<i>Ex Situ</i> Generation of Difluorodiazoethane (CF₂HCHN₂): Application in the Regioselective Synthesis of CF₂H-Containing Pyrazoles

Abstract

A new method for the <i>ex situ</i> generation of difluorodiazoethane (CF₂HCHN₂) and a procedure for its efficient use in [3 + 2] cycloaddition with nitroolefins by the AcOH/O₂ catalyst system were developed by using a simple two-chamber system. The method provides a facile and straightforward access to a series of 4-substituted 5-difluoromethyl-3-nitro-1<i>H</i>-pyrazoles that are of interest in medicinal chemistry. Interestingly, the key factor for the success of this method is the efficient preparation of CF₂HCHN₂ by an <i>ex situ</i> process.