JP5482233B2 - Method for producing diaryl disulfide compound - Google Patents

Description

  The present invention relates to a method for synthesizing a diaryl disulfide compound using an arylsulfonyl compound as a starting material and adding a bromine salt, a bromonium ion reducing agent, and sulfuric acid.

  Diaryl disulfide compounds are useful as, for example, synthetic intermediates for pharmaceuticals, agricultural chemicals, and functional materials, and as raw materials for synthesizing fluorinating agents.

  Examples of a method for synthesizing a diaryl disulfide compound from an arylsulfonyl compound include a reaction of hydroiodic acid (HI aqueous solution) with acetic acid (Non-Patent Documents 1 and 2), an acetic acid solution of sodium sulfite and hydrogen bromide (HBr) (Non-patent Document 3), tungsten hexachloride and sodium iodide or zinc (Non-patent Document 4), iodotrimethylsilane (Non-patent Document 5), or hydrogen bromide (HBr) A method based on a reaction between an acetic acid solution and phenol (Non-patent Document 6) has been known. However, each of the production methods has drawbacks such as complicated handling and difficulty in obtaining a reaction reagent, and thus has a problem as an industrial production method.

  Further, Patent Document 1 discloses a method based on a reaction between a catalytic amount of iodine or iodine salt, saturated aqueous sodium hydrogensulfite and acetic acid. However, in this patent document 1, there is no description about a bromine salt, and it has been reported that reaction progressed favorably with potassium iodide.

US2571740 (1951)

J. Chem. Soc., 1949, 3434 J. Chem. Soc., 1956, 3668 J. Chem. Soc., 1948, 769 Synthesis, 1999,500 J. Org. Chem., 47, 4806 (1982) Journal of Fluorine Chemistry, 112,287 (2001)

  The object of the present invention is to solve the above-mentioned problems, and without requiring a complicated operation, and a method capable of producing a diaryl disulfide compound in a high yield by using an easily available reaction reagent Is to provide.

  As a result of intensive studies, the present inventors have found that a diaryl disulfide compound is produced in high yield by adding a bromine salt, a bromonium ion reducing agent, and sulfuric acid using an arylsulfonyl compound as a starting material, The present invention has been completed.

（式中、Ａｒは置換基を有していても良いアリール基又はヘテロアリール基を示し、Ｌは脱離基を示す。）
で示されるアリールスルホニル化合物、一般式（２）

（式中、Ｍは金属イオン、四級アンモニウムイオン、又はホスホニウムイオンを示す。）で示される臭素塩、ブロモニウムイオンの還元剤、及び硫酸を添加することを特徴とする、一般式（３）

（式中、Ａｒは前記と同義である。）
で示されるジアリールジスルフィド化合物の製造方法によって解決される。 The subject of this invention is general formula (1) in presence of organic acid.

(In the formula, Ar represents an aryl group or heteroaryl group which may have a substituent, and L represents a leaving group.)
An arylsulfonyl compound represented by the general formula (2)

(Wherein M represents a metal ion, a quaternary ammonium ion, or a phosphonium ion), a bromine salt represented by the general formula (3), a reducing agent for bromonium ion, and sulfuric acid are added.

(In the formula, Ar has the same meaning as described above.)
It solves by the manufacturing method of the diaryl disulfide compound shown by these.

  According to the present invention, a diaryl disulfide compound can be produced in a high yield without requiring a complicated operation and using a readily available reaction reagent.

  The arylsulfonyl compound used in the reaction of the present invention is represented by the general formula (1). In the general formula (1), Ar represents an aryl group or heteroaryl group which may have a substituent, and includes various isomers. Examples of the aryl group or heteroaryl group include aryl groups such as phenyl group and naphthyl group, and pyridinyl group, pyrazolyl group, pyrazinyl group, triazolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, thienyl group, benzoyl group And heteroaryl groups such as thienyl, furanyl, benzofuranyl, pyrrolyl, and indolyl groups. Preferred Ar is an aryl group, for example, a phenyl or naphthyl group, preferably a phenyl group.

