Brønsted acid catalyzed mechanochemical domino multicomponent reactions by employing liquid assisted grindstone chemistry

Abstract

Here, we have demonstrated a metal-free energy-efficient mechanochemical approach for expedient access to a diverse set of 2-amino-3-cyano-aryl/heteroaryl-4H-chromenes, tetrahydrospiro[chromene-3,4'-indoline], 2,2'-aryl/heteroarylmethylene-bis(3-hydroxy-5,5-dimethylcyclohex-2-enone) as well as tetrahydro-1H-xanthen-1-one by employing the reactivity of 5,5-dimethylcyclohexane-1,3-dione/cyclohexane-1,3-dione with TsOH⋅H₂O as Brønsted acid catalyst under water-assisted grinding conditions at ambient temperature. The ability to accomplish multiple C-C, C=C, C-O, and C-N bonds from readily available starting materials via a domino multicomponent strategy in the absence of metal-catalyst as well as volatile organic solvents with an immediate reduction in the cost of the transformation without necessitates complex operational procedures, features the significant highlights of this approach. The excellent yield of the products, broad functional group tolerances, easy set-up, column-free, scalable synthesis with ultralow catalyst loading, short reaction time, waste-free, ligand-free, and toxic-free, are other notable advantages of this approach. The greenness and sustainability of the protocol were also established by demonstrating several green metrics parameters.

Figure 1

Examples of 2-amino-4H-chromene (A–D) and tetraketones (E–F) with potential therapeutic and optoelectronic application.

Figure 2

Liquid assisted grinding accelerated one-pot Brønsted acid-catalyzed domino multicomponent reactions for the synthesis of diverse complex-fused and spiro-heterocycles.

Figure 3

Optimization of reaction conditions for the synthesis of 2-amino-3-cyano-4H-chromenes.

Figure 4

Screening of LAGs for the synthesis of 4a with different loading of the catalyst.

Figure 5

Synthesis of 2-amino-3-cyano-4H-chromenes 4 under the standard conditions.

Figure 6

Synthesis of spirooxindoles 6 under the standard conditions.

Figure 7

Model reaction for optimization studies.

Figure 8

Synthesis of 2,2′-aryl/heteroaryl-methylene-bis(3-hydroxy-cyclohex-2-enone) under the standard conditions.

Figure 9

Synthesis of tetrahydro-1H-xanthen-1-one under the standard conditions.

Figure 10

Preparative gram scale experiments for the synthesis of 4d, 6b, 7b, and 9b.

Figure 11

Plausible mechanism for the synthesis of 2-amino-tetrahydro-spiro[[chromene-4,3′-indoline]-3-carbonitrile 6 and 2,2′-aryl/heteroaryl-methylene-bis(3-hydroxy-cyclohex-2-enone) 7.

Figure 12

Radial pentagon diagram of green chemistry metrics calculation for the synthesis of 4g, 6d, 7b, and 9b by Brønsted acid catalyzed water-assisted grinding via a mortar and pestle at ambient conditions.