Synthesis method of disulfide compound

Abstract

The invention belongs to the technical field of organic synthesis, and discloses a synthesis method of a disulfide compound. According to the invention, under the catalytic action of 1, 4, 7, 10, 13, 16-hexaoxacyclo-octadecane, halogenated hydrocarbon, sodium sulfide and sulfur react at the temperature of 50-60 DEG C to prepare the disulfide compound. The synthesis method of the disulfide compound has the advantages of being simple in process, small in catalyst dosage, mild in reaction condition, high in production efficiency, low in production cost, convenient for industrial production and the like, in addition, the reaction yield of the synthesis method can reach 94.8%-96.6%, and the purity of the obtained target product reaches up to 97.9%-99.3%. The method can be applied to preparation of the disulfide compound, and the obtained disulfide compound can be further applied to the fields of biomedicine, agriculture, chemical industry and the like.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and relates to a method for synthesizing a disulfide compound. Background Art

[0002] Disulfide compounds are important chemical raw materials and intermediates with a wide range of applications. In the biomedical field, disulfide bonds are an important component for maintaining the spatial structure of proteins. The more disulfide bonds there are, the greater the stability of protein molecules against external factors; in the chemical industry, disulfide compounds can be used as vulcanizers for rubber and artificial rubber to improve the tensile strength of rubber; in agriculture, disulfide compounds are often used in the synthesis of pesticides, such as using di-sec-butyl disulfide as a raw material, reacting with phosphorus trichloride to obtain S-sec-butyl-O-ethylthiophosphoric acid chloride, and then condensing with 2-thiazolidinone to obtain thiazophosphine insecticide. In the prior art, the synthesis method of disulfide compounds generally has the disadvantages of selecting high boiling point solvents, large amount of phase transfer catalysts, complex post-processing, and the yield needs to be improved. Summary of the invention

[0003] In view of the deficiencies in the prior art, the present invention provides a method for synthesizing a disulfide compound which does not use a high boiling point solvent, uses a relatively small amount of catalyst, is environmentally friendly, has simple post-treatment and has a high reaction yield.

[0004] In order to achieve the above-mentioned object of the invention, the embodiment of the present invention adopts the following technical solution: The invention provides a method for synthesizing a disulfide compound, which comprises the following steps: using 1,4,7,10,13,16-hexaoxacyclooctadecane as a catalyst, and subjecting halogenated hydrocarbons, sodium sulfide and sulfur to a nucleophilic substitution reaction to obtain the disulfide compound.

[0005] In the synthesis method of the disulfide compound provided by the present invention, 1,4,7,10,13,16-hexaoxacyclooctadecane is used as a catalyst, and the disulfide compound can be prepared by participating in the reaction of halogenated hydrocarbons, sodium sulfide and sulfur under mild conditions. 1,4,7,10,13,16-hexaoxacyclooctadecane has a ring structure of a specific size, and the six oxygen atoms inside can form a complex with metallic sodium ions, which can increase the solubility of sodium sulfide in the reaction, is more conducive to the two-phase reaction, helps to shorten the reaction time, improve the conversion rate of the reaction, and thus improve the production efficiency.

[0006] Preferably, the reaction temperature is 50° C. to 60° C. and the reaction time is 1 h to 3 h.

[0007] Preferably, the molar ratio of the 1,4,7,10,13,16-hexaoxacyclooctadecane to the halogenated hydrocarbon is 0.4:100 to 2:100.

[0008] Preferably, the molar ratio of the halogenated hydrocarbon, sodium sulfide and sulfur is 1:0.6~1.2:0.6~1.2.

[0009] Preferably, the molar ratio of the sodium sulfide to sulfur is 1:1 to 1.2:1.

[0010] Preferably, the halogenated hydrocarbon has a structural formula of RX, wherein R comprises propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, phenyl, chlorophenyl or phenyldiazo, and X comprises chlorine or bromine.

[0011] Preferably, sodium sulfide and sulfur are dissolved in water, the reaction solution is heated to boiling, and refluxed with stirring for 1 h to 2 h to obtain a disodium disulfide aqueous solution; 1,4,7,10,13,16-hexaoxacyclooctadecane is added to the disodium disulfide aqueous solution, and a halogenated hydrocarbon is added dropwise to carry out a nucleophilic substitution reaction to obtain a disulfide compound.

