JP2000191636A - Production of aromatic sulfur compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an aromatic thiol compound in a high yield by reacting a specific aromatic thioether compound with a Lewis acid and then hydrolyzing the reaction product. SOLUTION: This method for producing (C) an aromatic thiol compound of the formula: Yn-Ar-(SH)m comprises reacting (A) an aromatic thioether compound of the formula: Yn-Ar-(SR)m [Ar is an aromatic hydrocarbon residue; Y is a halogen, nitro or the like which is bound to the carbon atom of the aromatic ring in Ar; R is a monovalent secondary or tertiary hydrocarbon or the like: (m) is >=1; (n) is >=0] with (B) a Lewis acid (for example, aluminum trichloride or titanium tetrachloride) in a solvent such as methylene chloride or chloroform preferably at a temp. from room temperature to 200 deg.C and then hydrolyzing the reaction product preferably with an excessive amount of cold water and/or water. In the reaction, the component B is preferably used in an amount of 0.01-3 moles per mole of the component A.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing aromatic thiols from aromatic thioethers, and to a method for producing aromatic disulfides via the aromatic thiols. The present invention further relates to a method for producing aromatic thiols from the above-mentioned aromatic thioethers from an aromatic halogen compound, and to a method for producing aromatic disulfides via the aromatic thiols.

[0002]

2. Description of the Related Art General formula (Va):

Embedded image (Wherein Y may be the same or different,
Represents a chlorine atom, a bromine atom, an iodine atom, a nitro group, a nitrile group, and a sulfone group; m is an integer of 1 to 6,
n is 0 or an integer of 1 to 5, where m + n is 6
And an aromatic thiol represented by the following general formula (VIa):

Embedded image (Wherein Y and n are as defined 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, Industrial Chemistry Magazine Vol. 70 No. 8 114
To page 118 (1967), 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 mercapto one chlorine atom. Is described. According to this method, halogenated aromatic thiols can be obtained in high yield from polychlorinated benzene having 4 to 6 chlorine atoms, but the yield of dichlorothiophenol from trichlorobenzene is only 17 to 20%. In addition, there is the complexity of handling liquid ammonia, and there are industrial restrictions due to the high pressure reaction in the autoclave.

In Japanese Patent Publication No. 44-26100, a halogenated aromatic compound having an amino group is diazoniumized with sodium nitrite and concentrated hydrochloric acid, and then reacted with potassium O-ethyldithiocarbonate. A method for obtaining halogenated aromatic thiols by a refluxing method is disclosed. This method is not only complicated, but also involves a risk because it handles diazonium salts, and is not preferred.

[0006] JP-A-56-156257 discloses that
1,3,5-trichlorobenzene or 1-bromo-
A method for producing 3,5-dichlorothiophenol is disclosed in which 3,5-dichlorobenzene and an alkali metal sulfide are reacted in the presence of a solvent such as diethylene glycol. In this method, the desired product can be obtained by a relatively simple operation, but purification is difficult because the yield is low and there are many by-products.

[0007] Zhur. Org. Khim. 11: 1132 (1
No. 975), an aromatic halide is obtained by reacting an aryl halide with hydrogen sulfide in the presence of thorium oxide. However, the method requires a high temperature of 550 ° C. or higher, and the yield is not good.

Japanese Patent Application Laid-Open No. 2-48564 discloses that a diaryl sulfide having a nitro group on one benzene ring is introduced with a substituent such as a halogen atom or a nitro group into the other benzene ring by an electrophilic substitution reaction. Then, a method is disclosed in which an exchange reaction is carried out with thiophenol in the presence of a basic substance such as sodium hydroxide to obtain thiophenols whose nucleus is substituted by the substituent. However, this method is complicated and is not suitable for introducing a large number of substituents into the benzene ring of thiophenols.

Japanese Patent Application Laid-Open No. 61-72749 discloses an o-
An O, o-halophenyl-N, N-dialkyl carbamate is synthesized by reacting a halophenol with an N, N-dialkylcarbamoyl halide, and this is subjected to a rearrangement reaction by heating to obtain an S-o-halophenyl-N, N-dialkyl. It discloses a method for producing an o-halothiophenol after carbamate formation and hydrolysis. However,
This method is a complicated multi-stage reaction and requires the use of carbamoyl halide which is unstable and difficult to handle. Further, since the rearrangement reaction is carried out at a high temperature, a side reaction occurs, which is disadvantageous, particularly when a substituent other than halogen is introduced.

JP-A-2-295968 discloses 4-halobenzenesulfinic acid; JP-A-3-181455 discloses 4-halobenzenesulfonyl chloride;
JP-186418 discloses a method for producing a corresponding halogenated thiophenol by reducing a halobenzenesulfenyl halide with a metal powder such as zinc dust in the presence of a mineral acid. However,
All of these reactions require special equipment in order to carry out reduction in the presence of a mineral acid. JP-A-5-14008
No. 6 discloses a method of obtaining a halothiophenol by reacting a monohalobenzene with sulfur monochloride in the presence of a catalyst such as zinc chloride, and reducing the reaction product with a reducing agent such as zinc. Is disclosed. This method also has a similar problem because it is a reduction reaction as described above.

