Tosyl esters of cinchonidine and cinchonine alkaloids: the structure-reactivity relationship in the hydrolysis to 9-epibases.

In the crystal structures of the diastereoisomers of O-tosylcinchonidine [(9R)-cinchon-9-yl 4-methylbenzenesulfonate], (I), and O-tosylcinchonine [(9S)-cinchon-9-yl 4-methylbenzenesulfonate], (II), both C(26)H(28)N(2)O(3)S, both molecules are in an anti-closed conformation and, in each case, the position of the aryl ring of the tosylate system is influenced by an intramolecular C-H···O hydrogen bond. The molecular packing in (I) is influenced by weak intermolecular C-H···O and C-H···π interactions. The crystal structure of (II) features C-H···π interactions and van der Waals forces only. The computational investigations using RHF/6-31G** ab initio and AM1 semi-empirical methods performed for (I) and (II) and their protonated species show that the conformational and energetic parameters of the molecules are correlated with differences in their reactivity in hydrolysis to the corresponding 9-epibases.