Triflumezopyrim (TFM) is a novel mesoionic pyrido[1,2-]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 minutes 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-]pyrimidinones insecticide.

中文翻译：

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酯化-缩合-水解耦合高效连续合成三氟嘧啶关键中间体2-[3-(三氟甲基)苯基]丙二酸

三氟嘧啶（TFM）是一种新型介离子吡啶并[1,2-]嘧啶酮类杀虫剂，作用于烟碱型乙酰胆碱受体（nAChR），与其他杀虫剂无交叉耐药性。在此，我们首先开发了一种新的连续流方法来合成 2-[3-(三氟甲基)苯基]丙二酸（TFM 的关键中间体），并与酯化、缩合和水解偶联。所有三步反应均经过优化，转变为由三个微反应单元组成的连续合成模式。与间歇模式相比，总反应时间和总体分离收率分别从12 h以上和60%提高到18 min和73.38%。溶剂消耗和废物排放显着减少，这也为介离子吡啶并[1,2-]嘧啶酮类杀虫剂的开发和生产提供了环保高效的潜在工具。