Applications of long-range 13C,H nuclear spin–spin coupling constants in the study of imidazole tautomerism in L-histidine, histamine, and related compounds

Abstract

Three-bond 13C,H nuclear spin–spin coupling constants can be used to estimate the relative populations of the two possible tautomers of the imidazole ring in compounds containing this moiety. The mole fraction, XII of the 1-H tautomer (i.e. the tautomer having a proton bound to the nitrogen atom at position 1 of the ring, where the ring is numbered according to IUPAC–IUB convention) can be calculated from the following equation:[Formula: see text]Estimates of the predominant tautomer in L-histidine, histamine (both the neutral molecule and the monocation), and the dipeptide L-histidyl-L-glutamic acid indicate that the 1-H form is favored in basic aqueous solution. The results are compared with those obtained by other methods, and show that the present technique can provide a simple, rapid means of determining tautomeric equilibrium in imidazole derivatives.