HU200158B - Process for producing ethyl aminoacetate hydrochloride - Google Patents

Abstract

The process involves the reaction of aminoacetic acid, hydrochloric acid, ethyl alcohol with the equilibrium reaction leading to the formation of the aminoacetic acid ethyl ester hydrochloride at a temperature around the boiling point of the system in a homogeneous phase in a mixture of ethyl alcohol and hydrochloric acid. by cooling the solid phase to the amine acetic acid ethyl ester formation, the solid phase is separated from the liquid phase, the ethyl alcohol and hydrochloric acid remaining in the liquid phase, or recycled to produce the product.

Description

The present invention relates to a novel process for the preparation of ethyl aminoacetic acid hydrochloride.

The industrial importance of ethyl aminoacetic acid hydrochloride has recently increased significantly. It is made from N-phosphonomethylglycine (herbicide known as Glyphosate :)

1,3,5-tris (ethoxycarbonyl-raethyl) 1,3,5-triazine.

Further use: as a phase product in the synthesis of insecticidal pyrethroids.

In the synthesis of pyrethroids, it is advisable to use only pure product for economic and safety reasons, since the yield of the diazoester used in the synthesis strongly depends on the quality of the aminoacetic acid ethyl ester hydrochloride used. The impurities introduced with the aminoacetic acid ethyl ester start the decomposition process, which, in addition to the use of excess material, also endangers the operation, because during the synthesis the said decomposition process can be accelerated so much as to cause an explosion.

Two methods for preparing aminoacetic acid ethyl ester hydrochloride are described in the literature.

In one method, the aminoacetic acid is reacted with 95% aqueous ethanol and concentrated aqueous hydrochloric acid in the presence of benzene, and the unreacted ethanol, benzene and aqueous hydrochloric acid solution are removed from the system by distillation.

During the distillation, the system is practically evaporated to dryness. After the distillation is complete, fresh ethyl alcohol and benzene are added to the residue, followed by evaporation to dryness. The operation is repeated a third time. During the process 7.5 g of ethyl acetate and 350 ml of benzene are used to prepare 7.5 g of ethyl acetate.

(M. Dymicky, E. F. Mellon and L. Naghski, Analytical Biochemistry 41,487-491 / 1971)

In another known process, the aminoacetic acid is treated with ethanol and hydrochloric acid and then evaporated to dryness. Ethanol is then added to the distillation residue, followed by evaporation to dryness. The latter operation is repeated one more time. The resulting aminoacetic acid ethyl ester hydrochloride is not recovered but neutralized with NaOH and the liberated aminoacetic acid ethyl ester is purified by vacuum distillation (Houben Weyl, Methoden d Organischen Chemie, IV Vol. II / II, p. 355).

A common feature of the known processes is the formation of ethyl aminoacetic acid hydrochloride by dehydrating the reaction mixture. The water formed during the esterification reaction and the water introduced with the raw materials are removed from the reaction mixture by distillation and evaporation to dryness. The dewatering is carried out in several steps and the number of dewatering operations increases with the degree to which the ester equilibrium is to be shifted by removing the water formed during the reaction from the system. The amount of ethyl alcohol and benzene added to the system increases in proportion to the number of operations.

The realization of the known processes is a difficult technical task, since the dry-distillation operation can only be carried out in a dedicated plant. Multi-stage evaporations significantly increase the throughput time of the technology and thus the utilization of production equipment is unfavorable.

A further disadvantage is that during evaporation, thermal decomposition occurs. Degradation products and impurities in the raw materials are all present in the finished aminoacetic acid ethyl ester hydrochloride, since they are obtained by dry evaporation. The product thus obtained can be further processed only after separate purification. Losses during the cleaning operation reduce the yield.

In view of the complexity of the known processes and the very high material turnover and poor quality of the finished product, we have aimed to develop an economical and easy-to-use process for producing aminoacetic acid ethyl ester hydrochloride with good yield and quality.

It has now been found that by reacting the aminoacetic acid, ethanol and hydrochloric acid gas in an appropriate ratio at elevated temperature, a solution is formed which, upon cooling, crystallizes into aminoacetic acid ethyl ester hydrochloride. The ratio of the reaction partners should be chosen such that both ethanol and hydrochloric acid gas are in excess of the aminoacetic acid. The ethanol is used in such an excess that it also acts as a reaction medium, i.e., sufficient to allow larger crystals of ethyl acetate free hydrochloride to form inclusions upon cooling of the reaction mixture. Preferably, the weight ratio of aminoacetic acid to ethanol is 1: 15, preferably 1: 2 to 6. Hydrogen chloride gas was introduced into the reaction mixture until saturation, so that its amount varied depending on whether more or less ethanol was used. The weight ratio of aminoacetic acid to hydrochloric acid introduced in the reaction mixture may range from 1: 0.5 to 3, preferably from 1: 1-2.

