Synthesis and DFT studies of novel aryloxymaleimides via nucleophilic substitution of tosyloxy group

Abstract

Maleimide skeleton distributes widely in a great many substances, and maleimides are very useful building blocks in organic synthesis and many related disciplines, like bioconjugation. As an excellent leaving group, tosyloxy (-OTs) group are very popular in organic synthesis; however, reports on use of -OTs group on maleimide scaffold are very rare. In this study, 3-tosyloxymaleimide was prepared from l-tartaric acid and used to react with various phenols or naphthols under PTC condition to give 3-aryloxymaleimides through nucleophilic substitutions. Yields of the reaction were not high due to a competitive transesterification reaction; however, this reaction would be practical if the side-reaction could be suppressed by appropriate reaction conditions. The reaction mechanism was investigated by theoretical computation. The intermediates and transition states of the reaction, as well as the potential barrier and reaction free energy, were calculated using density functional theory (DFT), and influencing factors of the reaction were discussed. Theoretical computations showed that this nucleophilic substitution is favorable both kinetically and thermodynamically, while electron-withdrawing groups on phenols are harmful to such reactions. This study will provide new knowledge and insights on the chemical properties of maleimide and tosyloxy group, as well as the related chemical reactions.