MXPA99009048A - Preparation of disodium ethylenediamine-n,n'-disuccinate - Google Patents

Abstract

A process is disclosed for isolating the disodium salt of a mixture of racemic and meso isomers of sodium salts of ethylenediamine-N,N'-disuccinic acid from alkaline aqueous solutions by adjusting the pH of the alkaline solution to from 5 to 10 by addition of an acid, followed by recovery of the solid disodium salt. The mixture of isomers can be prepared by reacting sodium maleate with ethylenediamine in an alkaline aqueous solution. This method is particularly suited to preparing the disodium salt tetrahydrate and avoids the formation of free acid. The final product biodegrades more rapidly than ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA).

Description

PREPARATION OF ETI LEN DIAMI NA-N-N '-DISUCCI NATQ DISODIUM Chelators, or chelating agents, are compounds that form covalent bonds coordinated with a metal ion to form salts. Chelants are coordination compounds in which a central metal atom is attached to two or more other atoms in at least one other molecule (the chelator) such that at least one heterocyclic ring is formed with the metal atom as part of the metal atom. ring. Chelators are used in a variety of applications including food processing, soaps, detergents, cleaning products, personal care products, pharmaceuticals, pulp and paper processing, water treatment, solutions for metal work and silver plating. metal, solutions for textile processing, fertilizers, animal feed, herbicides, rubber chemistry and polymers, photographic finishing and chemistry of oil fields. Some of these activities result in the invasion of chelators into the environment. For example, agricultural uses or detergent uses can result in measurable amounts of the chelating agents that are present in the water. It is desirable, therefore, that the chelants degrade after use. Of particular interest are chelating agents that are biodegradable, that is, susceptible to degradation by microorganisms. Ethylenediamine-N acid. N'-disuccinic acid (EDDS) has been found to be useful in several applications where ethylene-N, N, N ', N' -tetraacetic acid (EDTA) has been used. For example, Patent Application EP 0 532 003, published on March 17, 1993, describes the use of EDDS in photographic processing; World Patent Application 9428464, published on December 8, 1994, describes the use of EDDS in non-electrolytic plating; U.S. Patent 5,569,443 published October 29, 1996, describes the use of EDDS in reduction of hydrogen sulphide; and U.S. Patent 4,704,233 published November 3, 1987, discloses the use of EDDS in detergent formulations. The biodegradability of EDDS in relation to EDTA makes EDDS a favorable replacement for EDTA where a faster biodegradation regime is desired. A challenge in the EDDS production is its preparation in a pure, economic way. EDDS is generally obtained from reaction mixtures containing EDDS salts by acidifying the mixture to a pH of about 2. For example, Neal and Rose (Inorg. Chem., 7.2405 (1968)) describe the reaction of L-aspartic acid with ethylene dibromide in the presence of a base to give a mixture containing the tetrasodium salt of SS-EDDS which, by acidification, yields crude S. S-EDDS. Neutralizing the crude acid with base and re-acidifying gives pure S.S-EDDS. Similarly, the Kezerian and Ramsey procedure (US Patent 3, 158,635 published November 24, 1964) combines sodium maleate with ethylenediamine to give a product mixture containing racemic and meso tetrasodium EDDS. In order to isolate pure EDDS acid, the reaction mixture was acidified to pH of about 2, precipitating the racemic / meso EDDS acid. The EDDS (tetrahydrated and anhydrous) disodium salt preparation from ED DS acid was made by the addition of 2 equivalents of NaOH followed by crystallization. The preparation of disodium EDDS by the Kezerian et al. Procedure requires the addition of 4 equivalents of acid and six equivalents of base. Recent descriptions by Patel et al. (World Patent Application 9512570 published May 1, 1995) and Lin et al. (US Patent 5,466,867 published November 14, 1995) also describe methods for obtaining purified EDDS acid. These methods require complete neutralization of the tetrasodium salt (with four equivalents of acid), resulting in four equivalents of salt as a by-product. It would be desirable to have an economical method to isolate a pure form of EDDS from a good yield reaction mixture that uses a minimum of raw materials and with less by-product salt. A pure form of racemic / meso EDDS, preferably the tetrahydrated disodium salt, can be obtained from crude mixtures of reaction solution containing the sodium salts by acidification of the solution at a pH of 5 to 10. In one embodiment, the invention is a method for preparing a disodium salt of ethylenediamine-N, N'-disuccinic acid from an aqueous alkaline solution containing a mixture of racemic and meso isomers of sodium salts of ethylenediamine-N isomers. N'-disuccinate comprising adjusting the p H of the alkaline solution between 5 to 10 by the addition of an acid and recovering the solid disodium salt.