Examples of the substituent of the aryl group or heteroaryl group include alkyl groups such as methyl group, ethyl group, propyl group, butyl group, pentyl group, and hexyl group; cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cyclohexane Cycloalkyl group such as heptyl group; alkoxyalkyl group such as methoxymethyl group, ethoxymethyl group, propoxymethyl group, butoxymethyl group; halogen atom such as fluorine atom, chlorine atom, bromine atom, iodine atom; trifluoromethyl group, etc. A halogenated alkyl group, a cyano group, a nitro group, and the like. These groups include various isomers.
A preferred substituent is an alkyl group or a halogen atom.

  In the general formula (1), L represents a leaving group. The leaving group is a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. Preferred leaving groups are a chlorine atom, a bromine atom and an iodine atom, more preferably a chlorine atom.

  The bromine salt used in the present invention is represented by the general formula (2). In the general formula (2), M represents a metal ion, a quaternary ammonium ion, or a phosphonium ion.

  Examples of the metal ion include alkali metal ions such as lithium, sodium, potassium, and cesium; alkaline earth metal ions such as magnesium and calcium. Preferred metal ions are lithium, sodium, potassium, and cesium, and more preferably potassium ions.

  Examples of the substituent constituting the quaternary ammonium ion include alkyl groups such as a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, and a hexyl group; a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, Cycloalkyl groups such as cycloheptyl group; aralkyl groups such as benzyl group and phenethyl group; heteroaryl groups such as pyrrolyl group, furyl group and thienyl group; phenyl group, tolyl group, fluorophenyl group, xylyl group, biphenylyl group, naphthyl group And aryl groups such as an anthryl group and a phenanthryl group. These groups include various isomers. The substituent constituting the quaternary ammonium ion is preferably a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group or a benzyl group, more preferably an ethyl group, a propyl group, a butyl group or a benzyl group. is there.

  Specific examples of quaternary ammonium ions include tetramethylammonium, tetraethylammonium, tetrapropylammonium, tetrabutylammonium, tetraamylammonium, tetrahexylammonium, tetraheptylammonium, tetraoctylammonium, tetradecylammonium, decyltrimethylammonium, di Decyldimethylammonium, trimethylstearylammonium, dimethyldioctadecylammonium, benzyltrimethylammonium, benzyltriethylammonium, preferably tetraethylammonium, tetrapropylammonium, tetrabutylammonium and benzyltrimethylammonium can be mentioned.

  Examples of the substituent constituting the phosphonium ion include alkyl groups such as a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, and a hexyl group; a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cycloheptyl group. A cycloalkyl group such as a group; an aralkyl group such as a benzyl group or a phenethyl group; a heterocyclic group such as a pyrrolyl group, a furyl group or a thienyl group; a phenyl group, a tolyl group, a fluorophenyl group, a xylyl group, a biphenylyl group, a naphthyl group; Examples include an aryl group such as an anthryl group and a phenanthryl group. These groups include various isomers. The substituent constituting the phosphonium ion is preferably an ethyl group, a propyl group, a butyl group, or a phenyl group, and more preferably a phenyl group.

  Specific examples of phosphonium ions include tetraethylphosphonium, tetrapropylphosphonium, tetrabutylphosphonium, tetra-n-octylphosphonium, tributyl-n-octylphosphonium, tributyldodecylphosphonium, tributylhexadecylphosphonium, methyltriphenylphosphonium, ethyltriphenyl Examples include phosphonium, propyltriphenylphosphonium, butyltriphenylphosphonium, amyltriphenylphosphonium, hexyltriphenylphosphonium, heptyltriphenylphosphonium, benzyltriphenylphosphonium, tetraphenylphosphonium, and preferably tetraphenylphosphonium.

  Specific examples of the bromine salt include lithium bromide, sodium bromide, potassium bromide, cesium bromide, magnesium bromide, calcium bromide, preferably potassium bromide.

  The amount of the bromine salt used is 0.05 to 15.0 mol, preferably 0.1 to 10.0 mol, per 1 mol of the arylsulfonyl compound.

