Hydroxide-dependent breakdown of carbinolamides: A non-linear Hammett correlation for N-(hydroxymethyl)benzamide derivatives

ORGN 624

Richard W. Nagorski, rnagor@ilstu.edu, Department of Chemistry, Illinois State University, Box 4160, Normal, IL 61790-4160
Carbinolamides are a vital functionality in a variety of biological processes, most notably as an intermediate in the biosyntheses of mammalian peptide hormones. The studies presented here show the effects of electron-donating and electron-withdrawing groups on the hydroxide-dependent reaction of N-(hydroxymethyl)benzamide. It has been established, that when electron-withdrawing groups are attached to the aromatic ring the reaction proceeds through a specific-base catalyzed deprotonation of the hydroxyl group, followed by rate-limiting breakdown to the acyl amide anion and formaldehyde. Both a Ka and a rate for the breakdown of the deprotonated carbinolamide (k1) can be determined and a plot of log (k1X/k1H), when X is an electron-withdrawing group, leads to a linear correlation. However, when electron-donationg are placed on the aromatic ring the k1 values obtained from the fit of kobsd vs. [HO-] no longer fit on the same correlation. The results of the kinetic investigations and the reasons for this non-linear Hammett correlation will be discussed.