l-Proline catalyzed multicomponent one-pot synthesis of gem-diheteroarylmethane derivatives using facile grinding operation under solvent-free conditions at room temperature

Abstract

An efficient and straightforward L-proline catalyzed one-pot synthesis of a series of biologically relevant gem-(b-dicarbonyl)arylmethanes has been developed via a three-component reaction between indoles, aldehydes and C-H activated acids by grinding them together under solvent-free conditions at room temperature. Mild reaction conditions, high atom-economy, good yields, and eco-friendliness are some of the salient features of the present protocol.

Design of Organic Transformations at Ambient Conditions: Our Sincere Efforts to the Cause of Green Chemistry Practice

“…Recently, we reported a convenient, clean and highly efficient protocol for the synthesis of gem ‐(β‐dicarbonyl)arylmethanes ( 61 ) via a multicomponent reaction simply by grinding the mixture of indoles ( 14 ), C–H activated acids (4‐hydroxycoumarin, 4‐hydroxy‐6‐methyl‐2 H ‐pyran‐2‐one, dimedone, N , N ‐dimethylbarbituric acid, Meldrum's acid) ( 29 ) and aldehydes ( 31 ) in the absence of solvent under l ‐proline catalysis at room temperature (Scheme ) . l ‐Proline is a very useful and environmentally friendly organocatalyst to effect this useful transformation in a facile manner.…”

“…l ‐Proline is a very useful and environmentally friendly organocatalyst to effect this useful transformation in a facile manner. In addition to other notable outcomes such as mild and solvent‐free reaction conditions, operational simplicity and good yields, the major advantage of our present protocol is improved conditions for the synthesis of gem ‐(β‐dicarbonyl)arylmethane derivatives instead of the formation of the usual bis‐indoles …”

“…We have suggested a plausible mechanism for the l ‐proline‐catalyzed synthesis of the gem ‐(β‐dicarbonyl)arylmethanes 61 (Scheme ) . The initially formed iminium salt ( 62 ), arising from the reaction between aldehyde ( 31 ) and l ‐proline, undergoes a Mannich reaction with the C–H activated acid ( 29 ) to generate intermediate 64 , which immediately takes part in Michael addition with the indole moiety ( 14 ) to afford the desired product 61 .…”

Azo Dyes: Preparation Via Environmentally Benign Way

“…Grindstone Chemistry opened a research window where organic compounds could be constructed under ecofriendly conditions [27][28][29][30][31][32][33][34]. Moreover, the green organic synthesis via grinding at room temperature represents a benign way towards the green and sustainable context of Chemistry [35][36][37].…”

Environmentally green approach to synthesize azo dyes based on 1-naphthol using nano BF3·SiO2under solvent-free conditions

“…At the beginning of the new century, synthesis of organic compounds using grinding technique under solvent-free conditions (1)(2)(3)(4)(5)(6)(7)(8) has received much attention, as it provides manipulative simplicity, greater selectivity, easier workup, lesser reaction times, and higher yields which match with the green chemistry protocol. On the other side, more attention has been directed toward the application of solid acids in organic synthesis because such reagents not only simplify purification processes but also help prevent release of reaction residues into the environment (9,10).…”