新型烟碱类杀虫剂氟吡呋喃酮的合成

Synthesis of Novel Nicotinic Pesticide Flupyradifurone

以2-氯-5-氯甲基吡啶为起始原料,在三乙胺的作用下与2,2-二氟乙胺反应得到N-((6-氯-3-吡啶)甲基)-2,2-二氟乙胺;以丙二酸二甲酯为原料,与氢氧化钾反应,得到丙二酸甲酯单钾盐,然后在相转移催化剂四丁基溴化胺的作用下,与氯乙酸甲酯反应生成2-甲氧基-2-氧代乙基丙二酸甲酯,随后进行分子内关环得到4-羟基-2-氧-2,5-二氢-3-呋喃甲酸甲酯钠盐。最后N-((6-氯-3-吡啶)甲基)-2,2-二氟乙胺与4-羟基-2-氧-2,5-二氢-3-呋喃甲酸甲酯钠盐反应得到目的产物氟吡呋喃酮。经1HNMR光谱鉴定,产物与氟吡呋喃酮结构一致,总收率50.8%(以丙二酸二甲酯计算)。该工艺条件温和、方法简单,适合工业化生产。

N-[(6-chlorpyridin-3-yl)methyl)-2,2 difluorethylamin was firstly prepared through the reaction of 2-chloro-5-chloromethylpyridine with 2,2-difluoroethylamine in the presence of triethylamine. Secondly,themethyl malonate monopotassium salt was obtained via the reaction of malonic acid dimethyl ester with potassiumhydroxide, and it reacted with methyl chloroacetate to form the methyl 2-methoxy-2-oxoethylpropanedicarboxylate. Then,in the presence of phase transfer catalyst tetrabutylammonium bromide,the sodium 4-(ethoxycarbonyl)-5-oxo-2,5-dihydrofuran-3-oxide was obtained by the intra-molecular cyclizationof methyl 2-methoxy-2-oxoethylpropanedicarboxylate. Finally, the sodium 4-(ethoxycarbonyl)-5-oxo-2,5-dihydrofuran-3-oxide reacted with the N-[(6-chlorpyridin-3-yl)methyl)-2,2-difluorethylamine to produce thetarget product flupyradifurone. The product possesses the same structure with flupyradifurone indicated by1 H nuclear magnetic resonance spectroscopy characterization,and its total yield is 50.8%(Calculation based ondimethyl malonate). This process is suitable for industrial scale manufacture with mild conditions and simple operations.