Co-Acid Free Nitration of N,N-Dimethylanilines Using Traditional and Nontraditional Activation Methods

The nitration of aromatic compounds is a highly important transformation, contributing to the synthesis of dyes, agrochemicals, explosives, pharmaceuticals, fine chemicals, and plastics. They also serve as important intermediates in several chemical transformations, including their reduction to amines, or as building blocks in the synthesis of hydrazines, many of which are not commercially available. This study aimed to develop not only a greener, but safer method for the nitration of highly activated N,N-dimethylanilines. This work builds upon our previous studies on aromatic nitration where we developed a co-acid- and additional solvent-free method using dilute aqueous nitric acid and nontraditional activation methods. Reactions were carried out using dilute aqueous nitric acid and N,N-dimethylaniline as the test substrate for optimizations. The effect of several experimental variables was assessed, including acid concentration, stoichiometric equivalents, temperature, and time, while also exploring the use of various activation methods such as ultrasounds, microwaves, and high hydrostatic pressure. Microwave activation showed the greatest yields for most of the substrates while also maintaining low nitric acid concentrations and short reaction times. With some substrates, we observed demethylation of the compound, which is likely due to the harsh oxidation environment that nitration creates.