Kinetics of N-methylation reactions and X-ray data of quaternary thiazolium salts. The N ‘lone’ pair orientation in the thiazole ring

Abstract

Kinetic measurements show that in 2- and 4-substituted thiazoles bulkyl 4-alkyl substituents have a stronger deactivating effect upon N-methylation than 2-alkyl isomers. This experimental result, corrected for electronic effects (pK_a) and conformational preference, suggests that the ‘true’ steric hindrance of an alkyl substituent towards an electrophilic centre approaching nitrogen is greater for the 4-position (ΔΔΔG^‡= 570 cal mol^–1). The geometries of thiazole [microwaves (12)] and thiazolium salt (X-rays) allow an interpretation of this difference of apparent bulkiness in terms of ‘easier in plane bond distortion at C(2) in thiazole’ and ‘unsymmetrical orientation of the lone pair’. Its axis, rather than lying along the [graphic omitted] bisectrix (15) seems to be ‘nearer’ to the C(4) carbon.