Reusable Pd/TiO₂ nanocatalyst for regiospecific sonochemical synthesis of indolizine-based chromone isosters via...

A facile synthetic approach was established for producing high yields of novel chromone derivatives with an indolizine moiety at the C-3 position of the chromone framework. This was accomplished using a multicomponent reaction of chromone analogues with a terminal alkyne motif at C-3, pyridine-2-carboxyaldehyde, and dimethylamine, catalyzed by a Pd/TiO₂ nanocomposite and 1,4-diaza-bicyclo[2.2.2]octane (DABCO) under ultrasonic irradiation in water. The Pd/TiO₂ nanocatalyst revealed remarkable catalytic activity with considerably higher yields of the obtained products. Optimization experiments revealed that no product developed in the absence of the catalyst, which emphasizes its critical function. Several reaction conditions were tested, and the Pd/TiO₂@DABCO catalytic system under ultrasonic irradiation effectively generated the chromone-indolizine conjugates in 3 h. The synthesized derivatives were readily isolated using a simple work-up process. Furthermore, the Pd/TiO₂ nanocatalyst was recoverable and reusable with a slight loss of activity. A feasible reaction mechanism was provided, and the anticancer properties of the produced compounds were studied. The anticancer study demonstrated that the presence of morpholine and piperazine groups in compounds 4e and 4f significantly enhances their anticancer activity. Introducing nitrogen or oxygen atoms into the heterocyclic substituents notably improves this activity.