CN109134326B - Synthetic method of S-aryl thiosulfone compound - Google Patents

Abstract

The invention discloses a synthesis method of S-aryl thiosulfone compounds, which comprises the steps of carrying out addition reaction on phenyl boron tetrafluoride diazonium salt and thiourea in an organic solvent to form phenyl isothiourea salt to obtain thiophenol anions, and oxidizing the thiophenol anions into thiophenol free radicals by excited Rodamin6G under the irradiation of a light source; the single electron transfer of the phenyl boron tetrafluoride diazonium salt and the low-valence Rodamin6G occurs to obtain a phenyl radical, and the combination of the phenyl radical and the sulfur dioxide solid substitute obtains a benzenesulfonyl radical; the thiophenol free radical and the benzene sulfonyl free radical are coupled to generate a corresponding target product. The method has the advantages of mild conditions, simplicity, high efficiency, high reaction yield, good product purity, convenience for separation and purification and good application value.

Description

A kind of synthetic method of S-aryl thiosulfone compounds

technical field

The invention belongs to the technical field of organic chemistry, in particular to a method for synthesizing an S-aryl thiosulfone compound.

Background technique

Due to the potential biological activity and application value of compounds containing thioether and sulfonyl skeletons, such sulfur-containing compounds have always been key intermediates in organic synthesis. Among them, S-arylthiosulfone compounds, which can be used as a source of both benzenesulfonyl fragments and phenylene sulfide fragments, have attracted the attention of organic chemists. Due to the dual nature of these compounds, the synthetic routes and reaction properties of these compounds have been intensively studied. The synthetic routes of S-arylthiosulfone compounds can be roughly summarized into two points: (1) selective oxidation of disulfides using an oxidation strategy, (2) using existing sulfonyl reagents and thioether compounds Conjugate. These two strategies are widely used due to their mature and stable operation. The present invention aims to develop a kind of synthetic S-aryl thiosulfone compounds using simple and readily available raw materials under mild conditions without oxidation conditions.

Thiourea is a very simple and readily available small-molecule compound, which is commonly used in the synthesis of hydrogen substitution reactions on nitrogen atoms. Or react with a nucleophile to remove a molecule of urea to obtain a series of alkyl sulfide negative intermediates. This reaction utilizes the electrophilicity of phenylboron tetrafluoride diazonium salt to add thiourea to obtain phenylthiol anion after leaving urea. The benzenethiol anion is oxidized by the excited state photosensitizer to obtain the benzenethiol free radical. On the other hand, the phenylboron tetrafluoride diazonium salt reduced by the low-valent photosensitizer generates a phenyl radical, and the phenyl radical and the metabisulfite combine to obtain a benzenesulfonyl radical. The coupling of two free radicals can obtain S-arylthiosulfone compounds.

Based on this, the present invention adopts a reaction between three components of phenylboron tetrafluoride diazonium salt, thiourea and sulfur dioxide solid substitute catalyzed by a photosensitizer under the condition of visible light.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide a simple and efficient synthesis method of a series of S-aryl thiosulfone compounds.

The method of the invention utilizes boron tetrafluoride diazonium salt, a solid substitute for sulfur dioxide and thiourea to carry out catalytic free radical reaction under visible light to efficiently construct a series of S-aryl thiosulfone compounds.

The present invention is specifically realized through the following technical solutions:

A method for synthesizing S-aryl thiosulfone compounds. In an organic solvent, at room temperature, a 35-watt fluorescent lamp is used as a light source, Rodamin 6G is used as a photosensitizer, and phenylboron tetrafluoride diazonium salt is first mixed with After addition of thiourea to form phenylisothiourea salt, thiophenol anion is obtained. Under the irradiation of a 35W fluorescent lamp, the excited state of Rodamin 6G oxidizes the thiophenol anion to form the thiophenol radical. On the other hand, phenyl boron tetrafluoride diazonium salt and low-valence Rodamin 6G undergo single-electron transfer to obtain phenyl radicals, and the combination of phenyl radicals and sulfur dioxide solid substitutes yields benzenesulfonyl radicals. The thiophenol radical and the benzenesulfonyl radical undergo free radical coupling to obtain the corresponding target product.

