Date of Completion
Honors Thesis - Campus Access
DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) is an effective catalyst for a broad range of acylation reactions, including esterifications and amidations. In particular, we have previously shown that electrophilic carbonylazoles react quickly with alcohols to form esters in the presence of DBU; however, this reaction is undetectable in the absence of catalyst. Despite this intriguing catalytic ability, the mechanism of this DBU-catalyzed acylation is not yet known. Knowledge of the catalytic mechanism may inspire new DBU-catalyzed acylations with improved selectivity and efficiency. Two main mechanistic hypotheses are considered: either the DBU is deprotonating the nucleophile directly or DBU is hydrogen bonding to the nucleophile. In order to elucidate the mechanism, a model esterification reaction was developed and studied using standard kinetic techniques. Further evaluation of the model system involving kinetics-based solvent screening, competition experiments, and measurement of DBU-nucleophile hydrogen-bonding association constants via NMR titration suggest that the rate of esterification is strongly solvent dependent, that the rate of acylation is not directly dependent on the acidity of the nucleophile, and that DBU readily forms hydrogen-bond complexes with alcohols even in polar solvents. Taken together, these data lend support for a catalytic mechanism in which DBU is a hydrogen-bond acceptor rather than a Brønsted base.
Medlin, Abby and Heller, Stephen T., "Mechanistic Study of DBU-Catalyzed Esterifications of Acyl Imidazoles" (2020). Honors Thesis. 407.