JP-A-4-182463 discloses a method for obtaining halogenated thiophenols by reacting a polyhalogenated benzene with a sulfide such as sodium hydrogen sulfide, sodium sulfide or potassium sulfide. I have.

In these methods, since the reaction is slow, the halogenated aromatic thiols are liable to react with the starting halogenated benzene to form aromatic sulfides.
It reduces the yield of halogenated aromatic thiols.

JP-A-4-198162 discloses that a polyhalogenated benzene is reacted with a thioglycolate,
Methods for obtaining halogenated aromatic thiols are disclosed. JP-A-5-178816 discloses that a halogenated phenylthioglycolic acid is reacted with a sulfide such as sodium hydrogen sulfide or an aromatic thiol in the presence of a base to form a halogenated aromatic thiol. A method of obtaining is disclosed. However, these methods cannot obtain high-purity aromatic thiols with high yield.

JP-A-8-143533 discloses that a methyl group bonded to a sulfur atom of thioanisole is chlorinated with chlorine gas to obtain a halogenated thioanisole.
A method for obtaining a halogenated aromatic thiol by hydrolyzing it is disclosed. Further, Japanese Patent Application Laid-Open No. H8-143
No. 532 discloses that the above-mentioned hydrolysis of the halogenated thioanisole is carried out in the presence of a mineral acid, and that the halogenated aromatic thiol obtained by the hydrolysis reaction is oxidized with hydrogen peroxide such as hydrogen peroxide. It is disclosed that a halogenated aromatic disulfide can be obtained by oxidative dimerization with an agent. However, this method requires a complicated step of using volatile and odorous methyl mercaptan to obtain thioanisole, and introducing chlorine gas to chlorinate the methyl group. In addition, the reaction which removes a hydrocarbon group from an aromatic thioether by reaction with a Lewis acid to obtain an aromatic thiol is not known.

[0015]

SUMMARY OF THE INVENTION It is an object of the present invention to provide high-purity aromatic thiols and aromatic disulfides in an excellent yield over aromatic thioethers having a substituent at the carbon atom of the aromatic ring. Is to provide a way to gain.
Another object of the present invention is to provide a method for producing aromatic thiols and aromatic disulfides having a substituent from an aromatic halogen compound by a simple operation with excellent yield and purity. is there.

[0016]

Means for Solving the Problems The inventors of the present invention have conducted studies to solve the above problems, and as a result, it has been found that aromatic thioethers having a specific range of hydrocarbon groups can be easily reacted with Lewis acids. That the hydrocarbon group can be eliminated, and further utilizing this reaction, an aromatic halogen compound is reacted with a hydrocarbyl mercaptide alkali metal salt having a specific structure. The inventors have found that the object can be achieved by decomposition with an acid, and have completed the present invention.

That is, the present invention provides a compound represented by the general formula (IV): Y _n -Ar- (SR) _m (IV) wherein Ar represents an aromatic hydrocarbon residue;
a halogen atom bonded to a carbon atom of an aromatic ring in r,
R represents one or more substituents selected from the group consisting of a nitro group, a nitrile group, a sulfone group, a sulfamoyl group and a hydrocarbylsulfonyl group; R represents a monovalent secondary or tertiary hydrocarbon group; Or a general formula: —CH ₂ —R ¹ , —CH ₂ —CR ² ＝ C (R ² ) ₂ or —
CH ₂ —C≡CR ³ (wherein, R ¹ represents a monovalent aromatic ring group which may be substituted with a monovalent hydrocarbon group, and R ² may be the same or different. Represents a hydrogen atom or a monovalent hydrocarbon group; R ³ represents a hydrogen atom or a monovalent hydrocarbon group); and m represents
Is an integer of 1 or more; n is 0 or an integer of 1 or more], wherein the aromatic thioethers are reacted with (D) Lewis acid, and then hydrolyzed, general formula (V): Y _n -Ar- (SH) _m (V) wherein Y, Ar, m and n are as defined above; and a method for producing aromatic thiols represented by the formula: m is producing aromatic thiol is 1, then oxidized to the general formula _{(VI): Y n -Ar-} S-S-Ar-Y n (VI) ( wherein, Ar and Y is As described above; n is
Which is an integer of 0 or 1 or more).

Further, the present invention provides (A) a compound represented by the general formula (I): Y _n -Ar-X _m (I) wherein Ar and Y are as described above;
Represents a halogen atom bonded to a carbon atom of an aromatic ring in Ar; m is an integer of 1 or more; n is 0 or 1
(B) (1) General formula (II): RSM (II) (wherein R is as described above, and M is an alkali metal atom) And / or (2) (a) a hydrocarbyl mercaptan represented by the general formula (III): RSH (III) wherein R is as defined above. And (b) an alkali metal, hydroxide, carbonate, hydride or alkoxide thereof,
(C) reacting in the presence of an aprotic polar solvent to obtain a compound of the general formula (IV): Y _n -Ar- (SR) _m (IV) (where Y, Ar and R are as defined above; m
And n are as defined above) to produce the aromatic thioethers;
Similarly to the above, the present invention relates to a method for producing an aromatic thiol represented by the general formula (V). Further, by such a method, an aromatic thiol represented by the general formula (V) wherein m is 1 is produced and then oxidized to obtain an aromatic thiol represented by the general formula (V)
The present invention relates to a method for producing an aromatic disulfide represented by I).

