JP5604255B2 - Method for producing alkylsulfinyl chloride - Google Patents

Description

The present invention relates to a method for producing alkylsulfinyl chloride useful as an intermediate for production of various pharmaceuticals, agricultural chemicals and the like.

Conventionally, as a method for producing alkylsulfinyl chloride useful as an intermediate for production of various pharmaceuticals, agricultural chemicals and the like, for example, a method of obtaining tert-butylsulfinyl chloride by reacting tert-butylsulfinic acid with thionyl chloride, A method of obtaining tert-butylsulfinyl chloride by reacting butyl tert-butanethiosulfinate with chlorine (Patent Document 1 above), tert-butyl tert-butanethiosulfinate and chloride in a methylene chloride solvent A method of obtaining tert-butylsulfinyl chloride by reacting with sulfuryl (Non-patent Document 1) is known.

International Publication No. 03/076374 Pamphlet

Organic Letters, Vol. 1, No. 1 5, p. 783-786 (1999)

According to the methods described in Patent Literature 1 and Non-Patent Literature 1, impurities having physical properties similar to the target product are generated, and separation and purification are difficult. Therefore, in order to obtain a high-purity alkylsulfinyl chloride, for example, it is necessary to perform complicated purification such as a rectification operation with a high number of stages, and therefore, a proposal for a production method with a low impurity content is desired.
In addition, the method using chlorine described in Patent Document 1 is liable to cause an error in the charged amount due to blow-through, and there is a risk that alkylsulfinyl chloride cannot be obtained with a stable quality, and a reaction using gas as a raw material. The equipment corresponding to is required.
Furthermore, in the method described in Non-Patent Document 1, methylene chloride used as a solvent is a harmful substance to the environment, and it is necessary to strictly control the disposal. It was not an advantageous production method.

An object of the present invention is to provide a method for producing a highly pure alkylsulfinyl chloride by an industrially advantageous method.

（式中、Ｒ^１およびＲ^２は、それぞれ独立して、炭素数１〜６のアルキル基または炭素数３〜６のシクロアルキル基を示す。）で表されるアルキルアルカンチオスルフィネートと塩化スルフリルとを無溶媒下で反応させる、式（２）：

（式中、Ｒ^１は、式（１）におけるＲ^１と同じ基を示す。）で表されるアルキルスルフィニルクロライドの製造方法。
項２．式（１）におけるＲ^１が、炭素数１〜６のアルキル基であり、Ｒ^２がＲ^１と同じ基である、項１に記載のアルキルスルフィニルクロライドの製造方法。 The present invention relates to a method for producing alkylsulfinyl chloride as shown below.
Item 1. Formula (1):

(Wherein R ¹ and R ² each independently represents an alkyl group having 1 to 6 carbon atoms or a cycloalkyl group having 3 to 6 carbon atoms) and an alkylalkanethiosulfinate represented by Reaction with sulfuryl in the absence of solvent, formula (2):

(Wherein, R ¹ has the formula (1) represents the same group as R ¹ in.) Alkylsulfinyl chloride method of manufacturing which is represented by.
Item 2. Item 2. The method for producing an alkylsulfinyl chloride according to Item 1, wherein R ¹ in Formula (1) is an alkyl group having 1 to 6 carbon atoms, and R ² is the same group as R ¹ .

The present invention relates to a method for producing an alkylsulfinyl chloride, in which an alkylalkanethiosulfinate and a sulfuryl chloride are reacted in the absence of a solvent. The present invention is described in detail below.

In the production method according to the present invention, “under no solvent” means that substantially no solvent is used. Further, “substantially no solvent” means that no reaction solvent is used, and does not exclude, for example, a trace amount of solvent remaining in alkylalkanethiosulfinate or sulfuryl chloride.
The reason why a high-purity alkylsulfinyl chloride can be easily obtained by reacting an alkylalkanethiosulfinate with sulfuryl chloride in the absence of a solvent is not clear, but in the presence of the solvent, It is considered that the affinity works and the by-product is likely to remain as an impurity in the reaction system. The impurities include not only by-products generated as a side reaction of the reaction but also compounds generated by the reaction of the by-products with each other, and these have similar properties to the target product. Therefore, separation and purification are considered difficult.
On the other hand, in the present invention, by using a predetermined alkylalkanethiosulfinate and sulfuryl chloride, it becomes possible to cause a reaction without using a solvent, and as a result, impurities caused by the solvent are generated. It is possible to produce a high-purity alkylsulfinyl chloride by suppressing it.
Furthermore, in the production method according to the present invention, the reason why high-purity alkylsulfinyl chloride can be easily obtained by using sulfuryl chloride as the chlorinating agent is not clear, but is due to the difference in reactivity between sulfuryl chloride and chlorine. it is conceivable that.

