CN111373857B - Preparation method of di (2-ethylthioethyl) thioether compound - Google Patents

Abstract

The invention discloses a preparation method of a bis (2-ethylthioethyl) sulfide compound, which uses dimercaptoethyl sulfide to replace dichloroethyl sulfide (mustard gas) as a raw material, and under the protection of inert atmosphere, potassium carbonate is used as an acid-binding agent to react with iodoethane to prepare the bis (2-ethylthioethyl) sulfide. The method has good safety, and the obtained bis (2-ethylthioethyl) sulfide can be used as a thioether chemical warfare agent simulant to reduce experimental risks in research aspects such as protective equipment development, digestion technology and the like.

Description

Preparation method of di (2-ethylthioethyl) thioether compound

Technical Field

The invention relates to a preparation method of a long-chain thioether compound, in particular to a preparation method of a di (2-ethylthioethyl) thioether compound.

Background

The thioether compound is a compound which is inflammable and generates a large amount of corrosive gas after high-temperature combustion, can be used as a combustion aid to assist in damaging steel and human respiratory tracts, has the biochemical toxicity of attacking guanine bases of DNA to perform substitution reaction so as to cross-link bimolecules of the DNA, and interfering gene replication and expression, and is a huge-harm erosive toxicant, such as chlorinated thioether compounds with double-alkylation property, such as mustard gas, sesquimustard gas, bis (2 chloroethylthiomethyl) ether, oxydisultic mustard gas and the like. In the research aspects of protective equipment development, digestion technology and the like, in order to reduce the experimental risk, homologous compounds which reduce the number of chlorine atoms or do not contain chlorine elements are mainly used as substitutes or simulators to replace chemical warfare agents for carrying out certain property experiments.

As indicated above, the document "reactions and derivatives of β -dichloreethyl sulfate [ J]Journal of the American Chemical Society, 1920 (42): 1208 + 1232Is provided with 3S-C₂H₄The unit bis (2-ethylthioethyl) sulfide and the preparation method thereof can be used as a thioether chemical agent simulator to reduce the experimental risk of real thioether chemical agents, but the raw material required for synthesizing the thioether chemical agent simulator is dichloroethyl sulfide, namely mustard gas, which belongs to erosive chemical agents and has no effective treatment method, so the experimental risk is higher.

Disclosure of Invention

In order to solve the defect of high toxicity in the synthetic process of the bis (2-ethylthioethyl) sulfide in the prior art, the invention provides a preparation method of the bis (2-ethylthioethyl) sulfide with higher safety.

The synthetic route of the compound of the invention is as follows:

the dimercaptoethyl sulfide is deprotonated under the action of alkali and then undergoes nucleophilic substitution reaction with excess iodoethane to generate a disubstituted product, namely bis (2-ethylthioethyl) sulfide.

The invention provides a preparation method of a bis (2-ethylthioethyl) sulfide compound, which takes dimercaptoethyl sulfide as a raw material and comprises the following steps:

A. adding dimercaptoethyl sulfide and acetonitrile into a reaction bottle with Ar gas protection, magnetic stirring, a thermometer and a reflux device in sequence, wherein the volume of the added acetonitrile in every 1g of dimercaptoethyl sulfide is 50-100 mL; adding potassium carbonate, and reacting at the temperature of 40-60 ℃ for 1-2 h, wherein the molar ratio of dimercaptoethyl sulfide to potassium carbonate is 1: 3-4;

B. slowly dripping acetonitrile solution containing the iodoethane into the reaction bottle for 6-8 hours; heating and refluxing for 2-4 d under the protection of Ar gas, filtering, evaporating the filtrate under reduced pressure, extracting with dichloromethane, filtering to remove insoluble substances, washing with a large amount of water, adding magnesium sulfate, drying, filtering, and evaporating under reduced pressure; obtaining a colorless liquid crude product, standing at the temperature of minus 40 ℃ for 1d, filtering out a white solid byproduct, and performing column separation and refining to obtain bis (2-ethylthioethyl) sulfide, wherein the molar ratio of the dimercaptoethyl sulfide to the iodoethane is 1: 2.5-3, and the volume of acetonitrile is 25-100 mL for every 1g of the iodoethane in the acetonitrile solution of the iodoethane.