In the present specification, the term “aromatic thiols” refers to aromatic monothiols, aromatic dithiols, aromatic trithiols, and other aromatic compounds having a plurality of mercapto groups, unless otherwise specified. It is used as a concept including compounds.

The production process of the present invention is typically carried out by the above reaction according to the general formula (IVa):

Embedded image (Wherein, Y is as described above; m is an integer of 1 to 6; n is 0 or an integer of 1 to 5;
+ N is 6 or less), or an aromatic thioether represented by the general formula (Ia):

Embedded image (Wherein X and Y are as described above; m and n are as described above, provided that m + n is 6 or less). Va):

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

Embedded image Wherein Y is as described above; n is 0 or 1
Which is an integer of from 5 to 5).

[0021]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described step by step with respect to a method using an aromatic halogen compound as a starting material. As described above, the method of the present invention is applied to, for example, an aromatic primary amine. Sodium nitrite and acid are reacted to form an aromatic diazonium salt, which is reacted with sodium hydrocarbyl mercaptide and then dediazonated to obtain an aromatic diazonium salt. The method also includes performing the second step and subsequent steps using thioethers as a starting material.

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

The aromatic halogen compound (A) 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. Ar
Is a residue of an aromatic ring such as a benzene ring, a biphenyl ring, a terphenyl ring, a naphthalene ring, an anthracene ring and a pyrene ring; and a hydrocarbon group such as methyl, ethyl, propyl, or butyl substituted on the ring Things. From the viewpoint of reactivity with (B), an aromatic ring residue which is not substituted with the above hydrocarbon group is preferred, and a benzene ring residue is particularly preferred.

X is a halogen atom which binds to the carbon atom of the aromatic ring in Ar and contributes to the reaction with (B), and is exemplified by a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. A chlorine atom or a bromine atom is preferred because (A) is easily available and the treatment of by-products is easy.

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

Y is bonded to a carbon atom of an aromatic ring in Ar and introduced as a substituent into the target aromatic thiols or aromatic disulfides, and (A) and (B) ) 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, chlorine atom, bromine atom and iodine atom, and 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 or different from X.

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

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

Contained in the molecules of (1) and (a),
The monovalent hydrocarbon group R bonded to the sulfur atom can be selected from a wide range. That is, as R, isopropyl, s-butyl, s-pentyl, s-hexyl,
s-octyl, s-decyl, s-dodecyl, 1,4,4
Secondary alkyl groups such as trimethylpentyl; secondary alkenyl groups such as isobutenyl and isopentenyl; monovalent secondary groups such as aromatic hydrocarbon-containing secondary hydrocarbon groups such as 1-phenylethyl and benzhydryl. Higher hydrocarbon groups; and t-butyl, t-pentyl, t-hexyl, t-octyl, t-decyl, t-dodecyl, 1-methyl-1-ethylpropyl, 1,1-diethylpropyl, 1,1, Tertiary alkyl groups such as 4-trimethylpentyl; 1-methyl-1-phenylethyl, 1,1-
A monovalent tertiary hydrocarbon group such as an aromatic ring-containing tertiary hydrocarbon group such as diphenylethyl and trityl can be used.

Further, R represents a general formula: —CH ₂ —R ¹ , —CH ₂ —CR ² ＣC (R ² ) ₂ or —
A specific range of a monovalent hydrocarbon group represented by CH ₂ —C≡CR ³ (wherein R ¹ , R ² and R ³ are as described above) can be used. R ¹ is a monovalent aromatic ring group such as phenyl and 1-naphthyl; and a group in which the aromatic ring group is further substituted with a monovalent hydrocarbon group such as tolyl, xylyl and 4-biphenylyl. Is exemplified. Examples of R ² and R ³ include a hydrogen atom, an alkyl group such as methyl, ethyl, propyl, and butyl; an alkenyl group such as vinyl; and an aryl group such as phenyl. Examples of such a monovalent primary hydrocarbon group include a hydrocarbon group in which an aromatic ring is bonded to a methylene group bonded to a sulfur atom, such as benzyl and 1-naphthylmethyl; and allyl, 2-butenyl and cinnamyl And propargyl, such as a hydrocarbon group having an unsaturated bond between the hydrocarbon groups at the -2 and -3 positions. Among them, (1) or (a) can be easily obtained, the handling is easy, and the hydrocarbon group can be easily eliminated by reaction with a wide range of Lewis acids, so that isopropyl, t-butyl, benzhydryl and Benzyl is preferred, and t-butyl is particularly preferred.

M contained in the molecules of (1) and (b) is an alkali metal atom and includes lithium, sodium, potassium, cesium and the like, and sodium and potassium are preferred.

