Sodium dithionite mediated one-pot, tandem chemoselective reduction/cyclization for the synthesis of pyrrole fused N -heterocycles

• Published in: Green chemistry : an international journal and green chemistry resource : GC Vol. 25; no. 1; pp. 161 - 166
• Main Authors: Laha, Joydev K., Panday, Surabhi, Gupta, Pankaj, Seth, Shiv Raj
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 03.01.2023; Royal Society of Chemistry
• Subjects: Aldehydes; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Crystallization; Dithionite; Functional groups; Green & Sustainable Science & Technology; Green chemistry; Physical Sciences; Quinoxalines; Reaction time; Reagents; Reduction; Room temperature; Science & Technology; Science & Technology - Other Topics; Sodium; Sodium dithionite; Substrates; 2-FORMYLAZOLES; REDUCTION; AMINES; ACIDS; STRATEGY; EFFICIENT SYNTHESIS; INHIBITORS; CLEAVAGE; DERIVATIVES; COPPER-CATALYZED ANNULATION
• ISSN: 1463-9262; 1463-9270
• DOI: 10.1039/D2GC03749A

A chemoselective reduction of a nitro group in the presence of an aldehyde or ester group integrated with another synthetic transformation leading to the expedient synthesis of important heterocycles is the subject of this current investigation. The chemoselective reductive cyclization of N -(2-nitrophenyl)pyrrole-2-carboxaldehydes accompanied exclusively by an industrial reagent sodium dithionite (Na 2 S 2 O 4 ) yielding diversely substituted pyrrole fused N -heterocycles has been developed for the first time. The amino group generated in situ via chemoselective reduction of the nitro group undergoes condensation with the aldehyde group to form quinoxalines, or undergoes reaction with the ester group to form quinoxalones. The protocol features an efficient one-pot, tandem reductive cyclization performed at room temperature, very short reaction time (1 h), no aqueous work up, purification by crystallization, isolated yields generally >90%, appreciable functional group tolerance, and wide substrate scope. The scalability of the developed protocol is further demonstrated by a gram-scale synthesis.