Effects of substitution on the effective molarity (EM) for five membered ring-closure reactions – A computational approach

Abstract

DFT molecular orbital calculations of kinetic parameters for ring closing reactions of substituted 4-bromobutyl alcohols 1–5 and 4-bromobutyl amines 6–10 (Brown’s system) indicate that accelerations in ring closing rate in both systems are largely the result of strain effects as opposed to the currently advanced proximity orientation. Furthermore, the calculated effective molarity (EM) values derived from the DFT data reveal that replacing the nitrogen (6–10, Brown’s system) with an oxygen (1–5, alcoholic analog) results in a decrease in demands on directional flexibility to form 5-membered ring, thus enhancing the rate of the cyclization reaction. In the absence of experimental data the DFT approach could be utilized to predict effective molarities (EM) for intramolecular processes.