JP2005336210A - Method for producing aromatic thioether compounds - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing an aromatic thioether compound, by which the aromatic thioether compound having substitutents can be produced in simple operations in a high yield and in good purity. <P>SOLUTION: This method for producing the aromatic thioether compound is characterized by reacting (A) an aromatic halogen compound having substituents with (B) (1) an alkali metal hydrocarbylmercaptide having a hydrocarbon group within a specific range and/or (2) a hydrocarbylthiol and an alkali metal compound in the presence of (C) an aprotic polar solvent. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a method for producing aromatic thiols from an aromatic halogen compound, and also relates to a method for producing aromatic disulfides via the aromatic thiols.

（式中、
Ｙは、たがいに同一でも異なっていてもよい、塩素原子、臭素原子、ヨウ素原子、ニトロ基、ニトリル基およびスルホン基を表し；
ｍは、１〜６の整数であり、ｎは、０または１〜５の整数であり、ただし、ｍ＋ｎは６以下である）
で示される芳香族チオール類、および一般式（VIａ）：

（式中、Ｙおよびｎは、上記のとおりである）で示される芳香族ジスルフィド類は、医薬、農薬などの中間体として広く用いられる。また、芳香族ジチオール類は、電子材料などの中間体として用いられている。 General formula (Va):

(Where
Y represents a chlorine atom, a bromine atom, an iodine atom, a nitro group, a nitrile group and a sulfone group, which may be the same or different;
m is an integer of 1-6, n is an integer of 0 or 1-5, provided that m + n is 6 or less)
And the general formula (VIa):

Aromatic disulfides represented by the formula (wherein Y and n are as described above) are widely used as intermediates for pharmaceuticals, agricultural chemicals and the like. Aromatic dithiols are used as intermediates for electronic materials and the like.

  Several methods have been proposed for producing aromatic monothiols, aromatic dithiols or aromatic disulfides having such substituents.

  For example, Non-Patent Document 1 discloses a method for producing halogenated aromatic thiols in which polychlorinated benzene is reacted with sodium hydrogen sulfide dissolved in liquid ammonia in an autoclave to mercaptoize one chlorine atom. Is described. According to this method, halogenated aromatic thiols can be obtained in a high yield from polychlorinated benzene having 4 to 6 chlorine atoms, but the yield for obtaining dichlorothiophenol from trichlorobenzene is only 17 to 20%. However, there are industrial restrictions due to the complexity of handling liquid ammonia and the high-pressure reaction in the autoclave.

  In Patent Document 1, a halogenated aromatic compound having an amino group is diazonium converted with sodium nitrite and concentrated hydrochloric acid, then reacted with potassium O-ethyldithiocarbonate, and then refluxed by adding sodium hydroxide. A method for obtaining functionalized aromatic thiols is disclosed. This method is not only complicated but also dangerous because it deals with a diazonium salt.

  Patent Document 2 discloses 3,5-dichlorothio, in which 1,3,5-trichlorobenzene or 1-bromo-3,5-dichlorobenzene and an alkali metal sulfide are reacted in the presence of a solvent such as diethylene glycol. A method for producing phenol is disclosed. In this method, the target product can be obtained by a relatively simple operation. However, since the yield is low and there are many by-products, purification is difficult.

  In Non-Patent Document 2, aromatic thiols are obtained by reacting an aryl halide with hydrogen sulfide in the presence of thorium oxide, but a high temperature of 550 ° C. or higher is required and the yield is not good.

  In Patent Document 3, a substituent such as a halogen atom or a nitro group is introduced into a diaryl sulfide having a nitro group on one benzene ring by an electrophilic substitution reaction on the other benzene ring, and then, such as sodium hydroxide. It discloses a method for obtaining thiophenols that are nucleus-substituted with the substituent by conducting an exchange reaction with thiophenol in the presence of a basic substance. However, this method is complicated and is not suitable for introducing a large number of substituents into the benzene ring of thiophenols.

  In Patent Document 4, N-N-dialkylcarbamoyl halide is reacted with o-halophenol to synthesize O-o-halophenyl-N, N-dialkylcarbamate, which is rearranged by heating to produce S-o. Disclosed is a method for producing o-halothiophenol by hydrolysis after -halophenyl-N, N-dialkylcarbamate. However, this method is a complicated multistage reaction, and it is necessary to use a carbamoyl halide which is unstable and difficult to handle. Further, this is disadvantageous because side reactions occur because the rearrangement reaction is carried out at a high temperature, and is particularly disadvantageous when a substituent other than halogen is introduced.

  Patent Document 5 includes 4-halobenzenesulfinic acid, Patent Document 6 includes 4-halobenzenesulfonyl chloride, Patent Document 7 includes halobenzenesulfenyl halide, and a metal such as zinc powder in the presence of a mineral acid. A method for producing a corresponding halogenated thiophenol by reduction using a powder is disclosed. However, all of these reactions require special equipment in order to carry out the reduction in the presence of a mineral acid. Patent Document 8 discloses a method in which monohalobenzene is reacted with sulfur monochloride in the presence of a catalyst such as zinc chloride, and the reaction product is reduced with a reducing agent such as zinc to obtain halothiophenols. Is disclosed. This method also has the same problem since it is a reduction reaction as described above.

  Patent Document 9 discloses a method of obtaining a halogenated thiophenol by reacting a polyhalogenated benzene with a sulfide such as sodium hydrogen sulfide, sodium sulfide, or potassium sulfide.

  In these methods, since the reaction is slow, the halogenated aromatic thiols easily react with the halogenated benzene of the raw material to become aromatic sulfides, and the yield of the halogenated aromatic thiols is reduced. Yes.

  Patent Document 10 discloses a method of obtaining a halogenated aromatic thiol by reacting a polyhalogenated benzene with a thioglycolate. Patent Document 11 discloses a method of obtaining halogenated aromatic thiols by reacting halogenated phenylthioglycolic acid with a sulfide such as sodium hydrogen sulfide or aromatic thiol in the presence of a base. Has been. However, these methods cannot obtain high-purity aromatic thiols with high yield.