（式中、Ｒ^１およびＲ^２は、それぞれ独立して、炭素数１〜６のアルキル基または炭素数３〜６のシクロアルキル基を示す。） The alkylalkanethiosulfinate used in the present invention is represented by the formula (1).

(In the formula, R ¹ and R ² each independently represent an alkyl group having 1 to 6 carbon atoms or a cycloalkyl group having 3 to 6 carbon atoms.)

Examples of the alkyl group having 1 to 6 carbon atoms represented by R ¹ and R ² include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert- A butyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl, n-hexyl and the like can be mentioned.
The alkyl group having 1 to 6 carbon atoms may be linear or branched.

Examples of the cycloalkyl group having 3 to 6 carbon atoms represented by R ¹ and R ² include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.
Among these, alkylalkanethiosulfinates in which R ¹ is an alkyl group having 1 to 6 carbon atoms and R ² is the same group as R ¹ are preferably used because they are easily available.

Specific examples of the alkylalkanethiosulfinate represented by the formula (1) include, for example, methylmethanethiosulfinate, ethylmethanethiosulfinate, n-propylmethanethiosulfinate, isopropylmethanethiosulfinate. Nate, n-butylmethanethiosulfinate, isobutylmethanethiosulfinate, sec-butylmethanethiosulfinate, tert-butylmethanethiosulfinate, n-pentylmethanethiosulfinate, isopentylmethanethios Ruffinate, sec-pentylmethanethiosulfinate, tert-pentylmethanethiosulfinate, neopentylmethanethiosulfinate, n-hexylmethanethiosulfinate, cyclohexylmethanethiosulfinate, methylethane Sulfinate, ethyl ethanethiosulfinate, n-propylethanethiosulfinate, isopropylethanethiosulfinate, n-butylethanethiosulfinate, isobutylethanethiosulfinate, sec-butylethanethiosulfinate, tert-butylethanethiosulfinate, n-pentylethanethiosulfinate, isopentylethanethiosulfinate, sec-pentylethanethiosulfinate, tert-pentylethanethiosulfinate, neopentylethanethiosulfate Nate, n-hexylethanethiosulfinate, cyclohexylethanethiosulfinate, methyl n-propanethiosulfinate, ethyl n-propanethiosulfinate, n-propyln-propanethiosulfate , Methyl isopropane thiosulfinate, ethyl isopropane thiosulfinate, n-propyl isopropane thiosulfinate, isopropyl isopropane thiosulfinate, methyl n-butane thiosulfinate, ethyl n-butane thiosulfinate, n-propyl n-butanethiosulfinate, isopropyl n-butanethiosulfinate, n-butyl n-butanethiosulfinate, isobutyl n-butanethiosulfinate, sec-butyl n-butanethiosulfinate Tert-butyl n-butanethiosulfinate, methyl tert-butanethiosulfinate, ethyl tert-butanethiosulfinate, n-propyl tert-butanethiosulfinate, isopropyl tert-butanethios Rufinate, n-butyl tert-butanethiosulfinate, isobutyl tert-butanethiosulfinate, sec-butyl tert-butanethiosulfinate, tert-butyl tert-butanethiosulfinate, methyl n-pentanethios Ruffinate, ethyl n-pentanethiosulfinate, n-propyl n-pentanethiosulfinate, isopropyl n-pentanethiosulfinate, n-butyl n-pentanethiosulfinate, isobutyl n-pentanethiosulfinate , Sec-butyl n-pentanethiosulfinate, tert-butyl n-pentanethiosulfinate, n-pentyl n-pentanethiosulfinate, methyl n-hexanethiosulfinate, ethyl n-hexanethios Rufinay , N-propyl n-hexanethiosulfinate, isopropyl n-hexanethiosulfinate, n-butyl n-hexanethiosulfinate, isobutyl n-hexanethiosulfinate, sec-butyl n-hexanethiosulfinate Tert-butyl n-hexane thiosulfinate, n-pentyl n-hexane thiosulfinate, isopentyl n-hexane thiosulfinate, sec-pentyl n-hexane thiosulfinate, tert-pentyl n-hexane Thiosulfinate, neopentyl n-hexanethiosulfinate, n-hexyl n-hexanethiosulfinate, cyclohexyl n-hexanethiosulfinate, methylcyclohexanethiosulfinate, ethylcyclohexanethiosulfinate , N-propylcyclohexanethiosulfinate, isopropylcyclohexanethiosulfinate, n-butylcyclohexanethiosulfinate, isobutylcyclohexanethiosulfinate, sec-butylcyclohexanethiosulfinate, tert-butylcyclohexanethiosulfinate , N-pentylcyclohexanethiosulfinate, isopentylcyclohexanethiosulfinate, sec-pentylcyclohexanethiosulfinate, tert-pentylcyclohexanethiosulfinate, neopentylcyclohexanethiosulfinate, n-hexylcyclohexanethios Examples include ruffinate and cyclohexylcyclohexanethiosulfinate. Among these, methylmethane thiosulfinate, ethyl ethane thiosulfinate, n-propyl n-propane thiosulfinate, isopropyl isopropane thiosulfinate, n-butyl n-butane thiosulfinate, isobutyl isobutane Osulfinate, sec-butyl sec-butanethiosulfinate, tert-butyl tert-butanethiosulfinate, n-pentyl n-pentanethiosulfinate, isopentylisopentanethiosulfinate, sec-pentyl sec- Pentane thiosulfinate, tert-pentyl tert-pentane thiosulfinate, and neopentyl neopentane thiosulfinate are preferably used.
Commercially available alkylalkanethiosulfinates may be used, and those obtained by various known methods may be used.

