Fathy M. Abdelrazek

Studies on alkylheteroaromatic compounds: the reactivity of alkyl polyfunctionally substituted azines towards electrophilic reagents

Abstract Several new alkylpyridine, pyridazine and pyrimidine derivatives are synthesized from acyclic intermediates. The reactivity of these alkylazines towards aromatic aldehydes and arylidenemalononitrile is reported. New synthesis for substituted phthalazines cinnolines and quinazolines could be achieved.

The reaction of ethyl benzoylacetate with malononitrile: a novel synthesis of some pyridazine, pyridazino[2,3-a]quinazoline and pyrrole derivatives

Abstract Ethyl benzoylacetate undergoes Claisen condensation reaction with malononitrile to afford 2-cyano-5-phenyl-3,5-dioxopentanonitrile which could be cyclized into 2-aminopyran and coupled with diazonium salts to afford azo derivatives. These azo derivatives and those of ethyl benzoylacetate could be cyclized into 4-oxo-, 6-oxo- and 6-iminopyridazines and pyridazino[2,3- a ]quinazolines, respectively. The 6-iminopyridazines could be transformed into the 6-oxopyridazines. The imino- and oxopyridazines could be transformed into pyrrole derivatives.

Novel Synthesis of N-Arylpyrrole, Pyrrolo[1,2-a]quinazoline, and Pyrrolo[3,4-d]pyridazine Derivatives

Abstract Phenacyl-malononitrile derivatives 1a,b react with dimethyl formamide dimethyl acetal (DMFDMA) in refluxing toluene to afford the enaminones 2a,b respectively. Compounds 2a and 2b react with the aromatic amines (aniline, p-toluidine, p-anisidine) in refluxing ethanol to afford the pyrroles 4a–f and with anthranilonitrile and methyl anthranilate to afford the pyrrolo[1,2-a]quinazolines 5a,b and 6a,b respectively. The pyrrole derivatives 4a–f react with hydrazine hydrate and phenyl hydrazine in refluxing ethanol to afford the pyrrolo[3,4-d] pyridazine derivatives 7a–f and 8a–f respectively.

Heterocyclic Synthesis with Nitriles: Synthesis of Some New Thiophene, Pyridazine, Oxazine, Thiopyran, Pyrrole, and Pyrrolo[1,2‐b]pyridazine Derivatives

Abstract 2‐Phenyl‐1,1,3‐tricyanopropene[α‐(cyanomethyl)benzylidene‐malononitrile] undergoes bromination with N‐bromosuccinimide (NBS) to afford 2‐phenyl‐1,1,3‐tricyano‐3‐bromopropene: [α(bromocyanomethyl)benzylidene malononitrile]. This bromo derivative undergoes reactions with sodium hydrogen sulfide, hydrazine hydrate, phenyl hydrazine, hydroxylamine hydrochloride, ethyl thioglycollate, urea derivatives, and cyanacetohydrazide to afford thiophene, 4H‐pyridazines, 4H‐oxazine and 4H‐thiopyran, N‐substituted pyrrole, and pyrrolo[1,2‐b]pyridazine derivatives respectively. * This work has been presented at the 9th Ibn Sina international conference on pure and applied heterocyclic chemistry, held 11–14 December, 2004 at Sharm El Sheikh, Egypt, and organized by the Egyptian Society of Heterocyclic Chemistry, Conference Book p. 194.

Further studies on the reaction of ethyl benzoylacetate with malononitrile: synthesis of some novel pyridine and pyridazine derivatives

Abstract 2-Cyano-5-phenyl-3,5-dioxopentanonitrile undergoes alcoholysis followed by Knoevenagel condensation to afford ethyl 4,4-dicyano-3-phenyl-3-butenoate, a thermo dynamically controlled product, which undergoes cyclization in acid medium to afford 2,6-dihydroxy-4-phenylnicotinonitrile. Some azo derivatives of nicotinonitriles and of 2-aminopyran are described. 5-Arylazo-2-aminopyrans are transformed by acid treatment into pyridazine derivatives, whereas without the arylazo substituent pyridines are obtained.

Synthesis of Some New N‐Substituted Pyrroles, Pyrrolo[1,2‐a]quinazoline, and Diaza‐as‐indacene Derivatives

Abstract 2‐Phenyl‐1,1,3‐tricyano‐3‐bromopropene 1 reacts with the aromatic amines 2a–f and 6a–c to afford the N‐substituted pyrroles 4a–d, the pyrrolo[1,2‐a]quinazoline derivatives 5a, b, and the diaza‐as‐indacene derivatives 7a–c and 8a–c, presumably via elimination of hydrogen bromide followed by cyclization of the formed acyclic intermediates. All structures are confirmed by analytical and spectral data.

