The goal of this study was to develop a continuous multistep synthesis for the preparation of N-methyl-N-nitroso-p-toluenesulfonamide (3, MNTS, Diazald) starting from p-toluenesulfonyl chloride (1), making use of microreaction technology (MRT). MNTS is an important precursor for diazomethane, a highly reactive and selective reagent for the production of pharmaceuticals and fine chemicals. Due to the properties of the successive reaction steps (exothermic reactions, use of toxic and highly reactive reagents), it was envisaged that MRT could provide advantages when compared to its batch-wise preparation. The research strategy included preliminary batch investigations, in which the effects of the solvent system, feed concentration, relative molar ratio, temperature, and residence time were established. Starting from these results, the reactions were translated into the MRT setup. As a result, the amidation of 1 to N-methyl-ptoluenesulfonamide (2) as the first reaction step is performed continuously in >90% yield and maximum space-time yields of up to 75 kg L -1 h -1 . By making use of salting-out effects, the product separates nearly quantitatively in high concentrations in organic solution from the saline-waste stream. It is continuously converted to 3 by addition of NaNO 2 with quantitative conversions: yields of >90% and maximum space-time yields of up to 9 kg L -1 h -1 . The method presented allows for the connection of the diazomethane precursor preparation to its continuous liberation by addition of a base, and conversion with a substrate, as previously demonstrated using MRT (
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