In the method for producing alkylsulfinyl chloride of the present invention, the use ratio of sulfuryl chloride is preferably 0.8 to 10.0 moles per mole of alkylalkanethiosulfinate, and is preferably 1.0 to 3. More preferably, it is 0 mol. If the use ratio of sulfuryl chloride is less than 0.8 mol, the reaction may not be completed and the yield may decrease. If it exceeds 10.0 mol, there is no effect commensurate with the use amount, which is not economically advantageous.

In the present invention, the method of mixing the alkylalkanethiosulfinate and sulfuryl chloride in the absence of a solvent is not particularly limited, and examples thereof include a method of adding and mixing sulfuryl chloride with the alkylalkanethiosulfinate. Can do. As the addition method, methods such as gradual addition or dropwise addition can be mentioned, but the reaction of the present invention is an exothermic reaction, and the heat removal efficiency may decrease and the reaction solution may accumulate heat. The method of adding is preferable.

The reaction temperature for reacting the alkylalkanethiosulfinate with sulfuryl chloride is preferably not lower than the melting point of the alkylalkanethiosulfinate, for example, preferably 10 to 100 ° C., 10 to 70 More preferably, it is ° C. If the reaction temperature is less than 10 ° C, the reaction rate may be slow and a long time may be required for the reaction. If the reaction temperature exceeds 100 ° C, a side reaction may occur, resulting in a decrease in yield.

Moreover, although reaction time changes with reaction temperature, it is preferable that the retention time after completion | finish of sulfuryl chloride dripping is 0.5 to 2 hours, for example. In addition, since the said reaction concerning this invention prevents decomposition | disassembly etc. of alkylsulfinyl chloride, it is preferable to carry out in nitrogen atmosphere.

（式中、Ｒ^１は、式（１）におけるＲ^１と同じ基を示す。） The alkylsulfinyl chloride obtained as described above can be isolated by a usual simple unit operation. Specifically, for example, alkylsulfinyl chloride can be easily isolated by distilling the reaction solution after completion of the reaction under reduced pressure.
The alkylsulfinyl chloride obtained as described above is represented by the formula (2).

(In the formula, R ¹ represents the same group as R ¹ in formula (1).)

