Simplifying Nucleophilic Aromatic Substitutions: Microwave-Assisted Solvent Free Synthesis of 5-Alkylamino-2-nitroanilines

Background: Substituted 2-nitroanilines are synthetic intermediates used in the synthesis of important bioactive compounds. Nucleophilic aromatic substitution reactions with activated substrates, such as substituted 5-chloro-2-nitroanilines, usually involve the use of a solvent, high pressure conditions and prolonged reaction times. We describe a simple and straightforward protocol to prepare 5-substituted 2-nitroanilines that addresses these drawbacks. Methods: Utilizing microwave irradiation and solvent free conditions, a series of 5-alkylamino-2- nitroanilines (1-14) have been efficiently prepared by reacting 4,5-dichloro-2-nitroaniline with different primary and cyclic secondary amines. Results: The reactions proceeded in short periods of time (5-35 min) without side products, facilitating the isolation of 1- 14 in 55-93% yields. Reactions under microwave conditions were faster than those achieved with conventional heating. Conclusion: This simplified approach can be a suitable alternative to synthetic methods involving conventional heating. The reported methodology can be applied to generate a variety of 5-substituted 2-nitroanilines which serve as precursors to compounds of pharmaceutical interest.