and 60 grams of isopropyl alcohol. The pH is adjusted to 5.5, and the resulting mixture is heated to 75 ° C. The solution is stirred and cooled to 25 ° C for a period of 3 hours. The mixture is centrifuged to obtain a solid and a colored centrifuged substance. The solid is transferred to a stirred solution by mechanical means of 5 grams of water and 30 grams of isopropyl alcohol, stirred and centrifuged to obtain a solid which is dried under vacuum to obtain a mixture of 4-sulfophenyl - [(1-) oxinonyl) amino] hexanoate and 4-sulfophenyl - [(1-oxidecyl) amino] -hexanoate.

Claims (12)

NOVELTY DJ THE INVENTION CLAIMS

1. - A process for the preparation of a purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate which includes the steps of: a) providing a source of 4-sulfophenyl- [1-oxyalkanoyl) amino] alkanoate; b) mixing that source with a water-based purification system to form a purification mixture, and this water-based purification system will have water at a ratio of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate with with respect to water between 1: 0.05 and 1: 50, preferably between 1: 0.1 and 1: 40, most preferably between 1: 1 and 1:40; c) separating a purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate from that purification mixture; and d) collecting said purified salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate.

2. The process according to claim 1, further characterized in that the aforementioned water-based purification system includes a processing aid, preferably selected from linear or branched Ci to C6 diols or alcohols, Ci to C6 ketones. linear or branched, Ci to Ce linear or branched esters, cyclic or acyl cyclic or acyclic ethers, linear or branched, cyclic or acyclic Ci to Ce sulphoxides and sulfones and mixtures thereof, most preferably selected from ethyl alcohol, alcohol propyl, isopropyl alcohol, acetone and mixtures thereof.

3. The process according to claim 2, further characterized in that the aforementioned processing aid has a density lower or equivalent to 1,1-tetrahydrothiophene dioxide.

4. The process according to claim 2 or 3, further characterized in that the aforementioned processing aid is present in a ratio of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate with respect to the processing aid between 1: 0.1 and 1: 50, preferably between 1: 1 and 1: 20.

5. The process according to any of the preceding claims, further characterized in that the aforementioned mixing step further includes the step of heating the purification mixture described above to a temperature of about 30 ° C to about 100 ° C. .

6. The process according to any of the preceding claims, further characterized in that the source of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate described above includes a polar aprotic reaction solvent selected from dialkylacetamides, dialkylsulfoxides, dialkyl ethers of polyethylene glycol and cyclic or acyclic alkylsulfonates, preferably 1,1-tetrahydrothiophene dioxide.

7. The process according to claim 6, further characterized in that the source of 4-sulfophenyl - [(1-oxyalkanoyl) amino] -alkanoate comprises less than 5% reaction solvent and the ratio of 4-sulfophenyl- [ (1-oxyalkanoyl) amino] alcahsato with respect to the aforementioned water is between 1: 1 and 1.40,

8. The process according to claims 1 to 5, further characterized in that the source of 4-sulfophenyl - [( 1-oxyalkanoyl) amino] -alkanoate mentioned above is a reaction product containing a salt of 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate obtained by (1) reacting a salt of 4-hydroxybenzenesulfonic acid with an anhydride carboxylic acid in a reaction solvent selected from dialkylacetamides, dialkylsulphoxides, dialkyl ethers of polyethylene glycol and cyclic or acyclic alkylsulphonates, preferably 1,1-tetrahydrothiophene dioxide, to form a reaction mixture with a salt of 4-acyloxybenzenesulfonic acid and a carboxylic acid and (2) add a [(1-oxyalkanoyl) amino] alkanoic acid and at least one transesterification catalyst to that reaction mixture and heat at a temperature between 120 ° C and 200 ° C during a lapse of between 0.5 and 10 hours at a pressure sufficient to maintain the reflux of that reaction solvent, to obtain the aforementioned reaction product.

9. The process according to claim 8, further characterized in that the aforementioned reaction solvent is 1.1-tetrahydrothiophene dioxide, and the aforementioned ratio of 4-sulfophenyl - [(1-alkanoyl) amino] alkanoate with Regarding water, it is located between 1: 03 and 1: 3.

10. - The conjuring procedure with claims 8 or 9, further characterized in that the method includes the additional steps of removing the aforementioned reaction solvent from the aforesaid reaction product, before adding the purification system described above.

11. The process according to claims 1 to 5, further characterized in that the source of the 4-sulfophenyl - [(1-oxyalkanoyl) amino] alkanoate is a reaction product containing a salt of 4-sulfophenyl - [(1) -oxyalkanoyl) amino] alkanoate obtained by (1) reacting an alkali metal salt of 4-hydroxybenzenesulfonic acid with a C2 to C4 carboxylic anhydride at sufficient temperature and time, in a reaction solvent selected from dialkylacetamides , dialkylsulphoxides, dialkyl ethers of polyethylene glycol and cyclic or acyclic alkylsulphonates, preferably 1,1-tetrahydrothiophene dioxide, to form a reaction mixture with an alkali metal salt of 4-acyloxybenzenesulfonic acid and a carboxylic acid of C2 to C4, further characterized because the alkali metal salt of 4-hydroxybenzenesulfonic acid and the carboxylic anhydride of C2 to C4 are present in a molar ratio of between 1: 1 and 1: 40, respectively, and the reaction solvent is present in a ratio by weight of between 1: 1 and 20: 1 based on the weight of the alkali metal salt of 4-hydroxybenzenesulfonic acid, on the understanding that the excess carboxylic anhydride is removed under reduced pressure from the reaction vessel and (2) add [(1-oxyalkanoyl) amino] alkanoic acid and at least one iransesterification catalyst to that reaction mixture and heat at a temperature of between 120 ° C and 220 ° C for a period of between 0.5 and 10 hours and a sufficient pressure to maintain the reflux of that reaction solvent and remove the carboxylic acid from C2 to C4 of the reaction vessel, to form the aforementioned reaction product further characterized because the moles of the [(1-oxyalkanoyl) amino] alkanoic acid added are from 0.7 to 5 times the amount of moles of alkali metal salt of 4-hydroxybenzenesulfonic acid.

12. The process according to claim 11, further characterized in that the aforementioned reaction solvent is recovered from the purification mixture mentioned above once the purified salt of 4-sulfophenyl [(1-oxyalkanoyl) amino has been separated. ] alkanoate described above. "? ^ -i__!