  Patent Document 12 discloses a method in which a methyl group bonded to a sulfur atom of thioanisoles is chlorinated with chlorine gas to form halogenated thioanisoles, which are hydrolyzed to obtain halogenated aromatic thiols. ing. Furthermore, Patent Document 13 discloses that the halogenated thioanisoles are hydrolyzed in the presence of a mineral acid, and that the halogenated aromatic thiols obtained by the hydrolysis reaction are as hydrogen peroxide. It is disclosed that halogenated aromatic disulfides can be obtained by oxidative dimerization with an oxidizing agent. However, in this method, in addition to using volatile and odorous methyl mercaptan to obtain thioanisoles, a complicated process of introducing chlorine gas to chlorinate the methyl group is required.

Japanese Patent Publication No. 44-26100 JP 56-156257 A Japanese Patent Laid-Open No. 2-48564 JP-A-61-72749 JP-A-2-295968 Japanese Patent Laid-Open No. 3-181455 JP-A-5-186418 JP-A-5-140086 JP-A-4-182463 Japanese Patent Laid-Open No. 4-198162 Japanese Patent Laid-Open No. 5-178816 JP-A-8-143533 JP-A-8-143532 Occupational Chemical Magazine Vol.70, No.8, pp.114-118 (1967) Zhur. Org. Khim. 11: 1132 (1975)

  An object of the present invention is to provide a method for producing an aromatic thiol having a substituent and an aromatic disulfide from an aromatic halogen compound with an excellent yield and purity by a simple operation.

  As a result of repeated studies to solve the above problems, the present inventors have reacted an aromatic halogen compound with a hydrocarbyl mercaptide alkali metal salt having a specific structure, and converted the resulting aromatic thioether with a protonic acid. It was found that the purpose can be achieved by decomposing, and the present invention has been completed.

（式中、
Ｒ¹、Ｒ²およびＲ³は、それぞれアルキル基またはアリール基を表し、ただし、Ｒ¹、Ｒ²およびＲ³のいずれか２個がアリール基の場合、残余は水素原子でもよく；
Ｍは、アルカリ金属原子を表す）
で示されるヒドロカルビルメルカプチドアルカリ金属塩；および／または
（２）（ａ）一般式（III）：

（式中、Ｒ¹、Ｒ²およびＲ³は、前述のとおりである）
で示されるヒドロカルビルメルカプタン、および
（ｂ）アルカリ金属、その水酸化物、炭酸塩、水素化物もしくはアルコキシドを、
（Ｃ）非プロトン極性溶媒
の存在下に反応させて、一般式（IV）：

（式中、Ｙ、Ａｒ、Ｒ¹、Ｒ²、Ｒ³、ｍおよびｎは、前述のとおりである）
で示される芳香族チオエーテル類を製造し；
得られた該チオエーテル類を
（Ｄ）プロトン酸
と反応させることを特徴とする、一般式（Ｖ）：
Ｙ_n−Ａｒ−（ＳＨ)_m （Ｖ）
（式中、Ｙ、Ａｒ、ｍおよびｎは、前述のとおりである）
で示される芳香族チオール類を製造する方法に関する。また、このような方法によって、一般式（Ｖ）で示され、ｍが１である芳香族チオール類を製造し、ついでこれを酸化して、一般式（VI）：
Ｙ_n−Ａｒ−Ｓ−Ｓ−Ａｒ−Ｙ_n （VI）
（式中、ＡｒおよびＹは、前述のとおりであり；ｎは、０または１以上の整数である）
で示される芳香族ジスルフィド類を製造する方法に関する。 That is, the present invention
(A) General formula (I):
_{Y n -Ar-X m (I} )
(Where
Ar represents an aromatic hydrocarbon residue;
X represents a halogen atom bonded to a carbon atom of an aromatic ring in Ar;
Y represents one or more substituents selected from the group consisting of a halogen atom, a nitro group, a nitrile group, a sulfone group, a sulfamoyl group, and a hydrocarbylsulfonyl group bonded to a carbon atom of an aromatic ring in Ar. Representation;
m is an integer greater than or equal to 1;
n is 0 or an integer of 1 or more)
In the aromatic halogen compound represented by
(B) (1) General formula (II):

(Where
R ¹ , R ² and R ³ each represents an alkyl group or an aryl group, provided that when any ^{two of} R ¹ , R ² and R ³ are aryl groups, the remainder may be a hydrogen atom;
M represents an alkali metal atom)
And / or (2) (a) the general formula (III):

(Wherein R ¹ , R ² and R ³ are as described above)
And (b) an alkali metal, its hydroxide, carbonate, hydride or alkoxide,
(C) The reaction is carried out in the presence of an aprotic polar solvent to give the general formula (IV):

(Wherein Y, Ar, R ¹ , R ² , R ³ , m and n are as described above)
An aromatic thioether represented by:
The obtained thioethers are reacted with (D) a protonic acid, the general formula (V):
_{Y n -Ar- (SH) m (} V)
(Wherein Y, Ar, m and n are as described above)
It relates to a method for producing an aromatic thiol represented by Further, by such a method, an aromatic thiol represented by the general formula (V) and m = 1 is produced, and then oxidized to obtain the general formula (VI):
_{Y n -Ar-S-S-} Ar-Y n (VI)
(In the formula, Ar and Y are as described above; n is 0 or an integer of 1 or more)
It relates to a method for producing an aromatic disulfide represented by

  In the present specification, “aromatic thiols” includes aromatic monothiols, aromatic dithiols, aromatic trithiols, and other aromatic compounds having a plurality of mercapto groups, unless otherwise specified. Use as a concept.

