Catalyst free sequential one‐pot reaction for the synthesis of 3‐indole propanoates/propanoic acid/propanamides as antituberculosis agents

Abstract

A highly efficient catalyst free one pot four component synthesis of highly functionalized three‐substituted indole derivatives has been reported. Thus, sequential catalyst free condensation of readily available aldehydes with Meldrum's acid followed by Michael addition of indole resulting three carbon component condensed product and concurrent decarboxylation by the nucleophilic attack of ethanol/water/amines affords three‐indole propanoates/propanoic acid/propanamides in affordable yields. Further, synthesized compounds and standard drugs were evaluated against Mycobacterium tuberculosis H37Rv strain by Alamar blue assay method. Majority of the compounds exhibited the superior activity and specifically compound 4d has MIC 1.6 μg/ml, which is better than the reference drugs used.

The Molecular Diversity Scope of Meldrum's Acid in Multicomponent Reactions

“…[80] A possible mechanistic for ZnCl In 2021, Rajeev and co-workers designed the reaction of indoles 33, Meldrum's acid 1, and aldehydes 13 in DMF at room temperature followed by decarboxylation by EtOH/ H 2 O/amines as a nucleophile to afford the indole-3-propranoates/propanoic acid/propanamides 184 (Scheme 81). [81] Synthesis of indole and quinolone tricarboxamides 187-188 was accomplished via the MCR of 2-formylindole 185 or 2-chloro-3-formyl quinolones 186, isocyanides 20, amines 171, and Meldrum's acid 1 in CH 2 Cl 2 by Shiri and co-workers (Scheme 82). [82] A three-component reaction of 4-imino-1-phenyl imidazolidine-2-one 189 with aldehydes 13 and Meldrum's acid 1 was developed in EtOH in the presence of N-methylmorpholine by Krylov and co-workers to produce imidazo[4,5-b]pyridine-2,5(4H,6H)-diones 190, which was hydrolyzed to form 1-phenylhydantoins 191 (Scheme 83).…”

“…In 2021, Rajeev and co‐workers designed the reaction of indoles 33 , Meldrum's acid 1 , and aldehydes 13 in DMF at room temperature followed by decarboxylation by EtOH/H 2 O/amines as a nucleophile to afford the indole‐3‐propranoates/propanoic acid/propanamides 184 (Scheme 81). [81] …”

Frustrated Lewis pairs in two-dimensional borocarbonitride for the facile synthesis of 3-aminoimidazo[1,2-α]pyridines using TMSCN as an isonitrile substitute

“…23,24 Among metal-free catalysts, [25][26][27][28][29] boron (B)-based nonmetallic catalysts have attracted much attention in present research for various applications. [30][31][32][33][34][35][36] However, as an electron-deficient Lewis acid catalyst, the empty sp 2 orbital of boron can interact with the lone pair of electrons of nitrogen, which suppresses the catalytic activity of BCN. 37,38 Thus, to address the issue, we tried to explore the synergistic effect of the dual-site catalytic behavior of boron carbon nitride with unsaturated B and N atoms as an FLP for cyclization reactions.…”

Synthesis, Characterization and Evaluation of Some Meldrum's Acid Derivatives as Lubricant Additives

“…and heterocyclic compounds [13,14]. Meldrum's acid derivatives also exhibit a wide spectrum of biological activities; they act as antimicrobials [15][16][17], antituberculosis agents [18], antimalarial, and antioxidants [19]. In our work, 5-aminomethylene derivatives of Meldrum's acid were synthesized by multicomponent reactions (MCRs) of Meldrum's acid, triethyl orthoformate, and different substituted aromatic amines.…”