An Oxidant-Free and Mild Strategy for Quinazolin-4(3 H)-One Synthesis via CuAAC/Ring Cleavage Reaction

Yueling He; Zhongtao Yang; Danyang Luo; Xiai Luo; Xiaodong Chen; Weiguang Yang

doi:10.3390/molecules28155734

An Oxidant-Free and Mild Strategy for Quinazolin-4(3 H)-One Synthesis via CuAAC/Ring Cleavage Reaction

Molecules. 2023 Jul 28;28(15):5734. doi: 10.3390/molecules28155734.

Authors

Yueling He^{1

2}, Zhongtao Yang¹, Danyang Luo¹, Xiai Luo^{1

3}, Xiaodong Chen⁴, Weiguang Yang^{1

4}

Affiliations

¹ The Marine Biomedical Research Institute of Guangdong Zhanjiang, Guangdong Medical University, Zhanjiang 524023, China.
² School of Environmental Science and Engineering, Donghua University, Shanghai 201620, China.
³ Hunan Province Key Laboratory for Synthetic Biology of Traditional Chinese Medicine, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua 418000, China.
⁴ Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524023, China.

Abstract

An oxidant-free and highly efficient synthesis of phenolic quinazolin-4(3H)-ones was achieved by simply stirring a mixture of 2-aminobenzamides, sulfonyl azides, and terminal alkynes. The intermediate N-sulfonylketenimine underwent two nucleophilic additions and the sulfonyl group eliminated through the power of aromatization. The natural product 2-(4-hydroxybenzyl)quinazolin-4(3H)-one can be synthesized on a large scale under mild conditions with this method.

Keywords: CuAAC/ring cleavage reaction; ketenimine; natural product; nucleophilic addition; quinazolin-4(3H)-ones.

Grants and funding

We thank the Weiguang Yang’s project of Technology Planning Program of Zhanjiang (2021A05247) and Medical Scientific Research Foundation of Guangdong Province (A2021037); and Xiai Luo’s project of Natural Science Foundation of Hunan Province, China (2023JJ40465) for support.