DE2122491C3 - Process for the production of D1L-methionine - Google Patents

Description

The invention relates to an improved process for the preparation of D, L-methionine accordingly the preceding claims.

For the production of D.L-methionine via 5- (2-methylmercaptoethyl) -hydantoin and its saponification, various methods are known, which can be represented by the following equations:

CN NH ₄ C-

i We »A

H ₁ CS-CH ₁ ^ CH ₁ -C

HCN

Whom B

Processes for the synthesis of D, L-methionine according to route A are known from US-PS 25 27 366, US-PS 25 57 913 and GB-PS 6 30 139, while those according to route B are described in]. Atner. Chem. Soc. 70 (1948), 1450-51, GB-PS 6 53 803 and Japanese Patent Publication 14 688/1964.

However, there are some disadvantages associated with these methods. So z. B. a very large amount of methyl mercaptan is required in the production of 3-methyl mercaptopropionaldehyde by addition of methyl mercaptan to acrolein and, moreover, the yield of 3-methyl mercaptopropionaldehyde is not high enough. Path B includes two stages; it is therefore a relatively complicated reaction. In addition, in the procedure according to route B, a catalyst is normally required for the addition reaction of the hydrocyanic acid. H ₁ CS-CH ₂ -CH, -CH - C = O

HN NH

Il ο

NH ₄
CO.,

H ₁ CS-CH ₁ CH ₁ -CH-CN

OH

It is therefore an object of the invention to provide a method for the production of D, L-methionine, which can be carried out easily and economically.

It is another object of the present invention to provide a method according to which very pure D, L-methionine can be obtained in high yield.

In attempts to find an improved method for the synthesis of D, L-methionine using Vei Working out acrolein as a starting material, it has been shown that acrolein cyanohydrin is used as the starting material can use that easily by reaction of acrolein with hydrocyanic acid or alkali metal cyanide accessible at low cost.

The method according to the invention can be represented by the following reaction equation:

C = CH-CH-CN + CH., SH + NH / + CO,> H ₁ CSCH ₂ CH ₂ CH-C = O

OH

HN

hydrolysis

D.i. methionine

An essential feature of the present invention consists in the addition of methyl mercaptan the double bond of acrolein cyanohydrin with accompanying hydantoin formation in one step. The The resulting hydantoin is hydrolyzed as a crude product to very pure D, L-methionine in a high bulge. It is worth noting. that in the invention

Process no catalyst has to be added, since the reactant required for hydantoin formation, e.g. B. ammonium carbonate, can serve as a catalyst for the addition reaction of methyl mercaptan with acrolein cyanohydrin. It can be carried out easily and in this way enables D, L-methionine to be produced economically.

Some of the advantages achieved with the method according to the invention over the known methods for the production of D, L-methionine are the following: particularly high yield (based on acrolein cyanohydrin), high purity of the end product (titer of D, L-methionine = 99 to 99.5%).

The inventive method can advantageously without being adversely affected by the presence of Water can be carried out in the reaction mixture. As can be seen from the diagram below, the methionine yield is only slightly reduced; even if the water content in aqueous methanol than Solvent is 50 percent by weight.

Since acrolein anhydrin is unstable under alkaline conditions, run in the presence of a base in the Usually side reactions such as decomposition and polymerization decrease, so that ultimately most of the Acrolein cyanohydrins is converted into resinous substances. In the method according to the invention becomes acrolein cyanohydrin with methyl mercaptan and a compound necessary for hydantoin formation implemented. Although the latter is often a basic substance, the side reactions mentioned remain in Presence of methyl mercaptan, so that the desired reaction according to the invention in one basic reaction system can proceed smoothly without the formation of resinous substances.

In order to illustrate the effect achieved with the method according to the invention, the following was made Comparative experiment carried out: Acrolein cyanohydrin was with ammonium carbonate in the absence of Methyl mercaptan implemented. Contrary to expectations that 5-vinylhydantoin would form, was obtained a resinous substance of unknown structure. So it must be seen as surprising that according to the invention, the addition of methyl mercaptan to acrolein cyanohydrin and hydantoin formation through The action of a compound which produces ammonia or ammonium ions and a carbon dioxide or Carbonate ions supplying compound in one step, without undesired side reactions such as decomposition and Polymerization of acrolein cyanohydrin can be carried out.

