JPH07330758A - Production of cyclic sulfur-containing organic compound - Google Patents

Abstract

PURPOSE:To highly selectively produce the subject compound useful as, e.g. an intermediate for synthesis of a herbicide and a raw material for sweetenings in a high yield by reacting a specified 3-halogenothiopropionic acid ester with a thioglycolic acid ester in the presence of a base. CONSTITUTION:The production of this 4,5-dihydro-3-mercaptothiophene-2- caraboxylic acid ester of formula III is carried out by reacting (A) a compound of formula I (R<1> is a 1 to 4C alkyl; X is a halogen) with (B) a compound of formula II (R<2> is R<1>) in the presence of (C) a base such as sodium methylate or sodium hydroxide. In addition, the amount of used component (C) is preferably 0.02 to 10 times mol based on the component (A).

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid which is a compound useful as a synthetic intermediate for agricultural chemicals such as herbicides and a raw material for thiophensaccharin which is a sweetener. The present invention relates to a method for producing an acid ester.

[0002]

2. Description of the Related Art Conventionally, as a method of introducing a mercapto group into a thiophene ring having a substituent, for example, a method of reducing a compound obtained by the method of Rossay et al. it can.

[0003]

[Chemical 2]

In the formula, Ts represents a tosyl group. According to the above method, methyl 3-oxotetrahydrothiophene-2-carboxylate was reacted with tosyl chloride to form a tosylate body, and then reacted with sodium disulfide to obtain 3,
3'-dithiobis (4,5-dihydrothiophene-2-
Carboxylic acid) dimethyl [Journal of Organic Chemistry (J. Org. Chem.), 45
Vol., P. 617 (1980)],
A 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid ester is obtained.

As a method for obtaining 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid ester, for example, Japanese Patent Application No. 5-32 filed by the applicant of the present invention.
The following method described in No. 25 is mentioned.

[0006]

[Chemical 3]

According to this method, 3-oxotetrahydrothiophene-2-carboxylic acid ester is reacted with hydrogen sulfide and hydrogen chloride to give the desired product, 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid. An ester is obtained.

[0008]

In the above method, the acrylic acid ester and the thioglycolic acid ester are reacted to obtain 3-thiaadipic acid diester, which is reacted with a base to cyclize the starting material. -Oxotetrahydrothiophene-2-carboxylic acid ester. This is further reacted with hydrogen sulfide and hydrogen chloride to obtain the desired 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid ester.

However, in the above cyclization reaction, as described below, in addition to 3-oxotetrahydrothiophene-2-carboxylic acid ester substituted at the 2-position in the raw material synthesis process, 3 substituted at the 4-position as an isomer. -Oxotetrahydrothiophene-4-carboxylic acid ester was by-produced, and a process for separating the by-produced isomer was required, and the yield was lowered. Therefore, there were drawbacks in terms of raw material supply as an industrial production method. .

[0010]

[Chemical 4]

In view of the above situation, it is an object of the present invention to provide a method for efficiently producing 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid ester without by-products such as isomers. To do.

[0012]

DISCLOSURE OF THE INVENTION The inventors of the present invention have conducted extensive studies to achieve the above object, and as a result, 3-halogenothionopropione represented by the following general formula (I), which can be easily synthesized, is shown. By reacting an acid ester with a thioglycolic acid ester represented by the general formula (II) in the presence of a base, 4,5-dihydro-3-mercaptothiophene-2- represented by the general formula (III) is obtained. The inventors have found that the carboxylic acid ester can be obtained in a high yield without by-products such as isomers, and reached the present invention.

[0013]

[Chemical 5]

In the formula, R ¹ and R ² are the same or different,
It represents an alkyl group having 1 to 4 carbon atoms, and X represents halogen.

Examples of the alkyl group having 1 to 4 carbon atoms include linear or branched alkyl groups, and examples thereof include methyl, ethyl, n-propyl, n-butyl, isobutyl and sec.
-Butyl, tert-butyl, etc. can be illustrated. Examples of halogen include chlorine atom and bromine atom, and among them, chlorine atom is preferably used.

That is, the present invention eliminates the disadvantages in the supply of raw materials in the conventional method, and uses a thionoester having a thioxo group, for example, 3-halogenothionopropionic acid ester as a raw material, which is used as a thioglycolic acid ester. Focusing on the reaction, the thioxo group changes to a mercapto group, and the target 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid ester is obtained in high yield without by-products such as isomers. It was done.

