JPH08143530A - Production of cyanobenzenesulfonyl chloride - Google Patents

Abstract

PURPOSE: To provide a method for industrially and readily producing cyanobenzenesulfonyl chloride in high yield at a low cost. CONSTITUTION: Cyanothiophenol of formula I, dicyanodiphenyl disulfide of formula II or a mixture thereof is reacted with a chlorinating agent (e.g. chlorine, sulfuryl chloride or phosphorus pentachloride) in the presence of water at -20 to +50 deg.C, preferably -5 to +30 deg.C temperature to provide cyanobenzenesulfonyl chloride of formula III. The raw material compound in the reaction is obtained by halogenating methylthiobenzonitrile of formula IV and then hydrolyzing the resultant compound. When the hydrolysis is carried out in the presence of oxygen, the compound of formula I produced by the hydrolysis is partially oxidized to produce a compound of formula II, which is prepared by oxidizing the compound of formula I.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel method for producing cyanobenzenesulfonyl chloride. Cyanobenzenesulfonyl chloride is a compound useful as a raw material for pharmaceutical intermediates and the like.

[0002]

2. Description of the Related Art Conventionally, the following methods are known as methods for producing cyanobenzenesulfonyl chloride.

Method of reacting 4-aminosulfonylbenzoic acid with phosphorus pentachloride

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Method of reacting 4-cyanobenzenelithium with sulfur dioxide and subsequently with sulfuryl chloride

[Chemical 4]

However, these methods have the following drawbacks. That is, the method (1) has a problem in the inexpensive production method of 4-aminosulfonylbenzoic acid used as a raw material, and must use phosphorus pentachloride which is problematic in terms of pollution. Since the method (1) uses a lithium compound that is expensive and difficult to handle, it cannot be said to be industrially advantageous. As described above, none of the known manufacturing methods is industrially satisfactory.

[0006]

DISCLOSURE OF THE INVENTION The inventors of the present invention have earnestly studied to provide a method for industrially inexpensively and easily producing cyanobenzenesulfonyl chloride by eliminating the above drawbacks.

As a result, as shown below, the cyanothiophenol represented by the general formula (1), the dicyanodiphenyl disulfide represented by the general formula (2) or a mixture thereof is reacted with a chlorinating agent in the presence of water. It was found that by doing so, the cyanobenzenesulfonyl chloride represented by the general formula (3) can be easily obtained.

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In the present invention, chlorine, sulfuryl chloride, phosphorus oxychloride, phosphorus pentachloride and the like can be used as the chlorinating agent. Industrially, from an economic point of view,
Chlorine is preferably used.

The amount of the chlorinating agent used varies depending on the composition of cyanothiophenol, dicyanodiphenyldisulfide or a mixture thereof used as a raw material and cannot be generally stated. , 2 to 8 times by mole, preferably 3 to 7 times by mole.

The amount of water added in this step is not particularly limited, but good results can be obtained if the amount is 0.3 to 20 times the weight of cyanothiophenol, dicyanodiphenyl disulfide or a mixture thereof. .

The reaction temperature is usually about -20 to about 50 ° C,
It is preferably in the range of about -5 to about 30 ° C. If the reaction temperature is too low, the reaction rate will be slow, while if it is too high, side reactions will occur and cause a decrease in yield.

[0012] The solvent is not particularly required, and an aqueous solvent reaction is possible, but a solvent inert in this reaction can be used. For example, ethers such as tetrahydrofuran and dioxane, polar solvents such as DMF and DMSO, hydrocarbons such as hexane, cyclohexane and heptane, halogenated hydrocarbons such as dichloroethane, dichloromethane and chloroform, benzene, toluene, xylene and chlorobenzene, Aromatic hydrocarbons such as dichlorobenzene and trichlorobenzene can be mentioned. When a solvent is used, the amount used is not particularly limited, but is usually 0. 0 with respect to cyanothiophenol, dicyanodiphenyl disulfide or a mixture thereof.
It is 1 to 10 times the weight.

Although the reaction time cannot be generally stated, it is usually
It is in the range of 1 to 30 hours.

The cyanobenzenesulfonyl chloride represented by the general formula (3) thus produced can be isolated by crystallization or the like according to a conventional method.

The cyanobenzenesulfonyl chloride obtained in the present invention includes 2-cyanobenzenesulfonyl chloride, 3-cyanobenzenesulfonyl chloride and 4-cyanobenzenesulfonyl chloride.
Cyanobenzenesulfonyl chloride may be mentioned.

