Direct Uncatalyzed Amination of 2-Chloropyridine Using a Flow Reactor

Abstract

Chloropyridines are efficiently converted into 2-amino­pyridines by uncatalyzed nucleophilic aromatic substitution (S_NAr) in NMP using a continuous-flow reactor. A variety of secondary amines undergo S_NAr with both electron-rich and electron-deficient 2-chloropyridines to afford 2-aminopyridines in good to excellent yield. The flow reactor, which provides a short reaction time and high temperatures up to 300 °C, can overcome the activation barrier for reactions with unactivated substrates. Short reaction times result in fewer side products and can afford milligram to multigram ­quantities of product using continuous flow.

Key words

amination - nucleophilic aromatic substitution - flow synthesis - microflow reactor

References and Notes

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14

In addition, the reactions we wished to investigate required pressures and temperatures beyond the range of commercially available chip-based devices.