Nonstationary Two-Dimensional Nuclear Magnetic Resonance: A Method for Studying Reaction Mechanisms in Situ.

Nuclear magnetic resonance spectroscopy (NMR) is a versatile tool of chemical analysis allowing one to determine structures of molecules with atomic resolution. Particularly informative are two-dimensional (2D) experiments that directly identify atoms coupled by chemical bonds or a through-space interaction. Thus, NMR could potentially be powerful tool to study reactions in situ and explain their mechanisms. Unfortunately, 2D NMR is very time-consuming and thus often cannot serve as a "snapshot" technique for in situ reaction monitoring. Particularly difficult is the case of spectra, in which resonance frequencies vary in the course of reaction. This leads to resolution and sensitivity loss, often hindering the detection of transient products. In this paper we introduce a novel approach to correct such nonstationary 2D NMR signals and raise the detection limits over 10 times. We demonstrate success of its application for studying the mechanism of the reaction of AgSO4-induced synthesis of diphenylmethane-type compounds. Several reactions occur in the studied mixture of benzene and toluene, all with rather low yield and leading to compounds with similar chemical shifts. Nevertheless, with the use of a proposed 2D NMR approach we were able to describe complex mechanisms of diphenylmethane formation involving AgSO4-induced toluene deprotonation and formation of benzyl carbocation, followed by nucleophilic attacks.