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

Abstract

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 electrondonating 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.

Diols Speed Up Guanidine Base Catalyzed Claisen‐Schmidt Condensation to Produce New 15‐Arylidene Steroids

“…Hydrogen bond formation with a suitable donor molecule is known to accelerate of the reactions of carbonyl compounds by lowering the energy of their LUMO, the C=O π* orbital and activating the group towards nucleophilic attack, as well as by increasing the acidity of the proton on the α carbon [34] . For example, in the mechanism proposed by Choudhury et al [35] . for the Claisen‐Schmidt condensation in aqueous solution, water molecules are assumed to coordinate the reactants and accelerate the condensation.…”

Critical assessment of interactions between ct-DNA and choline-based magnetic ionic liquids: evidences of compaction

“…They are alternatives to aqueous and organic solvents due to their diverse physio-chemical properties, such as low vapor pressure, low toxicity, high thermal and chemical stability, biocompatibility, and high conductivity. 1 Owing to the diverse nature of ILs, their application is not only limited to electrochemical devices and synthetic chemistry, [2][3][4] but they can also act as a green solvent for biological applications. [5][6][7][8][9] The low cytotoxicity and biodegradability of ILs render them promising solvents for storing and extracting biomolecules.…”