Title:Simplifying Nucleophilic Aromatic Substitutions: Microwave-Assisted Solvent Free Synthesis of 5-Alkylamino-2-nitroanilines
Volume: 3
Issue: 3
Author(s): Pedro J. Trejo-Soto, Anuar Flores-Gahona, Rafael Castillo and Alicia Hernández-Campos
Affiliation:
Keywords:
5-Substituted 2-nitroaniline, amine, green chemistry, microwave-assisted synthesis, nucleophilic aromatic substitution,
solvent-free synthesis.
Abstract: 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.
