Sequential Knoevenagel Condensation/Cyclization for the Synthesis of Indene and Benzofulvene Derivatives

Abstract

Sequential Knoevenagel condensation/cyclization leading to indene and benzofulvene derivatives has been developed. The reaction of 2-(1-phenylvinyl)benzaldehyde with malonates gave benzylidene malonates, cyclized indenes, and dehydrogenated benzofulvenes. The product selectivity depends on the reaction conditions. The reaction with piperidine, AcOH in benzene at 80 °C for 1.5 h gave a benzylidene malonate in 75% yield as a major product. The reactions with piperidine, AcOH in benzene at 80 °C for 17 h and with TiCl 4 -pyridine at room temperature gave an indene derivative in 56 and 79% yields, respectively, as a major product. The reaction with TiCl 4 -Et 3 N gave a benzofulvene in 40% yield selectively. Indene was transformed to a benzofulvene derivative using the reagents TiCl 4 -Et 3 N and 2,3-dichloro-5,6dicyano-1,4-benzoquinone (DDQ). The reaction of variously substituted aryl derivatives with dimethyl malonate gave indene and benzofulvene derivatives. The reactions of 2-(1-phenylvinyl)benzaldehyde with Meldrum's acid or malononitrile also gave cyclized compounds in the suitable sequential or stepwise conditions. Furthermore, the reaction of 2-arylbenzaldehydes has been investigated. The limitation and scope have been described. The reaction mechanism of the cyclization steps has been examined by DFT calculations.

Novel Pyridinium Based Ionic Liquid Promoter for Aqueous Knoevenagel Condensation: Green and Efficient Synthesis of New Derivatives with Their Anticancer Evaluation

“…Moreover, PPARγ, activated by natural and synthetic ligands, is a promising option for preventing and treating cancer. Knoevenagel condensation is a substantial reaction for generating carbon-carbon bonds via the interaction between active methylene and carbonyl derivatives [23,24]. The α,β-unsaturated carbonyl molecules created by the Knoevenagel reaction could be utilized to design essential precursors for a variety of high-value substances including pharmaceuticals, cosmetics, natural products, fine chemicals, and multifunction polymers [25,26].…”