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tert-Butyl Hydroperoxide Promoted the Reaction of Quinazoline-3-oxides with Primary Amines Affording Quinazolin-4(3H)-ones

Jin Luo*, Juelin Wan, Lianlian Wu, Lingyun Yang and Tao Wang*

*Jiangxi Province Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi 330022, P. R. China, Email: wangtaojxnu.edu.cn

J. Luo, J. Wan, L. Wu, L. Yang, T. Wang, J. Org. Chem., 2022, 87, 9864-9874.

DOI: 10.1021/acs.joc.2c00898


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Abstract

An efficient and facile reaction of quinazoline-3-oxides with primary amines provides a broad range of quinazolin-4(3H)-ones under metal-free and mild reaction conditions employing tert-butyl hydroperoxide as the oxidant. Remarkably, a precursor for the synthesis of bioactive evodiamine and rutaempine was conveniently obtained in good yield.

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Details

The article presents a novel, efficient, and metal-free method for synthesizing quinazolin-4(3H)-ones by reacting quinazoline-3-oxides with primary amines using tert-butyl hydroperoxide (TBHP) as an oxidant. This approach is applicable to a wide range of substrates and operates under mild conditions. The method yields various quinazolin-4(3H)-one derivatives, which are significant due to their broad spectrum of bioactivities, including anticancer, antifungal, antibacterial, antiviral, anti-inflammatory, antiallergic, antihypertensive, and HIV-1 integrase inhibition properties. The study highlights the synthesis of 3-(2-(1H-indol-3-yl)ethyl)quinazolin-4(3H)-one, which serves as a precursor for bioactive compounds like evodiamine and rutaempine. The reaction mechanism involves nucleophilic attack, ring opening, and radical-mediated pathways. The method's efficiency and broad applicability make it a valuable addition to synthetic organic chemistry, particularly for producing biologically active quinazolinone derivatives. Further research is ongoing to expand the method's applications in organic synthesis and the preparation of biologically active products.


Key Words

quinazolin-4(3H)-ones, tert-butyl hydroperoxide


ID: J42-Y2022