基于乙酸为溶剂和催化剂的芳乙酮Mannich反应

采用乙酸作溶剂和催化剂, 将芳乙酮与甲醛和二级胺进行Mannich反应及热解反应, 并未得到预期的Mannich碱或α,β-不饱和酮(2), 而是以较高产率(65%~73%)生成了乙酸(2-芳甲酰基)烯丙酯(3a~3o). 通过核磁共振波谱、 高分辨质谱和红外光谱表征了化合物3a~3o的结构, 研究了此“异常”反应的发生条件, 并提出了可能的反应机理. 结果表明, 芳乙酮的特殊结构及反应中过量的乙酸是产生化合物3a~3o的决定因素.

Mannich Reaction of Aromatic Ketones Based on Acetic Acid as Solvent and Catalyst†

Mannich reaction is one of the most important methods for preparation of β-amino ketones and aldehydes and α,β-unsaturated carbonyl compounds, as well as one of the most important basic reaction types in organic chemistry and it is widely applied as a key step in the synthesis of numerous pharmaceuticals and natural products. However, during the synthesis of 1-aryl acrylic ketone 2 by the Mannich reaction of aromatic ketones, formaldehyde and secondary amine using acetic acid as solvent and catalyst, the Mannich base and expected α,β-unsaturated ketones 2 were not obtained and another kind of compounds 3, 2-aryl formyl allyl acetate were obtained in moderate to good yields(65%—73%). The structure of compounds 3 was confirmed by ¹H NMR, ¹³C NMR, HRMS and IR spectra. The reasons of producing compounds 3 were studied and the results suggested that the special structure of aromatic ketones and excess acetic acid in reaction are responsible for the exceptional Mannich reaction. In addition, the reaction mechanism was postulated.