A Practical Green Visit to the Functionalized [1,2,4]Triazolo[5,1‐b]quinazolin‐8(4H)one Scaffolds Using the Group‐Assisted Purification (GAP) Chemistry and Their Pharmacological Testing

Abstract

Herein, we established a straightforward synthetic route for biological relevant [1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)one scaffolds using the group‐assisted purification (GAP) chemistry via one‐pot and three component reaction of 3‐Amino‐5‐methylthio‐1H‐1,2,4‐triazole (1), Aryl aldehyde(2 a–g), and 1,3‐cyclodione (3 a–b) using L‐proline and aqueous ethanol (1:1, v/v) as green catalyst and reaction media respectively. This work shows some key features such as practical low Environment factor (E‐factor) values, excellent atom economy, reaction mass efficiency, mild reaction condition, metal‐free synthesis, and no use of column chromatography. In preliminary biological screening, the compounds, 2‐(methylthio)‐9‐(4‐nitrophenyl)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 i) and 6,6‐dimethyl‐2‐(methylthio)‐9‐(pyridin‐4‐yl)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 l) were found most potent against Gram‐negative bacteria (E. coli) than the standard drugs ampicillin and chloramphenicol. Moreover, compounds 2‐(methylthio)‐9‐phenyl‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 a) and 9‐(4‐methoxyphenyl)‐6,6‐dimethyl‐2‐(methylthio)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 f) exhibited excellent potency in comparison with the standard drugs ampicillin, chloramphenicol, and ciprofloxacin against Gram‐positive bacteria (S. aeruginosa and S. pneumoniae). In antifungal screening compounds, 9‐(4‐methoxyphenyl)‐2‐(methylthio)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 e) and 2‐(methylthio)‐9‐(4‐nitrophenyl)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 i) efficiently inhibited C. albicans fungi strain than that of standard drug griseofulvin. Noteworthy compounds 6,6‐dimethyl‐2‐(methylthio)‐9‐phenyl‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 b), 9‐(4‐chlorophenyl)‐6,6‐dimethyl‐2‐(methylthio)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 d), and 2‐(methylthio)‐9‐(pyridin‐4‐yl)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 k) were exhibited better potency against M. Tuberculosis.

Hypervalent Iodine (III) Catalyzed Regio- and Diastereoselective Aminochlorination of Tailored Electron Deficient Olefins via GAP Chemistry

“…Recently, our group has established a concept called GAP chemistry for greener synthesis where functionalities of special interest are incorporated into the substrates to facilitate the purification of crude products based on solubility without column chromatography or recrystallization. The pure products can be readily obtained simply by washing the crude mixture with common solvents or cosolvents (Wang et al, 2013 ; Chennapuram et al, 2014 ; Dommaraju and Prajapati, 2015 ; Seifert et al, 2016 ; Patel et al, 2019 ). Indeed, GAP chemistry would be the first concept consisting of both chemical aspects (reagent and reaction) and physical aspects (separation and purification).…”

Ecofriendly and Facile One‐Pot Multicomponent Synthesis of 5‐Phenyl‐5,10‐dihydropyrido[2,3‐d : 6,5‐d′]dipyrimidine‐2,4,6,8(1H,3H,7H,9H)‐tetraone Derivatives Catalyzed by CuII Immobilized on Functionalized Magnetic Mesoporous MCM‐41 (Fe3O4@MCM‐41‐GPTMS‐Gu‐CuII)

“…1,4‐Dihydropyridines (as nitrogen‐containing heterocycles) with a structure analogous to nicotinamide adenine dinucleotide (NAD) coenzyme have attracted considerable interest due to their different biological and medicinal applications [7,11–21] . They have increasingly‐popular worldwide applications such as antitumor, antisclerotic, antidiabetic, calcium channel blockers, anti‐inflammatory, and analgesic [22] .…”

Impact of an aryl bulky group on a one-pot reaction of aldehyde with malononitrile and N-substituted 2-cyanoacetamide

“…We performed this reaction via a one-pot strategy, which has been reported in many reactions, [5][6][7][8] because it has certain advantages based on green chemistry concepts such as the reduction of chemical waste, workup procedure, purication process, and time, which make the reaction greener. 9 In the literature, the one-pot reaction of aryl aldehyde, malononitrile and N-substituted 2-cyanoacetamide is mostly reported to use piperidine [10][11][12] as a catalyst.…”

“…Many ionic liquids or salts have been reported as reusable catalysts without the loss of their catalytic activities. 8,[15][16][17][18][19] Herein, we performed the one-pot reaction of aryl aldehyde, malononitrile and a N-benzyl-2-cyanoacetamide derivative using piperidinium acetate as a reusable catalyst. The reactants used in this reaction and other produced impurities are more soluble in diethyl ether or methanol, whereas the product is less soluble in diethyl ether or methanol.…”