In another aspect, the present invention is a method for the preparation of a disodium salt of EDDS comprising (a) reacting sodium maleate with ethylene diamine in an alkaline aqueous solution to form sodium salts of EDDS and (b) precipitating disodium EDDS. of the aqueous solution of sodium salts of EDDS adjusting the pH between 5 to 10 with an acid. The methods of the invention allow the isolation of a purified form of EDDS from reaction mixtures without the need to form the free acid. The method for obtaining the disodium salt is advantageous particularly in applications where the free acid is not required, such as where the chelating agent will be combined with a metal ion, for example, for use in photography where an iron chelate is used. In addition, a greater amount of disodium EDDS is recovered by the methods of the present invention. It has been found that a form of EDDS, specifically the tetrahydrated disodium salt of the mixture of racemic / meso isomers, can be obtained in high yield and purity from a mixture in solution. Generally, the mixture of isomers is that obtained from specific non-stereo processes known in the art for the preparation of EDDS, for example, EDDS formed by the reaction of DL-aspartic acid with ethylene dibromide. Preferably the mixtures of isomers is that obtained when maleate, ethylenediamine and caustic soda (NaOH) are reacted under conditions to produce tetrasodium EDDS as described in the U.S. Patent. , 3, 1 58, 635.

The mixtures of isomers used in the present invention are generally prepared under alkaline conditions. It has unexpectedly been found that the EDDS disodium salt can be separated from unreacted starting materials and by-products by acidifying the solution to a pH of 5 to 1 0. Preferably, the pH is adjusted from 6 to 8. In this pH range, the by-products such as maleate, fumarate, and ethylenediamine-N-monosuccinate (EDMS) are soluble and are easily removed from the EDDS salt mostly insoluble. This method requires half the amount of acid when compared to the amount that is required to precipitate the EDDS-free acid. This results in an economical and practical process for separating EDDS from the reaction mixture as a purified disodium salt. The reaction conditions are generally selected such that the amount of EDDS present, before the pH adjustment, is from 10 to 60 weight percent of the solution. Preferably, the EDDS is present in a concentration of 15 to 50 weight percent of the solution. More preferably, the amount of EDDS present is from 20 to 50 weight percent of the solution. The isolation of racemic EDDS / meso by this method is unexpected, since neither the dipotassium salt nor the diammonium salt of EDDS can be isolated by this method. Also surprisingly, the disodium salt of S, S-EDDS can not be isolated by this method. It was found that the S, S-isomer co-precipitates with the other isomers in the racemic / meso mixture, but does not precipitate when it is the only isomer in solution. In addition, in the absence of meso isomer, a mixture of [S, S] - and [R, R] -EDDS precipitates with low yield. The pH adjustment can be effected by a number of inorganic and organic acids, including, but not limited to, hydrochloric, hydrobromic, sulfuric, nitric, phosphoric, perchloric, formic, acetic, chloroacetic, dichloroacetic, trichloroacetic, trifluoroacetic, propionic, butyric acids. , methylsulfonic, trifluoromethylsulfonic, ethylsulfonic, methylphosphonic, and ethylphosphonic. Preferably, the acid is a strong mineral acid. More preferred are "strong, water-soluble, cheap acids having water-soluble sodium salts." Preferred acids include hydrochloric, sulfuric, nitric, phosphoric, acetic acid and mixtures thereof .The most preferred acids are sulfuric, hydrochloric and nitric. The addition of the acid to the reaction mixture containing the sodium salts of EDDS can be done using conventional equipment. The pH adjustment can be carried out in the temperature range from 0 to 1 10 ° C and preferably from 5 to 90 ° C. More preferably the acid addition is made in the temperature range from 10 to 80 ° C. The EDDS The insoluble disodium obtained by the process of the present invention can be recovered by normal procedures for the separation of liquid-solid systems. Such processes include filtration and centrifugation. Generally for ease of operation, the disodium EDDS is recovered by filtration. If desired, the recovered product can be further purified by washing the obtained crude material (eg the solid obtained by filtration) with water.

