Donaire-Arias Ana, Poulsen Martin L, Ramón-Costa Jaime, Montagut Ana Maria, Estrada-Tejedor Roger, Borrell José I
Grup de Química Farmacèutica, IQS School of Engineering, Universitat Ramon Llull, Via Augusta 390, E-08017 Barcelona, Spain.
Molecules. 2023 Nov 14;28(22):7576. doi: 10.3390/molecules28227576.
Chalcones are a type of molecule that can be considered as easily synthesizable through aldol condensation or that can be readily purchased from habitual commercial vendors. However, on reviewing the literature, one realizes that there are no standard procedures for such aldol condensations, that there exists a wide range of alternative methods for the aldol condensation (indicating that such a condensation is not always simple), and that, in many cases, low yields are obtained that involve purifications by recrystallization or column chromatography. To develop a robust standard protocol independent of the nature of the substituents present on the acetophenone or the benzaldehyde involved in the aldol condensation leading to the chalcone, we made a comparison between an aldol condensation in KOH/EtOH and a Wittig reaction between the corresponding ylide and benzaldehyde in water. We describe an improved procedure for the Wittig reaction and a protocol for the elimination of the PhP=O byproduct (and the excess of ylide used) by filtration of the crude reaction product through a silica gel plug. We thus demonstrate that such an improved procedure can be a general method for the synthesis of chalcones in high yield and excellent purity and is clearly an improvement on the classical aldol condensation.
查耳酮是一类分子，可通过羟醛缩合轻松合成，也可从常规商业供应商处轻易购得。然而，在查阅文献时发现，此类羟醛缩合并无标准程序，羟醛缩合存在多种替代方法（这表明此类缩合并非总是简单易行），而且在许多情况下，产率较低，还需通过重结晶或柱色谱法进行纯化。为了开发一种与羟醛缩合生成查耳酮所涉及的苯乙酮或苯甲醛上取代基性质无关的可靠标准方案，我们对氢氧化钾/乙醇中的羟醛缩合与相应叶立德和苯甲醛在水中的维蒂希反应进行了比较。我们描述了一种改进的维蒂希反应程序以及一种通过硅胶柱过滤粗反应产物来消除副产物PhP=O（以及过量使用的叶立德）的方案。因此，我们证明这种改进的程序可以作为一种高产率、高纯度合成查耳酮的通用方法，显然是对经典羟醛缩合的一种改进。