Specific examples of the alkylsulfinyl chloride represented by the formula (2) include, for example, methylsulfinyl chloride, ethylsulfinyl chloride, n-propylsulfinyl chloride, isopropylsulfinyl chloride, n-butylsulfinyl chloride, isobutylsulfinyl chloride, sec-butyl. Examples include sulfinyl chloride, tert-butylsulfinyl chloride, n-pentylbutylsulfinyl chloride, isopentylsulfinyl chloride, sec-pentylsulfinyl chloride, tert-pentylsulfinyl chloride, neopentylsulfinyl chloride, n-hexylsulfinyl chloride, cyclohexylsulfinyl chloride and the like. It is done.

According to the present invention, alkylsulfinyl chloride can be easily produced with high purity.

EXAMPLES The present invention will be specifically described below with reference to examples. However, the present invention is not limited to these examples.

Production Example 1
A 1 L four-necked flask equipped with a stirrer, thermometer, condenser and dropping funnel was charged with 60.1 g (0.40 mol) of diisopropyl disulfide and 200 g of acetic acid, and maintained at 35 ° C. with 30 wt% peroxidation. Hydrogen water 54.4g was dripped over 0.5 hour, and it stirred at the same temperature for 20 hours. After completion of the reaction, 200 g of 5 wt% aqueous sodium hydrogen sulfite was added dropwise while maintaining the temperature at 10 to 15 ° C. The separated organic layer was neutralized with 30% by weight NaOH aqueous solution and then washed with water. The solvent was distilled off to obtain 64.6 g of isopropylisopropane thiosulfinate. The yield of isopropyl isopropane thiosulfinate was 97.1% based on diisopropyl disulfide.

Production Example 2
In Production Example 1, sec- is the same as Production Example 1 except that 71.3 g (0.40 mol) of di-sec-butyl disulfide was used instead of 60.1 g (0.40 mol) of diisopropyl disulfide. 75.6 g of butyl sec-butanethiosulfinate was obtained. The yield of sec-butyl sec-butanethiosulfinate was 97.2% based on di-sec-butyl disulfide.

Production Example 3
In Production Example 1, tert-butyl disulfide was used in the same manner as in Production Example 1 except that 71.3 g (0.40 mol) of di-tert-butyl disulfide was used instead of 60.1 g (0.40 mol) of diisopropyl disulfide. 75.4 g of butyl tert-butanethiosulfinate was obtained. The yield of tert-butyl tert-butanethiosulfinate was 97.0% based on di-tert-butyl disulfide.

Example 1
A 200 mL four-necked flask equipped with a stirrer, thermometer, condenser and dropping funnel is charged with 58.2 g (0.35 mol) of isopropylisopropane thiosulfinate obtained in Production Example 1 and heated to 25 ° C. While maintaining, 61.4 g (0.46 mol) of sulfuryl chloride was added dropwise over 20 minutes, and the mixture was further stirred at the same temperature for 1 hour. The purity of isopropylsulfinyl chloride in the reaction solution after completion of the reaction was 87.3% according to an area percentage method (hereinafter, abbreviated as GC surface percent method) by GC (gas chromatography).
The reaction solution was distilled under reduced pressure (50 torr at 40 ° C., 5 torr at 45 to 55 ° C.) to obtain 29.2 g of isopropylsulfinyl chloride. The purity of the obtained isopropyl sulfinyl chloride according to the GC plane hundred method was 99.1%, and the yield of isopropyl sulfinyl chloride was 65.9% based on isopropyl isopropane thiosulfinate.

Example 2
A 200 mL four-necked flask equipped with a stirrer, thermometer, condenser and dropping funnel was charged with 68.0 g (0.35 mol) of sec-butyl sec-butanethiosulfinate obtained in Production Example 2. While maintaining at 25 ° C., 61.4 g (0.46 mol) of sulfuryl chloride was added dropwise over 20 minutes, and the mixture was further stirred at the same temperature for 1 hour. The purity of sec-butylsulfinyl chloride in the reaction solution after completion of the reaction was 87.5% according to the GC plane hundred method.
The reaction solution was distilled under reduced pressure (50 torr at 40 ° C., 5 torr at 45 to 55 ° C.) to obtain 32.0 g of sec-butylsulfinyl chloride. The purity of the obtained sec-butylsulfinyl chloride by GC plane hundred method is 99.0%, and the yield of sec-butylsulfinyl chloride is 65.0% with respect to sec-butyl sec-butanethiosulfinate. Met.

