Base-Promoted [4 + 1 + 1] Multicomponent Tandem Cycloaddition of Ortho-Substituted Nitroarenes, Aldehydes, and Ammonium Salts To Access 2,4-Substituted Quinazoline Frameworks

Abstract

We report a base-promoted, metal-free multicomponent tandem reaction, involving a [4 + 1 + 1] cycloaddition process between ortho-substituted nitroarenes, aldehydes, and ammonium salts. Modifying the substituents on the nitroaromatic compounds effectively provides structurally diverse 2-substituted and 4-alkenylquinazolines with good to excellent yields (77%–90% and quinazoline 51 examples) and high tolerance for various inorganic ammonium salts (13 examples, such as NH₃·H₂O, NH₄Cl, and NH₄HF₂). A new method for constructing 2,4-substituted quinazoline compounds with high selectivity from simple nitrogen source compounds was developed, and the reaction can be scaled up to a gram scale. Additionally, this method also facilitates the preparation of organic molecules with photophysical properties, offering new insights into the further transformation of quinazolines.