BmmimOAc-catalyzed direct condensation of 2-(arylamino) alcohols to synthesize 3-arylthiazolidine-2-thiones

Thiazolidine-2-thiones have attracted much attention because of their unique bioactivity and have been widely used in the fields of medicine and synthetic heterocyclic chemistry. In this work, a simple and convenient route for the synthesis of 3-arylthiazolidine-2-thiones by direct condensation of 2-(arylamino) alcohols with carbon disulfide (CS₂) catalyzed by the ionic liquid 1- butyl-2,3-dimethylimidazolium acetate (BmmimOAc) has been developed. A series of ionic liquids were used as catalysts in the model reaction of 2-(phenylamino) ethanol with CS₂. The results showed that only the acetate ionic liquids have catalytic activity, perhaps owing to the basicity of the acetate anion. Among these acetate ionic liquids, BmmimOAc showed the highest catalytic activity and was selected as the best catalyst. The effects of reaction time, reaction temperature, amount of BmmimOAc, and CS₂ to 2-(phenylamino) ethanol molar ratio were investigated in detail. The following were found to be the optimal reaction conditions for direct condensation of 2-(phenylamino) ethanol with CS₂: reaction time, 6 h; reaction temperature, 130 °C; 10% molar fraction of BmmimOAc; and CS₂ to 2-(phenylamino) ethanol molar ratio of 5: 1. Under these optimized reaction conditions, the product 3-phenylthiazolidine-2-thione was obtained in 97% yield. The reaction scope was explored by investigating the reactions of various 2-(arylamino) alcohols with CS₂. The results showed that the 2-(arylamino) alcohols with electron-donating substituents, electron-withdrawing substituents, or high steric hindrance could be smoothly converted to the corresponding products in excellent isolated yields of 83%–95%. NMR characterizations and mass spectrum indicated that the acetate anion of BmmimOAc could react spontaneously with CS₂ to form the thioacetate anion (CH₃COS⁻). Ionic liquid 1-butyl-2,3-dimethylimidazolium thioacetate (BmmimCOS) might be the actual catalyst in the reaction of 2-(arylamino) alcohols with CS₂.¹ H and¹³ C NMR spectroscopies were used to study the interactions between BmmimCOS and substrates 2-(phenylamino) ethanol and CS₂. The NMR spectra showed the hydrogen bonding interactions between BmmimCOS and 2-(phenylamino) ethanol. The CH₃COS⁻ anion of BmmimCOS could activate the 2-(phenylamino) ethanol in the catalytic system. Based on the characterization results, a possible reaction mechanism was proposed. Firstly, BmmimOAc reacted spontaneously with CS₂ to form BmmimCOS. Then, CH₃COS⁻ of BmmimCOS activated 2-(phenylamino) ethanol via hydrogen bonding. Subsequently, CS₂ reacted with the activated 2-(phenylamino) ethanol to form the intermediate. Finally, the intermediate was subjected to intramolecular cyclization to form the final product 3-phenylthiazolidine-2-thione.