The invention will be further clarified by a consideration of the following examples, which are intended to be purely exemplary of the present invention. All percentages are by weight unless otherwise indicated.

EXAMPLE 1: A 100 mL flask was charged with 35 g of an aqueous process solution containing 39.3 percent NaDSDS (13.8 g, 0.0362 mol); 5.17 percent Na2EDMS (1.81 g, 0.0082 mol); 1.00 percent disodium fumarate (0.35 g, 0.0022 mol); and 2.07 percent disodium maleate (0.72 g, 0.0045 mol). The tetrasodium EDDS mixture was obtained by the reaction of sodium maleate with ethylenediamine as described in the U.S. Patent. , 3, 1 58,635. Concentrated nitric acid was added until the pH was 7.0. The mixture was stirred using a magnetic stir bar for approximately four hours at room temperature. The mixture was allowed to stand overnight to complete the precipitation. Filtration of the mixture gave a white solid which was dried under vacuum (80 ° C). The yield was 12.5 g of N a2ED DS-4H20 (yield 0.0306 mol, 84.6 percent) essentially free of EDMS, maleate, and fumarate determined by N MR. That the product is a tetrahydrate was verified by elemental analysis: calculated for Na2EDDS-4H20: C 29.42, H 5.43, N 6.86, Na 1 1 .26 percent. Found: C 27.64, H 5.72, N 6.67, Na 1 1.76 percent.

EJ EM P LOS 2. 3 and 4: These examples were run in the same manner as Example 1, except that the pH was adjusted to 5, 6 and 8 respectively. The recovered crude productions were 16.2 g, 15.8 g and 9.5 g respectively. The sample that precipitated at pH 5 also contained maleate and fumarate.

COMPARATIVE EXAMPLE A (Preparation of EDDS Acid): A flask was charged with maleic acid (120.5 g, 1.03 mol); deionized water (120 g); and 50 percent aqueous NaOH (167 g, 2.08 mol). The mixture was stirred until the solution occurred and the resulting solution was transferred to an autoclave, using 40 g of deionized water as a rinse. Ethylenediamine (31.0 g, 0.51 mol) was added over a period of ten minutes, and the autoclave was sealed. The mixture was stirred and heated at 140 ° C for nine hours and then allowed to cool to room temperature. The product solution was acidified to a pH of about 2 with 37 percent aqueous HCl, resulting in the precipitation of racemic / meso EDDS acid. When the precipitation was complete, the product was removed by filtration; washed with deionized water (2 x 300mL); and dried overnight under vacuum at 60 ° C. The yield of EDDS acid, which was shown to be pure by H 1- and C 13 NMR, was 108 g (0.37 mol, 72 percent).

EXAMPLE COMMENT B: A 200 m L flask was charged with ED DS acid made in the manner of Comparative Example A (29.2 g, 0.100 mol) and water (71 g). Aqueous NaOH was added at 50 percent until the pH reached 7.0 (17.6 g, 0.220 mol). The rainfall was completed in one day. Filtration and vacuum drying gave 18.2 g of Na2EDDS-4H20 (recovery 0.045 mol, 45 percent). Comparative Examples A and B show that the yield of product obtained by these methods is substantially lower than that obtained by the method of the present invention.

