JP2565372B2 - Method for producing thiol compound - Google Patents

Description

TECHNICAL FIELD The present invention relates to a novel method for producing a thiol compound represented by the following general formula (I) which is useful as an intermediate for agricultural chemicals, pharmaceuticals, dyes, etc. The present invention relates to a process for producing a thiol compound, which comprises reacting a halide compound represented by the general formula (II) described below with thiourea in the presence of a mineral acid and water, and then treating the compound with an alkaline substance.

(Prior art and process leading to the present invention) Conventionally, many methods for producing a thiol compound represented by the following general formula (I) have been proposed. For example,
(1) Method of reacting halide compound with sodium hydrogen sulfide or potassium hydrogen sulfide (The Chemistry
Of the Thiol Group, Part 1, pages 163-2
Page 69, 1974, Seoul Patai, John Willie
(2) Method of reacting halide compound with thiourea in alcohol (JP-A-55-12)
4763), (3) a method of reacting a halide compound with thiosulfuric acid (the same as the literature of the above (1)), and the like.

However, in any of the methods, a bad odor is generated during the reaction operation, and it is difficult to take measures against it. In addition, the method (2), which is generally used, also has a relatively low reaction yield, and therefore improvement thereof is desired. ing.

The present inventors have paid attention to the reaction of the above method (2), conducted extensive studies on substances substituting for alcohol, and when using a mineral acid and water, not only the reaction yield remarkably increased, but also
We obtained the knowledge that no bad odor is generated. The method of the present invention is economically advantageous as compared with the conventional methods, and is also advantageous in the reaction operation and the post-treatment of the reaction product.

DISCLOSURE OF THE INVENTION That is, the present invention provides a compound represented by the general formula (I): R—SH ... (I) (wherein, R is a substituted or unsubstituted 5- or 6-membered aroma having 1 to 3 nitrogen atoms). Group II heterocyclic group), a process for producing a thiol compound represented by the general formula (II): R—X ... (II) (wherein R is as described above and X is a halogen atom). A) and a thiourea in the presence of a mineral acid and water, followed by treatment with an alkaline substance.

The substituent of the aromatic heterocyclic group represented by R in the general formula (I) is a halogen atom, an alkyl group which may be substituted with a halogen atom, an alkenyl group which may be substituted with a halogen atom, or phenyl. Group, carboxyl group, carbamoyl group, N, N-dialkylcarbamoyl group, cyano group, nitro group and the like. The number of the substituents is not particularly limited, and all or part of the aromatic heterocyclic group may be substituted with these substituents, but it is usually 1 to 4 and the number of the substituents is When is 2 or more, they may be the same or different.

The alkyl group preferably has 1 to 6 carbon atoms,
For example, a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group and the like can be mentioned. As the alkenyl group, those having 2 to 6 carbon atoms are preferable, for example, an ethenyl group, a propenyl group, a butenyl group, a pentenyl group, Examples thereof include a hexenyl group, and examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
In addition, the aromatic heterocyclic group may have a nitrogen atom of 1 to
3 groups are included, for example, pyrazolyl group, imidazolyl group, triazolyl group, pyridinyl group, pyrimidinyl group,
Examples thereof include a pyridazinyl group, a pyrazinyl group and a triazinyl group, and among them, the pyridinyl group is more preferable.

Here, preferable halide compounds for applying the method of the present invention are those represented by the following general formula (III).

General formula (III): (In the formula, Hal. Is a halogen atom, Q is a halogen atom, an alkyl group optionally substituted with a halogen atom, an alkenyl group optionally substituted with a halogen atom, a phenyl group, a carboxyl group, a carbamoyl group, N, N-dialkylcarbamoyl group, cyano group or nitro group, n is 0 or an integer of 1 to 4.) Examples of the mineral acid used in the method of the present invention include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid and the like. . Generally, these are used as an aqueous solution, but they may be used as those that generate a mineral acid in the reaction system, and among them, hydrochloric acid or sulfuric acid aqueous solutions are preferable. Further, the alkaline substance may be one used in a usual hydrolysis reaction, and examples thereof include hydroxides and carbonates of alkali metals or alkaline earth metals, and specifically, sodium hydroxide, potassium hydroxide. , Magnesium hydroxide, sodium carbonate and the like. These are usually used as an aqueous solution after they are once dissolved in water.

