Study On New Process For Preparation Of 2-Mercaptoisobutryic Acid

2-Mercaptoisobutyric acid is an important intermediate in the synthesis of biomedicine and materials.In the aspect of biomedical synthesis,it includes Bucilamine,drugs for the treatment of non-alcoholic steatohepatitis,2-thiazolidinethione derivatives with hepatoprotective activity,KCOs,CGRP receptor antagonists,orexin receptor antagonists,HDAC inhibitors based on mercaptoacetamide ligands,DPPIV inhibitors,selective GR regulators,ADC drugs,mercaptan probes for the detection of HNO,etc.In terms of material synthesis,it includes modified concrete material,elastomer material of tire,photosensitive material of printed board,modified keratin material,curing agents for modified epoxy resins and polyamide resins,etc.In view of the broad application prospect of2-mercaptoisobutyric acid,it is of great significance to study on new process for preparation of 2-mercaptoisobutryic acid.In this paper,2-mercaptoisobutyric acid was synthesized from ethyl 2-bromoisobutyrate and thiourea by two-step reaction.Firstly,the process route was determined by pre-experiment:ethanol as solvent,anhydrous sodium acetate as alkali reagent and sodium hydroxide aqueous solution as hydrolyzate system.The product was confirmed by FTIR,¹H NMR,¹³C NMR and MS as 2-Mercaptoisobutyric acid.Secondly,based on the pre-experiment,the first step of the reaction process was optimized by single-factor experiments.The molar ratio of anhydrous sodium acetate to ethyl 2-bromoisobutyrate,the molar ratio of thiourea to ethyl 2-bromoisobutyrate,the amount of solvent and the reaction time are investigated.The preferred process synthesis conditions obtained:4 g ethyl 2-bromoisobutyrate,the molar ratio of thiourea to ethyl 2-bromoisobutyrate was 1.6,the molar ratio of anhydrous sodium acetate and ethyl 2-bromoisobutyrate was 1.4,the solvent was 15 mL ethanol,the reaction time was 12 h,and the reaction temperature was peak reflux temperature.Through orthogonal experiments,the process was further optimized,and the best combination was obtained:4 g ethyl 2-bromoisobutyrate,the molar ratio of thiourea to ethyl 2-bromoisobutyrate was 1.6,the molar ratio of anhydrous sodium acetate and ethyl 2-bromoisobutyrate was 1.6,the solvent was 12 mL ethanol,the reaction time was 14 h,and the reaction temperature was peak reflux temperature,and the yield was81.59%.Finally,based on the pre-experiment,the second step of the reaction process was optimized by single-factor experiments.The effects of the mass fraction of sodium hydroxidesolution,themolarratioofsodiumhydroxideto5,5-dimethyl-2-imino-4-thiazolidone and the reaction time on the yield of2-mercaptoisobutyric acid were investigated.The preferred process synthesis conditions obtained:the mass fraction of sodium hydroxide solution was 5%,the molar ratio of sodium hydroxide to 5,5-dimethyl-2-imino-4-thiazolidinone was 4,and the reaction time was 36h,the reaction temperature was peak reflux temperature.Through orthogonal experiments,the process was further optimized,and the best combination was obtained:the mass fraction of sodium hydroxide solution was 6.5%,the molar ratio of sodium hydroxide to 5,5-dimethyl-2-imino-4-thiazolidinone was e,and the reaction time was 41h,the reaction temperature was peak reflux temperature,and the yield was 96.21%.