The preferred preparation method of the bis (2-ethylthioethyl) sulfide compound of the present invention comprises the following steps:

A. adding dimercaptoethyl sulfide and acetonitrile into a reaction bottle with Ar gas protection, magnetic stirring, a thermometer and a reflux device in sequence, wherein the volume of the added acetonitrile in every 1g of dimercaptoethyl sulfide is 50 mL; adding potassium carbonate, and stirring at 40 ℃ for 1-2 h, wherein the molar ratio of dimercaptoethyl sulfide to potassium carbonate is 1: 3;

B. adding an acetonitrile solution containing iodoethane into the reaction bottle, continuously reacting for 4d at 40 ℃ under the protection of Ar gas, and filtering; evaporating the filtrate under reduced pressure, extracting with dichloromethane, filtering to remove insoluble substances, washing with a large amount of water, adding magnesium sulfate, drying, filtering, and evaporating under reduced pressure; the obtained colorless liquid crude product is placed at the temperature of minus 40 ℃ for 1d, a white solid by-product is filtered, and bis (2-ethylthioethyl) sulfide is obtained by column separation and refining, wherein, the molar ratio of the dimercaptoethyl sulfide to the iodoethane is 1: 3, and the volume of acetonitrile is 25mL for every 1g of the iodoethane in the acetonitrile solution of the iodoethane.

The invention has the advantages that: compared with the comparison document of the invention, dimercaptoethyl sulfide is used as a raw material instead of mustard gas, so that serious biochemical toxicity is avoided, and the safety is better.

Detailed Description

Example 1

A. 1.23g of dimercaptoethyl sulfide and 60mL of acetonitrile are sequentially added into a reaction bottle with Ar gas protection, magnetic stirring, a thermometer and a reflux device, 3.4g of potassium carbonate is added, and the mixture is stirred for 1-2 hours at the temperature of 40 ℃.

B. 100mL of acetonitrile solution containing 4.0g of iodoethane was added to the reaction flask, and the reaction was continued for 4 days at 40 ℃ under Ar gas atmosphere, followed by filtration. The filtrate was evaporated to dryness under reduced pressure, extracted with 50mL of dichloromethane and the insoluble matter was filtered off and then washed with a large amount of water, followed by addition of magnesium sulfate, drying, filtration, and evaporation to dryness under reduced pressure; the obtained colorless liquid crude product is placed at the temperature of minus 40 ℃ for 1d, a white solid by-product is filtered out, and bis (2-ethylthioethyl) sulfide is obtained by column separation and refining, with the yield of 10.6%.

And (3) structural identification:

elemental analysis:

the molecular formula is as follows: c₈H₁₈S₃

Theoretical value: c, 45.66; h, 8.62; s, 45.72;

measured value: c45.69, H8.64, S45.67.

¹HNMR(DMSO-d₆，δ/ppm)：1.18(t，6H)，2.55(dd，4H)，2.70(m，8H)，

¹³CNMR(DMSO-d₆，δ/ppm)：14.73，24.89，31.05，31.36

Mass spectrum (EIS): molecular ion Peak 233.05(M + Na)⁺)，235.04(M+Na⁺Isotope peaks), fragment peaks 227.06, 229.06, 221.01, 223.00, 218.21.

The above analytical data confirm that the material obtained according to this synthesis is indeed bis (2-ethylthioethyl) sulfide.

Example 2

A. 1.23g of dimercaptoethyl sulfide and 100mL of acetonitrile are sequentially added into a reaction bottle with Ar gas protection, magnetic stirring, a thermometer and a reflux device, 3.8g of potassium carbonate is added, and the mixture is stirred for 1-2 hours at 50 ℃.

B. 200mL of an acetonitrile solution containing 3.4g of iodoethane was added to the reaction flask. The reaction is continued for 3d under the protection of Ar gas at 50 ℃ and then filtered. The filtrate was evaporated to dryness under reduced pressure, extracted with 50mL of dichloromethane and the insoluble matter was filtered off and then washed with a large amount of water, followed by addition of magnesium sulfate, drying, filtration, and evaporation to dryness under reduced pressure; the obtained colorless liquid crude product is placed at the temperature of minus 40 ℃ for 1d, a white solid by-product is filtered out, and bis (2-ethylthioethyl) sulfide is obtained by column separation and refining, wherein the yield is 8.6%.

Example 3

A. Sequentially adding 1.23g of dimercaptoethyl sulfide and 120mL of acetonitrile into a reaction bottle with Ar atmosphere protection, magnetic stirring, a thermometer and a reflux device, adding 4.4g of potassium carbonate, and stirring at 60 ℃ for 1-2 h.

