Ultrasound-assisted phase-transfer catalysis method in an aqueous medium to promote the Knoevenagel reaction: Advantages over the conventional and microwave-assisted solvent-free/catalyst-free method

• We report a simple ultrasound (US) method under phase transfer catalysis (PTC) conditions for the Knoevenagel reaction.
• The US-PTC method is more advantageous than the solvent and catalyst-free microwave irradiation (MWI) method.
• Reductions were obtained in the reaction times from 13 to 1.5 min and increased yields from 50% to 94%.
• Mild conditions and a convenient US-PTC protocol in organic synthesis are proposed.
• The US-assisted PTC method allows for carrying out reactions in aqueous mediums.

Given the broad spectrum of uses of acrylonitrile derivatives as fluorescent probes, AChE inhibitors, and others, it is necessary to find easy, efficient and simple methods to synthesize and diversify these compounds. We report the results of a comparative study of the effects of three techniques on the reactions between heterocyclic aldehydes and 2-(benzo[d]thiazol-2-yl)acetonitrile: stirring; ultrasound coupled to PTC conditions (US-PTC); and MW irradiation (MWI) under solvent and catalyst-free conditions. The effects of conditions on reaction parameters were evaluated and compared in terms of reaction time, yield, purity and outcomes. The US-PTC method is more efficient than the MWI and conventional methods. The reaction times were considerably shorter, with high yields (>90%) and good levels of purity. In addition, X-ray diffraction analysis and quantum mechanical calculations, at the level of density functional theory (DFT), ratify obtaining acrylonitrile isomers with E configurations. The crystal structure of 3c is stabilized by weak C–Ho⋯N intermolecular interactions (Ho⋯NC = 2.45 Å, Co⋯NC = 3.348(3) Å, Ho⋯NC = 162°), forming centrosymmetric ring R22 (20) along the crystallographic a axis.