（式中、ＸおよびＹは、前述のとおりであり；ｍは、１〜６の整数であり、ｎは、０または１〜５の整数であり、ただし、ｍ＋ｎは６以下である）
で示され、一般式（Ｖａ）：

（式中、Ｙは、前述のとおりであり；ｍおよびｎは、上記のとおりである）
で示される芳香族チオール類を製造する方法に関する。また、このような方法によって、一般式（Ｖａ）で示され、ｍが１である芳香族チオール類を製造し、ついでこれを酸化して、一般式（VIａ）：

（式中、Ｙは、前述のとおりであり；ｎは、０または１〜５の整数である）
で示される芳香族ジスルフィド類を製造する方法に関する。 In the production method of the present invention, typically, the aromatic halogen compound of (A) is converted into the general formula (Ia):

(Wherein X and Y are as described above; m is an integer of 1 to 6, n is an integer of 0 or 1 to 5, provided that m + n is 6 or less)
In general formula (Va):

Wherein Y is as described above; m and n are as described above.
It relates to a method for producing an aromatic thiol represented by Further, by such a method, an aromatic thiol represented by the general formula (Va) and m = 1 is produced, and then oxidized to obtain the general formula (VIa):

(Wherein Y is as described above; n is 0 or an integer of 1 to 5)
It relates to a method for producing an aromatic disulfide represented by

  ADVANTAGE OF THE INVENTION According to this invention, the aromatic thiols and aromatic disulfides which have a substituent can be manufactured with sufficient yield and purity from an aromatic halogen compound. The method of the present invention is particularly useful for the production of disubstituted aromatic thiols and disubstituted disulfides that cannot be obtained in good yield by other methods.

  The first step of the method for producing aromatic thiols of the present invention is a step of producing aromatic thioethers by reacting (A) an aromatic halogen compound with (B) an organic sulfur compound.

  The (A) aromatic halogen compound used in the present invention is a derivative of a carbon-based aromatic ring compound having at least one X bonded to a carbon atom of the aromatic ring.

  Ar is an aromatic hydrocarbon residue, and Ar is an aromatic ring residue such as a benzene ring, biphenyl ring, terphenyl ring, naphthalene ring, anthracene ring, pyrene ring; and methyl, ethyl, propyl And those substituted with a hydrocarbon group such as butyl. In view of reactivity with (B), an aromatic ring residue not substituted with the above hydrocarbon group is preferred, and a benzene ring residue is particularly preferred.

  X is a halogen atom that bonds to the carbon atom of the aromatic ring in Ar and contributes to the reaction with (B), and examples thereof include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. A chlorine atom or a bromine atom is preferable because (A) can be easily obtained and the by-product can be easily treated.

  m is an integer of 1 or more, and is an integer of 1 to 6 when Ar is a benzene ring. It is preferable that m is 1 when the reaction product is relatively simple, particularly when the resulting aromatic thiols are oxidized to obtain a product having a disulfide bond.

  Y is bonded to the carbon atom of the aromatic ring in Ar and introduced as a substituent into the target aromatic thiol or aromatic disulfide. Also, by the presence of Y, (A) and (B) The reaction is promoted. Y represents a halogen atom, a nitro group, a nitrile group, a sulfone group, a sulfamoyl group or a hydrocarbylsulfonyl group. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Examples of the hydrocarbylsulfonyl group include methylsulfonyl, phenylsulfonyl, p-toluylsulfonyl, and the like. When a plurality of Y are present, they may be the same or different. When Y is a halogen atom, it may be the same as or different from X.

  n is 0 or an integer of 1 or more, and is 0 or an integer of 1 to 5 when Ar is a benzene ring residue. The larger n is, the easier the reaction between (A) and (B) proceeds, and the yield of substituted aromatic thiols is higher due to the subsequent elimination reaction. In comparison, since substituted aromatic thiols can be obtained with relatively high yield and purity, n is preferably 2 or 3.

  (B) introduces a mercapto group into an aromatic ring by reaction with (A). As (B), the following (1) and / or (2) are used. That is, (1) is a hydrocarbyl mercaptide alkali metal salt having a monovalent hydrocarbon group having a specific structure in the molecule; (2) is a hydrocarbyl mercaptan having a monovalent hydrocarbon group similar to (a) And (b) a combination of an alkali metal, its hydroxide, carbonate, hydride or alkoxide. The combination (2) is a precursor that forms (1) in the system, and the produced (1) can react with (A) to obtain aromatic thioethers. Since it can be easily obtained, it is preferable to use the combination of (2) as (B).

（式中、Ｒ¹、Ｒ²およびＲ³は、前述のとおりである）
で示される、脂肪族または芳香族の１価の第三級炭化水素基、または１価のジアリール第二級炭化水素基であり、ｔ−ブチル、ｔ−ペンチル、ｔ−ヘキシル、ｔ−オクチル、ｔ−デシル、ｔ−ドデシル、１−メチル−１−エチルプロピル、１，１−ジエチルプロピル、１，１，４−トリメチルペンチルのような第三級アルキル基；１−メチル−１−フェニルエチル、１，１−ジフェニルエチル、トリチルのような第三級芳香族炭化水素基；およびベンズヒドリルのような、硫黄原子に結合する炭素原子に２個のアリール基が結合した第二級芳香族炭化水素基が例示され、合成が容易で、反応および酸による脱離が容易なことから、ｔ−ブチルおよびベンズヒドリルが好ましい。Ｍは、アルカリ金属原子であって、リチウム、ナトリウム、カリウム、セシウムなどが挙げられ、ナトリウムおよびカリウムが好ましい。 The monovalent hydrocarbon group contained in (1) and (2) has the general formula (VII):

(Wherein R ¹ , R ² and R ³ are as described above)
An aliphatic or aromatic monovalent tertiary hydrocarbon group or a monovalent diaryl secondary hydrocarbon group represented by the formula: t-butyl, t-pentyl, t-hexyl, t-octyl, tertiary alkyl groups such as t-decyl, t-dodecyl, 1-methyl-1-ethylpropyl, 1,1-diethylpropyl, 1,1,4-trimethylpentyl; 1-methyl-1-phenylethyl, Tertiary aromatic hydrocarbon groups such as 1,1-diphenylethyl and trityl; and secondary aromatic hydrocarbon groups in which two aryl groups are bonded to a carbon atom bonded to a sulfur atom, such as benzhydryl. Are preferred, and t-butyl and benzhydryl are preferred because they are easy to synthesize and can be easily removed by reaction and acid. M is an alkali metal atom, and examples thereof include lithium, sodium, potassium, cesium and the like, and sodium and potassium are preferable.