  Examples of the reducing agent for bromonium ions used in the reaction of the present invention include phenol compounds having at least one hydrogen atom in the ortho-position or para-position such as phenol, cresol, guaiacol, eugenol, thymol, preferably phenol; sodium sulfite And sulfites such as sodium bisulfite, potassium sulfite, and calcium bisulfite. The reducing agent for bromonium ions is preferably phenol or sodium sulfite.

  The amount of the bromonium ion reducing agent used is 0.5 to 10.0 mol, preferably 1.0 to 5.0 mol, per 1 mol of the arylsulfonyl compound.

  As the organic acid used in the reaction of the present invention, any organic acid can be used, and examples thereof include carboxylic acids such as acetic acid, propionic acid, butyric acid, valeric acid, oxalic acid, succinic acid, and benzoic acid. Preferably, acetic acid, propionic acid, more preferably acetic acid is used. These organic acids may be used alone or in admixture, and a second solvent that does not inhibit the reaction may be added depending on the solubility of the reaction reagent and the stirring ability.

  The amount of the organic acid used is 1.0 to 100 g, preferably 2.0 to 50 g, with respect to 1 g of the arylsulfonyl compound.

  As sulfuric acid used in the reaction of the present invention, concentrated sulfuric acid, chlorosulfuric acid, fuming sulfuric acid and the like can be used, and concentrated sulfuric acid is preferably used. Organic sulfonic acids such as methanesulfonic acid and ethanesulfonic acid can also be used. In addition, you may use these acids individually or in mixture.

  The usage-amount of the said sulfuric acid is 0.5-15.0 mol with respect to 1 mol of arylsulfonyl compounds, Preferably it is 1.0-10.0 mol.

  The reaction of the present invention is performed, for example, by a method in which an organic acid, a bromine salt, a bromonium ion reducing agent, an arylsulfonyl compound, and sulfuric acid are mixed, stirred, and reacted. The reaction temperature in that case is 20-200 degreeC, for example, Preferably it is 50-150 degreeC, and reaction time is 0.5-100 hours, for example, Preferably it is 1-30 hours. The reaction pressure is not particularly limited and can be preferably performed under atmospheric pressure.

  The diaryl disulfide compound obtained in the reaction of the present invention is represented by the general formula (3). In the general formula (3), Ar has the same meaning as Ar of the arylsulfonyl compound. The obtained diaryl disulfide compound is isolated and purified by a general production method such as neutralization, extraction, filtration, concentration, crystallization, column chromatography and the like after completion of the reaction.

  Hereinafter, the present invention will be described in detail by way of examples. However, this example does not limit the present invention.

  Reagents used in Examples and the like are commercially available, or can be prepared by those skilled in the art based on common general technical knowledge.

Reference Example 1 Synthesis of bis (2,6-difluorophenyl) disulfide In a four-necked flask equipped with a stirrer, a reflux condenser and a thermometer, 100 g (0.47 mol) of 2,6-difluorobenzenesulfonyl chloride, 45 g (0.48 mol) of phenol and 200 mL (1.04 mol) of 30% HBr-acetic acid were added and heated at 60 to 70 ° C. for 13 hours. In the middle, while confirming the progress of the reaction, 135 mL (0.70 mol) of 30% HBr-acetic acid was further added. To the reaction solution, 300 mL of n-heptane, 100 mL of methylene chloride, and 300 mL of water were added for liquid separation. The aqueous layer was extracted with 50 mL of n-heptane and 50 mL of methylene chloride, and the combined organic layer was washed with water, 1N NaOH aqueous solution and water. The organic layer was concentrated under reduced pressure, 60 mL of heptane and 10 mL of isopropanol were added to the concentrate, and the mixture was heated to 80 ° C. to obtain a homogeneous solution, then cooled to room temperature and crystallized. The precipitated crystals were collected by filtration and dried under reduced pressure at 50 ° C. to obtain 36.7 g (54%) of bis (2,6-difluorophenyl) disulfide as slightly yellow crystals.
The physical property values of the obtained bis (2,6-difluorophenyl) disulfide are as follows, and this obtained product was used as a standard product in the quantification of Example 1, Example 5, Example 8, and Example 9. .
¹ H-NMR (CDCl ₃ , 500 MHz) δ (ppm) 6.88-6.98 (4H, m), 7.30-7.40 (2H, m).
¹⁹ F-NMR (CDCl ₃ , 500 MHz) δ (ppm) -102.7 (4F, s).
EI-MS; 290 (M +)

