2-叠氮肉桂酸苄酯的催化加氢制备α-氨基酸

Catalytic Hydrogenation of Benzyl -Azidocinnamates to α-Amino Acids

摘要:

以叠氮乙酸乙酯与芳香醛为原料，通过醛酯缩合反应、皂化反应及苄酯化反应，合成了10个2-叠氮肉桂酸苄酯类化合物。通过对2-叠氮肉桂酸苄酯的加氢反应进行考察，筛选出最优反应条件为：Pd/C（Pd质量分数10%）用量为底物质量的30%、甲醇为溶剂、加氢压力为3 MPa。通过上述反应条件，可以一步实现底物中3个位点（叠氮基团、碳碳双键以及苄基酯）的加氢反应，以76%~89%的收率合成了一系列α-氨基酸。核磁监控体系表明：该转化的反应历程虽较为复杂，但最终产物单一。反应后处理简单，只需过滤去除Pd/C，即可得到纯净的α-氨基酸产物。

Abstract:

A new method for preparation of -amino acids was designed and realized by using a hydrogenation reaction as the key strategy. Ten benzyl -azidocinnamates were prepared from the ethyl 2-azidoacetate and aromatic aldehydes through the following combined processes of condensation of aldehyde and ester, saponification of methyl -azidocinnamates and esterification of the -azidocinnamic acids with benzyl alcohol. Then the hydrogenation of the benzyl -azidocinnamates was investigated, and the optimized conditions employed Pd/C (10% Pd) at 30% weight of the substrate as the catalyst, methanol as the solvent, and the pressure of hydrogen gas at 3 Mpa. The three-site conversion is featured with the combination of the reduction of azido group, the hydrogenation of C=C bond and the hydrogenolysis of benzyl ester, efficiently affording the corresponding -amino acids in 76~89% yields. Further, the substituents of chlorine and bromine on the aromatic ring of substrates were also removed during the hydrogenation reaction. The NMR analysis of the reaction mixture indicated that the conversion proceeded through the complicated hydrogenation process, while the ultimate product was clearly delivered. The pure -amino acids were obtained through a very simple filtration to remove the Pd/C catalyst.