Double Proton Tautomerism via Intra- or Intermolecular Pathways? The Case of Tetramethyl Reductic Acid Studied by Dynamic NMR: Hydrogen Bond Association, Solvent and Kinetic H/D Isotope Effects

Hans-Heinrich Limbach; Simone Baumgärtner; Roland Franke; Ferdinand Männle; Gerd Scherer; Gleb S Denisov

doi:10.3390/molecules26144373

Double Proton Tautomerism via Intra- or Intermolecular Pathways? The Case of Tetramethyl Reductic Acid Studied by Dynamic NMR: Hydrogen Bond Association, Solvent and Kinetic H/D Isotope Effects

Molecules. 2021 Jul 20;26(14):4373. doi: 10.3390/molecules26144373.

Authors

Hans-Heinrich Limbach^{1

2}, Simone Baumgärtner^{2

3}, Roland Franke², Ferdinand Männle^{1

2

4}, Gerd Scherer^{1

2

5}, Gleb S Denisov⁶

Affiliations

¹ Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
² Institut für Physikalische Chemie, Universität Freiburg, Albertstr. 21, 79104 Freiburg im Breisgau, Germany.
³ GKS Müllheim, Nußbaumallee 6, 79379 Müllheim, Germany.
⁴ Klingelberg Products AS, Nordåsveien 23, 1415 Oppegård, Norway.
⁵ Intertek AG, Tech Center Reinach, Kägenstrasse 18, CH-4153 Reinach, Switzerland.
⁶ Department of Physics, St. Petersburg State University, 198504 St. Petersburg, Russia.

Abstract

Using dynamic liquid-state NMR spectroscopy a degenerate double proton tautomerism was detected in tetramethyl reductic acid (TMRA) dissolved in toluene-d₈ and in CD₂Cl₂. Similar to vitamin C, TMRA belongs to the class of reductones of biologically important compounds. The tautomerism involves an intramolecular HH transfer that interconverts the peripheric and the central positions of the two OH groups. It is slow in the NMR time scale around 200 K and fast at room temperature. Pseudo-first-order rate constants of the HH transfer and of the HD transfer after suitable deuteration were obtained by line shape analyses. Interestingly, the chemical shifts were found to be temperature dependent carrying information about an equilibrium between a hydrogen bonded dimer and a monomer forming two weak intramolecular hydrogen bonds. The structures of the monomer and the dimer are discussed. The latter may consist of several rapidly interconverting hydrogen-bonded associates. A way was found to obtain the enthalpies and entropies of dissociation, which allowed us to convert the pseudo-first-order rate constants of the reaction mixture into first-order rate constants of the tautomerization of the monomer. Surprisingly, these intrinsic rate constants were the same for toluene-d₈ and CD₂Cl₂, but in the latter solvent more monomer is formed. This finding is attributed to the dipole moment of the TMRA monomer, compensated in the dimer, and to the larger dielectric constant of CD₂Cl₂. Within the margin of error, the kinetic HH/HD isotope effects were found to be of the order of 3 but independent of temperature. That finding indicates a stepwise HH transfer involving a tunnel mechanism along a double barrier pathway. The Arrhenius curves were described in terms of the Bell-Limbach tunneling model.

Keywords: dimer-monomer equilibrium; double proton transfer; dynamic NMR spectroscopy; kinetic HH/HD isotope effects; tautomerization; tetramethyl reductic acid; tunneling.