CS252564B1 - Method of 2-mercapoethaneulphonic acid production - Google Patents

Abstract

A new process for the production of 2-mercaptoethanesulfonic is solved acid and its salts, which consists in alkylating the alkali thioacetate metal with sodium 2-halosulfonate and in hydrolysis of the resulting 2- (S-acetylmercapto) ethanesulfonate sodium to 2-mercaptoethanesulfonic acid an acid which is isolated by an ion exchanger and optionally converted to the corresponding salt neutralization. Sodium salts of 2-mercaptoethanesulfonic acid can be used in the plastics industry as additives and stabilizers for copolymers and in the dyeing industry as sulphonate dyes on cotton, in pharmacy as a mucolytic agent and an antidote to arsenic and mercury, as well as a supplement cancerostatic agents.

Description

The present invention provides a process for the preparation of 2-mercaptoethanesulfonic acid and salts thereof.

The known preparations of mercaptoethanesulfonic acid and their salts are based on the reaction of sodium 2-bromoethanesulfonate with alkali metal hydrogen sulphide (the oldest work or thiourea, where the SH group is released from the thiuronium salt by treatment with ammonia). Similarly, the 2-mercaptoethanesulfonate is formed from an alkylxanthogenate alkane sulfonate.

Further, the preparation of said compound by the action of hydrogen sulphite on ethylene sulphide has been described.

The hydrolysis of S-tert also leads to the target. sodium butyl mercaptoethanesulfonate with hydrochloric acid.

SUMMARY OF THE INVENTION The present invention provides a novel process for the preparation of 2-mercaptoethanesulfonic acid by treating sodium alkali salt of thiol acetic acid in a solution or suspension of dimethylformamide or an alcohol containing 1 to 4 carbons per molecule or water solution at 50 to 160 ° C for 2 hours. up to 8 hours.

After isolation, the resulting sodium S-acetyl-2-mercaptoethanesulfonate is hydrolyzed by boiling with an aqueous methanolic or ethanolic solution of alkali carbonate or hydroxide for 10 to 160 minutes and then poured through an acidic ion exchange column under an inert atmosphere. After passing through the column with distilled water, the aqueous solution of 2-mercaptoethanesulfonic acid is concentrated to dryness under vacuum and the acid thus obtained is neutralized under an inert atmosphere with a calculated amount of methanolic or ethanolic sodium hydroxide solution or other appropriate alcohol-soluble hydroxide containing 1 to 4 carbons per molecule. The mixture is filtered on a frit or the mixture is evaporated to dryness under reduced pressure.

The advantages of the invention are in the simplicity of preparation, in accessible and inexpensive raw materials and practically waste-free technology, since only the inorganic salts are dispensed with, and the waste solvents from the evaporators can be returned to the process. In addition to elemental analysis, the purity of the products can also be monitored more quickly and during the reaction by isotachophoresis,

2-mercaptoethanesulfonic acid and its salts have been known for many years (from the 1950s) mainly as an antidote to arsenic and some heavy metals, later as a mucolytic agent (Mistabron). Furthermore, it has been found that mercaptoethanesulfonic acid (MESA) is part of coenzyme M, which is a growth factor for methanogenic bacteria, of importance in the anaerobic transformation of organic substances into methane.

Recently, mercaptoethanesulfonic acid sodium (MESNA) has been used in the administration of cytostatic drugs since it reduces their urotoxic effects. Due to the low toxicity and good tolerability of the substance itself, the use of this salt (MESNA) under the name Mitexan, later Uromitexan, was widespread. It has also been possible to incorporate mercaptoethanesulfonate chemically into a molecule of cyclophosphamide type substances, so that new drugs no longer have toxic side effects and thus have increased their importance in the prevention and treatment of urinary tract and other organ tumors.

The use of 2-mercaptoethanesulfonic acid and / or salts thereof results from the above literature review. Its importance and need for the pharmaceutical industry continues to grow. Other uses of this substance are also known, for example as an additive and a stabilizer for copolymers and in the dyeing industry as sulfur dyes for cotton.

The invention and its similar preparations are described in more detail in the following examples.

He did

To 11.4 g (0.1 mol) of potassium thiolacetate was added 100 ml of dimethylformamide and 16.6 g (0.1 mol) of sodium 2-chloroethanesulfonate and the mixture was heated at 90-100 ° C for 7 hours with stirring. While still hot (60-70 ° C), the mixture was filtered through a frit, the collected potassium chloride crystals were washed with 30 ml of dimethylformamide, and the solvent was distilled off under reduced pressure at 50-60 ° C. The solid residue was dissolved in 150 ml of water and filtered with carboraffin while hot. The filtrate was again evaporated to dryness under reduced pressure. The sodium 2- (S-acetylmercapto) ethanesulfonate dried at 130 Pa was weighed 13 g (60%) and recrystallized from methanol, m.p. 244-246 ° C. For C ₇ H ₂ O with Na ^ S calculated 31.08%, found 30.52% P. 'H NMR (done in D ₂ O in the delta-values): 2.38 (CH-CO- ); 3.00-3.40 m (-CH ₂ -CH ₂ -).

Example 2

First, 13.2 g (173.5 mmol) of thiol acetic acid were neutralized with 163 ml of 1 N potassium hydroxide solution and the solution was concentrated to dryness under reduced pressure. After drying and washing with benzene, 18.48 g (162 mmol) of potassium thiol acetic acid salt remained, to which were added 200 ml of ethanol and 34.2 g (162 mmol) of sodium 2-bromoethanesulfonate and the mixture was heated at reflux for 8 hours. Then 100 ml of ethanol were added and after cooling the crystallized product was filtered off.

