Article pubs.acs.org/JPCA
Computational Study of the Effects of Steric Hindrance on Amide Bond Cleavage Toshiaki Matsubara* and Chikako Ueta Department of Chemistry, Faculty of Science, Kanagawa University, 2946, Tsuchiya, Hiratsuka, Kanagawa 259-1293, Japan S Supporting Information *
ABSTRACT: The reaction mechanism of amide bond cleavages of the 2,2,6,6tetramethylpiperidine derivatives, which proceeds in methanol solvent under mild conditions, is examined by the density functional method (B3LYP) using a model substrate. We performed the calculations to clarify the reason why the amide bond is readily broken in the present system, on the basis of an experimentally proposed “proton switching pathway” that is different from the generally known mechanisms. As a result, it was found that the stepwise decomposition of the amide bond by the “proton switching pathway” significantly lowers the energy barrier. The delocalization of the π electron in the −C(O)N< part is hindered by the steric effect of the four Me groups of the piperidine so that the acetyl group can easily rotate around the CN axis and then the α-H migrates to the amide N. The subsequent amide bond dissociation, which is thought to be a rate-determining step in the experiment, was very facile. The reaction is completed by the addition of methanol to the formed ketene. Both the energy barriers of the α-H migration to the amide N and the methanol addition to ketene are largely decreased by the mediation of methanol solvent molecules. The rate-determining step of the entire reaction was found to be the α-H migration.
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longer has a π bond character, is easily hydrolyzed. Tani et al. have successfully synthesized 2-quinuclidone, which has a unique ring structure of the amide.10 In this compound, the two planes of −C(O)− and −N
