Ab initio study of gas phase and water-assisted tautomerization of maleimide and formamide

Abstract

Maleimide serves as an important starting material in the synthesis of drugs and enzyme inhibitors. In the present paper, knowing the importance of tautomerization in maleimide for its drug action, potential energy surface of maleimide is studied and its tautomerization has been discussed and compared with tautomerization of formamide. Gas phase tautomerization of maleimide requires large amount of energy (23-21 kcal/mol) in comparison to formamide (1505 kcal/mol) at HF/6-31+G* level. Thus making the proton transfer reaction a difficult process in gas phase. Water molecule lowers the energy barrier of tautomerization thus facilitating the tautomerization of maleimide to 5-hydroxy-pyrrol-2-one. Water assisted tautomerization of maleimide requires 19-60 kcal/mol energy at HF/6-31+G* and 17-63 kcal/mol energy at B3LYP/6-31+G* level, a decrease of 3-61 and 5-96 kcal/mol over gas phase tautomerization. Whereas, tautomerization of formamide requires 1416 and 12-84 kcal/mol energy, a decrease of 0-89 and 201 kcal/mol energy over gas phase tautomerization at HF/6-31+G* and B3LYP/6-31+G* level, respectively. Water-assisted tautomerization in maleimide and formamide showed that difference in energy barrier reduces to 2-83 kcal/mol from 10-41 kcal/mol (in gas phase) at B3LYP level, which resulted that maleimide readily undergoes tautomerization in water molecule. © Indian Academy of Sciences.