On-Demand Generation and Use in Continuous Synthesis of the Ambiphilic Nitrogen Source Chloramine

Organic Letters 22(21), 8392-8395, DOI: 10.1021/acs.orglett.0c03021

Herein, we demonstrate the on-demand synthesis of chloramine from aqueous ammonia and sodium hypochlorite solutions, and its subsequent utilization as an ambiphilic nitrogen source in continuous-flow synthesis. Despite its advantages in cost and atom economy, chloramine has not seen widespread use in batch synthesis due to its unstable and hazardous nature. Continuous-flow chemistry, however, provides an excellent platform for generating and handling chloramine in a safe, reliable, and inexpensive manner. Unsaturated aldehydes are converted to valuable aziridines and nitriles, and thioethers are converted to sulfoxides, in moderate to good yields and exceedingly short reaction times. In this telescoped process, chloramine is generated in situ and immediately used, providing safe and efficient conditions for reaction scale-up while mitigating the issue of its decomposition over time.