In the production method of the present invention, as shown below, 1-thiono-4-amino acid is once obtained by the reaction of 3-halogenothionopropionic acid ester and thioglycolic acid ester.
Thiadipic acid diester is formed, which is cyclized to form 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid ester. However, since the reaction rate of this cyclization reaction is fast, and one of the diesters is a thionoester (-C (= S) OR), if this is converted to an alkali, the isomer is not substantially produced as a by-product. Apparently, 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid ester is directly obtained from 3-halogenothionopropionic acid ester and thioglycolic acid ester.

[0018]

[Chemical 6]

Examples of the 3-halogenothionopropionic acid ester represented by the above general formula (I) include the following. Methyl 3-chlorothionopropionate, ethyl 3-chlorothionopropionate, 3-
Isopropyl chlorothionopropionate, n-propyl 3-chlorothionopropionate, n-butyl 3-chlorothionopropionate, isobutyl 3-chlorothionopropionate, sec-butyl 3-chlorothionopropionate, 3 -Tert-butyl chlorothionopropionate,
Methyl 3-bromothionopropionate, ethyl 3-bromothionopropionate, isopropyl 3-bromothionopropionate, n-propyl 3-bromothionopropionate, n-butyl 3-bromothionopropionate, 3 −
Isobutyl bromothionopropionate, sec-butyl 3-bromothionopropionate, tert-butyl 3-bromothionopropionate.

As the 3-halogenothionopropionic acid ester represented by the above general formula (I), those obtained by any method may be used.
Of Organic Chemistry (J. Org. Ch
em. ), Vol. 22, p. 1675 (1957)], and a method of treating imidic acid hydrochloride obtained from acrylonitrile, hydrogen halide and alcohol with hydrogen sulfide.

[0021]

[Chemical 7]

Examples of the thioglycolic acid ester represented by the above general formula (II) include the following. Methyl thioglycolate, ethyl thioglycolate, isopropyl thioglycolate, n-propyl thioglycolate, n-butyl thioglycolate, isobutyl thioglycolate, thioglycolic acid sec-
Butyl, tert-butyl thioglycolate.

The base used in the present invention is not particularly limited, and examples thereof include alkali metal alkoxides such as sodium methylate and sodium ethylate; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; Examples thereof include alkali metal carbonates such as sodium hydrogen carbonate, potassium hydrogen carbonate, lithium hydrogen carbonate, sodium carbonate, potassium carbonate and lithium carbonate.
Among them, alkali metal alkoxides or alkali metal hydroxides are preferably used, and among these, sodium methylate and sodium hydroxide are particularly preferably used in terms of economy, yield and operability during reaction. To be

The amount of the above-mentioned base to be used is usually 0.02 to 10 times by mole with respect to the 3-halogenothionopropionic acid ester, and if the amount is less than 0.02 times by mole, the reaction time becomes long. In some cases, the yield is lowered, and even if it exceeds 10 times by mole, the effect corresponding thereto is not obtained, and in some cases, the yield is lowered, which is not preferable. More preferably, it is 0.1 to 10 times mol.

The above reaction does not necessarily need to use a solvent, but can also be carried out using a solvent. The type of solvent is not particularly limited, but alcoholic solvents such as methanol, ethanol and propanol; aromatic solvents such as benzene, toluene and xylene; aliphatic solvents such as pentane, hexane and heptane; diethyl ether, dimethoxyethane, Examples thereof include ether solvents such as diethylene glycol dimethyl ether and tetrahydrofuran, and among them, alcohol solvents such as methanol, ethanol and propanol are preferably used from the viewpoint of yield.

The reaction temperature is preferably in the range of −20 to 50 ° C., and if it is lower than −20 ° C., the reaction rate is slow, and if it exceeds 50 ° C., by-products increase, which is not preferable. More preferably, it is in the range of 0 to 25 ° C.

4,5-dihydro-obtained according to the invention
Examples of the 3-mercaptothiophene-2-carboxylic acid ester include the following. 4,
Methyl 5-dihydro-3-mercaptothiophene-2-carboxylate, ethyl 4,5-dihydro-3-mercaptothiophene-2-carboxylate, 4,5-dihydro-3-
Isopropyl mercaptothiophene-2-carboxylate,
N-Propyl 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid, n-butyl 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid, 4,5-
Isobutyl dihydro-3-mercaptothiophene-2-carboxylate, sec-butyl 4,5-dihydro-3-mercaptothiophene-2-carboxylate, 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid ter
t-butyl.