[Comparative Example 1] Synthesis of bis (2,6-dimethyl-4-t-butylphenyl) disulfide In a glass container equipped with a stirrer and a reflux condenser, 0.54 g (5.8 mmol) of phenol and potassium bromide were added. 2.8 g (23 mmol), 2,6-dimethyl-4-t-butylbenzenesulfonyl chloride 1.0 g (3.8 mmol), and acetic acid 8.0 g were added. After heating at 80 ° C. for 1 hour, the reaction was conducted by heating at 105 to 110 ° C. for 15 hours. The reaction solution was diluted with methylene chloride, insoluble matters were filtered off, and 80.6 g of filtrate was obtained. About 3 g of this filtrate was precisely weighed, diluted with acetonitrile, and absolute quantified by liquid chromatography. As a result, 0.20 g (yield 27%) of bis (2,6-dimethyl-4-t-butylphenyl) disulfide was formed. Was.
The bis (2,6-dimethyl-4-t-butylphenyl) disulfide used as a standard product was synthesized according to the method described in US2008 / 0039660A1.
The physical properties of bis (2,6-dimethyl-4-tert-butylphenyl) disulfide used as a standard product are as follows.
¹ H-NMR (CDCl ₃ , 300 MHz) δ (ppm) 1.28 (18H, s), 2.21 (12H, s), 7.02 (4H, s).
EI-MS; 386 (M +)

[Comparative Example 2] Synthesis of p-tolyl disulfide In a glass container equipped with a stirrer and a reflux condenser, 10.5 g of acetic acid, 2.0 g (10.5 mmol) of p-tosyl chloride, 4.00 g of sodium sulfite (31 0.7 mmol) and 0.12 g (1.05 mmol) of potassium bromide were added. This reaction solution was heated and stirred at 70 ° C. for 3 hours and further at 80 ° C. for 4 hours. Methylene chloride and water were added to the resulting reaction solution to separate the layers. The aqueous layer was extracted with methylene chloride. As a combined organic layer, 123.7 g was obtained. About 5 g of this organic layer was precisely weighed, diluted with acetonitrile, and commercially available ditolyl disulfide (manufactured by Tokyo Chemical Industry Co., Ltd.) was used as a standard product. Yield 0.1%).

Comparative Example 3 Synthesis of p-Tolyl Disulfide In a glass container equipped with a stirrer and a reflux condenser, acetic acid 10.5 g, p-tosyl chloride 2.0 g (10.5 mmol), sodium sulfite 4.00 g (31 0.7 mmol) and 3.12 g (26.2 mmol) of potassium bromide were added. This reaction solution was heated and stirred at 70 ° C. for 3 hours and further at 80 ° C. for 4 hours. Methylene chloride and water were added to the resulting reaction solution to separate the layers. The aqueous layer was extracted with methylene chloride. 87.2 g was obtained as a combined organic layer. About 4 g of this organic layer was precisely weighed, diluted with acetonitrile, and commercially available ditolyl disulfide (manufactured by Tokyo Chemical Industry Co., Ltd.) was used as a standard product. When absolute quantification was performed by liquid chromatography, 0.001 g of ditolyl disulfide ( Yield 0.1%).

[Example 1] Synthesis of bis (2,6-difluorophenyl) disulfide In a glass container equipped with a stirrer and a reflux condenser, phenol 1.1 g (12 mmol), potassium bromide 5.7 g (48 mmol), 2 , 6-Difluorobenzenesulfonyl chloride 1.7 g (8.0 mmol) and acetic acid 15 g were added. While stirring at room temperature, 1.28 mL (24 mmol) of concentrated sulfuric acid was added dropwise. After heating at 50 ° C. for 1 hour, the reaction was carried out by heating at 70 to 73 ° C. for 10 hours. The reaction solution was diluted with methylene chloride, the insoluble material was filtered off, and 87.1 g of filtrate was obtained. About 3 g of this filtrate was precisely weighed, diluted with acetonitrile, and absolute quantified by liquid chromatography. As a result, 0.83 g (yield 72%) of bis (2,6-difluorophenyl) disulfide was formed.

