Microwave-assisted efficient one-pot synthesis of N 2-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines.

An efficient one-pot synthesis of N 2-(tetrazol-5-yl)-6-aryl/heteroaryl-1,3,5-triazine-2,4-diamine derivatives was developed by reacting 5-amino-1,2,3,4-tetrazole with aromatic aldehydes and cyanamide in pyridine under controlled microwave heating with high yields. X-ray crystallography confirmed the structure of the obtained products.

Densely functionalized cinnolines: Controlled microwave-assisted facile one-pot multi-component synthesis and in vitro anticancer activity via apoptosis induction.

There is an urging continuous need for novel anti-cancer agents due to persistent chemoresistance. Herein, newly synthesized cinnolines are evaluated for their possible anticancer activities and suggested mechanisms. In the current study, a simple and efficient synthesis of densely functionalized cinnolines has been developed that relied on multi-component reaction of ethyl 5-cyano-4-methyl-1-aryl-6-oxo-1,6-dihydropyridazine-3-carboxylates with aromatic aldehydes and nitromethane in dioxane/pipridine under controlled microwave heating. Selected cinnolines (4a-c, e, h, j-n, q-v) were tested for possible anticancer activity using in vitro one dose assay at National Cancer institute, USA. Only cinnoline 4b stood out as the most potent cinnoline derivative (mean GI%=26.33) with broad-spectrum antitumor activity against the most tested cancer cell lines from all subpanels. The target cinnoline 4b emerged as the most active derivative against both leukemia RPMI-8226 and melanoma LOX IMVI cell lines (GI% = 106.06 and 82.1) respectively, with IC50 values equal to 17.12 ± 1.31 and 12.32 ± 0.75 µg/mL, which are comparable to those of staurosporin; 24.97 ± 1.47 and 8.45 ± 0.42 µg/mL, respectively. Cinnoline 4b influenced cell cycle distribution causing pre-G1 apoptosis and cell growth arrest at G2/M phase. It also induced apoptosis in both cell lines as manifested by significant increase in the percent of annexin V-FITC positive apoptotic cells in leukemia RPMI-8226 cells (from 1.09% to 12.47%) and melanoma LOX IMVI (from 1.32% to 19.05%). In addition, it showed lower expression levels of anti-apoptotic Bcl-2 protein, and higher expression levels of pro-apoptotic proteins; Bax, p53, cytochrome c, caspases 3 and 9. CONCLUSION: Induction of mitochondrial intrinsic pathway of apoptosis is a possible mechanism by which cinnoline 4b may confer its anticancer activity.

Aroyl and acyl cyanides as orthogonal protecting groups or as building blocks for the synthesis of heterocycles.

α-Cyanoketones represent a synthetically attractive scaffold possessing bifunctional reactivity which enabled synthesis of a diversity of products. This involves reaction of nucleophiles with electrophilic carbonyl carbon performing an efficient and regioselective way to acylation reaction, cycloaddition of activated cyano function with dipolarophiles, metal-catalyzed cross-dehydrogenative coupling carbocyanation across C-C multiple bonds as well as hydrocyanation. This review provides the recent developments in the chemistry of α-cyanoketones which will be beneficial for researchers and scientists in such field.

A Novel Synthesis of Highly Functionalized Pyridines by a One-Pot, Three-Component Tandem Reaction of Aldehydes, Malononitrile and N-Alkyl-2-cyanoacetamides under Microwave Irradiation.

A convenient, fast and environmentally benign procedure for the synthesis of a new series of highly functionalized N-alkylated pyridines as privileged medicinal scaffolds was developed via a unique three-component reaction of easily available aromatic as well as heteroaromatic aldehydes, N-alkyl-2-cyanoacetamides and malononitrile in EtOH in the presence of K2CO3 as a base promoter under microwave irradiation. The presented tandem process is presumed to proceed via Knoevenagel condensation, Michael addition, intramolecular cyclization, autoxidation and subsequent aromatization. Particularly valuable features of this protocol, including high product yields, mild conditions, atom-efficiency, simple execution, short reaction times and easy purification make it a highly efficient and promising synthetic strategy to prepare substituted pyridine nuclei. The proposed mechanism of this novel one-pot reaction and structure elucidation of the products are discussed.

Recent developments in utility of green multi-component reactions for the efficient synthesis of polysubstituted pyrans, thiopyrans, pyridines, and pyrazoles.

Developments made since 2010 in the utilization of multi-component reactions as green efficient methodologies for the synthesis of polysubstituted pyrans, thiopyrans, pyridines, and pyrazoles are reviewed and the mechanisms of these processes are discussed. Reference is made to classical older synthetic methods developed earlier in our laboratories.

Synthesis and spectroscopic properties of new azo dyes derived from 3-ethylthio-5-cyanomethyl-4-phenyl-1,2,4-triazole.

New 1,2,4-triazole colorants were obtained, in high yields, by coupling 3-ethylthio-5-cyanomethyl-4-phenyl-1,2,4-triazole (1) with diazotized aniline derivatives 2, 4 and 6. The azo dyes prepared in this work may exist in three tautomeric forms. We found that the tautomerism is influenced mainly by the nature of substituent at the para position of the aniline coupling component. This tautomerisation was observed in the NMR spectra of the dyes. The dyes were characterized by IR, ¹H-NMR, ¹³C-NMR and MS spectroscopic techniques.

Green and highly efficient synthesis of 2-arylbenzothiazoles using glycerol without catalyst at ambient temperature.

A one-pot and clean synthesis of 2-arylbenzothiazoles via the ambient temperature reaction of 2-aminothiophenols and aromatic aldehydes without catalyst in glycerol as a green solvent has been reported.

Novel 1,2,4-triazolo[1,5-a]pyridines and their fused ring systems attenuate oxidative stress and prolong lifespan of Caenorhabiditis elegans.

In this paper we report the synthesis of some novel 1,2,4-triazolo[1,5-a]pyridine and azolotriazolopyridine ring systems. The products were screened for various types of activity like antibacterial, antifungal, and antioxidative activity. Compound 13 was found to pose an antioxidative activity. In addition, this compound was found to extend the life span of Caenorhabiditis elegans under standard laboratory conditions and reduces both heat and chemical induced oxidative stress in C. elegans in a dose-dependent manner. Furthermore, treatment of worms with compound 13 was found to significantly attenuate the formation of advanced glycation end products and malondialdehyde in a dose-dependent manner.

Regioselectivity in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal under controlled microwave heating.

The multicomponent reaction of 5-aminopyrazole derivatives with cyclic 1,3-dicarbonyl compounds and dimethylformamide dimethylacetal (DMFDMA) in DMF at 150 °C under controlled microwave heating afforded regioselectively 8,9-dihydropyrazolo[1,5-a]quinazolin-6(7H)-ones 6 rather than the corresponding dihydropyrazolo[5,1-b]quinazolin-8(5H)-ones 4.

Cerium (IV) ammonium nitrate (CAN) catalyzed one-pot synthesis of 2-arylbenzothiazoles.

A one-pot synthesis of 2-arylbenzothiazoles from the reaction of 2-aminothiophenol and aromatic aldehydes catalysed by cerium (IV) ammonium nitrate (CAN) is reported.