Novel Synthesis of Some New Pyridazine and Pyridazino[4,5-d]pyridazine Derivatives

Abstract Phenacyl-malononitrile derivatives 1a and b react with dimethylformamide dimethylacetal (DMFDMA) in refluxing toluene to afford the enaminones 2a and b respectively. Compounds 2a and 2b react with the hydrazine hydrate 3a and phenyl hydrazine 3b in refluxing ethanol to afford the pyridazine derivatives 5a–d, presumably via the intermediates 4. Compounds 5a–d, react with hydrazine hydrate 3a to afford the pyridazino[4,5-d]pyridazines 6a–d respectively. The pyridazines 5a and b and the pyridazino[4,5-d] pyridazines 6a and b could be oxidized into the full aromatic systems 7a and b and 8a and b respectively. Compounds 7a and b react also with hydrazine hydrate 3a to afford 8a and b respectively.

Reaction of Anthranilonitrile with Some Active Methylene Reagents: Synthesis of Some New Quinoline and Quinazoline Derivatives

Abstract Anthranilonitrile (1) reacts with ethyl cyanoacetate and its dimer, malononitrile, cyanothioacetamide and N‐arylidene cyanoacetohydrazides 12a–c to afford pyrano[2,3‐b]quinoline 5, cyanomethyl‐quinazoline 10, pyrazolo[2,3‐a]quinazoline 12 and triazolo[4,3‐a]‐quinoline derivatives 16a–c, respectively. Structures and conceivable mechanisms are discussed.

HETEROCYCLIC SYNTHESIS WITH NITRILES: SYNTHESIS OF SOME NOVEL PYRROLE, PYRROLO[1,2-a]QUINAZOLINE AND PYRROLO[1,2-a]TRIAZINE DERIVATIVES

Abstract α-(Bromothiocyanatomethyl) benzylidenemalononitrile 1 undergoes base catalysed reactions with primary aromatic amines, anthranilic acid derivatives and urea derivatives in refluxing ethanol to afford N-arylpyrrole-3-carbonitrile, pyrrolo[1,2-a]quinazolin-5-imine, pyrrolo[1,2-a]quinazolin-5-one and pyrrolo[1,2-a]triazine derivatives respectively.

SYNTHESIS OF SOME NOVEL THIAZOLE, THIADIAZOLE AND 1,4-PHENYLENE-BIS-THIAZOLE DERIVATIVES AS POTENT ANTITUMOR AGENTS

A novel series of 2-ethylidenehydrazono-5-arylazothiazoles 5a-h and 2-ethylidenehydrazono-5-arylazothiazolones 9a-d were prepared by cyclocondensation of hydrazonyl halides 3a-h and 7a-d with ethylidenethiosemicarbazide 2. In addition, reaction of 2 with N-phenylcarbohydrazonyl chloride (14), afforded 1,3,4-thiadiazole derivative 17 as the end product. Moreover, the thiosemicarbazide derivative 2 was reacted with various bromoacetyl compounds 19a-d and 1,1’-(1,4-phenylene)bis(2-bromoethanone) (21) furnished the respective thiazole derivatives 20a-d and 1,4-phenylene-bisthiazole derivative 22. The structures of the newly synthesized compounds were established on the basis of spectroscopic evidences and their alternative syntheses. The newly synthesized compounds were evaluated for their antitumor activities against hepatocellular carcinoma (HepG2) cell line and the results revealed promising activities of compounds 5h, 5d, 5g, 5f and 5e with IC50 equal 2.23 ± 0.28, 2.48 ± 0.34, 2.49 ± 0.24, 4.03 ± 0.11, and 5.32 ± 0.27 μM, respectively. Functionalized thiazole derivatives have received much attention due to their diverse biological activities such as antimicrobial,1 antiviral,2 cytotoxic and antitumor,3-6 and HIV-protease inhibitory agents.7 Compounds incorporating two thiazole rings either directly connected as in bisthiazoles or through a linker unit as in bisthiazolyl compounds, show pronounced biological activity as DNA replication inhibitors in the tumor cells8 and HIV-protease inhibitors.7-9 Pyridine deivatives also play a key role catalyzing both biological and chemical systems. In many enzymes of living organisms it is the prosthetic pyridine nucleotide (NADP) that is involved in various 954 HETEROCYCLES, Vol. 92, No. 5, 2016