Direct Evidence of Solid‐State Tautomerism by Diffraction Methods: Isomers, Equilibria, and Kinetics

Abstract

Application of X-Ray Diffraction to Study TautomerismX-ray diffraction analysis can be utilized as an alternative method to characterize tautomeric equilibria in the solid state. X-ray diffraction is oftentimes utilized to study tautomerism in the solid state, either as a stand-alone technique for structure elucidation or as an important complement to various single or multidimensional NMR spectroscopic techniques, as well as to a variety of steady-state and time-resolved electron and IR spectroscopies. As the most important and general asset, X-ray diffraction is a very useful tool that provides direct evidence of the three-dimensional molecular and crystal structure with atomic-scale resolution that complements structure-or energy-related spectroscopic data. Moreover, temperature-resolved, time-resolved, and spatially resolved diffraction studies could be implemented to unravel details on the kinetics, dynamics, and spatial progress of the reaction. At a qualitative level, diffraction methods can afford conclusive results that could aid in reaching a decision on the chemical identity of the tautomers from the viable chemical structures in the solid state. In more quantitative terms, X-ray diffraction analysis is of invaluable relevance in terms of the possibilities that it provides to directly probe the shape and depth of the potential well of the proton, simultaneously acquiring information on the atomic-scale-resolution geometry of the system of interest. Its applications range from routine structure determinations where diffraction methods are capable of determining the identity of the ''pure'' tautomers that exist in the crystal (in cases where the equilibrium is shifted toward one of the tautomeric forms and the dynamic proton is located on only one atom) to temperature-resolved studies in which variants of the technique are employed to monitor dynamic processes to obtain evidence of dynamic tautomeric equilibria where the proton is distributed between two or more atoms. The diffraction methods continue to provide a significant contribution to the understanding of the underlying tautomeric processes. In addition to steady-state diffraction, the recent advent of time-resolved (pump-probe) crystallography, currently available at several third-generation (synchrotron) light sources at 100 ps time scale, provides an additional means to peek into the structural rearrangement as it happens. The Tautomerism: Methods and Theories, First Edition. Edited by Liudmil Antonov.