4-甲氨基苯甲醛的合成研究

Synthesis of 4-(methylamino)benzaldehyde

4-甲氨基苯甲醛是重要的医药中间体和有机合成方法学片段,4-甲氨基苯甲醛可由4-溴苯甲醛通过甲胺在封管条件下经Ullmann反应合成,然而由于操作难度大而无法满足药物合成的大量需求,因此,通过对几种反应路线的考察实现了以4-乙酰氨基苯甲醛为原料,经缩醛保护、N-甲基化、碱性水解得到4-甲氨基苯甲醛工业化生产的路线,总收率为91%。该路线操作简单,收率高,所用试剂廉价易得,适合大量制备,具有很重要的经济价值。此外,该分子缩醛在强碱性条件下也可以水解成醛。

4-（methylamino）benzaldehyde is an important pharmaceutical intermediate and organic synthesis fragment. It is regularly synthesized by the classical Ullmann reaction in a sealed tube. However,this approach cannot be produced on a large scale to meet huge requirements of drug synthesis. Here,we describe a new method of synthesis of 4-（methylamino）benzaldehyde by taking N-（4-formylphenyl）acetamide as raw material,through acetalation,N-methylation,hydrolysis with the total yield of 91%. Furthermore,the acetalation component can be hydrolyzed in the strong alkaline environment.