In the method of the present invention, usually, a halide compound and thiourea are dissolved in a mineral acid or a mineral acid aqueous solution, but if necessary, an aliphatic carboxylic acid or an acid anhydride thereof is additionally used as a solvent, and used. They are reacted under heat and then treated with an alkaline substance. The amount of thiourea used is usually 1 mol or more, preferably 1 to 2 mol, per 1 mol of the halide compound. If it deviates significantly from this range, it is difficult to obtain the desired effect, which is not desirable. The amount of mineral acid and water used is usually 10 to 500% by weight, preferably 50 to 200% by weight, based on the halide compound. The amount of the alkaline substance used is usually 1 to 20 mol per mol of the thiol compound. The reaction of the halide compound and thiourea is usually carried out at a reaction temperature of 50 to 120 ° C, preferably 70 to 100 ° C, and a reaction time of 0.1 to 15 hours, preferably 0.5 to 10 hours. If the reaction temperature and the reaction time deviate significantly from the above ranges, it is difficult to obtain the desired effects.

As the treatment of the alkaline substance in the method of the present invention,
A usual treatment method in the hydrolysis reaction may be used. For example, after cooling the reaction mixture of the halide compound and thiourea, the mixture is put into an aqueous solution of an alkaline substance and mixed with stirring.
Then, the target product can be obtained by subjecting the product to usual post-treatments such as neutralization, filtration, and solvent extraction. The reaction product according to the method of the present invention includes a halide compound as a raw material,
Depending on the reaction conditions and the like, a small amount of each of the sulfide and disulfide compounds represented by the general formulas R—S—R and R—S—S—R (where R is as described above) is contained in addition to the desired thiol compound.

(Example) Next, in order to explain the method of the present invention in more detail, examples are described below, but these do not limit the method of the present invention.

Example 1 50 g of 2-chloro-3-trifluoromethylpyridine and 25.2 g of thiourea were dissolved in 50 g of a 2% hydrochloric acid aqueous solution to give 90-
The reaction was carried out at 95 ° C for 1.5 hours.

After completion of the reaction, the reaction mixture was allowed to cool and then poured into 250 g of 15% aqueous sodium hydroxide solution (37.5 g based on NaOH), the aqueous layer was washed with methylene chloride, adjusted to pH 6 to 7 with hydrochloric acid, and the precipitated crystals were collected. It was collected by filtration, washed with water and dried, and 42.5 g of 2-mercapto-3-trifluoromethylpyridine (yield 86.2
%: Based on the halide compound of the raw material) was obtained. No odor was generated in this reaction operation.

Comparative Example In the above Example 1, 181.5 g of 2-chloro-3-trifluoromethylpyridine and 25.2 g of thiourea were added.
A halide compound was prepared in the same manner as in Example 1 except that 114 g, 2% aqueous hydrochloric acid solution 50 ml were replaced with ethanol 1, reaction temperature 90 to 95 ° C. was changed to 80 ° C., and reaction time 1.5 hours was changed to 26 hours. After reacting with thiourea, the target product was 98.9g (55% yield: based on the halide compound as the raw material).
Stopped to get. Also, a foul odor was generated in this reaction operation.

Examples 2 to 13 Using the raw materials shown in Table 1-1 below, the following first
Table 1-2 shows the results of the reaction under the reaction conditions shown in Table 2 according to Example 1 above. However, in Examples Nos. 4 to 13, the aqueous layer in Example 1 was not washed with methylene chloride.

Halide compounds other than the above, such as 2-bromopyrazine, 3-bromopyridazine, 5-bromo-1-methyl-
Using 4-nitropyrazole, 3-bromo-1,2,4-triazole, 2-bromotriazine, the above-mentioned Examples 1-13
2-mercaptopyrazine, 3-
Mercaptopyridazine, 5-mercapto-1-methyl-
4-Nitropyrazole, 3-mercapto-1,2,4-triazole and 2-mercaptotriazine can be obtained, respectively.

(Effects of the Invention) A specific thiol compound can be easily obtained by reacting a specific halide compound and thiourea in the presence of a mineral acid and water, and then treating with an alkaline substance. According to this method, not only the reaction yield is remarkably improved, but also a bad odor is not generated during the reaction operation,
The post-treatment of the reaction product is simplified and its industrial applicability is enhanced.

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Claims (1)

(57) [Claims] 1. A compound represented by the general formula (I): R-SH ... (I) (wherein R is a substituted or unsubstituted 5- or 6-membered aromatic heterocyclic group having 1 to 3 nitrogen atoms). And a halide represented by the general formula (II): R—X ... (II) (wherein R is as described above and X is a halogen atom). A process for producing a thiol compound, which comprises reacting a compound with thiourea in the presence of a mineral acid and water, and then treating with an alkaline substance.