The cyanothiophenol represented by the general formula (1), the dicyanodiphenyl disulfide represented by the general formula (2) or a mixture thereof used in the present invention is not particularly limited. For example, as described below, it can be easily produced using methylthiobenzonitrile as a raw material. That is, it can be obtained by halogenating methylthiobenzonitrile represented by the general formula (4), which is industrially easily available, to obtain a halogenated methylthiobenzonitrile represented by the general formula (5), and further hydrolyzing it. .

[Chemical 6]

In the halogenated methylthiobenzonitrile represented by the above general formula (5), X is Cl, Br or I.
And m represents 1, 2 or 3, and X is preferably Cl. Further, in order to make the hydrolysis proceed smoothly, m is 2,
3 or mixtures thereof are preferred.

As the halogenating agent, chlorine, sulfuryl chloride, bromine, sulfuryl bromide and the like can be used, but chlorine is preferable from the economical point of view.

The amount of the halogenating agent used is 1.5 to 1.5 with respect to the methylthiobenzonitrile represented by the general formula (4).
It is a 7-fold molar amount, preferably a 2- to 5-fold molar amount.

The solvent is not particularly limited, and a solventless reaction is also possible. For example, hydrocarbons such as hexane, cyclohexane and heptane, halogenated hydrocarbons such as dichloroethane, dichloromethane and chloroform, and benzene. , Toluene, xylene, chlorobenzene,
Aromatic hydrocarbons such as dichlorobenzene and trichlorobenzene can be mentioned. When a solvent is used, the amount used is not particularly limited, but is usually 0.1 to 10 times the weight of methylthiobenzonitrile represented by the general formula (4).

The reaction temperature for halogenation is usually about -20.
To about 100 ° C, preferably about -5 to about 60 ° C. If the reaction temperature is too low, the reaction rate will be slow, while if it is too high, side reactions will occur and cause a decrease in yield.

Although it is possible to isolate the halogenated methylthiobenzonitrile thus produced,
It can be used in the hydrolysis step as it is without isolation.

Hydrolysis proceeds by simply adding water and heating to lead to the desired cyanothiophenol represented by the general formula (1). When this hydrolysis reaction is carried out in the presence of an acid, the reaction proceeds smoothly. The acid is not particularly limited, but mineral acids such as hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid are economically used. The amount of the acid used is usually 0.01 to 100 parts by weight with respect to the halogenated methylthiobenzonitrile represented by the general formula (5).
One time weight is sufficient.

At this time, if alcohol, especially lower alcohol, is added, the hydrolysis reaction proceeds more smoothly.
As the lower alcohol, methanol, ethanol, isopropanol, n-propanol, isobutanol,
Examples thereof include n-butanol and sec-butanol. The amount of alcohol used is not particularly limited, but is usually 0.5 to 10 times the weight of the halogenated methylthiobenzonitrile represented by the general formula (5).

The solvent is not particularly limited, and a solventless reaction is also possible. For example, the solvent used for halogenation can be used as it is. When a solvent is used, the amount used is not particularly limited, but is usually 0.1 to 10 times the weight of the halogenated methylthiobenzonitrile represented by the general formula (5).

The reaction temperature is usually in the range of about 20 to 100 ° C, preferably about 50 to 90 ° C. If the reaction temperature is too low, the reaction rate will be slow, while if it is too high, side reactions will occur and cause a decrease in yield. The reaction time is usually about 1-10.
It is a range of time.

The cyanothiophenol thus produced can be isolated by a conventional method.

When the hydrolysis step is carried out in the presence of oxygen, part of the cyanothiophenol produced by the hydrolysis is oxidized, and dicyanodiphenyldisulfide represented by the general formula (2) is also produced.

Further, in the case of obtaining dicyanodiphenyl disulfide represented by the general formula (2), the purpose can be easily achieved by adding an oxidation step after the above-mentioned hydrolysis. That is, an oxidizing agent may be added after hydrolysis.

The oxidizing agent does not need to be a special one, and commonly known ones can be used. Examples of the oxidation method include oxygen oxidation, air oxidation, halogen oxidation with chlorine, bromine, etc., oxidation with peroxides such as hydrogen peroxide, peracetic acid, hypochlorous acid such as sodium hypochlorite, sodium hypobromite, etc. Examples thereof include oxidation with an alkali metal salt of halogen acid.