The starting material used acrolein cyanohydrin can after purification by distillation or in Can be used in the form of a solution in a suitable solvent. Acrolein cyanohydrin is a compound which is stable when stored in acidic conditions and at low temperatures.

For the production of 5- (2-methylmercaptoethyl) hydantoin the reaction is carried out in an organic solvent or an aqueous organic Solvent carried out. As organic solvents, all those can be used that do not decompose during the reaction and are inert under the reaction conditions. Examples of this are common solvents such as alcohols. Alcohol ether. Nitriles, nitroalkanes, amides, amines, ethers. Hydrocarbons, halogenated hydrocarbons, ketones, aldehydes, organic carboxylic acids. Ester and the like Lower aliphatic alcohols, lower aliphatic nitriles, nitroalkanes, alcohol ethers, Dialkyl sulfoxides, dialkyl formamides, dialkyl acetamides, alcohol ethers, dialkyl sulfoxides, dialkyl formamides, dialkylacelamides, Hexaalkylphosphoramides, cyclic amines. Examples of preferred solvents are Methanol, ethanol, isopropanol, n-propanol, t-butanol, n-butanol, ethylcnglycol, acetonitrile, propionitrile, malonitrile, Succinic acid nitrile, ethylene glycol monomethyl ether, nitromelhan, nitroethane, dimethylformamide, Dimethylacetamide, N-methyl] pyrrolidone, dimethyl sulfoxide. Hexamethylphosphoramide, pyridine. The organizational Solvents can contain water. The water content is preferably not more than 50 Weight percent

The reaction of this stage is carried out at temperatures of about 50 to 150 ° C.

ίο The reaction time is not decisive; usually the reaction is complete in about 0.5 to 3 hours.

The methyl mercaptan to be used at this stage can be in the gaseous or liquid state. Theoretically, the amount of methyl mercaptan is one equivalent, based on acrolein cyanohydrin; however, it is preferably used in a slight excess.
Examples of compounds which produce ammonia or ammonium ions are gaseous ammonia and liquid ammonia. Ammonium carbonate, ammonium bromide. Ammonium sulfate, ammonium acetate, ammonium cyanide, ammonium carbamate, ammonium hydrogen carbonate. Examples of compounds which produce carbon dioxide or carbonate ions are gaseous carbon dioxide, solid carbon dioxide, ammonium carbonate, ammonium carbamate, ammonium hydrogen carbonate, sodium carbonate. The amount to be used is not decisive; usually 1 to 4 molar equivalents, preferably 1.5 to 3 molar equivalents, based on acrolein cyanohydrin. used.

The reaction can be carried out under atmospheric pressure while blowing or taking gaseous methyl mercaptan into the reaction system Overpressure while holding methyl mercaptan in a liquid state.

After completion of the reaction in the first stage, the reaction mixture as such or if necessary after distilling off solvent, hydrolyzed in the second stage, as is the case for the Hydrolysis of hydantoins is known, e.g. B. by heating with caustic soda.

After completion of the second stage, D ₁ L-methionine can easily be obtained in the form of pure crystals from the reaction mixture by isolating and purifying it in a conventional manner, e.g. B. by treatment with a suitable ion exchange resin or by neutralization.

example 1

83 g of acrolein cyanohydrin, 240 g of ammonium bicarbonate and 58 g of methyl mercaptan are added together with 1000 ml of methanol. The mixture was stirred and heated at 80 ° C. for 1.5 hours and then concentrated under reduced pressure. To the resulting brown paste, 600 ml of 3N NaOH was added, followed by 1.5 hours heated to 160 ° C. The reaction mixture was applied to a column with a strongly acidic, heteroporous cation

O ₁₀ exchanger applied, which was then eluted with 5% aqueous ammonia. The eluate was treated with activated charcoal and after concentration gave 120 g of crystalline D, L-methionine (80.7% of theory).