  Examples of such (1) include sodium t-butyl mercaptide, sodium t-pentyl mercaptide, sodium t-hexyl mercaptide, sodium t-dodecyl mercaptide, sodium-1,1-diphenylethyl mercaptide, sodium trityl. Examples are tertiary hydrocarbyl mercaptide sodium salts such as mercaptides; secondary hydrocarbyl mercaptide sodium salts such as sodium benzhydryl mercaptide; and the corresponding hydrocarbyl mercaptide lithium and potassium salts.

  (2) is a combination of (a) a hydrocarbyl mercaptan having a monovalent hydrocarbon group as described above and (b) an alkali metal, its hydroxide, carbonate, hydride or alkoxide. (A) is exemplified by hydrocarbyl mercaptan having a monovalent hydrocarbon group exemplified in the above (1), and t-butyl mercaptan and benzhydryl mercaptan are preferable.

  (B) includes, in addition to the above alkali metals; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; alkali metal carbonates such as lithium carbonate, sodium carbonate and potassium carbonate; hydrogen And alkali metal hydrides such as sodium hydride, lithium hydride; and sodium alkoxides such as sodium methoxide, sodium ethoxide, sodium propoxide, sodium isopropoxide, sodium butoxide, and corresponding lithium alkoxides and potassium alkoxides. It is done.

  Although the reaction proceeds even if one of the amounts of (a) and (b) used is excessive, the molar ratio of (b) to (a) is preferably 1.0 to 1.5, and preferably 1.0 to 1.1. Is more preferable, and 1.0 is most preferable, but when (a) does not remain, (b) may be used in a slight excess.

  The amount of (B) to be subjected to the reaction with (A) is converted to the theoretical amount of (1) generated in the system when (B) is used in the combination of (2), and X1 in (A) It is usually in the range of 1 to 3 moles relative to moles, preferably 1.0 to 1.1 moles, and 1.0 mole is most preferred because it avoids the trouble of removing (A) after the reaction.

  The (C) aprotic polar solvent used in the present invention is a reaction solvent that significantly accelerates the reaction of aromatic thiols by the reaction of (A) and (B). Examples of (C) include N-methyl-2-pyrrolidone, N, N-dimethylformamide, N, N-dimethylacetamide, sulfolane, dimethyl sulfoxide, and the like. preferable.

  The amount of (C) is the amount necessary to dissolve or disperse the compound involved in the reaction and to stir the system. Specifically, it is usually based on 1 mol of the total amount of (A) and (B). It is 200g or more, and the range of 400-1200g is preferable.

  The step of synthesizing an aromatic thioether from (A) an aromatic halide and (B) a sulfur compound is performed in the presence of the above (C) aprotic polar solvent. For example, when (1) a hydrocarbyl mercaptide alkali metal salt is used as (B), the (1) and (A) are dissolved in the above (C). When (2) is used as (B), that is, when (a) and (b) are used, (a) and (b) are dissolved in (C) and heated to 35 to 60 ° C., the reaction quickly As (1) is formed as it proceeds, it is then reacted with (A) as described above.

  The reaction of (A) and (B) can be allowed to proceed at room temperature to 200 ° C. When the total of n and m in (A) is relatively small, such as 2 to 4, it is effective to increase the temperature to 50 to 120 ° C. to promote the reaction. When m is 2 or more, it is preferable to make it react at 100-200 degreeC. When Y is a nitro group, and when Ar is a benzene ring and the total of n and m is 5 or 6, the reaction proceeds sufficiently even at room temperature, and therefore room temperature is preferred.

  In the second step of the method for producing aromatic thiols, the aromatic thioethers obtained by the first step in which the monovalent hydrocarbon group having the structure in the specific range as described above is bonded to a sulfur atom are combined with protonic acid. In this step, a hydrocarbon group is eliminated from the aromatic compound by reaction to obtain an aromatic thiol.

  Protic acids include hydrohalic acids such as hydrofluoric acid, hydrochloric acid, and hydrobromic acid; sulfuric acid; carboxylic acids such as acetic acid and trifluoroacetic acid; benzenesulfonic acid, p-toluenesulfonic acid, and methane. Examples thereof include sulfonic acids such as sulfonic acid, and have high catalytic ability, are non-volatile, suitable for heat reaction, and can effectively remove hydrocarbon groups. Therefore, p-toluenesulfonic acid and methanesulfonic acid are preferable. These protonic acids may be subjected to the reaction in the form of a hydrate. In this case, since the reaction is extremely slow, it is preferable to use after dehydration.

  (D) The amount of the protonic acid used is 1 mol of aromatic thioethers used for the reaction because an appropriate elimination reaction rate is obtained with respect to various hydrocarbon groups and an undesirable side reaction does not occur. Is usually in the range of 0.1 to 5 mol, preferably 0.2 to 3 mol, and particularly preferably 1.0 mol.

  In order to accelerate the reaction and suppress side reactions, the reaction is usually carried out at 100 to 200 ° C, preferably 100 to 150 ° C. Reaction temperature range such as toluene, xylene, mesitylene hydrocarbons, ethers such as anisole, etc. to facilitate control of reaction temperature and absorb hydrocarbons such as isobutylene generated by elimination reaction It is preferable to carry out the reaction under reflux of solvents having a boiling point. In particular, a solvent that can be azeotroped with water, such as toluene and anisole, can be added to the reaction system in the presence of hydrate or water, and the reaction can proceed while dehydrating.

  Thus, by combining the synthesis of aromatic thioethers with the elimination reaction of the hydrocarbon group of the thioethers, aromatic thiols can be synthesized with good yield and high purity.

  The aromatic thiols thus obtained may be used as intermediates for the synthesis of various compounds, and the aromatic thiols with m = 1 are dimerized by oxidation to produce aromatic disulfides. May be produced.

