Synthesis of 5-aryl-3,3′-bis-indolyl and bis-7-aza-indolyl methanone derivatives from 5-bromo-7-azaindoles via sequential methylenation using microwave irradiation, CAN oxidation, and Suzuki coupling reactions

Abstract

A catalyst-free methylenation of 7-aza indoles under MW irradiation and CAN oxidation of methylenated products to the respective ketones are achieved. Plausible mechanisms of the reactions and photophysical properties of the products are described.

I2/CAN as a Mild and Efficient Reagent for Oxidative Csp3‐Csp2 Cleavage of 3,3′‐Bis‐7‐azaindolylmethane: A Rapid One‐Pot Access to 3‐Formyl and 3‐Iodo‐7‐azaindoles

“…[22] Previously, when the 3,3'-bis-7-azaindolylmethane 2 a was treated with CAN yielded only the methylene oxidation product 3,3'-bis-7-azaindolylmethone. [24] On the other hand, conducting the above reaction with CAN and molecular I 2 in acetonitrile at RT produced oxidative CÀ C cleavage products 3 a and 4 a in excellent combined yield (Scheme 1). To optimize the condition, parameters such as the mole equivalent of reagent, solvent, temperature, and reaction time were considered (Table 1).…”

“…The starting materials 2 a – 2 l were prepared as per the previous report [22] . Previously, when the 3,3′‐bis‐7‐azaindolylmethane 2 a was treated with CAN yielded only the methylene oxidation product 3,3′‐bis‐7‐azaindolylmethone [24] . On the other hand, conducting the above reaction with CAN and molecular I 2 in acetonitrile at RT produced oxidative C−C cleavage products 3 a and 4 a in excellent combined yield (Scheme 1).…”

“…Recently, we have reported the synthesis of 5‐aryl‐3,3′‐bis‐7‐azaindolylmethanone derivatives via sequential microwave irradiated methylation followed by CAN oxidation (Scheme 1). [24] Notably, only oxidation occurred, and no oxidative cleavage product was observed [22] . Continuing our work on CAN as a one‐electron oxidant, a new method has been developed for synthesizing 7‐azaindole‐3‐ carboxaldehyde and 3‐iodo‐7‐azaindoles via oxidative cleavage of 3,3′‐bis‐7‐azaindolylmethane when CAN and I 2 combination emerged as a mild and powerful reagent system (Scheme 1).…”

The Application of Microwaves, Ultrasounds, and Their Combination in the Synthesis of Nitrogen-Containing Bicyclic Heterocycles

“…In a recent paper, Pavithra et al [ 118 ] developed a green method to synthesize methylenated derivatives of 7-azaindoles ( 79a – g ) under MW irradiation with an excellent yield. N-substituted-7-azaindoles, aqueous formaldehyde (37%) and montmorillonite K-10 50% w / w clay (used as a solid acid catalyst) were microwave-irradiated at 100 °C for 5 min ( Scheme 62 ).…”

“…For the 3-bromo-substituted compound, the methylenation reaction took place in the C-5 position to afford bis(3-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridin-5 yl) methane (79g). In a recent paper, Pavithra et al [118] developed a green method to synthesize methylenated derivatives of 7-azaindoles (79a-g) under MW irradiation with an excellent yield. N-substituted-7-azaindoles, aqueous formaldehyde (37%) and montmorillonite K-10 50% w/w clay (used as a solid acid catalyst) were microwave-irradiated at 100 • C for 5 min (Scheme 62).…”