[Example 2] Synthesis of bis (2,6-dimethyl-4-t-butylphenyl) disulfide In a glass container equipped with a stirrer and a reflux condenser, phenol 0.54 g (5.8 mmol), potassium bromide 2.8 g (23 mmol), 2,6-dimethyl-4-t-butylbenzenesulfonyl chloride 1.0 g (3.8 mmol), and acetic acid 8.0 g were added. While stirring at room temperature, 0.61 mL (12 mmol) of concentrated sulfuric acid was added dropwise. After heating at 50 ° C. for 1 hour, the reaction was carried out by heating at 70 to 73 ° C. for 10 hours. The reaction solution was diluted with methylene chloride, the insoluble material was filtered off, and 72.9 g of filtrate was obtained. About 3 g of this filtrate was precisely weighed, diluted with acetonitrile, and absolute quantified by liquid chromatography. As a result, 0.47 g (yield 63%) of bis (2,6-dimethyl-4-t-butylphenyl) disulfide was formed. Was.

[Example 3] Synthesis of p-tolyl disulfide In a glass container equipped with a stirrer and a reflux condenser, phenol 1.1 g (12 mmol), potassium bromide 5.6 g (47 mmol), p-toluenesulfonyl chloride 1. 5 g (7.9 mmol) and 15 g of acetic acid were added. While stirring at room temperature, 1.26 mL (24 mmol) of concentrated sulfuric acid was added dropwise. After heating at 50 ° C. for 2 hours, the reaction was carried out by heating at 70 ° C. for 10 hours. The reaction solution was diluted with methylene chloride, insoluble matters were filtered off, and 114 g of filtrate was obtained. About 2 g of the filtrate was precisely weighed, diluted with acetonitrile, and commercially available p-tolyl disulfide (manufactured by Tokyo Chemical Industry Co., Ltd.) was used as a standard product. 78 g (yield 80%) was produced.
The remaining filtrate was washed with water, aqueous sodium hydrogen carbonate, and water, and the organic layer was dried over magnesium sulfate. The organic layer was filtered and concentrated, and the concentrate was purified by column chromatography (solvent: n-hexane, silica gel: Daiso Gel 1002W) to give 0.69 g of p-tolyl disulfide as a white solid (yield 71%). I got it.
The physical properties of the obtained p-tolyl disulfide were as follows.
¹ H-NMR (CDCl ₃ , 300 MHz) δ (ppm) 2.32 (6H, s), 7.06-7.16 (4H, m), 7.34-7.44 (4H, m).
EI-MS; 246 (M +)

[Example 4] Synthesis of p-tolyl disulfide In a glass container equipped with a stirrer and a reflux condenser, 5.2 g of acetic acid, 1.0 g (5.25 mmol) of p-toluenesulfonyl chloride, 1.99 g of sodium sulfite ( 15.6 mmol) and 1.56 g (13.1 mmol) of potassium bromide were added, and 1.46 ml (26.3 mmol) of concentrated sulfuric acid was slowly added dropwise with stirring in an ice-water bath. This reaction solution was heated and stirred at 70 ° C. for 3 hours and further at 80 ° C. for 4 hours. The obtained reaction solution was diluted with methylene chloride, and insoluble matters were filtered off to obtain 73.1 g of a filtrate. About 2 g of this filtrate was precisely weighed, diluted with acetonitrile, and absolute quantification was performed by liquid chromatography using commercially available ditolyl disulfide (manufactured by Tokyo Chemical Industry Co., Ltd.) as a standard product. (Yield 88%).

