Manal M. El-Shahawi

Synthesis of Novel Indeno[1,2-c]isoquinoline Derivatives

Indeno[1,2-c]isochromene was prepared using the readily obtainable starting materials via the condensation of dimethyl homophthalate with 3,4-dimethoxybenzaldehyde in the presence of sodium methoxide in absolute methanol followed by saponification and cyclization with concentrated sulfuric acid at 0°C. The proclivity of cyclized product for undergoing nucleophilic addition has been tested by reaction with nitrogen nucleophiles. Structural assignments are based on spectroscopic data (infrared, 1H NMR, 13C NMR, and mass spectra) and confirmed by the single-crystal x-ray molecular structure (2 and 3).

Synthesis and Antifungal Activity of Novel Quinazolin-4(3H)-one Derivatives

Abstract A novel group of 6-iodoquinazolin-4(3H)-one derivatives was prepared starting from 6-iodo-2-ethoxy-4H-3,1-benzoxazin-4-one (3) via action of various nitrogen nucleophiles such as primary and secondary amines, hydrazine hydrate, and its derivatives. The 3-amino-2-hydrazinyl-6-iodoquinazolin-4(3H)-one (15) was used as a key starting material to prepare new heterocyclic compounds. The structures of all synthesized compounds were inferred from the infrared, mass spectral, and 1H NMR spectral data as well as elemental analysis. The fungicidal activities of the target compounds were preliminarily evaluated. GRAPHICAL ABSTRACT

NOVEL METHODS FOR THE SYNTHESIS OF SOME PYRIDAZINO-, FURO-, AND POLYSUBSTITUTED PYRIDAZINES

ABSTRACT 3,4-Diethoxycarbonyl-5,6-diphenylpyridazine 1 reacted with hydrazine hydrate to form tetrahydropyridazino [4,5-c]pyridazine 2, which reacted with ethyl bromoacetate to give 6,7-diethoxycarbonylmethyl-3,4-diphenyl-5,8-dioxopyridazino [4,5-c]pyridazine 3. However, acetylation of 2 with acetyl chloride gave three different pyridazino[4,5-c]pyridazines 4–6. The reaction of the starting diester 1 with different amounts of phenylmagnesium bromide gave different products 7–10. The structure of product 8 was elucidated by alkaline hydrolysis and hydrazinolysis to afford 11 and 13, respectively. Treatment of 13 with benzaldehyde in piperidine yielded the starting Grignard product 8 and benzalazine 17.

Novel isocoumarin and isoquinoline derivatives

A number of novel isoquinoline-1,3-dione derivatives have been synthesised using the readily obtainable anhydride formed from the Stobbe-type condensation of diethyl homophthalate with p-anisaldehyde. Primary amines form amides at the C-1 carbonyl group; recyclisation gives 4-(4-methoxybenzylidene)isoquinoline-1,3-diones.

Synthesis and reactions of 3,4-dicarboxy-5,6-diphenylpyridazine

Abstract Diethyl acetylenedicarboxylate 2 reacted with benzilmonohydrazone 1 to form 3,4-dicarboxycarbony 1-5,6-diphenylpyridazine 3, which upon alkaline hydrolysis gave the corresponding dicarboxylic acid 4. Decarboxylation of 4 gave 3,4-diphenyl-pyridazine 7. On treatment of 4 with acetyl chloride or thionyl chloride, 3,4-diphenyl-5,7-dioxofuro[3,4-c]pyridazine 8 was formed. Friedel-Crafts acylation on 8 gave 4-benzoyl-3-carboxy-5,6-diphenylpyridazine 9, 3-benzoyl-4-carboxy-5,6-diphenyl-pyridazine 10 and 4-benzoyl-5,6-diphenylpyridazine 11. Hydrazinolyis of 9 and 10 produced the isomeric pyridazino[4,5-]pyridazines 15 and 16, respectively. Reaction of 5,7-di-oxofuro[3.4-c]pyridazine 8 with distilled aniline gave the unexpected product 3,4-diphenyl-5-(N-phenyl) formamidopyridazine 17.

