Amides as key intermediates for the synthesis of 2,4-disubstituted quinazolines via acceptorless dehydrogenative coupling of alcohols

Abstract

A one-pot strategy for the receptorless dehydrogenative coupling of o-aminoaryl ketones with benzyl alcohols has been developed to afford 2,4-disubstituted quinazolines. Additionally, we have established a one-pot, two-step dehydrogenation protocol that employs secondary o-aminoaryl alcohols as surrogates for o-aminoaryl ketones, thereby enabling the synthesis of 2,4-disubstituted quinazolines. This approach employs the cost-effective MUV-10(Mn) catalyst and achieves excellent yields (up to 99%) without the use of solvents. Moreover, the catalyst demonstrated remarkable stability, maintaining its activity with almost no decline for five consecutive reuse cycles. Importantly, control experiments and DFT calculations reveal the reason why secondary o-aminoaryl alcohols require a two-step reaction. In-depth control experiments reveal that the reaction proceeds through critical amide intermediates, providing crucial insights into the mechanistic pathway. This discovery not only underscores the robustness of the catalytic system but also highlights the fundamental understanding of the reaction mechanism, paving the way for further advancements in sustainable and efficient synthetic chemistry.