JP2708617B2 - Method for producing 4,4-dialkyl-substituted thiazolidinethione - Google Patents

Description

The present invention relates to a method for obtaining a 4,4-dialkyl-substituted thiazolidinethione without by-producing a 5,5-dialkyl-substituted thiazolidinethione or the like.

(Prior Art) Conventionally, a method for synthesizing a substituted thiazolidinethione is described in, for example, Bulletin de la socie'te 'de France 1973 3 9
It was often produced by the method described on page 71. However, this document does not describe a method for producing 4,4-dialkyl-substituted thiazolidinethione. When the present inventors tried to produce 4,4-dialkyl-substituted thiazolidinethione (I) by the method described in this document, it was found that a clearly large amount of 5,5-dialkyl-substituted thiazolidinethione (II)
I) was a by-product.

A great deal of labor was required to separate the two.

Japanese Patent Application Laid-Open No. 57-192376 discloses a similar method, but this method cannot not only suppress the by-product of 5,5-dialkyl-substituted thiazolidinethione, but also generate oxazolidine in addition to thiazolidine. . This can easily be imagined from the fact that the substituted oxazolidine is produced under similar reaction conditions (J. Chem. Soc. Perkin Trans. I 1985, page 2361).

J. Amer. Chem. Soc., 1953, 75, 1490, 2,2
A method is described in which a dialkyl-substituted ethyleneimine (IV) or 2-amino-2,2-dialkyl-alkanol (V) is reacted with carbon disulfide in an autoclave. However, this method requires a special reaction apparatus called an autoclave, and uses 2,2-dialkyl-substituted ethyleneimine, which has a problem in safety, and is greatly restricted in industrial implementation. Also, the yield is not very good.

On the other hand, in J. Org. Chem., Vol. 30, pages 491 and 495, the same starting compound as in the present invention is reacted with an equimolar amount of potassium alkyl xanthate, but the yield is not good. In addition, in experiments performed by the present inventors, a large amount of 5,5-dialkyl-substituted thiazolidinethione was clearly produced as a by-product.

(Problems to be Solved by the Invention) As described above, the production of 4,4-dialkyl-substituted thiazolidinethione has a major problem of by-product of 5,5-dialkyl-substituted thiazolidinethione. There are various possible causes for this, but via ethyleneimine as an intermediate,
It is believed that the reactivity produces 5,5-dialkyl-substituted thiazolidinethiones.

(Means for Solving the Problems) The present invention provides a method for reacting 2-amino-2,2-dialkylethanol sulfate with 2 or more equivalents of an alkylxanthogenate alkali salt under non-aqueous conditions to obtain 5,5
Without by-producing 5-dialkyl-substituted thiazolidinethione,
The inventors have found that 4,4-dialkyl-substituted thiazolidinethiones can be selectively obtained in high yield, and have completed the present invention.

The 2-amino-2,2-dialkylethanol sulfate used in this reaction includes 2-amino-2,2-dimethylethanol sulfate, 2-amino-2-methyl-2-ethylethanol sulfate, -Amino-
2,2-diethylethanol sulfate, 2-amino-
Examples thereof include 2,2-dipropylethanol sulfate and 2-amino-2,2-dibutylethanol sulfate. Such 2-amino-2,2-dialkylethanol sulfate can be prepared from 2-amino-2,2-dialkylethanol and sulfuric acid by the method described in J. Org. Chem., Vol. 30, page 491, and page 495. Can be easily manufactured.

Examples of the alkali alkyl xanthate used in the reaction include sodium methyl xanthate, sodium ethyl xanthate, sodium propyl xanthate, sodium butyl xanthate, potassium methyl xanthate, potassium ethyl xanthate, potassium propyl xanthate, and butyl And potassium xanthate. As this compound, an isolated compound may be used, or more simply, a compound produced from an alkali metal alkoxide and carbon disulfide is used without isolation. In that case, the same alcohol as the alkoxide is used as the solvent.

This reaction is performed under non-aqueous conditions, and the solvent is preferably an alcoholic solvent such as methanol, ethanol, propanol, isopropanol, and butanol. The alcohol solvent from which the above-mentioned alkali salt of alkyl xanthate has been used can be used as a solvent as it is.

The reaction can be performed at a temperature ranging from room temperature to 150 ° C. More preferably, it is in the range of 40 to 100 ° C. The concentration of the reaction is not particularly limited, but is usually 5 to 50% by weight / volume.
It is performed in the range. The reaction is usually completed within 5 hours.

The most important factor in the present process is the molar ratio of 2-amino-2,2-dialkylethanol sulfate to alkali alkyl xanthate, which is 2-amino-2,2
The alkali alkyl xanthate must be at least 2 moles per mole of dialkyl ethanol sulfate. Preferably it is in the range of 2.0 to 3.5 moles.

After the completion of the reaction, the reaction mixture is acidified with hydrochloric acid, sulfuric acid, acetic acid, phosphoric acid, or the like, and then the solvent is usually removed by distillation under reduced pressure, and the desired product is obtained from the resulting residue by distillation, recrystallization, or the like.
Since the product obtained in this reaction contains almost no impurities, a product which can be used for ordinary organic chemical reactions can be obtained by merely performing extraction and concentration operations.

As the 4,4-dialkyl-substituted thiazolidinethione obtained in the present invention, 4,4-dimethylthiazolidinethione,
4,4-diethylthiazolidinethione, 4-methyl-4-
Ethyl thiazolidinethione, 4,4-dipropylthiazolidinethione, 4,4-dibutylthiazolidinethione and the like can be mentioned.

(Example) The production method of the present invention will be further described with reference to examples.

