Formation of the E-isomer as an impurity in the optimized flow synthesis of a Z-α-thio-β-chloroacrylamide; E/Z photoisomerization in batch and flow, and solid state characterization of both isomers

Abstract

N-(4-Methylphenyl)-Z-3-chloro-2-(phenylthio)propenamide (Z-3), which is valuable as a reactive substrate for a range of synthetic transformations, can be obtained by a three-step process involving both batch and flow methodologies. Compound Z-3 was isolated as a crystalline material of high purity, however, the E-isomer, E-3, was found to form in solid samples of Z-3 material during storage. Increased ratios of E-3 and pure isolated samples were obtained by photoisomerization in batch and flow modes, with the flow process being optimal in terms of process time. Crystal structure analysis of both the Z and E isomers highlighted key differences in molecular conformations and supramolecular interactions with greater deviation from planarity evident in E-3 relative to Z-3. Analysis of samples of Z-3 by PXRD and DSC after recrystallization from a variety of solvents gave data consistent with the determined crystal structure of Z-3.