JPH0318617B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an improved production method for consistently obtaining benzenethiols, which are useful as intermediates for pharmaceuticals, agricultural chemicals, and other industrial chemicals, in a stable manner with high yield and high purity. More specifically, as shown in the reaction formula below, the general formula () A general formula () characterized in that a sulfonyl chloride represented by is reduced with phosphorus and iodine in an aqueous hydrogen halide solution activated by heating. The present invention relates to an improved method for producing benzenethiols represented by: However, in the above formula, R represents a hydrogen atom, a halogen atom, or a lower alkyl group, and n represents an integer of 1 to 5. Conventionally, the manufacturing method for benzenethiols is as follows:
A common method is to reduce the corresponding benzenesulfonyl chloride, so as a reducing agent,
Zinc/acetic acid or zinc/mineral acid combinations, red phosphorus/potassium iodide/phosphoric acid combinations, red phosphorus/iodine/acetic acid combinations have been used. However, conventional methods using these reducing agents have the disadvantage that the yield of the target product is low in all cases. Furthermore, methods using zinc require the use of extremely large amounts of zinc, and methods using acetic acid and phosphoric acid have the disadvantage that it is extremely difficult to recover acetic acid and phosphoric acid after the reaction. . For such methods,
In the publication, when aromatic sulfochloride is reduced with red phosphorus and/or yellow phosphorus to produce aromatic mercaptan or/and aromatic disulfide, one of the alkali metal iodides is added in the presence of water.
Methods for producing aromatic mercaptans and aromatic disulfides have been proposed using one or more species as catalysts. However, when this method is used for production on an industrial scale, it has the disadvantage that the desired product cannot always be obtained stably in a high yield.

[Table] The present inventors have conducted extensive research in order to find an industrial production method that can consistently obtain the desired benzenethiols in high yield. As a result, when reducing benzenesulfonyl chlorides with red phosphorus and iodine, the system was activated in advance with an aqueous hydrogen halide solution, and benzenesulfonyl chlorides were added dropwise to the system, thereby improving the various drawbacks of the conventional method. The present invention was completed by discovering that benzenethiols can be produced in high yield and with high purity. In particular, the method of the present invention has the great advantage that benzenethiols can always be obtained in high yield and purity on an industrial scale, regardless of the type of target compound. The improved method for producing benzenethiols of the present invention will be explained in more detail as follows. That is,
Aqueous hydrogen halide solution is added to red phosphorus and iodine and heated to activate the system. Thereafter, benzenesulfonyl chloride dissolved in an inert solvent is gradually added dropwise under reflux, and after the dropwise addition is completed, a boost reaction is carried out to complete the reaction. In this reaction, the amount of red phosphorus is 2 to 3 times the molar amount of the raw material benzenesulfonyl chloride, the iodine is 0.05 to 0.2 times the molar amount, the water is 4 to 6 times the molar amount, and the hydrogen halide is
It may be 0.2 to 0.5 times the molar amount. Further, upon activation, heating and stirring at 100 to 110° C. for 0.5 to 1.5 hours is enough to activate the product. Boost reaction is 0.5 under reflux
The reaction is fully completed in ~1.5 hours. As a solvent for the raw material sulfonyl chloride, aromatic hydrocarbons such as benzene, toluene, and xylene, which are inert to the reaction system, aliphatic hydrocarbons such as heptane and octane, as well as acetic acid and propionic acid can be used. From the viewpoint of reaction temperature, solubility, post-treatment after reaction, etc., aromatic hydrocarbon solvents are preferred, and among these, toluene is particularly preferred. After the reaction, the organic layer is separated, washed with water, and the solvent is distilled off.
Almost pure benzenethiols can be obtained, but if necessary, distillation or addition of an alkali such as sodium hydroxide or potassium hydroxide to make a salt is extracted into an aqueous layer. Higher purity products can also be obtained by adding acids such as The method of the present invention will be specifically explained below with reference to Examples. Example 1

