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 2 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 N atom at position 1 of the ring) can be calculated from the following equation: XII .simeq. 1.705 - 0.164 3J(C5,H2)obs. 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.