Dynamic aspects of the stereochemistry of phenothiazines in solution. Part 2. Segmental motion and conformational analysis of the side-chain in promazines

Abstract

Some promazines and the model compound NN-dimethyl-3-phenylpropylamine have been studied, as protonated and unprotonated species, by ¹H and ¹³C n.m.r. spectroscopy. ¹³C T₁ relaxation times have shown that the mobility of the dimethylaminopropyl chain in chloroform solution varies depending on whether the chain is protonated or unprotonated, and whether it is attached to a phenyl or to a tricyclic system. Segmental motions were also detected in two compounds. The conformation of the side-chain has been deduced for different solvents. Remarkably, for protonated promazines the preferred conformations are gauche for the C_α-C_β fragment and trans for the C_β-C_γ in chloroform as well as in water solution, whereas the model compound exists preferentially in the fully extended trans–trans-conformation. In dioxan and in DMSO the population of the αβ-gauche forms decreases. The presence and the nature of the 2-substituent do not appear to have any effect, whereas the tricyclic system is predominant in the stabilization of the αβ-gauche form. This has been related to the ability of these molecules to aggregate in solution with a vertical stacking-type association.