NO2 reduction and amide bond formation in a one-pot, two-step procedure

A one-pot two-step reaction has been developed for the formation of amide bond from aromatic nitro compounds and carboxylic acids derivatives. This approach allows bypassing the synthesis and manipulation of toxic anilines giving straight access to valuable final products. The present method relies on the in situ reduction of NO2 by the HSiCl3-Et3N system1 to afford the amine intermediate directly undergoing acyl substitution. Functional group tolerance has been tested to establish generality and electrophiles of different nature have been screened. Extensive optimization of the reaction conditions aimed to mold an effective and robust strategy with potential for large scale application. The reduction step is performed under the mild and metal free conditions previously developed in our group,2 relying on the use of a green and cheap reactant – trichlorosilane. The amine formation mechanism having been already elucidated, further investigation have been performed to gain an insight into the coupling step. References: [1] M. Orlandi, F. Tosi, M. Bonsignore, M. Benaglia, Org. Lett. 2015, 17, 3941−3943. [2] M. Orlandi, M. Benaglia, F. Tosi, R. Annunziata, F. Cozzi J. Org. Chem. 2016, 81, 3037−3041