Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)



First Advisor

Richard D. Gandour


The geometry of the carboxylate-imidazolium hydrogen bond in the crystalline state and the effect of microenvironment are investigated in models of the aspartate-histidine (Asp-His) couple. Synthetic methods leading to the preparation of intramolecular models, possessing syn and anti-oriented hydrogen bonds, also are described. A single-pot procedure has been developed for converting phenoxyacetonitriles into their respective benzimidazole derivative in higher yields than the traditional two step procedure. An efficient single-pot procedure also has been developed for converting benzofuran to its acetylene derivative, 2-acetoxyphenylacetylene. This method involves in situ acetylation of the unstable phenol intermediate. Nine intermolecular imidazolium-benzoate couples have been prepared and their structures analyzed by single crystal X-ray crystallography. The structure of an intramolecular model also has been determined by single crystal X-ray crystallography. The orientation of all the imidazolium hydrogen bonds is syn relative to the carboxylate. Furthermore, syn hydrogen bonds are shorter than anti hydrogen bonds. The strength of the hydrogen bond increases as $\Delta$pK$\sb{\rm a}$ between the donor and acceptor decreases. The basicity of the carboxylate is governed by the number of hydrogen bonds accepted by it: successive hydrogen bonding to carboxylate decreases its basicity. Consequently, correlations of hydrogen-bond strength and basicity (pK$\sb{a}$ and PA) of carboxylates are more reliable when carboxylates accept equal number of hydrogen bonds. Stereoelectronics of syn hydrogen bonding to carboxylates are affected by the presence of strong and geometrically constrained anti hydrogen bonding. With respect to the plane of the carboxylate, syn hydrogen bonding lies (1) within 10$\sp\circ$ in the absence of anti hydrogen bonding, (2) out-of-plane (30-35$\sp\circ$) in the presence of one anti hydrogen bond, and (3) within 10$\sp\circ$ in the presence of two anti hydrogen bonds. Out-of-plane distortion in the presence of an anti-oriented hydrogen bond suggests a catalytic role for the anti-oriented Ser-214 side-chain in serine proteases.