Examples of such (1) include sodium isopropyl mercaptide, sodium s-butyl mercaptide, sodium s-hexyl mercaptide, sodium s-octyl mercaptide, sodium s-dodecyl mercaptide, sodium benzhydryl mercaptide Sodium hydrocarbyl mercaptide sodium salt such as peptide; sodium t-butyl mercaptide, sodium t-pentyl mercaptide, sodium t-hexyl mercaptide, sodium t-dodecyl mercaptide, sodium-1,1-diphenylethyl merca Tertiary hydrocarbyl mercaptide sodium salt such as peptide, sodium trityl mercaptide; primary hydrocarbyl such as sodium allyl mercaptide, sodium benzyl mercaptide Le mercaptide, sodium salt; and hydrocarbyl mercaptide lithium, and potassium salts corresponding to these are exemplified.

(2) (a) a hydrocarbyl mercaptan having a monovalent hydrocarbon group as described above; and (b)
Combinations with alkali metals, their hydroxides, carbonates, hydrides or alkoxides. As (a), the hydrocarbyl mercaptan having a monovalent hydrocarbon group exemplified in the above (1) is exemplified, and isobutyl mercaptan, t-butyl mercaptan, benzhydryl mercaptan and benzyl mercaptan are preferable.

(B) other than 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 Salts; 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 the corresponding lithium alkoxides And potassium alkoxide.

The reaction proceeds even if one of them is used in excess of (a) and (b), but the molar ratio of (b) to (a) is preferably 1.0 to 1.5, more preferably 1.0 to 1.5. 1.1 is more preferable, and 1.0 is most preferable. When the remaining (a) is not preferable, (b) may be used in a slightly excessive amount.

The amount of (B) subjected to the reaction with (A) is
When (B) is used in combination with (2), it is usually in the range of 1 to 3 moles per 1 mole of X in (A), when converted to the theoretical amount of (1) formed in the system. 0.0 to 1.1 mol is preferable, and 1.0 mol is most preferable in order to avoid the complexity of removing (A) after the reaction.

The aprotic polar solvent (C) used in the present invention is a reaction solvent that remarkably accelerates the reaction of aromatic thiols by the reaction between (A) and (B). Examples of (C) include N-methyl-2-pyrrolidone, N, N-dimethylformamide, N, N-dimethylacetamide, sulfolane, dimethylsulfoxide and the like. Dimethylsulfoxide is excellent because of its excellent reaction promoting effect. preferable.

The amount of (C) is an amount necessary to dissolve or disperse the compounds participating in the reaction and to stir the system.
Specifically, the amount is usually 200 g or more, preferably 400 to 1,200 g, per 1 mol of the total amount of (A) and (B).

The step of synthesizing aromatic thioethers from (A) an aromatic halide and (B) a sulfur compound is carried out in the presence of the above (C) aprotic polar solvent. For example, when (1) an alkali metal salt of hydrocarbyl mercaptide is used as (B), (1) and (A) are dissolved in (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 proceeds rapidly to form (1), which is then reacted with (A) as described above.

The reaction between (A) and (B) is performed at room temperature to 200 ° C.
Can be advanced. The sum of n and m in (A) is 2
When it is relatively small, such as ~ 4, it is preferably 50 ~ 1
It is effective to increase the temperature to 20 ° C. to accelerate the reaction. When m is 2 or more, the reaction is preferably performed at 100 to 200 ° C. When Y is a nitro group, or when Ar is a benzene ring and the sum of n and m is 5 or 6, the reaction proceeds sufficiently even at room temperature, so room temperature is preferable.

In the second step of the method for producing aromatic thiols, the aromatic thioethers obtained by the first step and having a monovalent hydrocarbon group having a specific structure as described above and bonded to a sulfur atom are used. In this step, a hydrocarbon group is eliminated from the aromatic compound by reacting with a Lewis acid and then hydrolyzing to obtain an aromatic thiol.

In the present invention, the Lewis acid is defined as a concept including its complex. (D) As Lewis acids, boron trifluoride, boron trichloride, boron tribromide,
Aluminum chloride, aluminum bromide, titanium tetrachloride,
For example, halides such as ferric chloride, tin tetrachloride, and antimony pentachloride; and complexes thereof such as boron trifluoride-diethyl ether complex are easy to handle and have high activity. Aluminum chloride, titanium tetrachloride and ferric chloride are preferred. In order to obtain aromatic thiols with high purity, those having no oxidizing action described below are more preferred, and aluminum chloride and titanium tetrachloride are particularly preferred.

(D) The amount of Lewis acid used depends on the type of aromatic thioethers, ie, Y, R, m and n, and the type of Lewis acid.
It can be arbitrarily selected up to an excess amount with respect to the aromatic thioethers. That is, the amount of the Lewis acid is used for the reaction because an appropriate elimination reaction rate is obtained for various hydrocarbon groups to be eliminated from the aromatic thioethers and an undesirable side reaction does not occur. Usually 0.01 to 3 mol, preferably 0.02 to 1 mol of aromatic thioethers.
The reaction proceeds in the presence of a small amount of Lewis acid as n increases and m decreases. The amount of the Lewis acid is more preferably from 0.02 to 0.1 mol of the catalyst based on the above-mentioned standard because of economical efficiency and easy removal of the remaining acid.

