RESUMO
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.
RESUMO
The synthesis of indoles and their derivatives, more specifically bis(indolyl)methanes (BIMs), has been an area of great interest in organic chemistry, since these compounds exhibit a range of interesting biological and pharmacological properties. BIMs are naturally found in cruciferous vegetables and have been shown to be effective antifungal, antibacterial, anti-inflammatory, and even anticancer agents. Traditionally, the synthesis of BIMs has been achieved upon the acidic condensation of an aldehyde with indole, utilizing a variety of protic or Lewis acids. However, due to the increased environmental awareness of our society, the focus has shifted towards the development of greener synthetic technologies, like photocatalysis, organocatalysis, the use of nanocatalysts, microwave irradiation, ball milling, continuous flow, and many more. Thus, in this review, we summarize the medicinal properties of BIMs and the developed BIM synthetic protocols, utilizing the reaction between aldehydes with indoles, while focusing on the more environmentally friendly methods developed over the years.