The present invention relates to a process for the preparation of ethyl aminoacetic acid hydrochloride by reacting a mixture of aminoacetic acid, ethanol and hydrochloric acid, characterized by a mixture of aminoacetic acid and ethanol in a weight ratio of 1:15, preferably 1: 2-6, below 80 ° C. with 1: 0.5-3, preferably 1: 1-2, by weight of hydrochloric acid gas, the resulting reaction mixture is cooled to 0-40 ° C, preferably 0-15 ° C, to precipitate solid aminoacetic acid ethyl 3.

The ester hydrochloride is isolated from the reaction mixture in a known manner and the remaining reaction medium is optionally recycled to the reaction medium.

According to the present invention, the aminoacetic acid-5-ethyl ether hydrochloride is prepared by slurrying the aminoacetic acid in ethanol with continuous stirring, followed by the addition of hydrogen chloride gas under continuous cooling at a temperature ranging from 60 to 75 ° C. When the solution becomes saturated with hydrochloric acid, as indicated by the breakage of the hydrochloric acid gas, the further introduction of the hydrochloric acid gas is stopped. The resulting solution is cooled, optionally with hydrogen chloride gas being added to the reaction mixture, the crystalline form of the aminoacetic acid ethyl ester hydrochloride is filtered off, the mother liquor adhering to the crystals is washed with ethanol and the product is dried. 20

The aminoacetic acid ethyl ester hydrochloride prepared according to the process does not need to be further purified prior to further processing because it does not decompose during synthesis and crystallizes from the reaction mixture into a very pure form of the aminoacetic acid ethyl ester hydrochloride. Contamination with aminoacetic acid - e.g. ammonium chloride - remains dissolved in the mother liquor and is thus removed from the product. 30

For economic reasons, it is advisable to regenerate the crystallization mother liquor and reuse the recovered ethanol. Ethanol can be recovered by fractional distillation. The crystallization mother liquor may be fractionated acidically or after neutralization, and accordingly the recovered ethanol contains water in the former case and hydrochloric acid in the latter case only water.

Regenerated ethanol, whether acidic or neutral, can be recycled to the manufacturing process.

The advantages of the present invention over the known methods are summarized below

Preparation of ethyl aminoacetic acid hydrochloride is simpler because of the lack of two operations, dehydration of the reaction mixture and separate purification of the final product; the product can be manufactured in conventional chemical plant installations without the need for a dedicated plant; the product is of good quality because the reaction mixture does not have to be dehydrated at high temperature and thus no foam decomposition occurs and recovery of the aminoacetic acid ethyl ester hydrochloride by crystallization is also used as a purification step as any impurities in the crystallization mother liquor are removed side (e.g., ammonium chloride);

the feedstock consumption is favorable because the yield of aminoacetic acid is good and the excess ethanol used can be traced back to the production process after regeneration.

Example 1

In a cooled, heated 4000 L enameled reactor equipped with a stirrer, thermometer, reflux condenser, gas inlet, 2400 kg of anhydrous ethanol are added followed by stirring with 215 kg of aminoacetic acid. While stirring and cooling, 500 kg of hydrochloric acid gas was introduced into the suspension at such a rate that the reaction temperature was 60-75 ° C. After the introduction of the hydrochloric acid gas, the reaction mixture was maintained at the same temperature for one hour to dissolve the larger aminoacetic acid crystals and then cooled gradually. During cooling, the ethyl aminoacetic acid hydrochloride precipitates as larger crystals. The precipitated crystals were removed from the reaction mixture by filtration, covered with anhydrous ethanol and dried. This gives 376 kg of ethyl acetic acid hydrochloride. Yield 94%.

The mother liquor obtained after filtration was supplemented with 240 kg of anhydrous ethanol and returned to the reactor. 215 kg of aminoacetic acid are added to the supplemented mother liquor with constant stirring and cooling, and 150 kg of hydrochloric acid gas are continuously introduced into the suspension at a temperature of 60-75 ° C. After the addition of hydrochloric acid gas, the reaction mixture was maintained at the same temperature for one hour, then cooled gradually, the precipitated crystals of aminoacetic acid ethyl ester hydrochloride were filtered off, the mother liquor was washed with anhydrous ethanol and the resulting product dried.

