Synthesis of Thiomorpholine via a Telescoped Photochemical Thiol-ene/Cyclization Sequence in Continuous Flow

A procedure for the continuous flow generation of thiomorpholine in a two-step telescoped format was developed. The key step was the photochemical thiol-ene reaction of cysteamine hydrochloride and vinyl chloride as low-cost starting materials under highly con-centrated (4 M) conditions, leading to the corresponding half-mustard intermediate in quantitative yield. Thiomorpholine was subsequently obtained by a base-mediated cyclization. The robust-ness of the process was demonstrated by performing the reaction for 7 h (40 min overall residence time) isolating the desired thio-morpholine via distillation.