Wafaa S. Hamama

PYRAZOLONES AS VERSATILE PRECURSORS FOR THE SYNTHESIS OF FUSED AND BINARY HETEROCYCLES

The reaction of pyrazolone bearing a β-ketoester moiety with aliphatic dibasic functional reagents in ethanol afforded the binary ring heterocycles 2, 6, and 10. Whereas, when using an excess of the dibasic reagent, the dipyrazolo [3,4-c: 3′, 4′-f] [1,2]diazepine derivative 5 was, obtained. On the other hand, when compound 1 reacted with hydrazine hydrate in acetic acid, it furnished the pyrazolo[3,4-b]pyridine derivative 7 in which the hydrazine hydrate acts as a monofunctional reagent. Also, the reaction of 1 with m-anisidine according to Knorr synthesis gave the α,β-unsaturated ketone derivative 9 in lieu of the anticipated quinolone derivative 8. Furthermore, treatment of compound 1 with aromatic dibasic functional reagents afforded 11 and 13. Eventually, compound 11 was annelated through its reaction with ammonium carbonate to give pyrazolo[3,4-b]pyrido[6,5-b]benzodiazepin 12.

Synthesis, antitumor and antioxidant evaluation of some new thiazole and thiophene derivatives incorporated coumarin moiety

Abstract3-Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of 2-aminothiazole derivative 3via bromination of 1 followed by treatment of the formed acetylbromide 2 with thiourea or via Bignailli reaction of 1. Treatment of 3 with 2 afforded the bis-coumarin 4, whereas, cyanoacetylation of 3 followed by treatment of the formed cyanoacetamide 6 with salicyaldehyde give the bis-coumarin 7. Reaction of 6 with phenyl isothiocyanate in DMF/KOH produced the potassium salt 8, which cyclized with chloroacetyl chloride to give the thiazolidinone 9. Acidification of 8 with HCl afforded the thiocarbamoyl 10, which condensed with 2 in DMF to give the mercapto derivative 12, whereas in DMF/TEA gave the thiophene derivative 13. The thiophenes 15a–c were achieved via treatment of the thiocarbamoyls 14a–c with 2 in DMF/TEA, whereas, in DMF gave the corresponding thiazoles 16a–c. Treatment of the components 17a, b with carbon disulfide in DMF/KOH followed by addition of 2 afforded the dithioacetals 19a, b. Cyclization of 19b under alkaline condition gave the desired thiophene 20. Representative compounds of the synthesized products were evaluated as antitumor and antioxidant agents.Graphical Abstract3-Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of different coumarin derivatives. Newly synthesized compounds were elucidated by analytical and spectral data. Representative compounds of the synthesized products were evaluated as antitumor and antioxidant agents.

Advances in the Chemistry of Aminoisoxazole

Abstract This review article is a survey of the literature on aminoisoxazoles. It describes the methods of synthesis and chemical reactions of aminoisoxazoles as building blocks for the synthesis of polyfunctionalized heterocyclic compounds. GRAPHICAL ABSTRACT

Efficient regioselective synthesis and potential antitumor evaluation of isoxazolo[5,4-b]pyridines and related annulated compounds.

The reaction of 5‐amino‐3‐methylisoxazole with appropriate α,β‐unsaturated ketones gave the corresponding isoxazolo[5,4‐b]pyridines. Treatment of 1 with 2,6‐dibenzylidenecyclohexanone or 2‐benzylidenedimedone afforded the corresponding isoxazolo[5,4‐b]quinoline derivatives. 4,6,8,9‐Tetrahydroisoxazolo[5,4‐b]quinolin‐5‐one derivative was also obtained by multicomponent condensation reaction of 1 with dimedone and benzaldehyde. Heterocyclic annulation of the isoxazolo[5,4‐b]pyridine system was achieved via reaction of 1 with benzylidene derivatives of indandione, quinuclidone, pyrazolone, and oxazolone. A representative of some newly synthesized compounds was evaluated as antitumor agents.

New synthetic approach to coumarino[4,3-b]pyridine systems and potential cytotoxic evaluation

The reaction of 4-aminocoumarin (2) with appropriate α,β-unsaturated ketones gave the corresponding coumarin [4,3-b]pyridines. Thus, treatment of 2 with (E)-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one, (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one, (Z)-ethyl 3-(4-chlorophenyl)-2-cyanoacrylate, and (2E,6E)-2,6-dibenzylidenecyclohexanone (3, 6 and 12) afforded the corresponding coumarino[4,3-b]pyridines 5, 7 and coumarino[4,3-b]quinoline derivatives 13, respectively. Heterocyclic annulations of coumarino [5,4-b]pyridine system were achieved via reaction of 2 (in situ) with benzylidene derivatives of indandione to give 15 which was also obtained by multicomponent condensation reaction of 2 (in situ) with indandione and benzaldehyde. A representative sample of new synthesized compounds was evaluated as cytotoxic agents.Graphical Abstract

Advances in the domain of 4-amino-3-mercapto-1,2,4-triazine-5-ones

This review summarizes results from a literature survey concerning the synthesis and reactions of 4-amino-3-mercapto-1,2,4-triazine-5-ones reported by research groups from 1983 to mid. 2015.

