Meglumine-Promoted Eco-Compatible Pseudo-Three-Component Reaction for the Synthesis of 1,1-Dihomoarylmethane Scaffolds and Their Green Credentials

Abstract

A simple, straightforward, and energy-efficient greener route for the synthesis of a series of biologically interesting functionalized 1,1-dihomoarylmethane scaffolds has been developed in the presence of meglumine as an efficient and eco-friendly organo-catalyst via one-pot pseudo-three-component reaction at room temperature. Following this protocol, it is possible to synthesize 1,1-dihomoarylmethane scaffolds of an assortment of C–H activated acids such as dimedone, 1,3-cyclohexadione, 4-hydroxy-6-methyl-2-pyrone, 4-hydroxycoumarin, and 1-phenyl-3-methyl-pyrazolone. The salient features of the present green protocol are mild reaction conditions, good to excellent yields, operational simplicity, easy isolation of products, no cumbersome post treatment, high atom economy, and low E-factor. In addition, this chemistry portrays several green advantages including the reusability of reaction media and product scalability, which makes protocol sustainably efficient. Additionally, several control experiments such as protection of catalyst reactive site, D 2 O exchange, and 1 H NMR studies revealed possible pathways for meglumine-promoted reactions. Inspired by the natural physiological environment of 1,1-dihomoarylmethane scaffolds, we reconnoitered the biological profile of our compounds and synthesized compounds that were promising for their antiproliferative and antibacterial activities.

Facile Synthesis of Bis‐Coumarins Using [BCMIM][Cl] Zwitter Ionic Liquid and Their Binding with Bovine Serum Albumin

“…Numerous substituted aryl aldehydes possessing electrondonating moieties such as À OH, À CH 3 , À OCH 3 , À N(CH 3 ) 2 and electron-withdrawing groups like À Cl, À NO 2 , À F, À Br, À CN at different positions furnished the corresponding products 7 a-7 r in good to excellent yields (up to 94%) with minimum variation in time (Table 3, entries 1-18). Also, we have successfully carried out the reaction using a few heteroaryl aldehydes containing thiophenyl, 9-ethyl-carbazolyl, pyridyl and quinolinyl moieties (Table 3, entries [19][20][21][22][23]. Interestingly, among the aliphatic aldehydes, such as formaldehyde, acetaldehyde, propionaldehyde, and butyraldehyde, only formaldehyde demonstrated the ability to produce the desired product 7 x within a duration of 45 minutes.…”

“…Bis‐coumarin synthesis involves a Knoevenagel‐Michael addition, which is vital for generating C−C bonds in synthetic organic chemistry. A detailed review of the literature discloses the utilisation of numerous catalysts such as viologen‐based ionic porous organic polymer, [13] Amberlyst 15, [14] nanocatalysts, [15] Mohr's Salt, [16] ionic liquids, [15c,17] Aegle marmelos fruit ash, [18] carbon‐based acid catalyst, [2a] thiamine hydrochloride, [19] biosurfactants, [20] Meglumine, [21] trityl bromide, [22] Phosphotungstic acids, [23] melamine, [24] deep eutectic solvents (DES), [25] choline hydroxide, [26] and so on for the synthesis of biscoumarin. Although most of the stated methods are useful, yet holds several drawbacks, such as critical reaction conditions, expensive catalyst preparation process, low yields, longer reaction durations, and complex work‐up procedures.…”

Visible Light Mediated Organophotoredox Catalyzed Synthesis of Tetraketones Using Tertiary Amines as Alkyl Synthons

“…A large number of reports demonstrate the synthesis of tetraketones by direct condensation of aldehyde and cyclic-1,3-diketones using different homogeneous and heterogeneous catalysts. Several catalytic systems like Meglumine, 10 PPA-SiO 2 , 11 Pd-NP, 12 Na 2 CaP 2 O 7 , 13 and biofabricated ZnO-NPs 14 have been employed for the synthesis of tetraketones. Most of the previous works require harsh conditions like high temperature, toxic metal-based catalysts, and expensive as well as specially designed catalyst systems.…”

Exploring the synthetic potential of a g-C3N4·SO3H ionic liquid catalyst for one-pot synthesis of 1,1-dihomoarylmethane scaffolds via Knoevenagel–Michael reaction

“…1,1-Dihomoarylmethane scaffolds are well-versed with interesting physical and chemical properties, including high lipophilicity, good bioavailability, and the ability to form stable complexes with metal ions. 1 These properties make these scaffolds promising candidates for drug development, as they serve as a basis for the synthesis of bioactive molecules with potential therapeutic applications. 1–3 These scaffolds have been explored for a variety of pharmacological activities namely anti-inflammatory, anticancer, and antimicrobial effects, and have shown promising properties in several studies.…”

“…1 These properties make these scaffolds promising candidates for drug development, as they serve as a basis for the synthesis of bioactive molecules with potential therapeutic applications. 1–3 These scaffolds have been explored for a variety of pharmacological activities namely anti-inflammatory, anticancer, and antimicrobial effects, and have shown promising properties in several studies. 4–8 The compounds displayed in Fig.…”