[3-(2-硝基-6-甲基)苯基]-4,5二氢异噁唑的合成工艺研究

Research for Synthesizing of [3-(2-Nitro-6-Methyl) Phenyl]-4,5 Dihydroisoxazole

[3-(2-硝基-6-甲基)苯基]-4,5二氢异噁唑是除草剂苯唑草酮重要中间体,本文提出并研究了该中间体的一种新合成方法。该方法以2,3-二甲基硝基苯为起始原料与亚硝酸酯进行亲核取代反应得到2-硝基-6甲基苯甲醛肟,随后与乙烯在次氯酸钠的存在下经1,3-偶极环加成反应获得目标产物。该方法在进行1,3-偶极环加成反应时,创新性地使用次氯酸钠作为卤代试剂,避免传统工艺中的剧毒氯气和NCS (伴随产生当量有机酰胺副产物)的使用。更重要的是,该工艺实现了一锅两步法进行1,3-偶极环加成反应,避免对肟酰氯中间产物的分离提纯操作。两步反应后目标产物总收率75.2%。

[3-(2-nitro-6-methyl) phenyl]-4,5-dihydroisoxazole is the vital synthetic intermediate of topramezone herbicides, this work highlighted a new method for synthesizing such intermediate. The 2-nitro-6-methylbenzaldehyde oxime have been prepared via the nucleophilic substitution reaction of 2,3-dimethylnitrobenzene and nitrous acid ester. Then, the 1,3-dipolar cycloaddition reaction of 2-nitro-6-methylbenzaldehyde oxime with ethylene in presence of sodium hypochlorite provided the desired [3-(2-nitro-6-methyl) phenyl]-4,5-dihydroisoxazole. In this work, sodium hypochlorite is innovatively used as halogenation reagent to avoid the use of highly toxic chlorine gas and NCS (usually yield equivalent organic amide by-products) in the traditional process. Most importantly, this method enabled the one-pot 1,3-dipolar cycloaddition reaction, avoiding the separation and purification of oxamoyl chloride intermediate. After the optimization of reaction conditions, the target [3-(2-nitro-6-methyl) phenyl]-4,5-dihydroisoxazole can be obtained in an overall yield of 75.2%.