Fast and flow compatible pseudo-3D diffusion NMR

Abstract

Flow NMR has become an indispensable tool for reaction monitoring. Consequently, a variety of NMR experiments have been developed to simplify the analysis of complex reaction mixtures. Among these, diffusion NMR shows high potential for resolving mixture components. However, signal overlap remains a concern in pseudo-2D diffusion NMR and can complicate DOSY analysis. Distributing spectral information over two chemical-shift dimensions can alleviate this problem by improving peak resolution and enabling the use of cross-correlations. Incorporating diffusion weighting into conventional 2D NMR experiments typically requires long acquisition times, making such approaches incompatible with the timescales of many chemical reactions. Here, we present a diffusion-weighted ultrafast COSY experiment with compensation for flow effects, enabling the acquisition of a full 3D dataset within approximately five minutes. The method is applied to the monitoring of the synthesis of an α-hydroxyphosphonate.