  The oxidation reaction can be performed by adding an oxidizing agent and stirring. As the oxidizing agent, chlorine, bromine, iodine, hydrogen peroxide, sulfuric acid, peracetic acid, ferric chloride, sodium hypochlorite and the like can be used. Iodine is preferred because it can be carried out simply and a good yield is obtained. Further, the oxidation reaction may be performed by introducing air or oxygen. The reaction proceeds even at room temperature, but may be performed by heating or cooling as necessary. Furthermore, in order to make the reaction proceed smoothly, the above reaction may be carried out after dissolving the aromatic thiols in an organic solvent such as toluene or xylene.

  Protic acids such as sulfuric acid are also used as a reactant in the synthesis of aromatic thiols from aromatic thioethers. Therefore, by using a protonic acid such as sulfuric acid that also functions as an oxidant and selecting appropriate reaction conditions, synthesis of aromatic thiols with m = 1 from aromatic thioethers, and aromatic disulfides Can be performed in one step. For example, when a hydrocarbon group elimination reaction is performed from aromatic thioethers using 95% concentrated sulfuric acid, if the reaction is simply carried out under reflux of toluene, the aromatic thiols are oxidized and dihydrogenated. Both quantified aromatic disulfides are obtained. In contrast, when the reaction proceeds while dehydrating by azeotropy with toluene, the aromatic thiols are not isolated from the aromatic thioethers, and the aromatics are obtained in a high yield of 70% or more based on the theoretical amount. Disulfides can be produced.

  Hereinafter, the present invention will be described in more detail by way of examples. In the examples, parts represent parts by weight, and% of the composition represents% by weight. In the following reaction formulas and tables, t-Bu represents a t-butyl group, Ph represents a phenyl group, and DMSO represents dimethyl sulfoxide. The present invention is not limited by these examples.

  Example 1

First Step: In a reactor equipped with a stirrer, a Dimroth cooler, a thermometer, and a dropping funnel, under a nitrogen atmosphere, 18.0 parts of t-butyl mercaptan, 200 parts of dimethyl sulfoxide and 15.4 parts of 85% potassium hydroxide Was stirred at 50 ° C. for 30 minutes to synthesize potassium t-butyl mercaptide in the system. Subsequently, 29.4 parts of 1,3-dichlorobenzene was added, the temperature was slowly raised while stirring, and the mixture was heated at 120 ° C. for 7 hours. Next, the mixture was cooled to room temperature, 200 parts of water and 200 parts of toluene were added and stirred, and then allowed to stand to separate. The organic phase was washed with saturated brine, dehydrated with anhydrous sodium sulfate, and then toluene was distilled off under reduced pressure. By vacuum distillation of the liquid residue, 33.0 parts of a colorless and transparent liquid was obtained as a fraction having a boiling point of 140 ° C./32 Torr.
¹ H-NMR (CDCl ₃ ): δ 7.54 (dd, J = 1.7, 2.0Hz, 1H), 7.41 (ddd, J = 1.3, 2.0, 7.6Hz, 1H), 7.34 (ddd, J = 1.3, 1.7, 7.6Hz, 1H), 7.25 (t, J = 7.6Hz, 1H), 1.29 (s, 9H).

  As a result, it was confirmed that the obtained product was 3-chlorophenyl t-butyl sulfide. The yield was 82% based on the theoretical amount.

Second Step In a reactor equipped with a stirrer, a Dimroth cooler, a thermometer, and a Dean Stark collector, 20.1 parts of 3-chlorophenyl t-butyl sulfide and p-toluenesulfonic acid monohydrate under a nitrogen atmosphere 19.0 parts of the product and 100 parts of toluene were charged, and the mixture was heated to reflux for 5 hours while removing water. After cooling to room temperature, 150 parts of water was added and stirred, and then allowed to stand to separate. To the organic phase, 200 parts of 10% aqueous sodium hydroxide solution was added, stirred, and allowed to stand to separate. A 12N hydrochloric acid aqueous solution was added to the aqueous phase to adjust the pH to 2. As a result, an oily substance was deposited at the bottom. Toluene (100 parts) was added, and the precipitated oil was extracted. The obtained organic phase was washed with saturated brine and dehydrated with anhydrous sodium sulfate. Subsequently, toluene was distilled off under reduced pressure, and 9.5 parts of a colorless and transparent liquid was obtained by distillation under reduced pressure as a fraction having a boiling point of 110 ° C./30 Torr.
¹ H-NMR (CDCl ₃ ): δ 7.25 (m, 1H), 7.12 (m, 3H), 3.48 (s, 1H).

  As a result, it was confirmed that the obtained product was 3-chlorothiophenol. The yield was 65% based on the theoretical amount.

  Example 2

First step First step of Example 1 except that 36.3 parts of 1,3,5-trichlorobenzene was added instead of 1,3-dichlorobenzene and the subsequent heating conditions were 80 ° C. for 5 hours. In the same manner, 37.8 parts of a colorless liquid having a boiling point of 75 ° C./0.4 Torr was obtained.
¹ H-NMR (CDCl ₃ ): δ 7.42 (d, J = 2.0Hz, 2H), 7.36 (t, J = 2.0Hz, 1H), 1.31 (s, 9H).

  As a result, it was confirmed that the obtained product was 3,5-dichlorophenyl t-butyl sulfide. The yield was 80% based on the theoretical amount.

Second Step Example 1 except that 23.5 parts of 3,5-dichlorophenyl t-butyl sulfide obtained in the first step was added in place of 3-chlorophenyl t-butyl sulfide and the reflux time was 3 hours. When the pH was adjusted to 2 in the same manner as in the second step, crystals were precipitated. This was filtered off to obtain 13.3 parts of colorless needle crystals.
Melting point: 62 ° C;
¹ H-NMR (CDCl ₃ ): δ 7.15 (s, 3H), 3.55 (s, 1H).

  As a result, it was confirmed that the obtained product was 3,5-dichlorothiophenol. The yield was 74% based on the theoretical amount.