The dry aminoacetic acid ethyl ester hydrochloride weighs 386 kg.

The crystallization mother liquor is recycled four times in total without regeneration and in each case proceeded as above. The crystallization mother liquor is then regenerated by fractional distillation. Ethanol obtained by distillation and containing a small amount of water and hydrochloric acid as the main product is recycled without further purification. A total of 1075 kg of aminoacetic acid is used in the production and 1919 kg of ethylacetate of aminoacetic acid are obtained.

Yield 95.97%. Aminoacetic acid ethyl ester hydrochloride Analytical assay yields: Aminoacetic acid ethyl ester the following origin hydrochloride 98.2% aminoacetic acid hydrochloride 1.4% ethanol 0.2% unidentifiable impurities Melting point: 143-144 ° C 0.2%

HU 200158 A

Example 2

Into a 0.5 liter cooled flask equipped with stirrer, thermometer, reflux condenser was added 230 g (5 moles) of absolute ethanol, 75 g (1 moles) of aminoacetic acid were added with stirring, and then hydrochloric acid gas was introduced into the suspension. The temperature rises rapidly when the temperature of the reaction mixture reaches 60 ° C, and cooling is started by adjusting the temperature during the introduction of the hydrochloric acid gas to 60-75 ° C. The reaction mixture total

91.3 g (2.5 mol) of hydrochloric acid gas were introduced. The reaction mixture was then heated at 70-75 ° C for an additional hour. During this time, all the aminoacetic acids are dissolved. The homogeneous solution was cooled to 15-20 ° C, the precipitated crystals were filtered off, washed with ethanol and dried at about 100 ° C. The resulting aminoacetic acid ethyl ester hydrochloride was 132 g. Yield 94.6%.

Product composition:

aminoacetic acid ethyl ester hydrochloride 98.6% aminoacetic acid hydrochloride 1.0% ethanol 0.2% not identified 0.2%

Melting point: 143.3-144 ° C

Example 3

Into a cooled 0.5 liter flask equipped with a stirrer, thermometer, reflux condenser, weigh 250 g of a mixture of water and ethanol containing 230 g (5 moles) of ethanol and 20 g of water. While stirring continuously, 75 g (1 mol) of aminoacetic acid are added and the hydrochloric acid gas is introduced into the suspension. The temperature of the reaction mixture is maintained under cooling at 60-75 ° C during the introduction of hydrochloric acid gas.

A total of 91.3 g (2.5 mol) of hydrochloric acid gas was introduced. The reaction mixture was stirred at 60-75 ° C for one hour. The homogeneous solution is crystallized from ethyl acetate hydrochloride under cooling. The reaction mixture was cooled to 15-20 ° C and the crystals were filtered off, washed with ethanol and dried at about 100 ° C. The product obtained is 130 g, 93.18% of the stoichiometric amount. The product melts at 143-144 ° C.

Ingredients:

aminoacetic acid ethyl ester hydrochloride 98.4% aminoacetic acid hydrochloride 0.9% ethanol 0.3% not identifiable 0.4%

Example 4

In a 3000 liter 5 enameled reactor equipped with a stirrer, thermometer, reflux condenser, 1000 kg of a mixture of regenerated and fresh ethanol containing 900 kg (19.6 km) of ethanol, 25 kg of hydrochloric acid and 75 kg of water are charged. Then, with constant stirring, 505 kg of wet aminoacetic acid was added, containing 375 kg of aminoacetic acid (5 km), 100 kg of ethanol (2.2 km) and 30 kg of water. While stirring the suspension, the introduction of hydrochloric acid gas is started. The reaction mixture was allowed to warm to 60 ° C, then at constant cooling, hydrogen chloride gas was added, controlling the cooling to maintain a temperature of 60-75 ° C during the introduction of hydrogen chloride gas to a total of 438 kg (12 km) of 20 hydrochloric acid gas. we introduce. The reaction mixture then becomes saturated with hydrochloric acid, which is indicated by the breakage of the hydrochloric acid gas. The temperature of the reaction mixture was then maintained at 60-75 ° C for an additional hour. The resulting solution was cooled to 1525 -20 ° C when the ethyl aminoacetic acid hydrochloride precipitated in crystalline form. The crystals were removed from the reaction mixture by filtration, washed with ethanol and dried. The product obtained was 634 kg, corresponding to a yield of 90.9%.