Isolation of the above 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid ester is carried out, for example, by
After the solvent is distilled off, it can be easily carried out by a known means such as distillation. In addition, the reaction solution containing the obtained 4,5-dihydro-3-mercaptothiophene-2-carboxylic acid ester is isolated or not isolated, and subsequently, by air oxidation in the presence of a catalyst, 3'-
Dithiobis (4,5-dihydrothiophene-2-carboxylic acid) diester can be obtained.

The obtained 3,3'-dithiobis (4,5-
Dihydrothiophene-2-carboxylic acid) diester is
It can be used as a raw material for pesticide intermediates and thiophensaccharin, a non-toxic sweetener.

[0030]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Production Example 1 Production of methyl 3-chlorothionopropionate 100 equipped with a stirrer, a thermometer, a cooling pipe, and a gas blowing pipe
A 0 ml four-necked flask was charged with 70 g of diethyl ether and 24 g (0.75 mol) of methanol, and then mixed with 39.8 g (0.75 mol) of acrylonitrile. Next, 54.7 g (1.5 mol) of hydrogen chloride gas was blown in, and the reaction was carried out at a temperature of 0 to 5 ° C. Subsequently, 34 g (2.0 mol) of ammonia gas was blown in to neutralize the hydrochloride. The generated salt was filtered off, the filtrate was washed with water, and then 63.2 g (1.86 mol) of hydrogen sulfide was blown thereinto at a temperature of -5 to 0.
The reaction was carried out at ° C. By distilling the filtrate obtained by filtering the reaction solution under reduced pressure, 86.0 g (0.62 mol) of methyl 3-chlorothionopropionate as a yellow oily matter was obtained as a fraction of 63 to 65 ° C./13 mmHg. Obtained. The yield based on acrylonitrile was 83%.

Example 1 300 m equipped with a stirrer, thermometer, cooling pipe, dropping funnel
Methyl thioglycolate 14.9 in a 4-necked 1-liter flask.
g, 50 g of methanol and 62 g (0.32 mol) of 28% sodium methylate were charged. After the mixed solution of 20 g (0.14 mol) of methyl 3-chlorothionopropionate obtained in Production Example 1 and 20 g of methanol was added dropwise to this mixed solution at a temperature of 30 to 35 ° C over 20 minutes. The reaction was completed by continuing stirring at a temperature of 19 to 21 ° C. for 3 hours. The solvent methanol was distilled off from the resulting reaction solution, water was added, and then 36% hydrochloric acid was added to acidify the hydrochloric acid. The target product was extracted from this solution with ether, and the ether was distilled off, followed by vacuum distillation to obtain methyl 4,5-dihydro-3-mercaptothiophene-2-carboxylate as a fraction at 97 to 99 ° C / 4 mmHg. 0.9 g (0.13 mol)
Got The yield based on methyl 3-chlorothionopropionate was 93%.

Example 2 4,5-Dihydro-3-mercaptothiophene was prepared in the same manner as in Example 1 except that 62 g of 28% sodium methylate was replaced with 12.8 g (0.32 mol) of sodium hydroxide. Methyl-2-carboxylate 19.4 g (0.
11 mol) was obtained. The yield based on methyl 3-chlorothionopropionate was 79%.

[0034]

According to the present invention, 3-halogenothionopropionic acid ester and thioglycolic acid ester are
By reacting in the presence of a base, 4,5-dihydro-3-mercaptothiophene-2, which is a cyclic sulfur-containing organic compound useful as an intermediate for pesticides such as herbicides and as a raw material for thiophensaccharin which is a sweetener -Carboxylic acid ester can be efficiently produced.

Claims (6)

[Claims] 1. A method of reacting a 3-halogenothionopropionic acid ester represented by the general formula (I) with a thioglycolic acid ester represented by the general formula (II) in the presence of a base. Represented by the general formula (III)
Process for producing 5-dihydro-3-mercaptothiophene-2-carboxylic acid ester. [Chemical 1] In the formula, R ¹ and R ² are the same or different and have 1 to 4 carbon atoms.
Represents an alkyl group, and X represents halogen. 2. The production method according to claim 1, wherein X is a chlorine atom. 3. The method according to claim 1, wherein R ¹ is methyl. 4. The production method according to claim 1, wherein R ² is methyl. 5. The method according to claim 1, wherein the base is sodium alkoxide. 6. The production method according to claim 1, wherein the base is sodium hydroxide.