  Example 3

In the same manner as in the first step of Example 2, 3,5-dichlorophenyl t-butyl sulfide was obtained. Under a nitrogen gas atmosphere, 23.5 parts of the 3,5-dichlorophenyl t-butyl sulfide, 100 parts of xylene and 1.9 parts of methanesulfonic acid were added to the reactor used in the second step of Example 1, and nitrogen was added. Heating and refluxing were performed for 10 hours while flowing gas to remove the generated isobutylene. Thereafter, the product was purified in the same manner as in the second step of Example 2 and the pH was adjusted to 2. As a result, crystals were precipitated. This was filtered off to obtain 12.4 parts of colorless needle crystals.
Melting point: 62 ° C;
¹ H-NMR (CDCl ₃ ): δ 7.15 (s, 3H), 3.55 (s, 1H).

  As a result, it was confirmed that the obtained product was 3,5-dichlorothiophenol. The yield was 69% based on the theoretical amount.

  Example 4

Step 1 Add 36.1 parts of t-butyl mercaptan and 29 parts of 85% potassium hydroxide, add 57.0 parts of hexachlorobenzene instead of 1,3-dichlorobenzene, and heat. The toluene was distilled off in the same manner as in the first step of Example 1 except that the mixture was stirred overnight at room temperature, to obtain a pale yellow crystalline residue. This was recrystallized from isopropanol to obtain 64.5 parts of colorless needle crystals.
Melting point: 142 ° C;
Calculated value C: 42.87%, H: 4.63%, measured value C: 42.64%, H: 4.27% as elemental analysis value C14H18Cl4S2;
¹ H-NMR (CDCl ₃ ): δ 1.42 (s, 9H).

  As a result, it was confirmed that the obtained product was bis (t-butylthio) tetrachlorobenzene. The yield was 83% based on the theoretical amount.

Step 2 Instead of 3-chlorophenyl t-butyl sulfide, 39.2 parts of bis (t-butylthio) tetrachlorobenzene obtained in Step 1 are added, the reflux time is 1 hour, and 10% is added after the separation. When the pH was adjusted to 2 in the same manner as in the second step of Example 1, except that the amount of the aqueous sodium hydroxide was 400 parts, crystals were precipitated. This was filtered off to obtain 26.0 parts of white crystals.
Melting point: 260 ° C;
¹ H-NMR (CDCl ₃ ); δ 4.86 (s, 1H).

  As a result, it was confirmed that the obtained product was tetrachlorobenzenedithiol. The yield was 93% based on the theoretical amount.

  Example 5

1st step Instead of 1,3-dichlorobenzene, 31.6 parts of p-nitrochlorobenzene was added under ice cooling, and the boiling point was the same as in the 1st step of Example 1 except that the mixture was stirred at room temperature for 30 minutes. A colorless liquid of 36.8 parts at 99 ° C./0.5 Torr was obtained.
¹ H-NMR (CDCl ₃ ): δ 8.17 (d, J = 8.9Hz, 2H), 7.68 (d, J = 8.9Hz, 2H), 1.35 (s, 9H).

  As a result, it was confirmed that the obtained product was 4-nitrophenyl t-butyl sulfide. The yield was 87% based on the theoretical amount.

Second Step Instead of 3-chlorophenyl t-butyl sulfide, 21.1 parts of 4-nitrophenyl t-butyl sulfide obtained in the first step was added, and the reflux time was changed to 4 hours. When the pH was adjusted to 2 in the same manner as in the second step, crystals were precipitated. This was filtered off to obtain 11.2 parts of pale yellow crystals.
Melting point: 77 ° C;
¹ H-NMR (CDCl ₃ ): δ 8.09 (d, J = 8.9Hz, 2H), 7.36 (d, J = 8.9Hz, 2H), 3.80 (s, 1H).

  As a result, it was confirmed that the obtained product was 4-nitrothiophenol. The yield was 72% based on the theoretical amount.

  Example 6

Step 1 Example 2 of Example 2 except that the addition amount of t-butyl mercaptan was 36.0 parts, the addition amount of 85% potassium hydroxide was 29 parts, and the heating condition after addition was changed to 130 ° C. for 3 hours. When toluene was distilled off in the same manner as in Step 1, a pale yellow crystalline residue was obtained. This was recrystallized from methanol to obtain 45.8 parts of colorless plate crystals.
Melting point: 89 ° C;
¹ H-NMR (CDCl ₃ ): δ 7.61 (t, J = 1.6Hz, 1H), 7.53 (d, J = 1.6Hz, 2H), 1.30 (s, 18H).

  As a result, it was confirmed that the obtained product was 3,5-bis (t-butylthio) chlorobenzene. The yield was 79% based on the theoretical amount.

Second Step Instead of 3,5-dichlorophenyl t-butyl sulfide, 28.9 parts of 3,5-bis (t-butylthio) chlorobenzene obtained in the first step is added, and the reflux time is 12 hours. 16.5 parts of colorless needle crystals were obtained in the same manner as in the second step of Example 2, except that the amount of 10% aqueous sodium hydroxide added later was 400 parts.
Melting point: 55 ° C;
¹ H-NMR (CDCl ₃ ): δ 7.03 (s, 3H), 3.47 (s, 2H).

  As a result, it was confirmed that the obtained product was 5-chloro-1,3-benzenedithiol. The yield was 93% based on the theoretical amount.

  Example 7

First Step In a reactor equipped with an auxiliary device similar to that used in the first step of Example 1, 300 parts of dimethyl sulfoxide and hydrogen with a concentration of 63.2% dispersed in mineral oil in a nitrogen atmosphere. 34.2 parts of sodium chloride was charged and stirred at room temperature for 30 minutes. Next, 81.2 parts of t-butyl mercaptan was slowly added dropwise, and the mixture was stirred at 40 ° C. for 30 minutes. Then, 36.2 parts of 1,3,5-trichlorobenzene was added, and the temperature was slowly raised, followed by 2 hours at 150 ° C. Heated. Next, the mixture was cooled to room temperature, and 400 parts of water and 200 parts of toluene were added and stirred. The mixture was allowed to stand and separated to obtain an organic phase, which was washed with a 10% aqueous sodium hydroxide solution and then with saturated brine, dehydrated with anhydrous sodium sulfate, and then toluene was removed under reduced pressure. The residue was recrystallized from isopropyl alcohol to obtain 41.0 parts of colorless plate crystals.
Melting point: 132-133 ° C .;
¹ H-NMR (CDCl ₃ ): δ 7.24 (s, 3H), 1.30 (s, 27H).

