Research on 1-AZA two-ring systems. 21. Basicities, stereochemistry, and 1H and 13C NMR spectra of pyrrolizidine and its homologs in aqueous and aqueous acetonitrile solutions. Prediction of the pKa value of trans-fused pyrrolizidine

Abstract

The basicities of pyrrolizidine and its homologs in aqueous and aqueous acetonitrile solutions at 25 ° C were determined. It is shown that among 3-alkylpyrrolizidines, the isomers with cis configurations have higher pKa values than the isomers with trans configurations. On the basis of a comparative study of the 1H and 13C NMR spectra it was concluded that cis-3,8-H-cis-5,8-H-3,5-dimethylpyrrolizidine in aqueous solutions exists chiefly in the trans-fused form, whereas conformationally heterogeneous pyrrolizidines with primarily cis-fused rings experience a shift of the equilibrium to favor an increase in the cis-fused conformations when a nonpolar solvent is replaced by a polar solvent. The basicity of the trans-fused conformation of pyrrolizidine is predicted on the basis of the data obtained.