The focus of this research project is to elucidate the mechanism of the ring-opening of the azetidine ring. The reactions that will be undertaken will involve the action of a series of meta- and para- substituted phenols on 1-alkylazetidines rand 1-alkyl-2-methylazetidines. The reaction products will be separated and isolated by fractional distillation and high performance liquid chromatography. Characterization of these reaction products will be made by IR, 1H and 13C NMR spectral studies. A second dimension of the project will involve kinetic studies of the ring- opening reactions by a suitable combination of spectral studies. During the previous funding period, research-size quantities of compounds possessing beta-adrenolytic properties (helpful in controlling hypertension, angina pectoris and cardiac arrhythmia) have been prepared by our laboratory using these reactions. During the proposed funding period this project will be aimed at providing a detailed understanding of the mechanism, with the ultimate objective of providing not only a convenient means of preparing new compounds but also new classes of compounds possessing more specificity for the treatment of the organs affected by these diseases--the heart and the blood vessels. The research design will involve: (1) the synthesis of N-substituted azetidines by various methods; (2) isolation of the products by distillation and/or various chromatographic techniques; (3) ring-opening of N-substituted azetidines with substituted phenols; (4) separation, isolation and characterization of the ring opening products; and (5) kinetic studies of the ring opening reactions. Students will participate in every aspect of this project, including preparation of starting materials, performing kinetics, interpreting data from IR and NMR spectra, etc.