Example 2

A number of experiments were carried out with different solvents as follows: Into a 100 ml stainless steel autoclave

3.32 g of acrolein cyanohydrin and 9.5 g of ammonium bicarbonate were added together with 40 ml of the respective organic solvent. The reaction vessel was externally with dry ice / methanol at - 30 ⁰ C cooled. 2.0 g of cold, liquid methyl mercaptan were introduced into the reaction vessel from a bomb. The reactor was then sealed and shaken in an oil bath at 8O ⁰ C for 1.5 hours. The solvent was then distilled off from the reaction mixture. 40 ml of 2N NaOH were added to the residue and the mixture was then diluted to a total of 50 ml with water. The. The mixture was heated to IbO C "for 1.5 hours and then worked up in the same manner as in Example 1, giving D,! .- methionine in the following yields.

Organic solvent

Yield to

D.i. methionine (%)

Methanol 87.9 Ethanol 84.0 Isopropanol 82.0 t-butanol 80.0 Ethylene glycol 83.5 Acetonitrile 85.2 Nitromethane 76.5 Dimelhylacetamide 83.3 Dimethylformamide 83.0 Tetrahydrofuran 72.1 Pyridine 84.5 Dimethyl sulfoxide 80.5 acetone 74.2 chloroform 72.2 benzene 70.5 Ethylene glycol monomethyl ether 75.5

Example 3

Under the reaction conditions specified in Example 2, a series of experiments with water-containing organic solvents. The results are summarized in the following table.

Aqueous organic solvent

Organic Amount of water Yield to solvent org. Lo crowd D.L meth solvent ionin (ml) (ml) (0/0) Methanol 40 3.5 85.0 Methanol 40 9.0 83.3 Methanol 40 15.0 81.5 Ethanol 40 3.5 81.5 Ethanol 40 9.0 79.5

Organic amount of water yield

Solvent org. Lö- quantity D, L-meth-

sungsmittcls ionin

(ml) (ml) (%)

Ethanol 40

Acetonitrile 40

Isopropanol 40

Dimethylformamide 40

ίο tetrahydrofuran 40

Acetone 40

Example 4

3.32 g of acrolein cyanohydrate, 2.0 g of methyl mercapane and the amount of NHj / CCh b / w indicated below were placed in a 100 ml autoclave. given to the corresponding salts together with 40 ml of methanol. Then the reaction as in Game 2 was carried out. The results are summarized in the following table zo.

15.0 81.2 3.5 85.2 3.5 82.9 3.5 81.0 3.5 72.5 3.5 74.0

NHi / CO; or. crowd Yield to corresponding salts D.l.-meth- ionin (G) (%) Ammonium carbonate 11.5 85.9 Ammonium bicarbonate 9.5 87.8 Liquid ammonia 2.0 83.6 Solid carbon dioxide 5.3 Ammonium carbamate 9.4 80.5 Example 5

3.32 g of acrolein cyanohydrin and 9.5 g of ammonium bicarbonate were dissolved in 40 ml of methanol and then placed in a 100 ml stainless steel autoclave. The outside of the reaction vessel was cooled to -30 ° C. with dry ice / methanol 2.0 g of cold liquid methyl mercaptan were introduced into the reaction vessel, which was then sealed. the Hydantoin synthesis (1st stage) was carried out at various temperatures indicated below. Then the solvent was removed from the reaction

distilled off mixed and 40 ml of 2 N NaOH are added to the residue. This mixture was then diluted with water to a total of 50 ml. The resulting mixture was ^{heated to 160 °} C. for 1.5 hours and worked up as in Example 1, D, L-methionine being used

obtained in the yields given below.

Reaction ^{temperature (0} C)
Response time (hours)
Yield of D, L-methionine,%

60 100 150 2 1 Oi 78 87 "69

1 sheet of drawings

Claims (2)

1 22 claims: 1. A process for the preparation of D, L-methionine, characterized in that acrolein cyanohydrin with methyl mercaptan, an ammonia or ammonium ion yielding compound and a carbon dioxide or carbonate ion yielding compound in an organic, optionally water-containing solvent at about 50 to 150 ^° C. and the hydantoin thus obtained is hydrolyzed in a manner known per se. 2. The method according to claim 1, characterized in that that you can do this in an organic solvent whose water content is no more than 50 percent by weight is carried out.