Synthesis of 1,2,4-triazoles, imidazoles, pyrimidines, quinazolines, 1,3,5-triazines, and 1,3-thiazines from 3-oxo-5,6-diphenyl-2,3-dihydro-pyridazine-4-carbonyl isothiocyanate

3-Oxo-5,6-diphenyl-2,3-dihydropyridazine-4-carbonyl isothiocyanate (1) was reacted with hydrazine hydrate, or phenyl hydrazine, to give 1,2,4-triazole derivatives in a one pot-reaction. However, reaction of 1 with benzoyl hydrazine afforded thiourea derivative that was cyclised to a differently substituted 1,2,4-triazole. Ethyl glycinate reacted with isothiocyanate 1 to give an adduct that was cyclised to imidazolidine derivative. Reaction of 1 with o-aminophenol, o-phenylenediamine or o-aminothiophenol afforded benzoxazole, benzimidazole or benzothiazole derivatives respectively. Reaction of 1 with thioglycolic acid gave 1,3-thiazine derivative, however, when 1 was treated with anthranilic acid a thiourea derivative was obtained which cyclised to a quinazoline derivative. Reaction of 1 with 2-cyanoacetamide or guanidine HCl yielded pyrimidine or triazine derivatives respectively. The structures of all compounds were confirmed by their micro analytical and spectral data.

Novel 1 H -2-benzopyran-1-one and 2,3-benzodiazepin-1-one derivatives

A number of novel 1H-2-benzopyran-1-one derivatives have been synthesised using the readily obtainable starting material obtained from the Stobbe-type condensation of diethyl homophthalate with p-anisaldehyde. Bromination, followed by hydrazinolysis, produced the tetrahydro-2,3-benzodiazepin-1-one derivative 5.

Utility of a Pyrimidin-2-Thione Derivative in Synthesis of New Fused Thiazolo[3,2-a]pyrimidines

A pyrimidin-2-thione derivative 2 was prepared and treated with 1,2-dibromoethane, chloroacetic acid and ethyl chloroacetate to give the alkylation products 3,4,9,5, respectively. Furthermore, the reaction of 2 with acrylonitrile and hydrazine hydrate yielded the pyrimidino[2,1-b]thiazine derivative 7, and [1,2,4]-triazolo[4,3-a]pyrimidine 8. Compound 9 was used as the key starting material for synthesis of thiazolo[3,2-a]pyrimidine and pyrano[2′,3′ :4,5]thiazolo[3,2-a]pyrimidine derivatives 10–13, through the reaction with ethyl acetate, malononitrile, hydrazine hydrate, β-aroylacrylic acid, and chalcone, respectively. Treatment of compound 5 with 3,5-dibromo-2-aminobenzoic acid in refluxing butanol gave the 3,1-benzoxazinone derivative 6. The structure assignment of the new compounds is based on chemical and spectroscopic evidence.

Novel Synthesis of Isoquinoline Derivatives Derived from (Z)-4-(1,3-Diphenylpyrazol-4-yl)isochromene-1,3-dione

Abstract A series of isoquinoline derivatives were synthesized via the reaction of the (Z)-4-(1,3-diphenylpyrazol-4-yl)isochromene-1,3-dione with different hydrazides, primary amines, diamines, 2-aminothiophenol, 2-aminobenzoic acid, p-aminoacetophenone, and ethyl 2-amino-4,5,6,7-tetrahydrobenzo-[b]thiophene-3-carboxylate. All the synthesized compounds were characterized by infrared, 1H NMR, and mass spectra besides the analytical data. GRAPHICAL ABSTRACT

Synthesis, Anticancer Screening and Molecular Docking Studies of New Heterocycles with Trimethoxyphenyl Scaffold as Combretastatin Analogues.

BACKGROUND In this study, synthesis, molecular docking and anticancer screening of new series of substituted heterocycles with trimethoxy phenyl scaffold as Combretastatin analogues were described. Substituted pyridines were synthesized via the reaction of (E)-3-(dimethylamino)-1-(3,4,5- trimethoxyphenyl)prop-2-en-1-one (2) with active methylene reagents. Substituted pyrimidines were prepared by the reaction of the enaminone (2) with heterocyclic amines and 6-amino thiouracil. Furthermore, a series of pyrazoles substituted with trimethoxyphenyl scaffold were prepared by the reaction of the enaminone 2, with selected examples of hydrazonoyl halides. CONCLUSION The cytotoxic effect of the newly compounds was evaluated against HePG-2, HCT-116, MCF-7 and PC3 cancer cell lines. Among the new products, compounds 2, 3, 7 and 10 were found to exhibit promising results as anticancer agents. The IC50 values of 2, 3 and 7 were 54.6, 77.4 and 47.4 on PC3 respectively. Also, compound 2 had IC50 28.06 on MCF7. Moreover, the selectivity index indicated that compounds 2 and 3 are safe.