The reaction between the aromatic thioethers and the Lewis acid may be carried out at a temperature from room temperature or lower to 200 ° C., depending on the strength of the acid.
The temperature can be selected from room temperature to 15
0 ° C. is preferred. As a reaction solvent, methylene chloride,
Halogenated hydrocarbons such as chloroform, carbon tetrachloride and ethylene dichloride; hydrocarbons such as toluene, xylene and mesitylene; ethers such as anisole are used. When boron trifluoride, boron tribromide, aluminum chloride, titanium tetrachloride, ferric chloride or the like is used as the Lewis acid, the reaction is preferably performed at room temperature in the presence of the above-mentioned solvents.

Next, by throwing the reaction product into water, the reaction product is hydrolyzed to produce aromatic thiols. Since the hydrolysis reaction proceeds in a short time and involves heat generation, it is preferable to use excess cold water and / or ice as water.

As described above, by combining the synthesis of the aromatic thioether and the elimination reaction of the hydrocarbon group of the thioether, the aromatic thiols can be synthesized with high yield and high purity.

The aromatic thiols obtained in this manner may be used as intermediates for synthesizing various compounds. In the third step, the aromatic thiols having m = 1 are oxidized to obtain the aromatic thiols. The aromatic disulfides may be produced by dimerization.

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

Some Lewis acids such as ferric chloride, tin tetrachloride and antimony pentachloride are also used as reactants in the synthesis of aromatic thiols from aromatic thioethers, as described above. . Therefore, by using a Lewis acid having the above-mentioned reactivity and also functioning as an oxidizing agent and selecting appropriate reaction conditions, synthesis of aromatic thiols having m of 1 from aromatic thioethers and aromatic thioethers The synthesis of aromatic disulfides can be performed in one step without isolation of aromatic thiols. As a Lewis acid used for one-step synthesis of aromatic disulfides from such aromatic thioethers, ferric chloride is preferred because of its strong oxidizing power.

[0051]

According to the present invention, aromatic thiols and aromatic disulfides can be obtained in excellent yield and high purity from aromatic thioethers having a substituent on the aromatic ring.

In the present invention, unexpectedly from the Friedel-Crafts reaction using a Lewis acid, the reaction proceeds in the presence of a catalytic amount of a Lewis acid. This facilitates the removal of the remaining acid, and is industrially extremely advantageous.

Also, based on the above findings, aromatic thiols and aromatic disulfides having substituents can be produced from aromatic halogen compounds having substituents in good yield and purity through aromatic thioethers. it can. The method of the present invention is particularly useful for the production of disubstituted aromatic thiols and disulfides derived therefrom, which cannot be obtained with high yield by other methods.

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

[0055]

The present invention will be described in more detail with reference to the following examples. In the examples, “part” indicates “part by weight”, and “%” of the composition indicates “% by weight”. In the following reaction formulas, i-Pr represents an isopropyl group, t-Bu represents a t-butyl group, Bzl represents a benzyl group, and DMSO represents dimethylsulfoxide. The present invention is not limited by these examples.

Embodiment 1

[0057]

Embedded image

A reaction vessel equipped with a stirrer, a calcium chloride tube, a thermometer and a dropping funnel was charged with 14.7 parts of aluminum chloride and 100 parts of toluene under a nitrogen atmosphere.
While cooling with ice, 23.5 parts of 3,5-dichlorophenyl t-butyl sulfide was added dropwise. After stirring at room temperature for 30 minutes, the reaction solution was added to 150 parts of ice, vigorously stirred, and allowed to stand still for liquid separation. 200 parts of a 10% aqueous sodium hydroxide solution was added to the organic phase, and the mixture was stirred and allowed to stand still for liquid separation. When the pH was adjusted to 2 by adding 12N hydrochloric acid to the aqueous phase, crystals precipitated. This was filtered to obtain 16.6 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 is
93% of theory.

Embodiment 2

[0061]

Embedded image

Boron bromide 2 instead of aluminum chloride
Except for using 7.6 parts, the procedure of Example 1 was repeated to obtain 15.2 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 is
It was 85% of the theoretical amount.

Embodiment 3

[0065]

Embedded image

16.9 parts of colorless needle crystals were obtained in the same manner as in Example 1, except that 20.9 parts of titanium tetrachloride was used instead of aluminum chloride, and the reaction conditions were changed to room temperature for 8 hours. 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 is
95% of theory.

Embodiment 4

[0069]

Embedded image

17.2 parts of colorless needle crystals were obtained in the same manner as in Example 1 except that the amount of aluminum chloride was 0.27 parts, the amount of toluene was 50 parts, and the reaction conditions were room temperature and 2 hours. Was. Melting point: 62 ° C .; ¹ H-NMR (CDCl ₃ ): δ 7.15 (s, 3H);
55 (s, 1H).

As a result, it was confirmed that the obtained product was 3,5-dichlorothiophenol. The yield is
96% of theory.