[0012] In the present invention, the time for dripping the halogenated hydrocarbon is controlled to be 0.5h~1h.

[0013] It can be seen from the above that the synthesis method of the disulfide compound provided by the present invention not only has the advantages of a wide range of halogenated hydrocarbons as reaction substrates, a simple synthesis process, mild reaction conditions, a relatively short reaction time, and a small amount of catalyst, but also the reaction yield of the synthesis method can reach 94.8% to 96.6%, and the purity of the target product obtained without the need for complex post-treatment steps is as high as 97.9% to 99.3%.

[0014] In summary, the synthesis method of the disulfide compound provided by the present invention has the advantages of simple process, small amount of catalyst, mild reaction conditions, high production efficiency, low production cost, high reaction yield and high purity of target product, and is easy to realize industrial production. The present invention can be applied to the preparation of disulfide compounds, and the obtained disulfide compounds can be further applied to the fields of biomedicine, agriculture and chemical industry. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0016] Figure 1 This is a gas chromatogram for determining the content of the target product di-sec-butyl disulfide in Example 2 of the present invention. DETAILED DESCRIPTION

[0017] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0018] The raw materials and reagents used in the present invention, unless otherwise specified, are conventional commercially available products; the methods used in the present invention, unless otherwise specified, are conventional methods in the art.

[0019] Example 1 This embodiment provides a method for synthesizing a disulfide compound, the method comprising the following steps: In a device equipped with a reflux condenser, a thermometer and a stirrer, 250 mL of water, 78 g (1.0 mol) of sodium sulfide and 32 g (1.0 mol) of sulfur powder were added in sequence. The reaction solution was heated to boiling, refluxed and stirred for 2 hours, and then cooled to 30°C to obtain an aqueous solution of disodium disulfide. 1.3 g (0.00492 mol) of 1,4,7,10,13,16-hexaoxacyclooctadecane was added to the obtained aqueous solution of disodium disulfide, and 78.5 g (1.0 mol) of 1-chloropropane was slowly added dropwise. After the addition was completed in 1 hour, the reaction was kept at 50°C for 3 hours. Samples were taken for gas phase analysis to detect that the relative content of 1-chloropropane was <0.1%. The reaction was completed, the reaction solution was cooled to room temperature, and allowed to stand for stratification to obtain 72.9 g of dipropyl disulfide liquid. The yield of the product was 95.8% based on 1-chloropropane. The content of the target product dipropyl disulfide in the product was 98.6% as determined by gas phase analysis.

[0020] Example 2 This embodiment provides a method for synthesizing a disulfide compound, the method comprising the following steps: In a device equipped with a reflux condenser, a thermometer and a stirrer, 250 mL of water, 93.6 g (1.2 mol) of sodium sulfide and 32 g (1.0 mol) of sulfur powder were added in sequence. The reaction solution was heated to boiling, refluxed and stirred for 1.5 hours, and then cooled to 30°C to obtain a disodium disulfide aqueous solution. 2.6 g (0.00984 mol) of 1,4,7,10,13,16-hexaoxacyclooctadecane was added to the obtained disodium disulfide aqueous solution, and 137 g (1.0 mol) of 2-bromobutane was slowly added dropwise. After the addition was completed in 0.5 h, the reaction was kept at 55°C for 2 hours. Samples were taken for gas phase analysis to detect that the relative content of 2-bromobutane was <0.1%. The reaction was completed, the reaction solution was cooled to room temperature, and allowed to stand for stratification to obtain 87.6 g of di-sec-butyl disulfide liquid. The yield of the product was 96.2% based on 2-bromobutane. The content of the target product di-sec-butyl disulfide in the product was 97.9% as determined by gas chromatography. The gas chromatogram is shown in FIG. Figure 1 shown.