[Example 5] Synthesis of bis (2,6-difluorophenyl) disulfide In a glass container equipped with a stirrer and a reflux condenser, acetic acid (5.2 g) and 2,6-difluorobenzenesulfonyl chloride (1.0 g) (4. 70 mmol), 1.78 g (14.1 mmol) of sodium sulfite and 1.12 g (9.4 mmol) of potassium bromide were added, and 1.31 ml (23.5 mmol) of concentrated sulfuric acid was slowly added dropwise with stirring in an ice-water bath. This reaction solution was heated and stirred at 50 ° C. for 30 minutes and further at 70 ° C. for 7 hours. The obtained reaction solution was diluted with methylene chloride, and insoluble matters were filtered off to obtain 79.3 g of a filtrate. The filtrate was concentrated, and the concentrate was purified by column chromatography (solvent: n-hexane, silica gel: Daiso gel 1002W) to give bis (2,6-difluorophenyl) disulfide as a white solid, 0.66 g (yield 97%).
The physical property values of the obtained bis (2,6-difluorophenyl) disulfide were as follows.
¹ H-NMR (CDCl ₃ , 300 MHz) δ (ppm) 6.88-6.98 (4H, m), 7.30-7.42 (2H, m).
EI-MS; 290 (M +)

[Example 6] Synthesis of p-tolyl disulfide In a glass container equipped with a stirrer and a reflux condenser, 10.5 g of acetic acid, 2.0 g (10.5 mmol) of p-toluenesulfonyl chloride, 4.00 g of sodium sulfite ( 31.7 mmol) and 0.62 g (5.25 mmol) of potassium bromide were added, and 2.95 ml (52.5 mmol) of concentrated sulfuric acid was slowly added dropwise with stirring in an ice-water bath. This reaction solution was heated and stirred at 70 ° C. for 3 hours and further at 80 ° C. for 4 hours. The obtained reaction solution was diluted with methylene chloride, insoluble matters were filtered off, and 91.2 g of a filtrate was obtained. About 1 g of this filtrate was precisely weighed, diluted with acetonitrile, and absolute quantification was performed by liquid chromatography using commercially available ditolyl disulfide (manufactured by Tokyo Chemical Industry Co., Ltd.) as a standard product. As a result, 1.06 g of ditolyl disulfide ( Yield 82%).

[Example 7] Synthesis of p-tolyl disulfide In a glass container equipped with a stirrer and a reflux condenser, 12.6 g of acetic acid, 2.0 g (10.5 mmol) of p-toluenesulfonyl chloride, 4.00 g of sodium sulfite ( 31.7 mmol) and 0.31 g (2.62 mmol) of potassium bromide were added, and 2.94 ml (52.5 mmol) of concentrated sulfuric acid was slowly added dropwise with stirring in an ice-water bath. This reaction solution was heated and stirred at 70 ° C. for 3 hours and further at 80 ° C. for 4 hours. The obtained reaction solution was diluted with methylene chloride, and insoluble matters were filtered off to obtain 99.5 g of a filtrate. About 2 g of this filtrate was precisely weighed, diluted with acetonitrile, and absolute quantification was performed by liquid chromatography using commercially available ditolyl disulfide (manufactured by Tokyo Chemical Industry Co., Ltd.) as a standard product. Yield 67%).

[Example 8] Synthesis of bis (2,6-difluorophenyl) disulfide In a glass container equipped with a stirrer and a reflux condenser, 12.6 g of acetic acid and 2.0 g of 2,6-difluorobenzenesulfonyl chloride (9. 41 mmol), 3.56 g (28.2 mmol) of sodium sulfite and 0.56 g (4.7 mmol) of potassium bromide were added, and 2.64 ml (47.0 mmol) of concentrated sulfuric acid was slowly added dropwise with stirring in an ice-water bath. This reaction solution was heated and stirred at 70 ° C. for 3 hours and further at 80 ° C. for 4 hours. The obtained reaction solution was diluted with methylene chloride, and insoluble matters were filtered off to obtain 109.4 g of a filtrate. About 1.5 g of this filtrate was precisely weighed, diluted with acetonitrile, and absolute quantified by liquid chromatography. As a result, 1.17 g (yield 86%) of bis (2,6-difluorophenyl) disulfide was formed.

