13C n.m.r. study of conformational equilibria in solutions of methyl N‐benzoyl‐l‐leucyl‐l‐histidinate monohydrate

Abstract

13C n.m.r. spectra for the title compound are reported in CDCl3 and also in pure and acidified DMSO solutions. In all cases, cis/trans isomerization about the amide bond occurs. For the cis isomers, severe steric compression shifts the ortho phenyl and leucyl β‐CH2 resonances to higher field. In CDCl3 solution, two imidazole conformations are present. In one, the imidazole group is freely rotating about the β‐CH2‐C(ring) bond, whilst the nitrogen‐bound proton participates in a dynamic tautomeric equilibrium, rapid on the n.m.r. time‐scale, between the two ring nitrogen atoms. In the other, the imidazole ring is protonated at N1 and held in a relatively rigid conformation by hydrogen‐bonding between N3, the water molecule, and the amide carbonyl group oxygen atom. The major imidazole species present in DMSO solution is the N1‐protonated tautomer. Small amounts of the N3 tautomer are also present, but in this solvent proton exchange between the two sites is slow on the n.m.r. time‐scale. In acidified DMSO, both nitrogen atoms are protonated.