Embodiment 5

[0073]

Embedded image

A colorless needle was prepared in the same manner as in Example 1 except that 26.9 parts of 3,5-dichlorophenylbenzyl sulfide was used instead of 3,5-dichlorophenyl tert-butyl sulfide, and the reaction conditions were set to 3 hours at room temperature. Crystal 16.
Three parts were obtained. 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 is
It was 91% of the theoretical amount.

Embodiment 6

[0077]

Embedded image

The procedure of Example 1 was repeated, except that 22.1 parts of 3,5-dichlorophenylisopropyl sulfide was used instead of 3,5-dichlorophenyl tert-butyl sulfide, and the mixture was heated and refluxed for 1 hour after completion of the dropwise addition. 15.7 parts of colorless needle crystals were obtained. 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 is
It was 88% of the theoretical amount.

Embodiment 7

[0081]

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The procedure of Example 1 was repeated, except that 20.1 parts of 3-chlorophenyl t-butyl sulfide was used instead of 3,5-dichlorophenyl t-butyl sulfide, and the reaction conditions were changed to 5 hours at room temperature. When the operation was performed until the pH of the aqueous phase was adjusted to 2, an oily substance was precipitated. After this was extracted with diethyl ether, the solvent was distilled off under reduced pressure.
Then, 8.8 parts of a colorless 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 61% based on theory.

Embodiment 8

[0085]

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The procedure of Example 1 was repeated, except that 21.1 parts of 4-nitrophenyl t-butyl sulfide were used instead of 3,5-dichlorophenyl t-butyl sulfide.
13.5 parts of pale yellow needle crystals were obtained. Melting point: 77 ° C .; ¹ H-NMR (CDCl ₃ ): δ 8.09 (d, J = 8.9 Hz, 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 87% based on theory.

Embodiment 9

[0089]

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Instead of 3,5-dichlorophenyl t-butyl sulfide, 28.8 parts of 3,5-bis (t-butylthio) chlorobenzene was used, the amount of aluminum chloride was 14.7 parts, and the reaction conditions were 8 at room temperature. 15.0 parts of colorless needle crystals were obtained in the same manner as in Example 1 except that the time was changed, and the amount of the 10% aqueous sodium hydroxide solution added in the post-treatment was changed to 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 85% of theory.

Embodiment 10

[0093]

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In a reactor similar to that used in Example 1, 17.8 parts of ferric chloride and toluene 1
Then, 23.5 parts of 3,5-dichlorophenyl t-butyl sulfide was added dropwise while cooling with ice. After stirring at room temperature for 30 minutes, the reaction product was added to 150 parts of ice, stirred vigorously, and allowed to stand still for liquid separation. 200 parts of a 10% aqueous sodium hydroxide solution was added to the organic phase, and the mixture was stirred and allowed to stand still. The liquid was separated and the organic phase was washed with a saturated saline solution and dried over anhydrous sodium sulfate. Evaporation under reduced pressure gave a pale yellow liquid. This was treated with methanol to obtain 13.3 parts of white crystals. Melting point: 65 ° C .; ¹ H-NMR (CDCl ₃ ): δ 7.33 (d, J = 1.7 Hz, 4H), 7.23 (t,
(J = 1.7Hz, 2H).

As a result, the product obtained from the organic phase was:
It was confirmed to be bis (3,5-dichlorophenyl) disulfide. The yield was 75% of theory.

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 1.3 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, the product obtained from the aqueous phase was:
It was confirmed to be 3,5-dichlorothiophenol. The yield was 7% based on theory.

Embodiment 11

[0099]

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Tin tetrachloride 28.7 instead of ferric chloride
Then, the system was heated after the dropwise addition of 3,5-dichlorophenyl t-butyl sulfide, and the reaction was carried out for 56 hours while refluxing toluene. 0 parts were obtained. Melting point: 65 ° C .; ¹ H-NMR (CDCl ₃ ): δ 7.33 (d, J = 1.7 Hz, 4H), 7.23 (t,
(J = 1.7Hz, 2H).

As a result, the product obtained from the organic phase was:
It was confirmed to be bis (3,5-dichlorophenyl) disulfide. The yield was 39% of theory.

Similarly, the aqueous phase was converted to colorless needle-like crystals 6.3.
Got a part. Melting point: 62 ° C .; ¹ H-NMR (CDCl ₃ ): δ 7.15 (s, 3H), 3.55 (s, 1H).

As a result, the product obtained from the aqueous phase
It was confirmed to be 3,5-dichlorothiophenol. The yield was 35% of theory.

Embodiment 12

[0105]

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First Step A reactor equipped with a stirrer, a Dimroth condenser, a thermometer and a dropping funnel was charged with 22.4 parts of sodium t-butyl mercaptide and 200 ml of dimethyl sulfoxide under a nitrogen atmosphere.
And 36.3 parts of 1,3,5-trichlorobenzene, and the mixture was slowly heated with stirring and heated at 80 ° C. for 5 hours. Then, the mixture was cooled to room temperature, 200 parts of water and 200 parts of toluene were added, and the mixture was stirred and allowed to stand still for liquid separation. The organic phase was washed with a saturated saline solution, dried over anhydrous sodium sulfate, and then toluene was distilled off under reduced pressure. By vacuum distillation of the liquid residue, 37.8 parts of a colorless and transparent liquid was obtained as a fraction having a boiling point of 75 ° C./0.4 Torr. ¹ H-NMR (CDCl ₃ ): δ 7.42 (d, J = 2.0 Hz, 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% of the theoretical amount.