B. 300mL of an acetonitrile solution containing 3.8g of iodoethane was added to the reaction flask. The reaction is continued for 2d under the protection of Ar gas at 60 ℃, and then the mixture is filtered. The filtrate was evaporated to dryness under reduced pressure, extracted with 50mL of dichloromethane and the insoluble matter was filtered off and then washed with a large amount of water, followed by addition of magnesium sulfate, drying, filtration, and evaporation to dryness under reduced pressure; the obtained colorless liquid crude product is placed at the temperature of minus 40 ℃ for 1d, a white solid by-product is filtered out, and bis (2-ethylthioethyl) sulfide is obtained by column separation and refining, with the yield of 6.6%.

Example 4

A. 1.23g of dimercaptoethyl sulfide and 70mL of acetonitrile are sequentially added into a reaction bottle with Ar gas protection, magnetic stirring, a thermometer and a reflux device, 3.6g of potassium carbonate is added, and the mixture is stirred for 1-2 hours at the temperature of 40 ℃.

B. 400mL of acetonitrile solution containing 4.0g of iodoethane was added to the reaction flask, and the reaction was continued for 4 days at 40 ℃ under Ar gas atmosphere, followed by filtration. The filtrate was evaporated to dryness under reduced pressure, extracted with 50mL of dichloromethane and the insoluble matter was filtered off and then washed with a large amount of water, followed by addition of magnesium sulfate, drying, filtration, and evaporation to dryness under reduced pressure; the obtained colorless liquid crude product is placed at the temperature of minus 40 ℃ for 1d, a white solid by-product is filtered out, and bis (2-ethylthioethyl) sulfide is obtained by column separation and refining, wherein the yield is 7.2%.

Claims (2)

1. A preparation method of a bis (2-ethylthioethyl) sulfide compound is characterized in that dimercaptoethyl sulfide is used as a raw material, and comprises the following steps:

A. adding dimercaptoethyl sulfide and acetonitrile into a reaction bottle with Ar gas protection, magnetic stirring, a thermometer and a reflux device in sequence, wherein the volume of the added acetonitrile in every 1g of dimercaptoethyl sulfide is 50-100 mL; adding potassium carbonate, and reacting at the temperature of 40-60 ℃ for 1-2 h, wherein the molar ratio of dimercaptoethyl sulfide to potassium carbonate is 1: 3-4;

B. slowly dripping acetonitrile solution containing the iodoethane into the reaction bottle for 6-8 hours; heating and refluxing for 2-4 d under the protection of Ar gas, filtering, evaporating the filtrate under reduced pressure, extracting with dichloromethane, filtering to remove insoluble substances, washing with a large amount of water, adding magnesium sulfate, drying, filtering, and evaporating under reduced pressure; obtaining a colorless liquid crude product, standing at the temperature of minus 40 ℃ for 1d, filtering out a white solid byproduct, and performing column separation and refining to obtain bis (2-ethylthioethyl) sulfide, wherein the molar ratio of the dimercaptoethyl sulfide to the iodoethane is 1: 2.5-3, and the volume of acetonitrile is 25-100 mL for every 1g of the iodoethane in the acetonitrile solution of the iodoethane.

2. The method for producing a bis (2-ethylthioethyl) sulfide compound according to claim 1, characterized by comprising the steps of:

A. adding dimercaptoethyl sulfide and acetonitrile into a reaction bottle with Ar gas protection, magnetic stirring, a thermometer and a reflux device in sequence, wherein the volume of the added acetonitrile in every 1g of dimercaptoethyl sulfide is 50 mL; adding potassium carbonate, and stirring at 40 ℃ for 1-2 h, wherein the molar ratio of dimercaptoethyl sulfide to potassium carbonate is 1: 3;

B. adding an acetonitrile solution containing iodoethane into the reaction bottle, continuously reacting for 4d at 40 ℃ under the protection of Ar gas, and filtering; evaporating the filtrate under reduced pressure, extracting with dichloromethane, filtering to remove insoluble substances, washing with a large amount of water, adding magnesium sulfate, drying, filtering, and evaporating under reduced pressure; the obtained colorless liquid crude product is placed at the temperature of minus 40 ℃ for 1d, a white solid by-product is filtered, and bis (2-ethylthioethyl) sulfide is obtained by column separation and refining, wherein, the molar ratio of the dimercaptoethyl sulfide to the iodoethane is 1: 3, and the volume of acetonitrile is 25mL for every 1g of the iodoethane in the acetonitrile solution of the iodoethane.