After systematic crystallization in methanol using carboraffin, 14.5 g (70%) were obtained.

Sodium 2- (S-acetylmercapto) ethanesulfonate, mp 245-247 ° C. For C ₄ H ₇ S ₂ O 4 Na calculated 31.08% S, found 30.65% S. The ¹ H-NMR spectrum (shown in D ₂ O) was consistent with that of the product isolated in Example 1.

Example3

To a solution of 8.55 g (0.15 mol) of potassium hydroxide in 200 ml of ethanol, a solution of 12.17 g (0.16 mol) of thiol acetic acid in 15 ml of absolute ethanol was added dropwise with stirring, and then the solvent was distilled off until dryness on a vacuum evaporator. After washing with benzene and drying, 14.8 g (0.13 mol) of potassium thiolacetate remained, to which 300 ml of propanol and 21.65 g (0.13 mol) of sodium 2-chloroethanesulfonate were added. The suspension was refluxed under nitrogen for 6 hours. After cooling, the propyl alcohol was distilled off under reduced pressure (it can be used for the next reaction after distillation) and 8.25 g of the product with m.p. Mp 240-248 ° C.

Example 4

To 820 ml of 1 N potassium hydroxide solution (0.82 mol) was added dropwise 64.2 g (0.844 mol) of thiol acetic acid under a nitrogen atmosphere and the mixture was distilled to dryness under reduced pressure. 100 ml of benzene-ethanol (4: 1) was added to the residue and the suspension was filtered off with suction on a frit and washed with 20 ml of the mixture, finally twice with 20 ml of petroleum ether (b.p. 45-60 ° C). After drying, 68 g of white crystals of the thiol acetic acid salt remained.

34.24 g (0.3 mol) of potassium thiol acetic acid salt and 300 ml of dimethylformamide were placed in a 1-liter two-necked flask and 50 g (0.3 mol) of sodium 2-chloroethanesulfonate were added portionwise at 50 ° C under stirring. under nitrogen atmosphere over 100 minutes, increasing the temperature gradually to 90 ° C. The reaction mixture was then heated at 95 ° C for an additional 3 hours. After cooling to 70 ° C, undissolved potassium chloride was filtered from the reaction mixture on a frit and dimethylformamide was distilled off under reduced pressure. The residue was then recrystallized three times (using carboraffin) in methanol. 20.1 g of product were obtained, from the mother liquors another 10.7 g (total 50% yield) of sodium 2-mercaptoethanesulfonate, m.p. Mp 240-245 ° C.

Example5

A mixture of potassium thiolacetate (11.4 g, 0.1 mol), sodium 2-chloroethanesulfonate (16.6 g, 0.1 mol) and water (60 ml) was heated at 95 ° C (bath temperature) under stirring under nitrogen for 3 hours. After cooling, the solution was filtered with the addition of carboraffin and the water was distilled off under reduced pressure. The residue is extracted by boiling with 300 ml of methanol and the extract is filtered while hot. Upon cooling from the solution, sodium S-acetyl-2-mercaptoethanesulfonate crystallizes with a melting point of 245-250 ° C. Yield 12-15 g (depending on mother liquor temperature).

Example 6

To a mixture of sodium 2- (S-acetylmercapto) ethanesulfonate (8.25 g, 40 mmol) with ethanol (35 ml) was added a solution of potassium hydroxide (7 g, 0.125 mol) in water (30 ml) and heated at reflux for 15 min. After cooling, the solution was poured onto a column of 100 ml cation exchange resin (Ostion, capacity 2 mval / 1 ml) and washed with 300 ml distilled water. After distilling off the water and the resulting acetic acid under reduced pressure (degassed with nitrogen), 5.6 g (39.5 mmol) of oily 2-mercaptoethanesulfonic acid remained. This was dissolved in 20 ml of ethanol, added slowly with cooling 39.5 ml of a 1N solution of sodium hydroxide in ethanol under a nitrogen atmosphere, and then ethanol and reaction water were distilled off under reduced pressure. After drying, 5.46 g of 2-mercaptoethanesulfonic acid sodium salt remained. To ^ 2 ^ 5 ^ 2 ^ 3 ^ 3 S calculated 39.01%, found 38.42% P. 'H NMR (done in D? O, the delta-values):

2.70-3.49 m (-CH ₂ CH ₂ -).

Claims (1)

SUBJECT OF THE INVENTION Process for the preparation of 2-mercaptoethanesulfonic acid and / or salts thereof, characterized in that the alkali metal salt of thiol acetic acid in a solution of water or in a solution or suspension of dimethylformamide or an alcohol containing 1 to 4 carbons per molecule at 50-160 ° C for for 3 to 8 hours treated with sodium 2-halenethanesulfonate, wherein the halogen is chlorine or bromine, and the resulting sodium 2- (S-acetylmercapto) ethanesulfonate is hydrolyzed by boiling with an aqueous methanolic or ethanolic alkali metal carbonate or hydroxide solution for 10 to 160 minutes whereupon the alkaline solution is poured over a column of acidic ion exchanger and, after isolation, water is distilled off from the aqueous solution of 2-mercaptoethanesulfonic acid under reduced pressure and optionally neutralized with the calculated amount of alcoholic alkali hydroxide solution corresponding to the prepared salt. carbon in the molecule and excreted salts 1 is filtered off or evaporated to dryness under reduced pressure.