The dicyanodiphenyl disulfide thus produced can be easily isolated by crystallization or the like.

As the cyanothiophenol represented by the general formula (1) obtained as described above, 2-cyanothiophenol, 3-cyanothiophenol and 4-cyanothiophenol are represented by the general formula (2). Examples of the dicyanodiphenyldisulfide to be used include 3,3′-dicyanodiphenyldisulfide, 2,2′-dicyanodiphenyldisulfide and 4,4′-dicyanodiphenyldisulfide. These compounds can also be used as the starting material of the present invention as they are as a reaction liquid without isolation.

[0033]

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

Example 1 50 equipped with a stirrer, thermometer, cooling pipe and gas introduction pipe
Add 4-cyanothiophenol 2 to a 0 ml four-necked flask.
7.0 g (0.2 mol), 1,2-dichloroethane 70
g and 30 g of water were charged, and chlorine was 9 at 4 ° C for 4 hours.
9.4 g (1.4 mol) were bubbled in. After completion of the reaction, the organic layer was separated and the solvent 1,2-dichloroethane was distilled off. The obtained crude crystals were recrystallized from carbon tetrachloride to give 4-
37.4 g of cyanobenzenesulfonyl chloride was obtained.
The yield based on 4-cyanothiophenol is 92.8%.
Met.

Example 2 The same operation as in Example 1 was conducted except that the starting material was changed to 26.8 g (0.1 mol) of 4,4'-dicyanodiphenyl disulfide, and 37.8 g of 4-cyanobenzenesulfonyl chloride was used. Got The yield based on 4,4'-dicyanodiphenyl disulfide was 93.8%.

Example 3 50 equipped with a stirrer, thermometer, cooling pipe and gas introduction pipe
Into a 0 ml four-necked flask, 29.8 g (0.2 mol) of 4-methylthiobenzonitrile and 100 g of monochlorobenzene were charged, and chlorine 42.6 was added at 25 ° C. for 4 hours.
g (0.6 mol) was bubbled in. Further, the solvent monochlorobenzene was distilled off, and a 95% aqueous methanol solution (50 g)
Was added and stirred under reflux for 2 hours to complete the hydrolysis.
At this time, part of 4-cyanothiophenol produced by hydrolysis was air-oxidized to produce 4,4′-dicyanodiphenyldisulfide. Then, water was added, and the precipitated crystals were filtered to obtain 4-cyanothiophenol and 4,4'-dicyanodiphenyldisulfide 8: 2.
23.8 g of a mixture of The yield based on 4-methylthiobenzonitrile was 88.3%.

Further, 23.8 g of this mixture, 70 g of 1,2-dichloroethane and 30 g of water were charged into a 500 ml four-necked flask equipped with a stirrer, a thermometer, a cooling pipe and a gas introduction pipe, and the mixture was placed at 5 ° C. for 4 hours. 85.2g chlorine over
(1.2 mol) was blown in. After completion of the reaction, the organic layer was separated and the solvent 1,2-dichloroethane was distilled off. The obtained crude crystals were recrystallized with carbon tetrachloride to obtain 32.7 g of 4-cyanobenzenesulfonyl chloride. The yield based on 4-methylthiobenzonitrile was 81.2%.

[0038]

INDUSTRIAL APPLICABILITY The method of the present invention provides a novel method for producing cyanobenzenesulfonyl chloride which is useful as a pharmaceutical intermediate or the like. When the method of the present invention is adopted,
The target product can be obtained in high yield by a simple process. Therefore, it has great economic and industrial value.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Hideaki Nishiguchi 1 346, Miyanishi, Harima-cho, Kako-gun, Hyogo Sumitomo Seika Chemical Co., Ltd.

Claims (3)

[Claims] 1. A cyanothiophenol represented by the general formula (1), a dicyanodiphenyl disulfide represented by the general formula (2), or a mixture thereof is reacted with a chlorinating agent in the presence of water. A method for producing a cyanobenzenesulfonyl chloride represented by the general formula (3). Embedded image 2. The method according to claim 1, wherein the chlorinating agent is chlorine. 3. A cyanothiophenol represented by the general formula (1), a dicyanodiphenyl disulfide represented by the general formula (2) or a mixture thereof is represented by the general formula (4).
The method according to claim 1 or 2, which is obtained by halogenating methylthiobenzonitrile represented by and further hydrolyzing it. Embedded image