A Theoretical Study of the Preferred Reaction Mechanism Between Chloroacetic Acid and Thiourea

2-iminothiazolidin-4-one derivatives are known to possess various biological activities such as anticancer, antiviral, antibacterial and antifungal, making them interesting lead compounds in the design of pharmaceutically useful drugs. For instance, recent studies have shown that 2-imino-thiazolidin-4-one derivatives are vital scaffold for the design of potent, orally active lysophospholipid receptor agonists selected for clinical development. Despite their potential application in drug development, the reaction mechanism for the formation of 2-iminothiazolidin-4-one is still a challenge. The current theoretical work attempts to study the mechanistic pathways for the formation of 2-iminothiazolidin-4-one from chloroacetic acid and thiourea. Calculations were performed with MP2 and DFT methods (with M06-2X and M11-L functionals) using the 6-31+G(d,p) and the 6-311++G(3df,2p) basis sets. The study was performed in vacuo and in water solution. The influence of water was assessed by predicting its role as bulk solvent. The results of the study show that the reaction between chloroacetic acid and thiourea may involve the iminothiol form of thiourea rather than the thione form. The reaction is spontaneous and prefers to occur in vacuo to occurring in water solution.