JPS5838276A - Preparation of 2-mercaptothiazoline-4-carboxylic acid - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate of pesticides and pharmaceuticals, from the easily and economically producible raw materials, under mild conditions, with simple procedure, in high yield, by reacting a beta- halogenoalanine with carbon disulfide in the presence of a basic substance. CONSTITUTION:The objective compound is prepared, economically in an industrial scale, by reacting a beta-halogenoalanine with carbon disulfide in an aqueous solution or in a hydrous organic solvent in the presence of a basic substance preferably at 0-40 deg.C for 5-30hr. The beta-halogenoalanine is usually beta-chloroalanine or beta-bromoalanine, and can be prepared easily from a halogenoacetaldehyde via beta-halogenopropionitrile. The amount of carbon disulfide is usually 1.0- 3.0mol per 1mol of the halogenoalanine, and that of the basic substance is 2.0- 4.0 equivalent (or 3.0-5.0 equivalent when mineral acid salt of beta-halogenoalanine is used as a raw material) based on the halogenoalanine.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 2-mercaptothiazoline-4-carboxylic acid. More specifically, it relates to a method for producing 2-mercaptothiazoline-4-carboxylic acid, which comprises reacting β-halogenoalanine with carbon disulfide in an aqueous solution or a water-containing organic solvent in the presence of a basic substance. .

2-Mercaptothiazoline-4-carboxylic acid is not only useful as an intermediate for agricultural medicines, but also a compound that itself has agricultural chemical activity. It is also a useful compound as a raw material for cysteine, which is a type of sulfur-containing amino acid.

Conventionally, methods for producing 2-mercaptothiazoline-4-carboxylic acid include 1) a method in which cysteine and carbon disulfide are reacted in the presence of sodium hydroxide (U.S. Pat. No. 3,6975L6); -Aminothiazoline-4
- A method of producing carboxylic acid by reacting it with hydrogen sulfide in a solvent is known (Japanese Unexamined Patent Publication No. 101゜671/1989). However, method 1) uses expensive cystine as a raw material and performs the reaction in alkaline conditions, which tends to induce side reactions such as oxidation of cysteine. It has drawbacks such as low yield. Furthermore, method 2) requires a significantly large excess of hydrogen sulfide in the autoclave reaction, which poses a problem in terms of reaction operation.

As described above, the conventionally known production methods are not always advantageous for industrial use.

The present inventors have intensively investigated the industrial production method of 2-mercaptothiazoline-4-carboxylic acid, and as a result, we have found that β-halogenoalanine is used as a raw material, and it is disulfidized in the presence of a basic substance in water or a water-containing organic solvent. By reacting with carbon under mild conditions, 2-mercaptothiazoline-4 can be produced in high yield.
- The method of the invention for producing carboxylic acids has been achieved. The method of the present invention is a unique production method that has not been known in the past. 1) The raw material β-halogenoalanine is a compound that can be easily and inexpensively produced, 2) The reaction conditions are mild, and It is a highly industrially valuable production method that has various advantages such as the ability to produce 2-mercaptothiazoline-4-carboxylic acid in high yields, and 3) simple reaction operations.

The β-nologeno77ine used in the method of the present invention can be obtained by producing β-halogenopropionitrile from halogenoacetaldehyde and hydrolyzing this with a mineral acid, or
Alternatively, it can be easily produced by ring-opening aziridine-2-carboxylate with hydrochloric acid or hydrobromic acid. As β-halogenoara, diamine, β-
There are no particular restrictions on the form in which chloroalanine or β-promoalanine is used, and it may be used in either free form or in the form of mineral acid salts such as hydrochloride or sulfate. Can be done.

In the method of the present invention, carbon disulfide is used in an amount of 1 equivalent or more relative to β-halogenoalanine. There is no particular restriction on the upper limit of the amount used, but it is industrially undesirable to use too much. Usually, the molar ratio to β-halogenoalanine is in the range of 10 to 6.0.

The basic substances used in the method of the present invention include alkali metal or alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, magnesium hydroxide or barium hydroxide, carbonate Carbonates or bicarbonates of alkali metals or alkaline earth metals such as sodium, sodium bicarbonate, potassium carbonate, potassium bicarbonate, lithium carbonate, lithium bicarbonate, calcium carbonate or calcium bicarbonate, calcium oxide or magnesium oxide, etc. Metal oxides or common inorganic bases such as ammonia can be used. The amount of these basic substances used is 2 equivalents or more when the raw material β-halogenoalanine is used in free form, and 3 equivalents or more when used as a mineral salt. If the amount of base used is less than the above amount, the reaction will not be completed and the yield of 2-mercaptothiazoline-4-carboxylic acid will decrease.