The concrete chemical reaction formula of described synthetic method is as follows:

In the formula, "SO ₂ "=Na ₂ S ₂ O ₅ , K ₂ S ₂ O ₅ or DABSO;

R is an electron-withdrawing or electron-donating aromatic ring substituent or an alkane, and the electron-withdrawing groups include fluorine, chlorine, bromine, ester, acyl, cyano, trifluoromethyl and their corresponding aryl substituents. Electron groups are alkyl, methoxy, phenyl and their corresponding aromatic substituted groups.

The synthetic method of above-mentioned S-aryl thiosulfone compound specifically comprises the following steps:

1) At room temperature, add phenylboron tetrafluoride diazonium salt, sulfur dioxide solid substitute, thiourea and Rodamin 6G to the reaction tube in turn, and place it in high-purity nitrogen or argon to replace the gas, so that the system is in an oxygen-free state. After the conditions, add organic solvent, place it around the light source and stir until the reaction is complete;

2) Following TLC monitoring the complete reaction, the reaction solution was directly concentrated under reduced pressure, and separated by column chromatography, and the mixed solution of petroleum ether and ethyl acetate was used as mobile phase to obtain corresponding S-aryl thiosulfones. compound.

Further, the organic solvent in the reaction system is selected from 1,2-dichloroethane (DCE) or acetonitrile (MeCN).

Further, in the reaction system, the amount of phenylboron tetrafluoride diazonium salt is 1.0 equivalent, the amount of sulfur dioxide solid substitute is 2 equivalent, and the amount of thiourea is 1.5 equivalent.

The solid substitutes for sulfur dioxide are sodium metabisulfite (Na ₂ S ₂ O ₅ ), potassium metabisulfite (K ₂ S ₂ O ₅ ) and DABCO.(SO ₂ ) ₂ or DABSO.

Further, the reaction temperature of the reaction system is room temperature 25° C.; the reaction time is 12 hours; the light source required for the reaction is a 35-watt fluorescent lamp, and other visible light sources such as Blue LED are also suitable for the reaction.

The beneficial effects of the present invention are:

The reaction of the present invention utilizes thiourea as the source of sulfur in S-aryl thiosulfone compounds, and utilizes metabisulfite as the source of sulfone group in S-aryl thiosulfone compounds under very mild visible light catalysis conditions . A series of S-arylthiosulfone compounds were constructed simply and efficiently. In this reaction, industrially very cheap and easily available raw materials (thiourea, metabisulfite) are used to synthesize S-arylthiosulfone compounds with broad application prospects. The reaction avoids the use of strong acidic raw materials in the synthesis of traditional sulfonyl compounds, can be used for large-scale industrial preparation, and has good application prospects in scientific research and industrial fields.

Detailed ways

The technical solutions of the present invention will be clearly and completely described below with reference to specific embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

Example 1

At room temperature, 0.4 mmol of phenylboron tetrafluoride diazonium salt, 0.4 mmol of sodium metabisulfite, 1.5 mmol of thiourea and 2.0 mmol% of Rodamin6G were successively added to the reaction tube. Replace the gas in pure nitrogen or argon to make the system in an oxygen-free condition, add 2 mL of 1,2-dichloroethane, and stir around a 35-watt fluorescent lamp until the reaction is complete. The target product Example 1 can be obtained with a yield of 63%.

The structural formula of the target product prepared in the present embodiment is as follows:

Structural characterization of target compounds:

¹ H NMR (400 MHz, CDCl ₃ ): δ 7.56 (d, J=8.0 Hz, 2H), 7.51-7.30 (m, 6H).

¹³ C NMR (101 MHz, CDCl ₃ ): δ 143.0, 136.5, 133.6, 131.4, 129.4, 128.8, 127.8, 127.5.

HRMS (ESI) calcd for C ₁₂ H ₁₁ O ₂ S ₂ ⁺ : 251.0195 (M+H ⁺ ), found: 251.0188.

