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CC BY 4.0 · SynOpen 2025; 09(04): 178-185
DOI: 10.1055/a-2689-2278
paper

PIFA-Mediated Ring-Opening/Coupling Reaction of Benzoxazoles: Access to 2-Hydroxy Diarylureas

Authors

  • Xizhong Song

    a   State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, P. R. of China
    b   Jiangxi Fangzhu Pharmaceutical Co., Ltd., Xinyu, 338000, P. R. of China

  • Wei Yin

    b   Jiangxi Fangzhu Pharmaceutical Co., Ltd., Xinyu, 338000, P. R. of China

  • Xiaowen Zeng

    b   Jiangxi Fangzhu Pharmaceutical Co., Ltd., Xinyu, 338000, P. R. of China

  • Wenping Zhang

    b   Jiangxi Fangzhu Pharmaceutical Co., Ltd., Xinyu, 338000, P. R. of China

  • Wenyan Fu

    c   The Second Affiliated Hospital of Nanchang University, Nanchang, 330008, P. R. of China

  • Limei Qian∗

    b   Jiangxi Fangzhu Pharmaceutical Co., Ltd., Xinyu, 338000, P. R. of China

  • Yi Jin∗

    b   Jiangxi Fangzhu Pharmaceutical Co., Ltd., Xinyu, 338000, P. R. of China

  • Ming Yang∗

    a   State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, P. R. of China

This research was funded by the National Natural Science Foundation of China (grant nos. 22267021 and 22067020), Yunnan Fundamental Research Projects (202401BF070001-021), the Leading Talent Project of Innovation of Double Thousand Plan in Jiangxi Province (S2021DQKJ2195), and the Project of Innovative Research Team of Yunnan Province (202405AS350010).
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Graphical Abstract

Abstract

An efficient method for synthesizing mixed unsymmetric 2-hydroxy diarylureas is developed via (bis(trifluoroacetoxy)iodo)benzene (PIFA)-mediated ring-opening/coupling of benzoxazoles with aryl isocyanates or isothiocyanates. This transition-metal-free protocol operates under mild conditions and utilizes Al2O3/H+ as a key additive, achieving high yields (up to 95%) with broad substrate scope. The reaction proceeds through a proposed PIFA-induced ring-opening of the benzoxazole followed by nucleophilic addition, providing direct access to pharmacologically and materially valuable 2-hydroxy diarylureas while avoiding the use of toxic reagents and high-pressure equipment. This strategy addresses limitations of traditional urea syntheses, offering operational simplicity and scalability.

Key words

2-hydroxy diarylureas - ring-opening reaction - benzoxazoles - metal-free synthesis

Supporting Information



Publication History

Received: 19 June 2025

Accepted after revision: 24 August 2025

Accepted Manuscript online:
24 August 2025

Article published online:
08 October 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by/4.0/)

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