Ashraf H. F. Abd El-Wahab

Synthesis of halogen derivatives of benzo[h]chromene and benzo[a]anthracene with promising antimicrobial activities

The synthesis of novel 7-(4-halophenyl)-8,9-dihydro-7H-12-oxa-9,11-diaza-benzo[a]anthracene derivatives has been reported. The key intermediate 3-amino-9-chloro-1-(4-halophenyl)-1H-benzo[h]chromene-2-carbonitrile (3) was obtained by treating 4-halobenzylidenmalononitriles (1a-c) and ethyl 4-halobenzylidenmalonates (1d-f) with 4-chloro-1-naphthol (2) in ethanolic piperidine solution. Antimicrobial activity was shown for most of the synthesized compounds.

Synthesis, reactions and antimicrobial activities of 8-ethoxycoumarin derivatives.

Condensation of 3-acetyl-8-ethoxycoumarin (3) with thiosemicarbazide gave ethylidenehydrazinecarbothioamide 5, which was transformed into the thiazolidin-4-one derivatives 6,7. Interaction of 3 with DMF/POCl3 gave β-chloroacroline derivative 8. Treatment of 3 with malononitrile gave benzo[c]chromone and 2-aminobenzonitrile derivatives 9 and 10, respectively with respect to the reaction conditions. Condensation of 3-(2-bromoacetyl)-8-ethoxycoumarin (4) with o-phenylenediamine gave 3-(quioxaline-2-yl)-8-ethoxycoumarin hydrobromide (11), while 4 reacted with 2-aminopyridine to give chromenopyridopyrimidine derivative 12. Condensation of 4 with potassium thio-cyanate/methanol gave an unexpected derivative, 2H-chromeno-3-carboxy(methyl-carbonimidic)thioanhydride 16, which upon treatment with (NH2)2·H2O gave 3-ethoxy-2-hydroxybenzaldehyde azine 19. Interaction of 4 with thiourea derivatives gave thiazole derivatives 20a–c. The structures of the newly synthesized compounds were confirmed by their spectra data. The newly synthesized compounds were also screened for their antimicrobial activity.

Synthesis, Reactions and Biological Evaluation of Some New Naphtho[2,1-b]furan Derivatives Bearing a Pyrazole Nucleus

Vilsmeier formylation of 2-(1-phenylhydrazonoethyl)naphtho[2,1-b]furan (2) gave 3-naphtho[2,1-b]furan-2-yl-1-phenyl-1H-pyrazole-4-carbaldehyde (3), which was reacted with C- and N-nucleophiles to afford naphthofuranpyrazol derivatives 4-8. Treatment of 2-[(3-(naphtho[2,1-b]furan-2-yl)-1-phenyl-1H-pyrazol-4-yl)methylene]-malononitrile (4a) with reactants having active hydrogen and Et₃N gave the corresponding pyrazoline, pyran and chromene addition product derivatives 10, 12 and 13, consisting of three different connected heterocyclic moieties. Reaction of 1-((3-(naphtho[2,1-b]furan-2-yl)-1-phenyl-1H-pyrazol-4-yl) methylene)-2-phenylhydrazone (6b) with AcONa and ethyl bromoacetate or chloroacetone afforded the thiazolidinone and methylthiazole derivatives 14 and 15, respectively. In addition, intramolecular cyclization of 6d with Ac₂O afford the corresponding 1,3,4-thiadiazol-2-yl acetamide derivative 16. The structures of the synthesized compounds were confirmed by IR, ¹H-NMR/¹³C-NMR and mass spectral studies. Compound 14 showed promising effects against the tested Gram positive and negative bacteria and fungi.

Synthesis, Reactions and Evaluation of the Antimicrobial Activity of Some 4-(p-Halophenyl)-4H-naphthopyran, Pyranopyrimidine and Pyranotriazolopyrimidine Derivatives

