An expeditious iodine-catalyzed synthesis of 3-pyrrole-substituted 2-azetidinones

• Published in: Molecules (Basel, Switzerland) Vol. 17; no. 10; pp. 11570 - 11584
• Main Authors: Bandyopadhyay, Debasish, Cruz, Jessica, Yadav, Ram N, Banik, Bimal K Banik
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2012
• Subjects: 2-azetidinone; Acids; Antibiotics; Azetidines - chemical synthesis; Cancer; catalysis; Catalysis - radiation effects; Chemistry; green synthesis; Iodine; Iodine - chemistry; microwave; Microwaves; pyrrole; Solvents
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules171011570

2-Azetidinones and pyrroles are two highly important classes of molecules in organic and medicinal chemistry. A green and practical method for the synthesis of 3-pyrrole-substituted 2-azetidinones using catalytic amounts of molecular iodine under microwave irradiation has been developed. Following this method, a series of 3-pyrrole- substituted 2-azetidinones have been synthesized with a variety of substituents at N-1 and at C-4. The procedure is equally effective for mono- as well as polyaromatic groups at the N-1 position of the 2-azetidinone ring. The C-4 substituent has no influence either on the yield or the rate of the reaction. Optically pure 3-pyrrole-substituted 2-azetidinones have also been synthesized following this methodology. No deprotection/rearrangement has been identified in this process, even with highly acid sensitive group-containing substrates. A plausible mechanistic pathway has also been suggested based on the evidence obtained from ¹H-NMR spectroscopy. The extreme rapidity with excellent reaction yields is believed to be the result of a synergistic effect of the Lewis acid catalyst (molecular iodine) and microwave irradiation.