[Example 9] Synthesis of bis (2,6-difluorophenyl) disulfide In a glass container equipped with a stirrer and a reflux condenser, 12.6 g of acetic acid and 2.0 g of 2,6-difluorobenzenesulfonyl chloride (9. 41 mmol), 3.56 g (28.2 mmol) of sodium sulfite and 0.28 g (2.35 mmol) of potassium bromide were added, and 2.64 ml (47.0 mmol) of concentrated sulfuric acid was slowly added dropwise with stirring in an ice-water bath. This reaction solution was heated and stirred at 70 ° C. for 3 hours and further at 80 ° C. for 4 hours. The resulting reaction solution was diluted with methylene chloride, and insoluble matters were filtered off to obtain 97.2 g of a filtrate. About 2 g of this filtrate was precisely weighed, diluted with acetonitrile, and absolute quantified by liquid chromatography. As a result, 1.00 g (yield 73%) of bis (2,6-difluorophenyl) disulfide was formed.

[Example 10] Synthesis of bis (2,6-dimethyl-4-t-butylphenyl) disulfide In a glass container equipped with a stirrer and a reflux condenser, 6.3 g of acetic acid and 2,6-dimethyl-4- 1.0 g (3.83 mmol) of t-butylbenzenesulfonyl chloride, 1.45 g (11.5 mmol) of sodium sulfite and 0.23 g (1.92 mmol) of potassium bromide were added, and concentrated sulfuric acid 1. 08 ml (19.2 mmol) was slowly added dropwise. This reaction solution was heated and stirred at 70 ° C. for 3 hours and further at 80 ° C. for 4 hours. The obtained reaction solution was diluted with methylene chloride, and insoluble matters were filtered off to obtain 78.5 g of a filtrate. About 2 g of this filtrate was precisely weighed, diluted with acetonitrile, and absolute quantified by liquid chromatography. As a result, 0.69 g (yield 93%) of bis (2,6-dimethyl-4-t-butylphenyl) disulfide was formed. Was.

    According to the present invention, a diaryl disulfide compound can be produced in high yield from an arylsulfonyl compound that is easily available and can be easily produced without requiring complicated operations. Diaryl disulfide compounds are useful as, for example, synthetic intermediates for pharmaceuticals, agricultural chemicals, and functional materials, and as raw materials for synthesizing fluorinating agents.

Claims (11)

In the presence of an organic acid, the general formula (1)

(In the formula, Ar represents an aryl group or heteroaryl group which may have a substituent, and L represents a halogen atom .)
An arylsulfonyl compound represented by the general formula (2)

(In the formula, M represents a metal ion, a quaternary ammonium ion, or a phosphonium ion.)
A bromine salt represented by general formula (3), a bromonium ion reducing agent, and sulfuric acid are added:

(In the formula, Ar has the same meaning as described above.)
The manufacturing method of the diaryl disulfide compound shown by these.   The manufacturing method of Claim 1 whose Ar is the aryl group which may have a substituent in General formula (1).   The manufacturing method of Claim 1 whose Ar is the phenyl group which may have a substituent in General formula (1).   The manufacturing method of any one of Claims 1-3 whose L is a chlorine atom in General formula (1). The production method according to any one of claims 1 to 4 , wherein the bromonium ion reducing agent is at least one compound selected from the group consisting of phenolic compounds and sulfites. The production method according to any one of claims 1 to 4 , wherein the reducing agent for bromonium ions is phenol or sodium sulfite. The production method according to any one of claims 1 to 6 , wherein the bromine salt is at least one compound selected from the group consisting of potassium bromide, lithium bromide, sodium bromide and cesium bromide. Bromine salt is potassium bromide method according to any one of claims 1-6. The production method according to any one of claims 1 to 8 , wherein the organic acid is at least one organic acid selected from the group consisting of acetic acid, propionic acid, butyric acid, and valeric acid. The manufacturing method according to any one of claims 1 to 8 , wherein the organic acid is acetic acid. Sulfuric acid, relative arylsulfonyl compound 1 mol, is added 0.5 to 15.0 mol, the production method according to any one of claims 1-10.