Deciphering the Knoevenagel condensation: towards a catalyst-free and water-mediated process

The Knoevenagel condensation constitutes one of the most well-studied and crucial transformations in organic chemistry, since it facilitates the synthesis of numerous valuable compounds. With the advent of green chemistry, several alternative protocols for the Knoevenagel reaction have been introduced and catalyst-free approaches to the Knoevenagel condensation have also been mentioned, however the harsh temperatures employed and the limited substrate scope restricted their application. Herein, we have performed an extensive study on the catalyst-free and water-mediated Knoevenagel reaction, with specific focus on optimising the green parameters and metrics of our methodology. Additionally, we directly compared our approach with previous catalyst-free methods, while providing a fast assembly of multiple compounds in parallel.