Computational study of maleamic acid cyclodehydration

The mechanism of cyclodehydration of alkyl (Bu) and aryl (Ph) substituted maleamic acids to the corresponding maleimides and isomaleimides using N , N ′‐dicyclohexylcarbodiimide as dehydration agent in CH 2 Cl 2 as the solvent was investigated by PM3/AMSOL semiempirical calculations. An addition intermediate between the dehydrating agent and the maleamic acid carboxyl group was considered to be formed at the very beginning of the reaction. Two mechanisms reported in the literature were considered, one involving initial formation of a cyclic anion intermediate and the other proposing an acyclic amide anion. Our computational results supported the latter mechanism and a new reaction step was proposed that could also explain the ratio between the maleimide and isomaleimide formation depending on the amide substituent (alkyl or aryl type). The computational data are in good agreement with reported experimental results. Copyright © 2003 John Wiley & Sons, Ltd.