Example 3
In a 200 mL four-necked flask equipped with a stirrer, thermometer, condenser and dropping funnel, 68.0 g (0.35 mol) of tert-butyl tert-butanethiosulfinate obtained in the same manner as in Production Example 3 was added. ), 61.4 g (0.46 mol) of sulfuryl chloride was added dropwise over 20 minutes while maintaining the temperature at 25 ° C., and the mixture was further stirred at the same temperature for 1 hour. The purity of tert-butylsulfinyl chloride in the reaction solution after completion of the reaction was 87.7% according to the GC area method.
The reaction solution was distilled under reduced pressure (50 torr at 40 ° C., 5 torr at 45 to 55 ° C.) to obtain 33.0 g of tert-butylsulfinyl chloride. The purity of the obtained tert-butylsulfinyl chloride according to the GC area method is 99.0%, and the yield of tert-butylsulfinyl chloride is 67.0% based on tert-butyl tert-butanethiosulfinate. Met.

Comparative Example 1
In accordance with the description in Non-Patent Document 1, a tert-butyl tert-butanethiosulfinate obtained in the same manner as in Production Example 3 was added to a 500 mL four-necked flask equipped with a stirrer, a thermometer, and a condenser. 0 g (0.35 mol) and 125 g of methylene chloride were charged. While maintaining the temperature at 5 ° C., a solution prepared by mixing 47.2 g (0.35 mol) of sulfuryl chloride and 20 g of methylene chloride was gradually added over 30 minutes, and the mixture was further stirred at the same temperature for 1 hour. The purity of tert-butylsulfinyl chloride in the reaction solution after completion of the reaction was 81.3% according to the GC plane hundred method.
The reaction solution was distilled under reduced pressure (50 torr at 40 ° C., 5 torr at 45 to 55 ° C.) to obtain 31.0 g of tert-butylsulfinyl chloride. The purity of the obtained tert-butylsulfinyl chloride by GC plane hundred method was 93.4%, and the yield of tert-butylsulfinyl chloride was 63.0% based on tert-butyl tert-butanethiosulfinate. Met.

Comparative Example 2
In a 200 mL four-necked flask equipped with a stirrer, a thermometer, a cooling pipe and a gas introduction pipe, 68.0 g (0.35) of tert-butyl tert-butanethiosulfinate obtained in the same manner as in Production Example 3 was added. 37.3 g (0.53 mol) of chlorine was blown in over 40 minutes while maintaining the temperature at 25 ° C., and further stirred at the same temperature for 1 hour. The purity of tert-butylsulfinyl chloride in the reaction solution after completion of the reaction was 84.5% according to the GC area method.
The reaction solution was distilled under reduced pressure (50 torr at 40 ° C., 5 torr at 45 to 55 ° C.) to obtain 32.0 g of tert-butylsulfinyl chloride. The purity of the obtained tert-butylsulfinyl chloride by GC plane hundred method was 96.5%, and the yield of tert-butylsulfinyl chloride was 65.0% with respect to tert-butyl tert-butanethiosulfinate. Met.

By using the method for producing alkylsulfinyl chloride of the present invention, it is possible to easily produce alkylsulfinyl chloride useful as an intermediate for production of various pharmaceuticals, agricultural chemicals and the like with high purity.

Claims (2)

Formula (1):

(Wherein R ¹ and R ² each independently represents an alkyl group having 1 to 6 carbon atoms or a cycloalkyl group having 3 to 6 carbon atoms) and an alkylalkanethiosulfinate represented by Reaction with sulfuryl in the absence of solvent, formula (2):

(Wherein, R ¹ has the formula (1) represents the same group as R ¹ in.) Alkylsulfinyl chloride method of manufacturing which is represented by. The method for producing an alkylsulfinyl chloride according to claim 1, wherein R ¹ in formula (1) is an alkyl group having 1 to 6 carbon atoms, and R ² is the same group as R ¹ .