Symmetry of NHN hydrogen bonds in solution☆

Abstract

A classic question regarding hydrogen bonds concerns symmetry. Is the hydrogen centered between the two donors or is it closer to one and jumping between them? These possibilities correspond to single- and double-well potentials, respectively. Isotopic perturbation of equilibrium can answer this question. This method is illustrated with 3-hydroxy-2-phenylpropenal. It is then applied to the intramolecular NHN hydrogen bonds in monoprotonated 1,8-bis(dimethylamino)naphthalenes and in N, N′-diaryl-6-aminofulvene-2-aldimines, and the OHO in 6-hydroxy-2-formylfulvene. Mixtures of d 0,3,6,9,12 isotopologs of 1,8-bis(dimethylamino)naphthalene and its 2,7-dimethoxy derivative were synthesized, as well as the pure α- d 1 isotopologs of 6-hydroxy-2-formylfulvene and two N, N′-diaryl-6-aminofulvene-2-aldimines. Deuterium-induced 13C isotope shifts were measured. The splittings and intensities are consistent with perturbation isotope shifts, intrinsic shifts, or a combination of both. The most dramatic are perturbation shifts of +376 and +223 ppb in 6-hydroxy-2-formylfulvene and N, N′-diphenyl-6-aminofulvene-2-aldimine. Perturbation shifts mean that all these hydrogen bonds are asymmetric and that each species is a pair of rapidly interconverting tautomers. This does not require a double-well potential, since solvation of one end of a single-well hydrogen bond could instantaneously stabilize one tautomer. Implications for the role of low-barrier hydrogen bonds in enzyme-catalyzed reactions are discussed. Moreover, an unusual stereochemical effect transmitted across the hydrogen bond is seen in 2,7-dimethoxy-1,8-bis(dimethylamino)naphthalene·H +, where the N-methyls show intrinsic isotope shifts both from the geminal CD 3 and from only one distant CD 3.