Magda A. Abdallah

New pyrazoles incorporating pyrazolylpyrazole moiety: Synthesis, anti-HCV and antitumor activity

Three series of novel pyrazole derivatives 2b-d, 4a-d and 6a-d were synthesized via two step procedure that utilizes hydrazonoyl chlorides 1a-d and enaminones 3a-d and 5a-d, respectively as starting materials. The structures of all the newly synthesized products have been established on the basis of analytical and spectral data. Moreover, some of the products 2-6 were tested against HCV and Subacute Sclerosing Panencephalitis (SSPE). In addition, compounds 2-6 were also tested for the inhibition of peroxynitrite-induced tyrosine nitration and antioxidant activity. The tested compounds are highly effective at very low concentration as anti-HCV, SSPE antioxidant and anticancer in the following ascending order 2d, 4c, 6b, 3b, 6c, 4d, 2b, 2c, 2a, 6a, 5b, 5a, 3a, 4b and 5c. It is worth to mention that all tested compounds are more potent than the reference standards used for comparing activity. All the measurements revealed that the mechanism of action of the anti cancer activities of all the tested compounds is topoisomerase I inhibitor.

The Chemistry of Heterocyclic Hydrazonoyl Halides

Publisher Summary Hydrazonoyl halides have emerged as an important class of intermediates, particularly for the synthesis of heterocyclic compounds. This chapter discusses the synthesis, properties, and reactions of Hydrazonoyl Halides. The mechanisms of some of the reactions and the structures of some of the products are outlined. Direct halogenation of arylhydrazone derivatives of both aliphatic and aromatic aldehydes with the appropriate halogen in glacial acetic acid is an excellent method for the synthesis of the corresponding hydrazonoyl halides. Halides are also obtained by refluxing with N- bromosuccinimide in dry carbon tetrachloride. Furthermore, bromination of aldehyde N-heteroarylhydrazones in acetic acid in the presence of sodium acetate sometimes leads to intramolecular cyclization of the initial hydrazonoyl bromides to yield the corresponding cyclized products. However, from the foregoing survey of heterocyclic hydrazonoyl halides, it appears that the main emphasis has been restricted to both their preparation and use as intermediates for further synthesis. Large areas of their chemistry, particularly regarding their physical and biological properties, remain to be developed.

Synthesis and Antimicrobial Activity of Some New 1,3,4-Thiadiazole Derivatives

New series of 1,3,4-thiadiazoles have been prepared via reaction of 1,3,4-thiadiazolenaminones 1 with N-phenyl 2-oxopropanehydrazonoyl chloride (2) in dioxane in the presence of triethylamine. Also, some new heterocycles incorporating 1,3,4-thiadiazole ring were obtained by reaction of 1,3,4-thiadiazolenaminones 1 with nitrogen-nucleophiles like hydrazine hydrate, 3-amino-1,2,4-triazole and 2-aminobenzimidazole. The structure of the new products was established based on elemental and spectral analysis. The relation between the structure of the products and their activity towards some microorganisms was studied and promising results were obtained.

New and efficient approach for synthesis of novel bioactive [1,3,4]thiadiazoles incorporated with 1,3-thiazole moiety

A series of novel 1,3,4-thiadiazoles incorporated with thiazole moiety was synthesized by reaction of 5-acetyl-2-benzoylimino-3-phenyl-1,3,4-thiadiazole thiosemicarbazone 2 with each of N-phenyl 2-oxo-propanehydrazonoyl chloride 3 and ethyl (N-aryl-hydrazono) chloroacetate 5 in dioxane in basic medium. Also, another series of 1,3,4-thiadiazole incorporated with thiazole moiety was prepared by reaction of 5-acetyl-2-benzoylimino-3-phenyl-1,3,4-thiadiazole thiocarbohydrazone with each of hydrazonoyl chlorides 3, 5 and 18 under the same reaction conditions. The mechanisms of the studied reactions were discussed and the assigned structure for each of the new products was identified via elemental and spectral data and by alternative method whenever possible. Moreover, the antimicrobial activity for some selected products was screened, and the results obtained exploring the high potency of some of the tested compounds compared with the employed standard bactericides and fungicide.

Synthesis and Tautomeric Structure of 7-Arylhydrazono-7H-[1,2,4]Triazolo[3,4-b][1,3,4]Thiadiazines

Two synthetic approaches were developed for the title compounds 8a-g via coupling of diazotized anilines with 7-acetyl-6-methyl-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine 7 , and reaction of N-aryl 2-oxopropanehydrazonoyl chlorides 9 with 4-amino-3-mercapto-5-phenyl-1,2,4-triazole 1 . The tautomeric structures of 8 were elucidated by their spectral analyses and correlation of their acid dissociation constants with Hammett equation.

Convenient Synthesis of 6H-[1,2,4,5]Tetrazino[3,2-b]quinazolin-6-ones

Summary. The reaction of 3-amino-2-thioxo-4(1H)-quinazolinone or its 2-methylthio derivative with hydrazonoyl halides in the presence of ethanol and triethylamine affords 6H-[1,2,4,5]tetrazino[3, 2-b]quinazolin-6-ones.

Synthesis and Evaluation of the Anti-Microbial Activity of New Heterocycles Containing the 1,3,4-Thiadiazole Moiety

A new series of thiadiazole-enaminones 4 were synthesized via reactions of 5-acetyl-1,3,4-thiadiazoles 3 with dimethylformamide-dimethylacetal (DMF-DMA). The simple phenyl substituted thiadiazole-enaminone 4f was used as a synthetic precursor for the preparation of a wide variety of new heterocyclic compounds, including the 5-substituted-1,3,4-thiadiazole derivatives 5, 6, 11, 12 and 13, which were obtained via reactions of 4f with nitrogen nucleophiles. Also, reactions of enaminone 4f with carbon nucleophiles afforded the respective 1,3,4-thiadiazoles 8a–d. In addition, the results of the antimicrobial activities of thiadiazole-enaminones 4 and their precursors 2 and 3 indicate that some members of this series display promising activities against all tested microorganisms.

New 2-heterocyclic perimidines: synthesis and antimicrobial activity

A new series of 2-(5-substituted-pyridazine-3,6-dion-4-yl)perimidine derivatives was synthesized in good yields via reaction of (1H-perimidin-2-yl) acetic acid hydrazide with ethyl N-arylhydrazonochloroacetate in dioxane in the presence of triethylamine reagent. The site selectivity of the studied reaction is discussed, and the structure of the products is established based on elemental and spectral data. Also, the antimicrobial activity of the products was evaluated with promising results being obtained.

A new one-pot synthesis of novel hetarylazo-heterocyclic colorants and study of their solvatochromic properties

A simple synthetic strategy for synthesis of new series of hetarylazo-heterocycles is described. The effects of solvent on their electronic absorption spectra were analyzed using Kamlet-Taft equation. The results of fitting coefficients indicated that the solvatochromism of the studied compounds is mainly due to the solvent polarity rather than the solvent basicity and acidity.

Synthesis and tautomeric structure of 1,2-bis-(7-arylhydrazono-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)ethanes

Two series of the title compounds were prepared by reaction of 1,2-bis(4-amino-5-mercapto- 4H-1,2,4-triazol-3-yl)ethane with N-aryl-2-oxopropane-hydrazonoyl chlorides. The spectral data of such compounds indicated that they exist predominantly in the bis-hydrazone tautomeric form.