Example 1 In an argon atmosphere, 92 g of carbon disulfide (1.2 g) was added to 232 g (1.2 mol) of a methanol solution of 28% sodium methoxide.
2 mol) was added dropwise over 20 minutes at a temperature of 20 ° C. or lower, and then stirred at room temperature for 1 hour. A methanol suspension (200 ml) of 102 g (0.6 mol) of 2-amino-2,2-dimethylethanol sulfate was added to the thus obtained solution containing methyl xanthate sodium salt. The reaction solution was heated and stirred for 2 hours while being heated to 55 ° C. After cooling, the mixture was neutralized to pH 6.8 with dilute hydrochloric acid, and 900 ml of water was further added. The mixture was extracted five times with 200 ml of methylene chloride, dried and concentrated to obtain a solid (94.8 g). The solid was recrystallized from methylene chloride-n-hexane to obtain 80.2 g of 4,4-dimethylthiazolidinethione. Yield 91%. Melting point 11
7.5-118.5 ° C.

When the reaction product was measured by high performance liquid chromatography, the formation ratio of 4,4-dimethylthiazolidinethione to 5,5-dimethylthiazolidinethione was about 10,000: 1.

High-performance liquid chromatography conditions Column: ODS-80TM, Eluent: acetonitrile: 0.5% ammonium acetate aqueous solution = 1: 3, measurement wavelength: 272 nm, flow rate: 1.
0 ml / min., Column temperature 40 ° C.

Comparative Example 1 Bulletin de la socie'te 'de France 1973 3 971
It carried out as follows according to the method of a page.

Under an argon atmosphere, 37.6 g (0.22 mol) of 2-amino-2,2-dimethylethanol sulfate and 100 ml of water were added. In addition, an aqueous solution containing 8 g (0.56 mol) of NaOH (8
0 ml) was added. 17.2 ml of carbon disulfide is added to the obtained homogeneous solution.
(0.29 mol) and refluxed for 2 hours. After cooling, the mixture was neutralized with dilute hydrochloric acid (pH 7.0 to 7.2), and cooled to 4 ° C. to precipitate crystals. When the crystals were measured by high performance liquid chromatography, the formation ratio of 4,4-dimethylthiazolidinethione to 5,5-dimethylthiazolidinethione was about 2: 1.

Comparative Example 2 Use of 2-amino-2,2-dialkylethanol sulfate sodium salt In Comparative Example 1, 80 g (0.42 mol) of 2-amino-2,2-dimethylethanol sulfate sodium salt was used. .2 g (0.63 mol) and carbon disulfide 32.4 m
When 1 (0.54 mol) was reacted, the production ratio of 4,4-dimethylthiazolidinethione to 5,5-dimethylthiazolidinethione was about 1: 9, and the target product was hardly produced.

Comparative Example 3 Influence of Molar Ratio of Alkyl Xanthogenate Under an argon atmosphere, 92 g of carbon disulfide was added to 145 g (0.75 mol) of a methanol solution of 28% sodium methoxide.
(0.39 mol) was added dropwise at a temperature of 20 ° C. or lower over 20 minutes, and then stirred at room temperature for 1 hour. 50 g of 2-amino-2,2-dimethylethanol sulfate (0.3 g) was added to the thus obtained solution containing methyl xanthate sodium salt.
(Mole) in methanol (200 ml). The reaction solution was heated and stirred for 2.5 hours while being heated to 65 ° C. After cooling, the mixture was neutralized to pH 6.8 with dilute hydrochloric acid, and 900 ml of water was further added. The mixture was extracted five times with 200 ml of methylene chloride, dried and concentrated. When the concentrate was measured by high performance liquid chromatography, the formation ratio of 4,4-dimethylthiazolidinethione to 5,5-dimethylthiazolidinethione was about 8: 2.

This concentrate was recrystallized as in Example 1 to give 8%
As a result, 8.9 g (21% yield) of 4,4-dimethylthiazolidinethione containing 5,5-dimethylthiazolidinethione was obtained.

Example 2 Under an argon atmosphere, sodium ethoxide 34 g
(0.5 mol) in ethanol solution (100 ml), carbon disulfide
38 g (0.5 mol) was added dropwise at a temperature of 20 ° C. or less over 20 minutes, and then stirred at room temperature for 1 hour. The thus obtained solution containing sodium ethyl xanthate was added with 2-
Amino-2,2-dimethylethanol sulfate 42.5 g
(0.25 mol) of an ethanol solution (200 ml) was added. The reaction solution was heated and stirred for 2 hours while being heated to 55 ° C. After cooling, neutralize to pH 6.8 with dilute hydrochloric acid and add 900 ml of water
Was added. Extraction with methylene chloride (200 ml) five times, drying and concentration gave a solid. This solid is treated with methylene chloride-n
Recrystallization from -hexane gave 32.4 g of 4,4-dimethylthiazolidinethione. 88% yield. When the crystals were measured by high performance liquid chromatography, the content of 5,5-dimethylthiazolidinethione was 0.1% or less.

Example 3 It carried out similarly to Example 1 except having used 2-amino-2,2-diethylethanol sulfate as 2-amino-2,2-dialkyl ethanol sulfate.

4,4-Diethylthiazolidinethione was obtained in a yield of 85%. In high-performance liquid chromatography analysis, 5,5-
Diethylthiazolidinethione was 0.1% or less.

Claims (1)

(57) [Claims] (1) General formula [Wherein R ₁ and R ₂ may be the same or different, and C _1-5
In the method for producing a 4,4-dialkyl-substituted thiazolidinethione represented by the formula: by reacting 2-amino-2,2-dialkylethanol sulfate with an alkali alkyl xanthate, A method for producing a 4,4-dialkyl-substituted thiazolidinethione, which comprises reacting at least two equivalents of an alkali salt of an alkyl xanthate under conditions.