Functionally substituted arylhydrazones as building blocks in heterocyclic synthesis: routes to pyridazines and pyridazinoquinazolines

Abstract

The arylhydrazones 2a-c were prepared via coupling acetoacetic acid with aromatic diazonium salts. These arylhydrazones condensed with ethyl cyanoacetate and malononitrile to yield the acyclic product 4 which cyclised only after long reflux into the pyridazines 5 or 6,11-dihydropyridazino[1,6-a]quinazoline-4-carbonitrile 6 depending on the nature of substituent on the aryl moiety. Compound 2b and 2c reacted with α,β-unsaturatednitriles 7 to yield the pyridazinoquinazoline 13 and 16 respectively.

Hantzsch‐like synthesis of isoquinolino[2,1‐a]quinoline‐12‐carbonitrile incorporating aryl or heteroaryl moieties at C‐13

“…Given the importance of the azachrysene moiety and as a part of an ongoing research program on C-C bond formation reactions [67][68][69][70][71][72] that include multicomponent [73], Michael addition [74][75][76][77][78], and Hantzsch [79] reactions we report herein the results of our investigations concerning the reactivity patterns of 2-(isoquinolin-1-yl)acetonitrile toward dimedone and the substituted aldehydes, or heteroaldehydes. The one-pot, three-component reaction of 2-(isoquinolin-1-yl)acetonitrile 1 with dimedone 2 and the appropriate aldehydes 3a-d in acetic acid at reflux afforded the corresponding the tetracyclic 13-arylisoquinolino[2,1-a]quinoline-12-carbonitriles 4a-d (Scheme 1).…”

Synthesis of Novel Diphenyl Ether-Based Bis-Heterocycles as Novel Hybrid Molecules via Michael and Other Cyclocondensation Reactions

“…Hybridization may lead to the development of anticancer drugs that are both safer and more potent than those now available on the market. , Furthermore, due to their extraordinary lipophilicity, hydrophobicity, ability to penetrate cell walls, and resistance to degradation, diaryl ether substructures are important in various medications and recently discovered agrochemicals. , They have been discovered to have a variety of bioactivities, including antiviral, anticancer, antibacterial, β-glucuronidase enzyme inhibitory action, radical scavenging, cytotoxicity, antitubercular, and antitubulin activity. − Bis-heterocyclic compounds are among the popular scaffolds frequently found in drugs and pharmaceutically relevant substances because combining different heterocycle systems produces novel hybrid molecules that may be more biologically active than their separate components. There have been several reports of the antibacterial, anticancer, antiallergic, and other disease-fighting effects of bis-heterocycles. , Encouraged by the findings above and as part of our ongoing research interest in the synthesis of heterocycles and their bis-heterocyclic analogues, − we present the design and synthesis of novel hybrid molecules composed of diphenyl ether linked to various heterocyclic systems. In this context, we recently investigated the Hantzsch reaction for the manufacture of bis-dihydropyridine and their corresponding fused derivatives based on diphenyl ether, and their antibacterial activity against various bacterial strains was evaluated .…”

Regioselective synthesis of fused pyrimidines and quinazolines linked to Phenoxy‐N‐arylacetamide moieties as novel hybrid molecules via Biginelli‐like reaction

“…These compounds hold a unique place in the field of biological and medicinal chemistry, inspiring researchers to create novel motifs with modified structures [26,27]. In the framework of our current research interest in carboncarbon bond-forming reactions [28][29][30][31][32][33][34][35] including Hantzsch reactions [15,[36][37][38], Michael addition [34,36,[39][40][41][42][43], Biginelli-like reaction [10,11,44,45] as well as on the synthesis of bis(heterocycles) [8,36,[46][47][48][49][50][51]. We report herein the regioselective synthesis of fused pyrimidines and quinazolines linked to phenoxy-Narylacetamide moieties as novel hybrid molecules via Biginelli-like reaction using aldehyde component (2-(4-formylphenoxy)-N-arylacetamides), nitrogen binucleophiles (3-amino-4H-1,2,4-triazole, or 2-amino-1Hbenzo [d]imidazole), and as the active methylene reagent (β-diketone or β-ketoester).…”