[0021] Example 3 This embodiment provides a method for synthesizing a disulfide compound, the method comprising the following steps: In a device equipped with a reflux condenser, a thermometer and a stirrer, 250 mL of water, 93.6 g (1.2 mol) of sodium sulfide and 38.4 g (1.2 mol) of sulfur powder were added in sequence. The reaction solution was heated to boiling, refluxed and stirred for 1 hour, and then cooled to 30°C to obtain a disodium disulfide aqueous solution. 5.3 g (0.02 mol) of 1,4,7,10,13,16-hexaoxacyclooctadecane was added to the obtained disodium disulfide aqueous solution, and 92.6 g (1.0 mol) of 2-chlorobutane was slowly added dropwise. After the addition was completed in 1 hour, the reaction was kept at 60°C for 1 hour. Samples were taken for gas phase analysis to detect that the relative content of 2-chlorobutane was <0.1%. The reaction was completed, the reaction solution was cooled to room temperature, and allowed to stand for stratification to obtain 85.8 g of di-sec-butyl disulfide liquid. The yield of the product was 95.3% based on 2-chlorobutane. The content of the target product di-sec-butyl disulfide in the product was 99.1% as determined by gas phase analysis.

[0022] Example 4 This embodiment provides a method for synthesizing a disulfide compound, the method comprising the following steps: In a device equipped with a reflux condenser, a thermometer and a stirrer, 250 mL of water, 78 g (1.0 mol) of sodium sulfide and 28.8 g (0.9 mol) of sulfur powder were added in sequence, the reaction solution was heated to boiling, refluxed and stirred for 1.5 hours, and then cooled to 30°C to obtain a disodium disulfide aqueous solution; 2.1 g (0.008 mol) of 1,4,7,10,13,16-hexaoxacyclooctadecane was added to the obtained disodium disulfide aqueous solution, and 92.6 g (1.0 mol) of 2-chloro-2-methylpropane was slowly added dropwise. After the addition was completed in 0.8 h, the reaction was kept at 55°C for 2 hours, and a sample was taken for gas phase analysis to detect that the relative content of 2-chloro-2-methylpropane was <0.1%. The reaction was completed, the reaction solution was cooled to room temperature, and allowed to stand for stratification to obtain 86.3 g of diisobutyl disulfide liquid. The yield of the product was 94.8% based on 2-chloro-2-methylpropane. The content of the target product diisobutyl disulfide in the product was 98.5% as determined by gas phase.

[0023] Example 5 This embodiment provides a method for synthesizing a disulfide compound, the method comprising the following steps: In a device equipped with a reflux condenser, a thermometer, and a stirrer, 250 mL of water, 62.4 g (0.8 mol) of sodium sulfide, and 25.6 g (0.8 mol) of sulfur powder were added in sequence. The reaction solution was heated to boiling, refluxed and stirred for 2 hours, and then cooled to 30°C to obtain a disodium disulfide aqueous solution; 1.3 g (0.0049 mol) of 1,4,7,10,13,16-hexaoxacyclooctadecane was added to the obtained disodium disulfide aqueous solution, and 126.6 g (1.0 mol) of benzyl chloride was slowly added dropwise. After the addition was completed in 0.5 h, the reaction was kept at 55°C for 2 hours. The relative content of benzyl chloride was detected by gas phase analysis and was less than 0.1%. The reaction was completed, the reaction solution was cooled to room temperature, and the reaction solution was allowed to stand for stratification to obtain 120.8 g of dibenzyl disulfide liquid. The yield of the product was 96.3% based on benzyl chloride; the content of the target product dibenzyl disulfide in the product was 98.2% as determined by gas phase analysis.

[0024] Example 6 This embodiment provides a method for synthesizing a disulfide compound, the method comprising the following steps: In a device equipped with a reflux condenser, a thermometer and a stirrer, 250 mL of water, 46.8 g (0.6 mol) of sodium sulfide and 19.2 g (0.6 mol) of sulfur powder were added in sequence. The reaction solution was heated to boiling, refluxed and stirred for 2 hours, and then cooled to 30°C to obtain a disodium disulfide aqueous solution. 2.6 g (0.00985 mol) of 1,4,7,10,13,16-hexaoxacyclooctadecane was added to the obtained disodium disulfide aqueous solution, and 137 g (1.0 mol) of tert-butyl bromide was slowly added dropwise. After the addition was completed in 0.5 h, the reaction was continued at 60°C for 2 hours. Samples were taken for gas phase analysis to detect that the relative content of tert-butyl bromide was <0.1%. The reaction was completed, the reaction solution was cooled, and allowed to stand for stratification to obtain 86.7 g of di-tert-butyl disulfide liquid. The yield of the product was 96.6% based on tert-butyl bromide. The content of the target product di-tert-butyl disulfide in the product was 99.3% as determined by gas phase analysis.