[Formula] Production of (p-methylbenzenethiol) (Reducing agent: red phosphorus, hydrogen chloride aqueous solution, iodine) In a 5-volume four-neck flask, 310 g (10 moles) of red phosphorus, 420 g of 10% hydrogen chloride aqueous solution, and 98 g of iodine.
(0.39 mol) and heated under reflux at 110°C for 1 hour. p-Toluenesulfonyl chloride 953 dissolved in 1200 ml of toluene in advance in this flask.
g (5 mol) was gradually added dropwise at 105°C under reflux,
After the completion of the dropwise addition, a boost reaction is carried out for 2 hours to complete the reaction. The reaction solution was cooled, the organic layer was separated, this organic layer was washed twice with 500 ml of water once, and the solvent was distilled off, p-methylbenzenethiol 605.4
g is obtained. Yield 97%, purity 99.5%, mp43
℃. Example 2

Production of benzenethiol (formula) (reducing agent: red phosphorus, aqueous hydrogen chloride solution, iodine) 92.9 g (3 moles) of red phosphorus, 108 g of 17% aqueous hydrogen chloride solution, and 50.8 g of iodine in a 1-volume four-necked flask.
g (0.2 mol) and heated under reflux at 100°C for 0.5 hour. In this flask, add benzene sulfochloride 176.6, previously dissolved in 250 ml of xylene.
g (1 mol) was gradually added dropwise at 110°C under reflux,
After the completion of the dropwise addition, a boost reaction is carried out for 2 hours to complete the reaction. The reaction solution is cooled, the organic layer is separated, the organic layer is washed twice with 100 ml of water each time, and the solvent is distilled off to obtain 106.9 g of benzenethiol. Yield 97%, purity 99%, bp 169.5℃. Example 3

[Formula] Production of (p-chlorobenzenethiol) (Reducing agent: red phosphorus, hydrogen chloride aqueous solution, iodine) 186 g (6 moles) of red phosphorus, 252 g of 10% hydrogen chloride aqueous solution, and 38.1 iodine in a 3-volume four-necked flask
g (0.15 mol) and heated under reflux at 105°C for 1.5 hours. To this flask, 633.2 g (3 mol) of p-chlorobenzenesulfonyl chloride, previously dissolved in 800 ml of toluene, was gradually added dropwise at 110° C. under reflux, and after completion of the dropwise addition, a boost reaction was carried out for 2 hours to complete the reaction. Cool the reaction solution, separate the organic layer, wash this organic layer twice with 300 ml of water each time,
When the solvent is distilled off, p-chlorobenzenethiol is
423.9g obtained. Yield 95%, purity 97.2%, mp53
℃. Example 4

[Formula] Production of (o-methylbenzenethiol) (reducing agent: red phosphorus, hydrogen chloride aqueous solution,
iodine) o-methylbenzenesulfonyl chloride 190.6
(1 mol), 62 g (2 mol) of red phosphorus, 252 g of 10% aqueous hydrogen chloride solution and 58.8 g (0.23 mol) of iodine were reacted in the same manner as in Example 1 to obtain 119 g of o-methylbenzenethiol. Yield 93%, purity
97%, bp194.2℃. Example 5

[Formula] Production of (m-fluorobenzenethiol) (reducing agent: red phosphorus, aqueous hydrogen chloride solution, iodine) m-fluorobenzenesulfonyl chloride 19.5
g (0.1 mole), red phosphorus 7.7 g (0.25 mole), 10% aqueous hydrogen chloride solution 9 g and iodine 3.8 g (0.015 mole)
The reaction was carried out in the same manner as in Example 1 using 12.6 g of m-fluorobenzenethiol. Yield 95%,
Purity 96.5%, bp62.3℃/13mmHg. Example 6

[Formula] Production of (4-fluoro-2,6-dimethylbenzenethiol) (reducing agent:
Red phosphorus, hydrogen iodide aqueous solution, iodine) 4-fluoro-2,6-dimethylbenzenesulfonyl chloride 22.3g (0.1 mol), red phosphorus 6.8g
(0.22 mol), 9 g of 10% aqueous hydrogen iodide solution and 2.5 g (0.01 mol) of iodine were reacted in the same manner as in Example 1 to obtain 15.1 g of 4-fluoro-2,6-dimethylbenzenethiol. Yield 94%, purity
97.4%, bp94-95℃/13mmHg. Example 7

Production of [Formula] (2,6-dichloro-4-fluorobenzenethiol) (ringing agent:
Red phosphorus, hydrogen bromide aqueous solution, iodine) 2,6-dichloro-4-fluorobenzenesulfonyl chloride 21.2g (0.08 mol), red phosphorus 6.2g
(0.2 mol), 7.2 g of a 10% aqueous hydrogen bromide solution and 3 g (0.012 mol) of iodine were reacted in the same manner as in Example 2 to obtain 15.4 g of 2,6-dichloro-4-fluorobenzenethiol. Yield 94%, purity
96.7%, mp32℃. Example 8

