Synthesis of α,β-Unsaturated Ketones in Water: The Claisen–Schmidt Condensation Revisited

Carrying out organic synthesis in an aqueous medium is always challenging. Herein, we present a highly efficient method for the synthesis of α,β-unsaturated ketones in water through the Claisen–Schmidt condensation by using a green catalyst, choline hydroxide (ChOH). The products were isolated without any chromatographic separation technique. The catalyst shows high substrate tolerance and works well with electron-donating and electron-withdrawing substituted aromatic aldehydes. Not only is the catalyst metal-free and nontoxic, but it also offers the advantage of forming strong hydrogen bonds with the transition state and intermediates, facilitating the reaction and enhancing the product yield. A variety of substrate scopes has been explored. The catalysis happens at 50 °C in water which is the significant finding of this study. The reaction mechanism of this hydrogen-bond-mediated catalysis was thoroughly investigated with density functional theory (DFT). The plausible reaction pathway was proposed based on the energetics of the reactants, intermediates, transition states, and product. Further, quantum theory of atoms in molecules (QTAIM) and noncovalent interactions (NCI) index analyses were done to demonstrate the effects of strong hydrogen bonds in the crucial steps of the reaction pathway. The obtained results correlate well with our hypothesis and validate our proposed mechanism, suggesting that the hydrogen-bond-mediated catalysis needs special attention in carrying out organic synthesis in water.