N-[3-(4-甲基苯基)-3-氧代-1-芳基丙基]乙酰胺的三氟乙酸催化合成

One-Pot Synthesis of N-[3-(4-Methylphenyl)-3-oxo-1-arylpropyl]acetamides Employing Trifluoroacetic Acid as an Efficient Catalyst

以对甲基苯乙酮、芳香醛和乙腈为主要原料,通过三氟乙酸催化的改进的Dakin-West反应,顺利得到28个N-[3-(4-甲基苯基)-3-氧代-1-芳基丙基]乙酰胺,最高收率可达95%.18个新化合物的结构经1H NMR,13C NMR和HRMS证实.结构测试发现,羟基苯甲醛参与Dakin-West反应后得到的全部是羟基乙酰化的产物.作者首次证实,羟基苯甲醛参与的Dakin-West反应不是串联反应,而是羟基苯甲醛首先经TFA催化转化为乙酰氧基苯甲醛,然后参与Dakin-West反应,最终生成羟基乙酰化产物.通过碱性水解,可以选择性高收率地制备对应的羟基化β-乙酰氨基酮,同时也反证了羟基乙酰化产物的存在.该研究扩展了TFA催化的Dakin-West反应,为β-乙酰氨基酮的合成提供了新的方法.

The synthesis of a series ofN-[3-（4-methylphenyl）-3-oxo-1-arylpropyl]acetamides using trifluoroacetic acid （TFA） as the catalyst was reported in this paper. It was achieved by a modified Dakin-West reaction using 4-methylacetophenone, aromatic aldehydes and acetonitrile as starting materials, The highest yield was up to 95% among the twenty eight target com- pounds synthesized. All the new compounds were characterized by 1H NMR, 13C NMR and HRMS spectra. This one-pot reac- tion offered several advantages including small catalyst loading （0.3 mol%）, moderate reaction temperatures （28-35℃） and simple post treatment procedure. A reaction mechanism was for the first time established, in which hydroxybenzaldehyde was first catalytically converted into corresponding acetoxybenzaldehyde prior to be involved in the subsequent Dakin-West reac- tion that eventually led to hydroxyl acetylated target compounds. The resultant hydroxyl acetylated β-acetamido ketones were selectively deacetylated in LiOH to produce the corresponding hydroxyl products with excellent yields. The current work fur- ther demonstrated that TFA was an efficient catalyst for Dakin-West reaction involving arylalkyl ketones, aromatic aldehydes and acetonitrile, which expanded significantly the scope of the substrates and provided a new synthetic route to β-acetamido ketones.