[0025] Comparative Example 1 This comparative example provides a method for synthesizing a disulfide compound, which is basically the same as Example 1, except that: in this comparative example, the catalyst "1,4,7,10,13,16-hexaoxacyclooctadecane 1.3 g" is replaced by "PEG300 3 g", and "after the dropwise addition is completed, react at 50°C for 3 hours" is replaced by "after the dropwise addition is completed, react at 50°C for 9 hours", and the remaining reaction step parameters are the same as those in Example 1 and are not repeated here.

[0026] The synthesis method of the disulfide compound provided in this comparative example was determined to obtain 71.8 g of dipropyl disulfide liquid. The yield of the product was 92.4% based on 1-chloropropane; and the content of the target product dipropyl disulfide in the product was 96.5% as determined by gas phase.

[0027] Comparative Example 2 This comparative example provides a method for synthesizing a disulfide compound, which is basically the same as Example 1, except that: in this comparative example, the catalyst "1.3 g of 1,4,7,10,13,16-hexaoxacyclooctadecane" is replaced by "3 g of tetrabutylammonium bromide", and "after the dropwise addition, react at 50°C for 3 hours" is replaced by "after the dropwise addition, react at 25°C for 6 hours", and the remaining reaction step parameters are the same as those in Example 1 and are not repeated here.

[0028] The synthetic method provided in this comparative example was determined to obtain 73.1 g of dipropyl disulfide liquid. The yield of the product was 90.6% based on 1-chloropropane; and the content of the target product dipropyl disulfide in the product was 88.3% as determined by gas phase.

[0029] Even if the amount of polyethylene glycol catalyst PEG300 or quaternary ammonium salt catalyst tetrabutylammonium bromide is increased and the reaction time after adding 1-chloropropane is prolonged in Comparative Example 1-2, under the condition that other reaction parameters are consistent with those in Example 1, the content and yield of the product obtained after the reaction in Comparative Example 1-2 are also lower than those in Example 1.

[0030] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modification, equivalent substitution or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing a disulfide compound, characterized in that: The synthesis method comprises the following steps: using 1,4,7,10,13,16-hexaoxacyclooctadecane as a catalyst, halogenated hydrocarbons, sodium sulfide and sulfur undergo a nucleophilic substitution reaction to obtain a disulfide compound.

2. The method for synthesizing a disulfide compound according to claim 1, wherein: The reaction temperature is 50°C to 60°C and the reaction time is 1h to 3h.

3. The method for synthesizing a disulfide compound according to claim 1, wherein: The molar ratio of the 1,4,7,10,13,16-hexaoxacyclooctadecane to the halogenated hydrocarbon is 0.4:100 to 2:

100.

4. The method for synthesizing a disulfide compound according to claim 1, wherein: The molar ratio of the halogenated hydrocarbon, sodium sulfide and sulfur is 1:0.6~1.2:0.6~1.

2.

5. The method for synthesizing a disulfide compound according to claim 4, characterized in that: The molar ratio of the sodium sulfide to sulfur is 1:1 to 1.2:

1.

6. The method for synthesizing a disulfide compound according to claim 1, wherein: The structural formula of the halogenated hydrocarbon is RX, wherein R includes propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, phenyl, chlorophenyl or phenyldiazo, and X includes chlorine or bromine.

7. The method for synthesizing a disulfide compound according to claim 1, wherein: The synthesis method specifically comprises: dissolving sodium sulfide and sulfur in water to obtain a disodium disulfide aqueous solution; adding 1,4,7,10,13,16-hexaoxacyclooctadecane to the disodium disulfide aqueous solution, and dripping a halogenated hydrocarbon to perform a nucleophilic substitution reaction to obtain a disulfide compound.

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