On-Demand Generation and Consumption of Diazomethane in Multistep Continuous Flow Systems

Hongwei Yang, Benjamin Martin, Berthold Schenkel

Index: 10.1021/acs.oprd.7b00302

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Abstract

Diazomethane is an exceptionally versatile C1 building block in organic synthesis. However, reactions involving the use of diazomethane impose significant challenges for safe scale-up. This review aims to highlight the recent developments in processes and equipment concepts for the generation and consumption of diazomethane in continuous mode. We focus specifically on the continuous processes and equipment solutions that have, either individually or together, enabled the entire sequence consisting of synthesis of the diazomethane precursor, subsequent generation and purification of diazomethane, and the downstream reaction to achieve the target product. The discussions are performed mainly from an industrial perspective, and the processes are categorized by the capability to generate specific forms of diazomethane: as a neat gas, gas-diluted, or in organic solution. Lab processes and pilot processes are reviewed separately to demonstrate the options available to process diazomethane on different scales.