Conformational and tautomeric studies of acylguanidines. Part 1. Synthesis, ultraviolet spectroscopy, tautomeric preference, and site of protonation in some model compounds

Abstract

Six of the ten possible acylguanidine conformers have been prepared as model compounds in fixed form; all protonate on the imino nitrogen. The expected close u.v. resemblance between the cations is found for the major band near 200 nm but there are complications origin to a second band at higher wavelength and of very variable intensity whose origin is traced to an electronic transition involving σ-resonance. There is a clear distinction between the u.v. spectra of the ‘through-conjugated’ and ‘cross-conjugated’ free base forms, but with unexpected complications in certain cases which are believed to be due to the co-existence of near-planar and severely twisted species. There is a large tautomeric preference for the ‘through-conjugated’ forms, the extent of which is complicated by perturbations due to the molecular scaffolding. An attempt to allow for this and to predict the pK_a values for the nominal parent compounds leads to the conclusion that, for the anti-conformers, tautomeric ratio is ca. 300. Reasons are given for believing that these compounds are good models for related guanidinoheterocycles active as histamine H₂-receptor antagonists.