A series of naphthopyran derivatives 3a–f were prepared. Reaction of 2-amino-4-(p-chlorophenyl)-7-methoxy-4H-naphtho[2,1-b]pyran-3-carbonitrile (3b) with Ac2O afforded two products, 2-acetylamino-7-methoxy-4-(p-chlorophenyl)-4H-naphtho-[2,1-b]pyran-3-carbonitrile (4) and 10,11-dihydro-3-methoxy-9-methyl-12-(p-chloro-phenyl)-12H-naphtho[2,1-b]pyran[2,3-d]pyrimidine-11-one (5) and treatment of 3b with benzoyl chloride gave the pyranopyrimidin-11-one derivative 6. While treatment of 3b with formamide afforded 11-amino-3-methoxy-12-(p-chlorophenyl)-12H-naphtho[2,1-b]pyrano[2,3-d]pyrimidine (7). Reaction of 3b with triethyl orthoformate gave the corresponding 2-ethoxymethyleneamino-7-methoxy-4-(p-chlorophenyl)-4H-naphtho-[2,1-b]pyran-3-carbonitrile (8). Hydrazinolysis of 8 in EtOH at room temperature yielded 10-amino-10,11-dihydro-11-imino-3-methoxy-12-(p-chlorophenyl)-12H-naphtho[2,1-b]pyrano-[2,3-d]pyrimidine (9), while aminolysis of 8 with methylamine or dimethylamine gave the corresponding pyranopyrimidine and N,N-dimethylaminomethylene derivatives 10 and 11. Condensation of 9 with some carboxylic acid derivatives afforded triazolopyrimidine derivatives 12–16, while reaction of 9 with benzaldehyde gave 10-benzalamino-10,11-dihydro-11-imino-3-methoxy-12-(p-chlorophenyl)12H-naphtho[2,1-b]pyrano[2,3-d]pyrimidine (17). The structures of the newly synthesized compounds were confirmed by spectral data. The synthesized compounds were also screened for their antimicrobial activity.

Synthesis and Biological Screening of 4-Benzyl-2H-phthalazine Derivatives

Preparation of 4-benzyl-2-substituted phthalazin-1-one derivatives 2-8 is reported. Condensation of 4-benzyl-1-chlorophthalazine (9) with a series of different nucleophiles gave 4-benzylphthalazin-1-ylamino derivatives (10-13 and 16) and 4-amino-2-[N′-(4-benzylphthalazin-1-yl)-hydrazino]-6-arylpyrimidine-5-carbonitriles (14a,b). Interaction of 9 with ambident anions was also studied. 5-Benzyl-6,6a,12-triazobenzo[a]-anthracen-7-one (15) is obtained from 9 and anthranilic acid derivatives. Treatment of 16 with (EtO)3CH/Ac2O under reflux afforded the corresponding ethoxymethylene derivative 17, while aqueous ammonium hydroxide treatment afforded carboxamide derivative 18. The structures of the newly synthesized derivatives were confirmed by their elemental analysis, IR, 1H NMR, 13C NMR and mass spectral studies. Antimicrobial activities of some selected compounds were also studied and some of these were found to exhibit promising effects against Gram-positive and Gram-negative bacteria and fungi.

Synthesis and characterization of new diiodocoumarin derivatives with promising antimicrobial activities.

Summary A series of 6,8-diiodocoumarin-3-N-carboxamides (4–11) were prepared. Treatment of ethyl 6,8-diiodocoumarin-3-carboxylate (1) with ethyl cyanoacetate/NH4OAc gave ethyl 2-(3-carbamoyl-6,8-diiodocoumarin-4-yl)-2-cyanoacetate (12) and 2-amino-4-hydroxy-7,9-diiodocoumarino[3,4-c]pyridine-1-carbonitrile (13), and treatment with acetone in the presence of NH4OAc or methylamine gave the ethyl 4-oxo-2,6-methano-2-methyl-3,4,5,6-tetrahydro-8,10-diiodobenzo[2,1-g]-2H-1,3-oxazocine-5-carboxylate derivatives 14a,b. All compounds were evaluated for their antimicrobial activity and the compounds 12–14a,b exhibited a pronounced effect on all tested microorganisms.

ANTIMICROBIAL ACTIVITY OF THE REACTION PRODUCTS OF 2-ACETYL- AND 2-(2,2-DICYANO-1-METHYLVINYL)NAPHTHO[2,1-b] FURAN WITH SOME NUCLEOPHILIC AND ELECTROPHILIC REAGENTS

The reaction of 2-acetyl and 2-(2,2-dicyano-1-methylvinyl)naphtho[2,1-b]furan with malononitrile, phenylhydrazine, α-cyanocinnamonitriles, anisaldehyde and other differenet reagents were discussed. The structure of the reaction products were supported by HNMR, CNMR, IR and mass spectra data. The biological activity of the compounds cited in this article were reported.