EJ EM PLOS COM PARATIVOS C v D: These examples were carried out in the manner of Example Comparative B, except that in place of aqueous NaOH, 45 percent aqueous KOH (25 g, 0.200 mol) and 28 percent aqueous N H3 (14.8 g, 0.240 mol) were used. No solution gave a precipitate after 5 days. Eventually, enough water was evaporated from both solutions to give solid products.

COMPARATIVE EXAMPLE P: This example was run in the manner of Comparative Example B, except that purified [S, S] -EDDS acid was used. No precipitate was formed for five days. After ten days, enough water had evaporated to give a solid product.

EXAMPLE COMPA RATIVE F: A 10 mL flask was charged with [S, S] -EDDS acid (1.0 g, 3.4 mmol): acid [R, R] - ED DS (1.0 g, 3.4 mmol); and deionized water (5.0 g). The pH of the mixture was raised to 7.0 with 50 percent aqueous NaOH (1.1 g, 14.4 mmol). After several hours, a white precipitate formed. This was removed by filtration and dried to 0.85 g, reaching up to 2.1 mmoles of Na2EDDS-rac-4H20 (yield 31 percent). The evaporation of water resulted in the recovery of more product.

COMPARATIVE EXAM PLO G: A 100 μL flask was charged with [S, S] -EDDS acid (10.6 g, 0.0363 mol); deionized water (12.8 g); and 50 percent aqueous NaOH (11.6 g, 0.145 mol). The mixture was stirred until all the acid was dissolved, and then concentrated HNO3 was added to lower the pH to 7.0. No precipitate was formed in twenty hours, even after the addition of Na2EDDS-4H20 (racemic / meso). Other embodiments of the invention will be apparent to those skilled in the art from a consideration of this specification or practice of the invention described herein. It is intended that the specification and examples be considered as exemplary only, with the true scope and spirit of the invention being indicated by the following claims.

Claims (9)

1. REVIVAL NAME IS 1 . A method for isolating a disodium salt of ethylenediamine-N, N'-disuccinic acid from an aqueous alkaline solution containing a mixture of racemic and meso isomers of sodium salts of ethylenediamine-NN '-disuccinic acid comprising (1) adjust the pH of the alkaline solution to between 5 to 10 by adding an acid and (2) recovering the solid disodium salt.
2. 2. The method of claim 1 wherein the mixture of racemic and meso isomers of sodium salts of ethynediamine-N, N'-disuccinic acid is prepared by reacting sodium maleate with ethylenediamine in an aqueous alkaline solution.
3. 3. The method of claim 1 or 2 wherein the acid is hydrochloric, hydrobromic, sulfuric, nitric, phosphoric, perchloric, formic, acetic, chloroacetic, dichloroacetic, trichloroacetic, trifluoroacetic, propionic, butyric, methylsulfonic, trifluoromethylsulfonic, ethylsulphonic, methylphosphonic, and ethylphosphonic.
4. 4. The method of claim 3 wherein the acid is sulfuric, nitric or hydrochloric. The method of claim 3 wherein the pH is adjusted to between 6 to 8. The method of claim 1 wherein the disodium salt of ethylenediamine-N acid. N'-di succinic is the tetrahydrate. 7. The method of claim 2 wherein the sodium salt of ethylenediamine-N acid. N '-disuccin ico is the tetrasodium salt. 8. The method of claim 1 wherein the alkaline aqueous solution is at a temperature of 0 to 1 10 ° C when the acid is added to adjust the pH. 9. The method of claim 1 wherein the disodium salt is a mixture of racemic and meso isomers. • > • - 13 / SUMMARY A process for isolating the disodium salt of a mixture of racemic and meso isomers of sodium salts of ethylene diamine N, N'-disuccinic acid from aqueous alkaline solutions is described by adjusting the pH of the alkaline solution from 5 to 10 by addition of an acid, followed by recovery of the solid disodium salt. The mixture of isomers can be prepared by reacting sodium maleate with elite diamine in an aqueous alkaline solution. This method is adequate 10 particularly for preparing the tetrahydrated disodium salt and preventing the formation of free acid. The final product biodegrades more rapidly than ethylenediamine-N, N, N ', N'-tetraacetic acid (EDTA).