Mervat Mohammed Abdelkhalik

Enaminones as Building Blocks in Heterocyclic Syntheses: Reinvestigating the Product Structures of Enaminones with Malononitrile. A Novel Route to 6-Substituted-3-Oxo-2,3-Dihydropyridazine-4-Carboxylic Acids

The reported structures of reaction products of enaminones with malononitrile in ethanolic piperidine are revised. A novel route to 2,3-dihydropyridazine-4-carboxylic acids 4a-c via reactions of 2-cyano-5-(dimethylamino)-5-arylpenta-2,4-dienamides 8a-c with nitrous acid or with benzenediazonium chloride is reported. Compounds 8a-c are converted to 1,2-dihydropyridine-3-carboxylic acid and 1,2-dihydropyridine-3-carbonitrile derivatives upon reflux in EtOH/ HCl and in AcOH.

Synthesis of 5-Substituted 3-Amino-1H-Pyrazole-4-Carbonitriles as Precursors for Microwave Assisted Regiospecific Syntheses of Pyrazolo[1,5-a]Pyrimidines

A simple route to 3-oxoalkanonitrile 5, a precursor of the title compounds is described. Reaction of enaminones 2 with hydroxylamine hydrochloride in ethanol yielded aldoximes 3 that were converted readily into 5 in basic medium. This method has been successfully applied with a number of substrates and resulted in excellent yields of the products. Reacting 5 with trichloroacetonitrile afforded 3-amino-2-aroyl-4,4,4-trichloro-2-butenenitriles 6 that condensed with hydrazines to yield 3-amino-1H-pyrazole-4-carbonitrile derivatives 8. Substituted pyrazolo[1,5-a]pyridmidines have been prepared with regioselective condensation reactions of 8 with nonsymmetrical dielectrophiles. The structures of compounds obtained were deduced based on 1H-NMR, 1H-15N HMBC- measurements.

Studies with functionally substituted enamines: synthesis of 2-aroyl-3-dimethylamino-2-propenenitrile and their reactivity toward nitrogen nucleophiles

A facile and efficient synthesis of 2-substituted 3-dimethylamino-2-propenenitrile 4a-c is described. Reaction of 4a-c with hydrazine hydrate afforded 3-substituted-1H-4-pyrazole carbonitrile 9a-c. Compounds 4a-c reacted with 5-methyl-1H-pyrazol-3-amine to give 7-substituted pyrazolo[1,5-a]pyrimidine-6-carbonitrile 12a-c and 2-substituted 5-aminopyrazolo[1,5-a]pyrimidine 16a,b, and with 1H-benzo[d]imidazol-2-amine to give 3-substituted 2-aminobenzo[4,5]imidazo[1,2-a]pyrimidine 19a,b and 4-substituted benzo[4,5]imidazo[l,2-a]pyrimidine 3-carbonitrile 21c. The structures of compounds obtained were deduced based on 1 HNMR, HMBC- 15 N and NOE difference experiments.

Studies with condensed thiophenes: reactivity of condensed aminothiophenes toward carbon and nitrogen electrophiles

The condensed aminothiophenes 5–7a,b react with 1,4-naphthoquinone in refluxing ethanol to yield products of addition followed by hydrogen sulfide elimination in a Diels–Alder type reaction. When the reaction is carried out under microwave irradiation a dipolar addition occurred affording products of substitution at C-l. Compounds 5–7a,b coupled with aromatic diazonium salts to yield arylazo derivatives 15 and 16 where coupling occurred at C-1. The condensed aminothiophenes 5–7a,b reacted with dimethylformamide dimethylacetal to yield amidines 17–19.

Novel C-alkylation Reaction of Condensed Thiophenes with Enaminones, Enaminonitriles, Ethoxymethylene Malononitrile, Aryl Vinyl Ketones and ω-Nitrostyrenes

While the thienocoumarin 1 reacts with aryl vinyl ketones, ω-nitrostyrene and ethoxymethylene malononitrile to yield only C-1 alkylation products, it reacts with enaminones (3a–c) to yield either N-alkylated derivatives (4a–c) or a mixture of 4a–c and α,β-unsaturated ketones (9a–c), the former rearranged into the latter on prolonged boiling under reflux in 1,4-dioxane solution in the presence of diethylamine.