Second step The thus obtained 3,5-dichlorophenyl t-
As in Example 3, colorless needle-like crystals were obtained using 23.5 parts of butyl sulfide and 20.9 parts of titanium tetrachloride.
9 parts were obtained. 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 is
95% of theory.

Embodiment 13

[0111]

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First Step In a reactor used in the first step of Example 12, 18.0 parts of t-butyl mercaptan, 200 parts of dimethyl sulfoxide and 14.5 parts of 85% potassium hydroxide were placed under a nitrogen atmosphere.
The resulting mixture was stirred at 50 ° C. for 30 minutes to synthesize potassium t-butyl mercaptide in the system. Subsequently, 31.6 parts of p-nitrochlorobenzene was added under ice cooling, and the mixture was stirred at room temperature for 30 minutes. Then, after adding water and toluene, the boiling point was 9
36.8 parts of a colorless liquid of 9 ° C./0.5 Torr was obtained. ¹ H-NMR (CDCl ₃ ): δ 8.17 (d, J = 8.9 Hz, 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 theory.

Second Step Using 21.1 parts of 4-nitrophenyl t-butyl sulfide thus obtained and 14.7 parts of aluminum chloride, as in Example 8, pale yellow needle-like crystals 13. 5
Got a part. Melting point: 77 ° C .; ¹ H-NMR (CDCl ₃ ): δ 8.09 (d, J = 8.9 Hz, 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 87% based on theory.

Embodiment 14

[0117]

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First step: The addition amount of t-butyl mercaptan was 36.0 parts, 85%
First step of Example 13 except that the addition amount of potassium hydroxide was 29 parts, 36.3 parts of 1,3,5-trichlorobenzene was added instead of p-nitrochlorobenzene, and the mixture was heated at 130 ° C. for 3 hours. When toluene was distilled off in the same manner as described above, 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 = 1.6 Hz, 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% of theory.

Step 2 28.8 parts of 3,5-bis (t-butylthio) chlorobenzene thus obtained and aluminum chloride 1
In the same manner as in Example 9 using 4.7 parts, 15.0 parts of colorless needle crystals were obtained. 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 85% of theory.

Embodiment 15

[0123]

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First Step In a reactor equipped with ancillary equipment similar to that used in the first step of Example 12, 300 parts of dimethyl sulfoxide and a concentration of 63.2 dispersed in mineral oil were added under a nitrogen atmosphere. % Sodium hydride and stirred at room temperature for 30 minutes. Next, 81.2 parts of t-butyl mercaptan was slowly dropped, and the mixture was stirred at 40 ° C. for 30 minutes.
-36.2 parts of trichlorobenzene was added, the temperature was slowly raised, and the mixture was heated at 150 ° C for 2 hours. Then, 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, and the organic phase was separated. The organic phase was washed with a 10% aqueous sodium hydroxide solution, then with a saturated saline solution, dried over 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, the obtained products were 1,3,5
-Tris (t-butylthio) benzene was confirmed. The yield was 60% of theory.

Second Step In a reactor used in Example 1, under a nitrogen atmosphere, 4.0 parts of aluminum chloride and 500 parts of toluene were charged, and while cooling with ice, the 1,3,5 -34.3 parts of tris (t-butylthio) benzene were added dropwise. After stirring at room temperature for 5 hours, the reaction product was added to 150 parts of ice and stirred vigorously. The mixture was allowed to stand, liquids were separated, the organic phase was taken, and 600 parts of a 10% aqueous sodium hydroxide solution was added thereto and stirred. The solution was allowed to stand, separated, separated into an aqueous phase, and concentrated hydrochloric acid was added to adjust the pH to 2, whereby crystals were precipitated. This was separated by filtration to obtain 16.9 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, the obtained products were 1,3,5
-It was confirmed that it was trimercaptobenzene. The yield was 97% based on theory.

Embodiment 16

[0129]

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The same reactor as used in Example 1 was charged with 3,5-dichlorothiophenol 1 obtained in Example 1.
After 7.9 parts, 50 parts of toluene and 50 parts of water were charged and uniformly dispersed by stirring, a solution in which 12.7 parts of iodine was dissolved in 30 parts of toluene was added dropwise. After stirring at room temperature for 30 minutes, the mixture was allowed to stand, and the organic phase was separated to separate 5%
Washed with aqueous sodium thiosulfate and saturated saline,
After dehydration with anhydrous sodium sulfate, toluene was distilled off under reduced pressure to obtain 17.3 parts of colorless needle crystals. Melting point: 65 ° C .; ¹ H-NMR (CDCl ₃ ): δ 7.33 (d, J = 1.7 Hz, 4H), 7.23 (t,
(J = 1.7Hz, 2H).

As a result, the product obtained was bis (3,3)
(5-dichlorophenyl) disulfide. The yield was 98% of theory.

