杀菌剂叶菌唑的合成

Synthesis of Fungicide Metconazole

[目的]改进叶菌唑的合成技术。[方法]以己二酸二甲酯为主要原料,通过迪克曼缩合制备2-氧代环戊烷羧酸甲酯,再与溴甲烷进行甲基化反应,在甲醇钠体系中进行异构化反应,得中间体2-甲基-5-乙氧羰基环戊酮,然后与对氯氯苄加成得中间体2-甲基-5-(4-氯苄基)-5-乙氧羰基环戊酮,与溴甲烷进行二甲基化反应,在酸性条件下进行脱羧得关键中间体2,2-二甲基-5-(4-氯苄基)环戊酮,环氧化后得环氧化产物4,4-二甲基-7-(4-氯苄基)-1-氧代-螺[2,4]庚烷,最后与三氮唑钠盐反应最终制得产品。[结果]路线总收率可达69.7%,产品纯度97.8%(HPLC),适合工业化生产。

[Aims] The study aims to improve the synthesis technology of metconazole. [Methods] Starting from diethyladipate, 2-oxocyclopentanecarboxylate was obtained by dieekmann condensation, followed by methylation with bromomethane, translocation under sodium methanolate conditions to afford the intermediate 2-methyl-5- carbethoxycyclopentanone, and then this intermediate was reacted with p-chlorobenzylchloride to synthesize 5- （4-chlorobenzyl）-2-methyl-5-carbethoxycyclopentanone. The key intermediate 4,4-dimethyl-7-（4-chlorobenzyl）-1-oxo- spiro [2,4] can be achieced by methylation with bromomethane, decarboxylation under acidic conditions and epoxidation reaction. Finally Metconazole was given by reacting this key intermediate with the sodium salt of triazole. [Results] The total yield of this route was 69.7% and the purity of the product was 97.8% （HPLC）. This react route was suitable for industrial production.