Acetic acid-catalyzed selective synthesis of N-substituted 2-amino-3-cyanopyrroles via a three-component reaction between carbohydrates, primary amines and malononitrile

• Main Authors: Xia, Mengxin, Moussa, Ziad, Judeh, Zaher M. A.
• Other Authors: School of Chemical and Biomedical Engineering
• Format: Article
• Language: English
• Published: 2022
• Subjects: Engineering::Chemical engineering; Carbohydrates; Cascade Reactions
• Online Access: https://hdl.handle.net/10356/163329
• Institution: Nanyang Technological University

Direct conversion of unprotected carbohydrates to N-heterocycles is challenging and highly desirable. A simple three-component synthesis of N-substituted 2-amino-3-cyanopyrrole key framework is developed from the reaction between unprotected carbohydrates, malononitrile, and primary amines. The reaction proceeded under mild reaction conditions (AcOH catalyst, EtOH, 60 °C, 2 hours), tolerated a wide substrate scope, worked smoothly on a 4 g scale, and gave the pyrroles in up to 86% yield. The pyrroles were also converted into functional intermediates to demonstrate their versatility. NMR and LC–MS experiments supported a proposed cascade reaction mechanism. The approach demonstrates a robust upcycling process for the challenging synthesis of highly functionalized N-heterocyclic compounds from unprotected carbohydrates.