 ────────────────────────────────────────────────── ─── Continuing from the front page (72) Inventor Yoko Hida 12-8, Sasamekitamachi, Toda City, Saitama Japan Nippon Fine Chemical Co., Ltd. Toda Laboratory F-term (reference) 4H006 AA02 AC63 BA10 BA11 BA18 BA37 BA67 BA69 BB11 BB12 BB15 BC10 BC34 BE05 BE32 BE53 BE56 BE61 TA04

Claims (14)

[Claims] 1. A compound of the general formula (IV): Y _n —Ar— (SR) _m (IV) wherein Ar represents an aromatic hydrocarbon residue;
a halogen atom bonded to a carbon atom of an aromatic ring in r,
R represents one or more substituents selected from the group consisting of a nitro group, a nitrile group, a sulfone group, a sulfamoyl group and a hydrocarbylsulfonyl group; R represents a monovalent secondary or tertiary hydrocarbon group; Or a general formula: —CH ₂ —R ¹ , —CH ₂ —CR ² ＝ C (R ² ) ₂ or —
CH ₂ —C≡CR ³ (wherein, R ¹ represents a monovalent aromatic ring group which may be substituted with a monovalent hydrocarbon group, and R ² may be the same or different. Represents a hydrogen atom or a monovalent hydrocarbon group; R ³ represents a hydrogen atom or a monovalent hydrocarbon group), and m represents
Is an integer of 1 or more; n is 0 or an integer of 1 or more], wherein the aromatic thioethers are reacted with (D) Lewis acid, and then hydrolyzed, general formula (V): Y _n A method for producing an aromatic thiol represented by -Ar- (SH) _m (V) (wherein Y, Ar, m and n are as described above). 2. A compound of the general formula (IVa): (Wherein, Y is as described above; m is an integer of 1 to 6; n is 0 or an integer of 1 to 5;
+ N is 6 or less) from an aromatic thioether represented by the general formula (Va): The method according to claim 1, wherein the aromatic thiols represented by the formula: wherein Y, m and n are as defined above, are produced. 3. The method according to claim 1, wherein Y is a chlorine atom. 4. The method according to claim 1, wherein n is 2. 5. The method according to claim 1, wherein m is 1. 6. The process according to claim 1, wherein the Lewis acid is used in an amount of 0.01 to 3 mol per 1 mol of the aromatic thioether. 7. The process according to claim 6, wherein the Lewis acid is used in an amount of 0.02 to 0.1 mol per 1 mol of the aromatic thioether. 8. An aromatic thiol represented by the general formula (V) wherein m is 1 is produced by the method according to any one of claims 1 to 7, and then oxidized to obtain an aromatic thiol. formula _{(VI): Y n -Ar-} S-S-Ar-Y n (VI) ( wherein, Ar and Y are as described above; n is
0 or an integer of 1 or more). 9. An aromatic thiol represented by the general formula (V) is produced by using (D) ferric chloride as a Lewis acid, and the aromatic thiol is oxidized without isolation. The method according to claim 8, wherein the aromatic disulfide represented by the general formula (VI) is produced. (A) General formula (I): Y _n —Ar—X _m (I) (where Ar and Y are as described above; X is
Represents a halogen atom bonded to a carbon atom of an aromatic ring in Ar; m is an integer of 1 or more; n is 0 or 1
(B) (1) General formula (II): RSM (II) (wherein R is as described above, and M is an alkali metal atom) And / or (2) (a) a hydrocarbyl mercaptan represented by the general formula (III): RSH (III) wherein R is as defined above. And (b) an alkali metal, hydroxide, carbonate, hydride or alkoxide thereof,
(C) reacting in the presence of an aprotic polar solvent to obtain a compound of the general formula (IV): Y _n -Ar- (SR) _m (IV) (where Y, Ar and R are as defined above; m
Is an integer of 1 or more; n is 0 or an integer of 1 or more), and the obtained thioethers are reacted with (D) Lewis acid,
Then hydrolyzed, the general formula (V): (wherein, Y and Ar are is as described above; m and n are same as described _{above) Y n -Ar- (SH) m} (V) with A method for producing the aromatic thiols shown. 11. A compound of the general formula (Ia): Wherein X and Y are as described above;
An integer of 6 and n is 0 or an integer of 1 to 5, provided that m + n is 6 or less) from an aromatic halogen compound represented by the general formula (Va): The method according to claim 10, wherein the aromatic thiols represented by the formula: wherein Y is as described above; and m and n are as described above. 12. The method according to claim 10, wherein X is a chlorine atom. 13. As (B), (2), that is, (a) a hydrocarbyl mercaptan represented by the general formula (III), and (b) an alkali metal, a hydroxide, a carbonate, a hydride or an alkoxide thereof. Using a combination of
A method according to any one of claims 10 to 12. 14. An aromatic thiol represented by the general formula (V) wherein m is 1 is produced by the method according to any one of claims 10 to 13, which is then oxidized to obtain an aromatic thiol. family disulfides _{(VI): Y n -Ar-} S-S-Ar-Y n (VI) ( wherein, Ar and Y are as described above; n is
0 or an integer of 1 or more).