Example 2

At room temperature, 0.4 mmol of 4-chlorophenylboron tetrafluoride diazonium salt, 0.4 mmol of sodium metabisulfite, 1.5 mmol of thiourea and 2.0 mmol% of Rodamin 6G were sequentially added to the reaction tube, and the reaction tube was plugged with a stopper. Then put it in high-purity nitrogen or argon to replace the gas, so that the system is in anaerobic conditions, then add 2 mL of 1,2-dichloroethane, and stir around a 35-watt fluorescent lamp until the reaction is complete. The target product Example 2 can be obtained.

The structural formula of the target product prepared in the present embodiment is as follows:

Structural characterization of target compounds:

¹ H NMR (400 MHz, CDCl ₃ ): 7.52 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.4 Hz, 2H), 7.34 (q, J=8.4 Hz, 4H).

¹³ C NMR (101 MHz, CDCl ₃ ): δ 141.3, 140.6, 138.6, 137.7, 129.9, 129.3, 128.9, 126.0.

HRMS(ESI) calcd for C ₁₂ H ₉ Cl ₂ O ₂ S ₂ ⁺ : 318.9416(M+H ⁺ ), found: 318.9426.

Example 3

At room temperature, 0.4 mmol of 4-fluorophenylboron tetrafluoride diazonium salt, 0.4 mmol of sodium metabisulfite, 1.5 mmol of thiourea and 2.0 mmol% of Rodamin 6G were successively added to the reaction tube, and the reaction tube was plugged with a stopper. Then put it in high-purity nitrogen or argon to replace the gas, so that the system is in anaerobic conditions, then add 2 mL of 1,2-dichloroethane, and stir around a 35-watt fluorescent lamp until the reaction is complete. The target product Example 3 can be obtained.

The structural formula of the target product prepared in the present embodiment is as follows:

Structural characterization of compound example 3:

¹ H NMR (400 MHz, CDCl ₃ ): 7.56-7.46 (m, 2H), 7.33-7.25 (m, 2H), 7.05 (t, J=8.5 Hz, 2H), 6.98 (t, J=8.6 Hz, 2H) ).

¹³ C NMR (101 MHz, CDCl ₃ ): δ 166.9, 166.1, 164.3, 163.6, 138.9, 138.8, 130.5, 130.4, 117.0, 116.8, 116.3, 116.1.

HRMS(ESI) calcd for C ₁₂ H ₉ F ₂ O ₂ S ₂ ⁺ : 287.0007(M+H ⁺ ), found: 287.0011.

Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principle and spirit of the invention Variations, the scope of the invention is defined by the appended claims and their equivalents.

Claims (4)

1. a synthetic method of S-aryl thiosulfone compound, is characterized in that, described synthetic method specifically comprises the following steps: 1) At room temperature, add phenylboron tetrafluoride diazonium salt, sulfur dioxide solid substitute, thiourea and rhodamine 6G to the reaction tube in turn, and place it in high-purity nitrogen or argon to replace the gas, so that the system is in a free-flowing state. Add organic solvent after oxygen condition, place it around the light source and stir until the reaction is complete; 2) Following TLC monitoring the complete reaction, the reaction solution was directly concentrated under reduced pressure, and separated by column chromatography, and the mixed solution of petroleum ether and ethyl acetate was used as mobile phase to obtain corresponding S-aryl thiosulfones. compound; The structural formula of described phenylboron tetrafluoride diazonium salt is:

The structural formula of described S-aryl thiosulfone compounds is:

wherein R is selected from fluorine, chlorine, bromine, alkyl or methoxy; Described organic solvent is selected from 1,2-dichloroethane or acetonitrile; The solid substitute for sulfur dioxide is sodium metabisulfite, potassium metabisulfite or DABSO. 2. the synthetic method of a kind of S-aryl thiosulfone compound according to claim 1 is characterized in that, in the reaction system, taking phenylboron tetrafluoride diazonium salt as 1.0 equivalent, sulfur dioxide solid substitute The amount of thiourea was 2 equivalents, and the amount of thiourea was 1.5 equivalents. 3 . The method for synthesizing an S-aryl thiosulfone compound according to claim 1 , wherein the reaction temperature of the reaction system is room temperature 25° C.; the reaction time is 12 hours. 4 . 4 . The method for synthesizing an S-aryl thiosulfone compound according to claim 1 , wherein the light source required for the reaction is a 35-watt fluorescent lamp. 5 .