There is no particular restriction on the upper limit of the amount used, but there is no need to use it in excess. Usually, it is used in an amount of 20 to 40 equivalents relative to β-halogenoalanine (3.0 to 50 equivalents when a mineral salt of β-halogenoalanine is used as a raw material).

The reaction is carried out in water or a water-containing organic solvent.

As the water-containing organic solvent, a mixture of water and an alcohol such as methanol, ethanol or isopropanol, or an organic solvent such as acetone, dioxane or tetrahydrofuran is used. There is no particular restriction on the amount of solvent used.

There are no particular restrictions on the reaction method or the order of addition of raw materials, but usually β-chloroalanine is dissolved or suspended in water or a water-containing organic solvent, carbon disulfide is added, and then a base is added to cause the reaction.

The reaction temperature and time are -20 to 70°C for 0.5 to 50 hours, preferably 0 to 40°C for 0.5 to 60 hours, and the end point of the reaction can be easily determined by means such as thin layer chromatography. .

After the reaction, 2-mercaptothiazoline-4-carboxylic acid is removed from the reaction system by distilling excess carbon disulfide out of the system using an appropriate method, and then acidifying it with a mineral acid such as hydrochloric acid or sulfuric acid. can be released.

The present invention will be explained below with reference to Examples.

Example 1 After suspending 12.35 g of β-chloroalanine in 20.9 g of water and adding 11.49 g of carbon disulfide,
While stirring, add 15.0 g of 29 thiammonia water to approximately 15
It was then added dropwise. The reaction was carried out at 15-20'O for 15 hours, and after the reaction, excess carbon disulfide was distilled off under reduced pressure. Subsequently, 20 g of concentrated hydrochloric acid was added and the mixture was cooled to 500 ml. The precipitate was separated, washed with a small amount of cold water, and then dried.

・Yield: 13.49 (yield: 82%/based on β-chloroalanine) Melting point: 167-168.5°C The crude product was recrystallized from 50 rrrl of water and had a melting point of 169-168.5°C.
11.5 g of white columnar crystals of 2-mercaptothiazoline-4-carboxylic acid were obtained at 1695°C.

Actual value (@, 29ro9 5.15 8.56
59.4(] Proton NMTIL spectrum and infrared absorption spectrum also confirmed that this product was 2-mercaptothiazoline-4-carboxylic acid.

Example 2 In Example 1, 45% was used instead of 29% ammonia water.
The same procedure as in Example 1 was conducted except that 196 g of sodium hydroxide was used. 12.2g (yield 75ti/β-chloroalanine) of 2-mercaptothiazoline-4-carboxylic acid was obtained.

Example 12.35g of β-chloroalanine was suspended in 50ml of water, 114g of carbon disulfide was added,
The mixture was allowed to react at 5 to 40°C for 5 hours.

After the reaction, the same treatment as in Example 1 was carried out.

12.8 g (yield: 78.5%/β-chloroalanine) of 2-mercaptothiazoline-4-carboxylic acid was obtained.

Example 4 160 g of β-chloroalanine hydrochloride was dissolved in 50 me of water, 11.4 g of carbon disulfide was added, and the mixture was heated at 15 to 20 degrees.
After gradually charging 135 g of calcium hydroxide at step C,
The mixture was heated to 0°C and reacted at the same temperature for 8 hours. After the reaction, excess carbon disulfide was distilled off under reduced pressure, and 36 g of concentrated hydrochloric acid was added.
When 2-mercaptothiazoline-4-carboxylic acid was added, 2-mercaptothiazoline-4-carboxylic acid was precipitated. After cooling to 50C, it was separated, washed with cold water, and then dried. Crude crystals 12.5.9 of 2-mercaptothiazoline-4-carboxylic acid (yield 76.7%/β-chloroalanine) were obtained. Melting point 166-167°C0 Patent applicant Mitsui Toatsu Chemical Co., Ltd.

Claims (1)

[Claims] (1) A method for producing 2-mercaptothiazoline-4-carboxylic acid, which comprises reacting β-halogen, r-alanine, and carbon disulfide in the presence of a basic substance.