  As a result, it was confirmed that the obtained product was 1,3,5-tris (t-butylthio) benzene. The yield was 60% based on the theoretical amount.

Second Step In the reactor used in the second step of Example 1, 34.3 parts of 1,3,5-tris (t-butylthio) benzene obtained as described above in a nitrogen gas atmosphere, xylene 100 parts and 9.6 parts of methanesulfonic acid were added, and refluxed with heating for 7 hours while flowing nitrogen gas to remove the generated isobutylene. Subsequently, while adding 500 parts of toluene dropwise, the mixture was heated to reflux the toluene for 5 hours and a part was distilled off to completely remove isobutylene. Subsequently, it cooled to room temperature, 100 parts of water was added and stirred, and it liquid-separated, and took the organic phase. To this, 600 parts of 10% aqueous sodium hydroxide solution was added and stirred. The aqueous phase was separated by liquid separation, and the product was purified in the same manner as in the second step of Example 2 to adjust the pH to 2. However, crystals were deposited. This was filtered off to obtain 13.0 parts of colorless needle crystals.
Melting point: 56-59 ° C .;
¹ H-NMR (CDCl ₃ ): δ 6.94 (s, 3H), 3.41 (s, 3H).

  As a result, it was confirmed that the obtained product was 1,3,5-trimercaptobenzene. The yield was 75% based on the theoretical amount.

  Example 8

First Step In the same reactor used in the first step of Example 2, 44.0 parts of diphenylmethanethiol, 200 parts of dimethyl sulfoxide and 12.4 parts of sodium methoxide having a purity of 96% were charged in a nitrogen atmosphere. And stirred at 50 ° C. for 30 minutes. Subsequently, 36.3 parts of 1,3,5-trichlorobenzene was added, and toluene was distilled off in the same manner as in the first step of Example 2 except that the heating conditions were set at 80 ° C. for 3 hours. As a result, a colorless oily residue was obtained. The residue was recrystallized from methanol to obtain 64.8 parts of colorless plate crystals.
Melting point: 54 ° C .;
¹ H-NMR (CDCl ₃ ): δ 7.40 (d, J = 7.4Hz, 4H), 7.31 (t, J = 7.4Hz, 4H), 7.24 (t, J = 7.4Hz, 2H), 7.09 (t, J = 1.7Hz, 1H), 7.06 (d, J = 1.7Hz, 2H), 5.56 (s, 1H).

  As a result, it was confirmed that the obtained product was 3,5-dichlorophenyl (benzhydryl) sulfide. The yield was 94% based on the theoretical amount.

Second Step: The procedure was carried out except that 34.5 parts of 3,5-dichlorophenyl (benzhydryl) sulfide obtained in the first step was added in place of 3,5-dichlorophenyl t-butyl sulfide and the reflux time was changed to 8 hours. When the pH was adjusted to 2 in the same manner as in the second step of Example 2, crystals were precipitated. This was filtered off to obtain 11.6 parts of white crystals.
Melting point: 62 ° C;
¹ H-NMR (CDCl ₃ ): δ 7.15 (s, 3H), 3.55 (s, 1H).

  As a result, it was confirmed that the obtained product was 3,5-dichlorothiophenol. The yield was 65% based on the theoretical amount.

  Example 9

First Step In the same reactor used in the first step of Example 2, 22.4 parts of sodium t-butyl mercaptide, 200 parts of dimethyl sulfoxide and 1,3,5-trichlorobenzene 36 are added under a nitrogen atmosphere. 3 parts was added, and the mixture was heated at 80 ° C. for 5 hours. Thereafter, 37.8 parts of a colorless liquid having a boiling point of 75 ° C./0.4 Torr was obtained in the same manner as in the first step of Example 2. The ¹ H-NMR (CDCl ₃ ) chart of this product was the same as the product of the first step of Example 2.

  As a result, it was confirmed that the obtained product was 3,5-dichlorophenyl t-butyl sulfide. The yield was 80% based on the theoretical amount.

Second Step A glass autoclave is charged with 21.8 parts of 3,5-dichlorophenyl t-butyl sulfide obtained in the first step and 161.8 parts of an acetic acid solution containing 25% hydrogen bromide in a nitrogen atmosphere. The mixture was heated under reflux for 3 hours under pressure. Then, the reaction product was cooled to room temperature, transferred to another container, and after adding 150 parts of water and 100 parts of toluene and stirring, it was allowed to stand to separate. Thereafter, when the same treatment as in Example 2 was performed, crystals were precipitated. This was filtered off to obtain 15.1 parts of white crystals.
Melting point: 62 ° C;
¹ H-NMR (CDCl ₃ ): δ 7.15 (s, 3H), 3.55 (s, 1H).

  As a result, it was confirmed that the obtained product was 3,5-dichlorothiophenol. The yield was 84% based on the theoretical amount.

  Example 10

In a reactor similar to that used in the second step of Example 1, 23.5 parts of 3,5-dichlorophenyl t-butyl sulfide obtained in the first step of Example 2 under a nitrogen atmosphere, 95% Concentrated sulfuric acid (10.3 parts) and toluene (50 parts) were charged, heated with stirring and refluxed for 3 hours. After cooling to room temperature, 150 parts of water and 50 parts of toluene were added and stirred, and then allowed to stand to separate. To the organic phase was added 200 parts of a 10% aqueous sodium hydroxide solution, and the mixture was stirred and separated again to take the organic phase. This was washed with saturated brine, dehydrated with anhydrous sodium sulfate, and then toluene was distilled off under reduced pressure. As a result, a pale yellow liquid was obtained. This was treated with methanol to obtain 8.8 parts of colorless needle crystals.
Melting point: 65 ° C;
¹ H-NMR (CDCl ₃ ): δ 7.33 (d, J = 1.7Hz, 4H), 7.23 (t, J = 1.7Hz, 2H).

