High-throughput screening of Ullmann reaction conditions and study of their regularity

doi:10.6023/cjoc202507012

Chinese Journal of Organic Chemistry

Ullmann反应条件的高通量筛选及其规律性研究

郭在翔^†, 邹昀^†, 程沛浩, 李富军, 陶胜洋^*

大连理工大学化学学院大连 116024

收稿日期:2025-07-09 修回日期:2025-10-16
基金资助:
国家自然科学基金(No. 22372025)和中央高校基本科研业务费(No. DUT22LAB607 and DUT22QN226)资助项目.

High-throughput screening of Ullmann reaction conditions and study of their regularity

Guo Zaixiang^†, Zou Yun^†, Cheng Peihao, Li Fujun, Tao Shengyang^*

School of Chemistry, Dalian University of Technology (DUT), Dalian, 116024

Received:2025-07-09 Revised:2025-10-16
Contact: ^*E-mail: taosy@dlut.edu.cn
Supported by:
National Natural Science Foundation of China (No. 22372025), and Fundamental Research Funds for the Central Universities (No. DUT22LAB607 and DUT22QN226).

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Abstract

Although classical physical organic chemistry theories have undergone significant development, it remains challenging to rapidly determine the optimal reaction conditions and elucidate possible mechanisms for specific reactions. In recent years, high-throughput experimentation and data-driven analysis have emerged as powerful tools to address these challenges. In this study, we employed an automated high-throughput experimental platform combined with big data and machine learning techniques to optimize the reaction conditions and investigate the mechanism of the Ullmann coupling for the synthesis of pirfenidone (5-methyl-1-phenylpyridin-2(1H)-one). A total of 984 different reaction conditions were screened using the automated platform. This approach not only identified the optimal copper/ligand combination but also revealed, through a combination of machine learning and statistical analysis, that oxalamide ligands and short Cu-L interaction distances are key factors contributing to higher yields in the Ullmann coupling for pirfenidone synthesis.

Key words: High-throughput experiments, C-N coupling, Machine learning, Big data

Cite this article

Guo Zaixiang, Zou Yun, Cheng Peihao, Li Fujun, Tao Shengyang. High-throughput screening of Ullmann reaction conditions and study of their regularity[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202507012.

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Ullmann反应条件的高通量筛选及其规律性研究

High-throughput screening of Ullmann reaction conditions and study of their regularity

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