Energetics of a Low Barrier Hydrogen Bond in Nonpolar Solvents

Abstract

A measure of the strength of a low barrier hydrogen bond (LBHB) in apolar organic media was obtained using synthetic molecules derived from Kemp's triacid. The structures feature unusually rigid conformations that enforce intramolecular hydrogen bonds in a dicarboxylic acid, its corresponding acid-amide and their respective conjugate bases. Analysis of proton and deuterium NMR spectra established the formation of a LBHB in the conjugate base of the diacid and a conventional hydrogen bond in the conjugate base of the acid-amide. Through deprotonation equilibria with organic bases, it was determined that the conjugate base of the diacid was more stable than the conjugate base of the acid-amide by 2.4 kcal/mol in benzene and 1.4 kcal/mol in dichloromethane. These figures set the upper limits for the free energy of the additional stabilization arising from the LBHB at 25 °C. This value is far lower than many estimates but is closer to the recent determinations of Schwartz and Drueckhammer [J. Am. Chem. Soc. 1995, 117, 11902−11905].