[Formula] Production of (pentachlorobenzenethiol) (reducing agent: red phosphorus, aqueous hydrogen chloride solution, iodine) Pentachlorobenzenesulfonyl chloride 17.4
(0.05 mol), 4 g (0.13 mol) of red phosphorus, 11.6 g of a 15% aqueous hydrogen chloride solution and 2.3 g (0.0009 mol) of iodine were reacted in the same manner as in Example 3 to obtain 13.7 g of pentachlorobenzenethiol. Yield 93
%, purity 96.0%, mp240℃. Comparative Example 1 According to the method of Japanese Patent Publication No. 49-25255

Production of [Formula] (compound name: p-methylbenzenethiol) (reducing agent: potassium iodide, red phosphorus, water) 193.3 g (6.2 mol) of red phosphorus, 166.7 g of potassium iodide ( 1 mol) and water
Charge 270 g (15 mol) of p-
953 g (5 moles) of methylbenzenesulfonyl chloride was added dropwise, and after completion of the dropwise addition, the mixture was left at the same temperature for 3 hours to complete the reaction. After cooling the reaction solution and adding 1500 g of water, the upper layer was separated and toluene was distilled off to obtain 597 g of p-methylbenzenethiol. Yield 78%, purity 81%, mp43℃. Comparative example 2

Production of [formula] (p-methylbenzenethiol) (reducing agent: zinc, dilute sulfuric acid) A 5-capacity four-necked flask was charged with 300 g (4.6 mol) of zinc powder, 600 g (6.1 mol) of concentrated sulfuric acid, and 1800 ml of water. 162 g (0.85 mol) of p-methylbenzenesulfonyl chloride was slowly added dropwise into the solution, and after the addition was completed, the mixture was refluxed for 4 hours to complete the reaction. Thereafter, the reaction solution was subjected to steam distillation, ether was added to the distillate to extract the product, the ether layer was separated, and the ether was distilled off to obtain 116.8 g of p-methylbenzenethiol. Yield 75%, purity 79%, mp43
℃. Comparative example 3

Production of [Formula] (benzenethiol) (reducing agent: red phosphorus, water, iodine) 62 g (2 moles) of red phosphorus in a 1-volume four-necked flask,
76 g (4.2 moles) of water and 19.6 g (0.08 moles) of iodine were charged, and 176.6 g of benzenesulfonyl chloride dissolved in 240 ml of toluene in advance.
g (1 mol) was gradually added dropwise. After the completion of the dropwise addition, a boost reaction is carried out for 2 hours to complete the reaction. The reaction solution was cooled, the organic layer was separated, the organic layer was washed with water, and the toluene was distilled off to remove benzenethiol.
Obtain 90.6g. Yield 56%, purity 68%, bp169.5
g. Comparative example 4

Production of [formula] (benzenethiol) (reducing agent: red phosphorus, iodine, acetic acid) 73.5 g (2.4 mol) of red phosphorus, 3.5 g (0.014 mol) of iodine, and 300 ml of acetic acid in a 1-volume four-necked flask.
176.6 g (176.6 g) of benzenesulfonyl chloride dissolved in 240 ml of toluene in advance.
mol) is gradually added dropwise under reflux. After dropping about 5 g of benzenesulfonyl chloride, the dropping was stopped, and the system was refluxed for 1 hour, and then the remaining toluene solution of benzenesulfonyl chloride was added dropwise.
The boost reaction is carried out under reflux for 3 hours to complete the reaction. Thereafter, 53 g of water was added to the reaction solution and the mixture was refluxed for 1 hour, followed by steam distillation of the reaction solution to obtain 77.9 g of benzenethiol. Yield 53%, purity 75%, b.
p.169.5℃.

Claims (1)

[Claims] 1. In a system in which an aqueous hydrogen halide solution containing phosphorus and iodine is heated and activated, the general formula (In the formula, R represents a hydrogen atom, a halogen atom, or a lower alkyl group, and n represents an integer of 1 to 5.) (wherein R and n are as described above) A method for producing benzenethiols.