  As a result, it was confirmed that the product obtained from the organic phase was bis (3,5-dichlorophenyl) disulfide. The yield was 49% based on the theoretical amount.

A 12N aqueous hydrochloric acid solution was added to the combined aqueous phase to adjust the pH to 2, and the precipitated crystals were separated by filtration to obtain 4.3 parts of colorless needle crystals.
Melting point: 62 ° C;
¹ H-NMR (CDCl ₃ ): δ 7.15 (s, 3H), 3.55 (s, 1H).

  As a result, it was confirmed that the product obtained from the aqueous phase was 3,5-dichlorothiophenol. The yield was 24% based on the theoretical amount.

  Example 11

The reaction was performed in the same manner as in Example 8 except that the amount of toluene used as the reaction solution was 100 parts and refluxing was performed for 3 hours while removing water, and the reaction product was purified in the same procedure. From the organic phase, 12.9 parts of colorless needle crystals having a melting point of 65 ° C. were obtained. The ¹ H-NMR chart was in good agreement with the ¹ H-NMR chart of the crystal obtained from the organic phase of Example 8. From this, it was confirmed that the product obtained from the organic phase was bis (3,5-dichlorophenyl) disulfide. The yield was 72% based on the theoretical amount.

From the combined aqueous phase, 0.4 parts of colorless needle crystals having a melting point of 62 ° C. were obtained. Similarly, from the ¹ H-NMR chart, it was confirmed that the product was 3,5-dichlorothiophenol. The yield was 2% based on the theoretical amount.

  Example 12

In a reactor similar to that used in the second step of Example 1, 17.9 parts of 3,5-dichlorothiophenol obtained in the second step of Example 6 and 95% concentrated sulfuric acid under a nitrogen atmosphere. 20.7 parts and 100 parts of toluene were charged and refluxed for 6 hours while removing water. After cooling to room temperature, 150 parts of water was added and stirred, and then allowed to stand to separate. To the organic phase, 200 parts of 10% aqueous sodium hydroxide solution was added and stirred, and then allowed to stand. The organic phase was separated by liquid separation, washed with saturated brine, dehydrated with anhydrous sodium sulfate, and toluene was removed under reduced pressure. Distilled off to obtain 17.5 parts of colorless needle crystals.
Melting point: 65 ° C;
¹ H-NMR (CDCl ₃ ): δ 7.33 (d, J = 1.7Hz, 4H), 7.23 (t, J = 1.7Hz, 2H).

  As a result, it was confirmed that the obtained product was bis (3,5-dichlorophenyl) disulfide. The yield was 98% based on the theoretical amount.

  Example 13

In a reactor similar to that used in Example 10, 17.9 parts of the same 3,5-dichlorothiophenol, 50 parts of toluene and 50 parts of water were stirred and dispersed uniformly. A solution prepared by dissolving 7 parts in 30 parts of toluene was dropped. After stirring at room temperature for 30 minutes, the mixture is allowed to stand, and the organic phase is separated by separation, washed with 5% aqueous sodium thiosulfate solution and saturated brine, dehydrated with anhydrous sodium sulfate, and then toluene is distilled off under reduced pressure. As a result, 17.3 parts of colorless needle crystals were obtained.
Melting point: 65 ° C;
¹ H-NMR (CDCl ₃ ): δ 7.33 (d, J = 1.7Hz, 4H), 7.23 (t, J = 1.7Hz, 2H).

  As a result, it was confirmed that the obtained product was bis (3,5-dichlorophenyl) disulfide. The yield was 98% based on the theoretical amount.

  The aromatic thiols and aromatic disulfides obtained by the present invention are useful as intermediates for pharmaceuticals, agricultural chemicals, electronic materials and the like.

Claims (7)

(A) General formula (I):
_{Y n -Ar-X m (I} )
(Where
Ar represents an aromatic hydrocarbon residue;
X represents a halogen atom bonded to a carbon atom of an aromatic ring in Ar;
Y represents one or more substituents selected from the group consisting of a halogen atom, a nitro group, a nitrile group, a sulfone group, a sulfamoyl group, and a hydrocarbylsulfonyl group bonded to a carbon atom of an aromatic ring in Ar. Representation;
m is an integer greater than or equal to 1;
n is 0 or an integer of 1 or more)
In the aromatic halogen compound represented by
(B) (1) General formula (II):

(Where
R ¹ , R ² and R ³ each represents an alkyl group or an aryl group, provided that when any ^{two of} R ¹ , R ² and R ³ are aryl groups, the remainder may be a hydrogen atom;
M represents an alkali metal atom)
And / or (2) (a) the general formula (III):

(Wherein R ¹ , R ² and R ³ are as described above)
And (b) an alkali metal, its hydroxide, carbonate, hydride or alkoxide,
(C) The reaction is carried out in the presence of an aprotic polar solvent, represented by the general formula (IV):

(Wherein Y, Ar, R ¹ , R ² , R ³ , m and n are as described above)
A method for producing an aromatic thioether represented by the formula: The aromatic halogen compound (A) is represented by the general formula (Ia):

(Wherein X and Y are as described above; m is an integer of 1 to 6, n is an integer of 0 or 1 to 5, provided that m + n is 6 or less)
The method of claim 1, wherein   The method according to claim 1 or 2, wherein X is a chlorine atom.   The method according to any one of claims 1 to 3, wherein Y is a chlorine atom.   The method according to any one of claims 1 to 4, wherein n is 2.   The method according to claim 1, wherein m is 1.   A combination of (2), (a) a hydrocarbyl mercaptan represented by general formula (III), and (b) an alkali metal, its hydroxide, carbonate, hydride or alkoxide, as (B). The method according to any one of 1 to 6.