BmmimOAc-Catalyzed Direct Condensation of 2-(Arylamino) Alcohols to Synthesize 3-Arylthiazolidine-2-thiones

Thiazolidine-2-thiones have attracted muchattention because of their unique bioactivity and havebeen widely used in the fields of medicine and syntheticheterocyclic chemistry. In this work, a simple andconvenient route for the synthesis of 3-arylthiazolidine-2-thiones by direct condensation of 2-(arylamino) alcoholswith 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 catalystsin the model reaction of 2-(phenylamino) ethanol with CS2. The results showed that only the acetate ionic liquids havecatalytic activity, perhaps owing to the basicity of the acetate anion. Among these acetate ionic liquids, BmmimOAc showedthe 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 werefound to be the optimal reaction conditions for direct condensation of 2-(phenylamino) ethanol with CS2: reaction time, 6 h;reaction temperature, 130 degrees 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. Thereaction scope was explored by investigating the reactions of various 2-(arylamino) alcohols with CS2. The results showedthat the 2-(arylamino) alcohols with electron-donating substituents, electron-withdrawing substituents, or high sterichindrance could be smoothly converted to the corresponding products in excellent isolated yields of 83%-95%. NMRcharacterizations and mass spectrum indicated that the acetate anion of BmmimOAc could react spontaneously with CS(2)to form the thioacetate anion (CH3COS-). Ionic liquid 1-butyl-2,3-dimethylimidazolium thioacetate (BmmimCOS) might bethe actual catalyst in the reaction of 2-(arylamino) alcohols with CS2. H-1 and C-13 NMR spectroscopies were used to studythe interactions between BmmimCOS and substrates 2-(phenylamino) ethanol and CS2. The NMR spectra showed thehydrogen bonding interactions between BmmimCOS and 2-(phenylamino) ethanol. The CH3COS- anion of BmmimCOScould activate the 2-(phenylamino) ethanol in the catalytic system. Based on the characterization results, a possiblereaction 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 theactivated 2-(phenylamino) ethanol to form the intermediate. Finally, the intermediate was subjected to intramolecularcyclization to form the final product 3-phenylthiazolidine-2-thione.