Melting point: 143-144 ° C.

Product composition:

aminoacetic acid ethyl ester hydrochloride 98.5% aminoacetic acid hydrochloride 1.0% ethanol 0.2% not identified 0.3%

The crystallization mother liquor, which contains hydrochloric acid, is recovered by fractional distillation to give ethanol containing hydrochloric acid and water as the main product. The latter is mixed with fresh ethanol to replace the ethanol used in the production process and recycled to the production process.

Example 5

A 3,000 liter reactor with stirrer, thermometer, reflux heater, is charged with 1060 kg of a mixture of regenerated and fresh ethanol containing 900 kg (19.6 km) of ethanol, 86 kg of hydrochloric acid and 74 kg of water. In the following, the procedure of Example 4 is followed. The product obtained was of the same quality as in Example 4. The dry product weighs 630 kg and yields 90.4%.

Example 6

In a 3000 liter enameled reactor equipped with a stirrer, a thermometer, a reflux condenser, 1000 liters of a mixture of generated and fresh ethanol (920 kg) was charged into 1000 liters of enamelled reactor.

EN 200158 Contains (20 km) ethanol and 80 kg water. In the following, the procedure of Example 4 is followed. The product obtained was of the same quality as in Example 4. The product weighs 627 kg and yields 90%.

The crystallization mother liquor was neutralized and the ethanol was recovered as a crude product by fractional distillation. The recovered ethanol is mixed with fresh ethanol to replace the ethanol used in production. In this way, ethanol containing 5-8% by weight of water is obtained and can be recycled.

Example 7

The procedure of Example 2 was followed except that during the crystallization, hydrogen chloride gas was continuously passed through the reaction mixture.

The dry weight of the aryl acetic acid ethyl ester hydrochloride was 133 g, corresponding to a yield of 95.34%.

The product quality is the same as in Example 2.

Example 8 (Comparative Example)

Analytical Biochemistry 41, 487-491 (1971)

Weigh into a 500 ml flask with a stirrer, thermometer and condenser:

0.1 g of 7.5 g glycine in 200 ml of 95% ethyl alcohol, 150 ml of benzene and ml of concentrated hydrochloric acid solution are then distilled under stirring and on a reflux condenser. The azeotropic mixture begins to distil at 66 ° C. 200 ml distillate (azeotropic mixture) was collected over 30 minutes. The temperature rises to 72 ° C. The reaction mixture was then quenched with 95% ethyl alcohol (150 mL) and benzene (150 mL) and distilled to 72-74 ° C. Again, 200 ml of distillate are distilled off over 30 minutes. The mixture was then heated to reflux for 90 minutes and then 50 ml of 95% ethanol and 50 ml of benzene were added. The reaction mixture was distilled using a land cooler, ca. Collect 100 ml of distilled water over 15 minutes. The mixture is then heated to gentle boiling for 60 minutes. The reaction mixture was cooled to 50 ° C and concentrated in vacuo under a stream of nitrogen. After evaporation of the solvent, an oily residue was obtained, which was cooled, mixed with 100 ml of diethyl ether, filtered and dried at 50 ° C in vacuo.

Weight of the crude product: 9.0 g Analysis of the product obtained:

chloride content: 27.5% glycine ethyl ester, HV1: 80.0% glycine HCl: 20%

Yield: 51.61%.

Claims (2)

25 PATENT CLAIMS 1.) A process for preparing ethyl acetate of aminoacetic acid by reaction of aminoacetic acid, ethanol, hydrochloric acid, characterized in that: A mixture of 30 aminoacetic acid and ethanol in a ratio of 1:15, preferably 1: 2-6 by weight, is reacted at a temperature of up to 80 ° C with hydrochloric acid gas of 1: 0.5-3, preferably 1: 1-2 by weight, to form the aminoacetic acid. The reaction mixture is cooled to 0-40 ° C, preferably 0-15 ° C, and the precipitated solid aminoacetic acid ethyl ester hydrochloride is removed from the reaction mixture by filtration in a known manner, the residual mother liquor being ethanol or ether. The acid content of bó40 is optionally recycled to the manufacturing process. 2. A process according to claim 1 wherein hydrogen chloride gas is introduced into the reaction mixture during cooling after the esterification reaction.