Citation: Yuexiang Liu, Xiangqiao Yang, Tong Lin, Guantian Yang, Xiaoyong Xu, Bubing Zeng, Zhong Li, Weiping Zhu, Xuhong Qian. Efficient continuous synthesis of 2-[3-(trifluoromethyl)phenyl]malonic acid, a key intermediate of Triflumezopyrim, coupling with esterification-condensation-hydrolysis[J]. Chinese Chemical Letters, ;2025, 36(1): 109747. doi: 10.1016/j.cclet.2024.109747 shu

Efficient continuous synthesis of 2-[3-(trifluoromethyl)phenyl]malonic acid, a key intermediate of Triflumezopyrim, coupling with esterification-condensation-hydrolysis

Yuexiang Liu ^a ,
Xiangqiao Yang ^a ,
Tong Lin ^a ,
Guantian Yang ^a ,
Xiaoyong Xu ^a ,
Bubing Zeng ^{a, b} ,
Zhong Li ^{a, c} ,
Weiping Zhu ^{a, c, d} ,
Xuhong Qian ^{a, c, e, *,}

a.
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
b.
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
c.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
d.
Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
e.
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, China

xhqian@ecust.edu.cn

Received Date: 25 December 2023
Revised Date: 23 February 2024
Accepted Date: 5 March 2024
Available Online: 11 March 2024

Figures(6)

Triflumezopyrim (TFM) is a novel mesoionic pyrido[1,2-α]pyrimidinones insecticide, which acts on nicotinic acetylcholine receptors (nAChRs) and has no cross-resistance with other insecticides. Herein, we firstly developed a new continuous flow approach to synthesis 2-[3-(trifluoromethyl)phenyl]malonic acid, a key intermate of TFM, coupling with esterification, condensation, and hydrolysis. All three-step reactions were optimized and transformed into a continuous synthesis mode by three micro reaction units. Compared with the batch mode, the total reaction time and overall separation yield were improved from more than 12 h and 60% to 18 min and 73.38%, respectively. The solvent consumption and waste emission were significantly reduced, which also provides an eco-friendly and efficient potential tool for the development and production of mesoionic pyrido[1,2-α]pyrimidinones insecticide.
- Triflumezopyrim (TFM),
- 2-[3-(Trifluoromethyl)phenyl]malonic acid,
- Continuous flow synthesis,
- Micro-reactor
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