Synthesis, antioxidant, and antitumor evaluation of certain new N-substituted-2-amino-1,3,4-thiadiazoles

Reaction of 2-amino-1,3,4-thiadiazole (1) with chloroacetyl chloride afforded the chloroacetamide 2 which used as starting compound for the synthesis of 2-thiocyanatoacetamide 3 and N-(1,3,4-thiadiazol-2-yl)acetamides 5–9 via reaction of 1 with various reagents. Treatment of 9 with 4-(piperidin-1-yl)benzaldehyde or DMF-DMA afforded the arylidenes 10 and 11, respectively. Cyclization of the later compound with hydrazine hydrate gave the pyrazole derivative 12. Furthermore, coupling of 9 with 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-diazonium chloride afforded hydrazone derivative 13, which cyclized in acetic acid to afford 1,2,4-triazine derivative 14. Moreover, 1,3,4-thiadiazoles 15, 19, 22, and 23 were achieved via reaction of 1 with different nucleophiles. Finally, 1-phenyl-1H-pyrazol-5(4H)-one when subjected to react either with 15 or with diazonium salt of 1 afforded pyrazole derivative 16 or bis-1,3,4-thiadiazole derivative 18, respectively. Some of these compounds were screened for their cytotoxicity and antioxidant activities which showed promising results.Graphical AbstractIn an effort to establish new candidates with improved activities, we reported herein the synthesis and antitumor and antioxidant evaluation of various series of N-substituted-2-amino-1,3,4-thiadiazoles. Newly synthesized compounds were characterized by (IR, 1H NMR, 13C NMR, high resolution mass spectra, and mass spectra). The representative compounds were evaluated as antitumor and antioxidant activities. Some of the prepared compounds exhibited promising activities.

Developments in the Chemistry of 2-Pyridone

Abstract The focus of our review is on the methods of synthesis and chemical reactivity of 2-pyridone and some derivatives as 2-chloro-3-nicotinonitrile in addition to the biological activity of the 2-pyridone moiety. GRAPHICAL ABSTRACT

Synthesis and antimicrobial and antioxidant activities of simple saccharin derivatives with N-basic side chains

A new class of N-basic side chains was obtained from 2,3-dihydro-2H-3-oxobenzo[d]isothiazole and aliphatic or aromatic aldehydes. Secondary amines (morpholine, N-methylpiperazine and ethyl isonipecotate) afforded tertiary N-basic side chains (4–6), while dibasic secondary amines (such as piperazine) gave bis-tertiary N-basic side chains (2). On the other hand, the use of mono- or dibasic primary amines namely; aniline, anisidine, phenyl hydrazine, o-hydroxy benzoic acid hydrazide, hydrazine hydrate, and ethylenediamine (instead of secondary amines) afforded secondary N-basic side chain as mono component or as bis component 7a-c, 9a-c, 11 and 12a-c. In addition, secondary Mannich base was synthesized via Michael addition to the corresponding aldimine. The new compounds were investigated for antioxidant and antimicrobial activities. Compounds 2, 7c and 12a exhibited significant antimicrobial activity, whereas compounds 7a, 7b, 9b, 9c and 11 exhibited high antioxidant activity as compared to ascorbic acid, These compounds showed the best protective effect against DNA damage induced by bleomycin.

Synthesis and Antioxidant Evaluation of Some New 3-Substituted Coumarins

3‐Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of 2‐aminothiazole derivative 3 via bromination of 1 to afford acetylbromide 2 followed by treatment with thiourea or via Biginelli reaction of 1. Treatment of 3 with 5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde, 2‐methyl‐4H‐benzo[d][1,3]oxazin‐4‐one, furo[3,4‐b]pyrazine‐5,7‐dione or 2‐methyl‐5,6,7,8‐tetrahydro‐4H‐benzothieno[2,3‐d][1,3]oxazin‐4‐one afforded diazine derivatives 4–7. Also, pyridopyrimidine 8 was obtained via a one pot reaction of 6‐aminothiouracil, p‐chlorobenzaldehyde and 3‐acetylcoumarin. Moreover, refluxing of 6‐aminothiouracil with one equivalent amount of 2 afforded the thiazolopyrimidine 9, while the pyrrolothiazolopyrimidine 10 was revealed when two equivalent amounts of 2 was used. Furthermore, treatment of enamine 11 with 2‐aminobenzothiazole or 6‐aminothiouracil afforded the pyrimidine derivatives 12 and 13, respectively. Transamination of enamine 11 with m‐anisidine followed by cyclization of the resulting enaminone 14 gave the desired quinoline 15. Also, treatment of 11 with thiophenol in dioxane gave the mercapto derivative 16. Moreover, coupling of 11 with 4,6‐dimethyl‐1H‐pyrazolo[3,4‐b]pyridin‐3‐yl‐diazonium chloride, followed by complete cyclization of the resulting product afforded the pyridopyrazolothiazine 19 via the intermediate 18. Furthermore, the pyrazolopyrimidine 20 was revealed via a one pot condensation of 11, 3‐methyl‐1‐phenyl‐1H‐pyrazol‐5(4H)‐one and ammonium acetate. The thiadiazine derivatives 21–23 were obtained via treatment of 2 with the corresponding o‐aminothiols. Desulphonation of 23 afforded the pyrazolotriazine 24. Finally, reaction of 2 with 2‐hydroxybenzaldehyde gave benzofuran derivative 25. Representative compounds of the synthesized products were evaluated as antioxidant agents.