Synthesis and characterization of mono- and bicyclic heterocyclic derivatives containing 1,2,4-triazole, 1,3,4-thia-, and -oxadiazole rings

A series of new N- and S-substituted 1,3,4-oxadiazole derivatives were synthesized. 5-Pyridin-3-yl-3-[2-(5-thioxo-4,5-dihydro-l,3,4-thiadiazol-2-yl)ethyl]-1,3,4-oxadiazole-2(3H)-thione and 5-[(5-(pyridin-3-yl)-1,3,4-oxadiazol-2-ylthio)methyl]-N-phenyl-1,3,4-thiadiazol-2-amine were formed by cyclization of 3-(5-pyridin-3-yl-2-thioxo-1,3,4-oxadiazol-3(2H)-ylpropanimidohydrazide and 2-[(5-pyridin-3-yl-1,3,4-oxadiazol-2-yl)thio]thiosemicarbazide with CS₂ and H₂SO₄. On the other hand, a number of new bicyclic 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives were synthesized. 6-Pyridin-3-ylbis[1,2,4]‐triazolo[3,4-b:4′,3′-d][1,3,4]thiadiazole-3(2H)-thione was synthesized by reaction of 6-(hydrazino)-3-pyridine-3-yl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole with CS₂/KOH/EtOH. The structures of the newly synthesized compounds were elucidated by the spectral and analytical data IR, Mass, and ¹H NMR spectra. Correspondence: Adel A.-H. Abdel-Rahman, Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koam, Egypt; Wael A. El-Sayed, National Research Centre, Department of Photochemistry, Cairo, Egypt.     

Synthesis of Some New Thieno[2,3-b]pyridines,Pyrimidino[4′,5′:4,5]thieno[2,3-b]-pyridines,and 2,3-Dihydro-1,3,4-thiadiazoles

Thieno[2,3-b]pyridines were synthesized from 6-benzofuran-2-yl-4-phenyl-2-sulfanylpyridine-3-carbonitrile and each of chloro acetone, ethyl chloroacetate, ω -bromoacetophenone, and chloroacetonitrile. These compounds were conveniently converted into novel pyrido[4′,5′:4,5]thieno[3,2-d]pyrimidines. Also, 2,3-dihydro-1,3,4-thiadiazole was synthesized from hydrazonoyl halides and 2-benzofuran-2-yl-3-(phenylamino)-3-thioxopropanenitrile. The structures of the products have been elucidated by elemental analyses, spectral data studies, and alternative syntheses whenever possible. The newly synthesized compounds were tested towards microorganisms.     

Syntheses of 6-fluoro-7-piperazin-1-yl-9-cyclopropyl-2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-dione and 6-fluoro-7-piperazin-1-yl-9-p-fluorophenyl-2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-dione

The syntheses of 6-fluoro-7-piperazin-1-yl-9-cyclopropyl (or 9-p-fluorophenyl)-2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-diones as well as novel synthesis of isothiazolo-3(2H)-one system are described. Key steps include the regiospecific displacement of a sulfinyl group and the amination of the resultant mercapto derivative followed by an intramolecular nucleophilic displacement cyclization reaction to generate the novel 2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-dione nucleus.     

水溶性稠杂环均三唑并噻二唑体系的合成及生物活性(I): 哌嗪取代衍生物

4-氨基-5-吡啶-4-基-均三唑硫醇(1)在复合催化剂DMAP和TBAB作用下与对卤代苯甲酸经环缩合反应以高收率得到中间体6-(5-氯-3-甲基-1-取代苯基-1H-吡唑-4-基)-3-吡啶-3-基-均三唑并[3,4-b][1,3,4]噻二唑(2a～2c), 接着苯环卤原子与取代哌嗪在聚乙二醇催化作用下发生亲核取代反应得到相应的哌嗪游离碱(3a～3c). 其中, 单取代哌嗪游离碱3a与含功能基的卤代物缩合得到功能基取代的哌嗪衍生物(4a～4g). 这些产生的游离碱与盐酸反应得到相应的水溶性盐酸盐. 所合成新化合物的结构经元素分析和光谱数据表征, 并评价了它们的体外抗菌活性及构效关系.     

Synthesis of 3-pyridin-4-yl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazepines

A method for the synthesis of the previously inaccessible 3-pyridin-4-yl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazepines was developed. The X-Ray diffraction data for 8-tert-butyl-3-pyridin-4-yl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazepine are presented.     

Synthesis of Derivatives of 8-Cyano-6-ethoxycarbonyl-3-hydroxy-5-methylimidazo[1,2-a]pyridine and 9-Alkoxycarbonyl- (or 9-Carboxy)-3-ethoxycarbonyl-2-methyl-10H-benzo[b]-1,8-naphthyridine-5-one from the Reaction of 2-Chloro-5-ethoxycarbonyl-6-methylnicotinonitrile with Amino Acids

2-Substituted 8-cyano-6-ethoxycarbonyl-3-hydroxy-5-methylimidazo[1,2-a]pyridine was formed from the interaction of 2-chloro-5-ethoxycarbonyl-6-methylnicotinonitrile with -amino acids in DMF. The same nitrile on boiling with anthranilic acid or its esters in butanol gave, respectively, 2-(2-carboxyanilino)- or 2-(2-alkoxycarbonylanilino)-5-ethoxycarbonyl-6-methylnicotinonitriles which cyclized on heating in PPA to give 9-alkoxycarbonyl(or 9-carboxy)-3-ethoxycarbonyl-2-methyl-10H-benzo[b]-1,8-naphthyridin-5-ones.     

Reactions of 3-isopropenyltropolones with bromine and N-bromosuccinimide: Formation of 8H-cyclohepta[b]furan-8-one derivatives

3-Isopropenyltropolones 1a-c were treated with bromine in carbon tetrachloride to give 3-methyl-8H-cyclohepta[b]furan-8-ones 2a-c and their corresponding 7-bromo-substituted compounds 3a-c , while reactions in acetic acid gave the bromo-substituted compounds 3a-c . On the other hand, bromination of 1a-c with N-bromosuccinimide afforded 7-bromo-3-(2-bromo-1-methylethenyl)tropolones 5a-c . The compound 2a was treated with bromine to give 2-bromo-3-methyl-8H-cyclohepta[b]furan-8-one ( 4 ). The tropolones 5a-c were heated in the presence of potassium carbonate to give the cyclized compounds 3a-c .     

Synthesis of novel 1,2,3,4-tetrahydrobenzo[c]-1,5-naphthyridines from pyrrolo[1,2-b]isoquinolines

1,2,3,4-Tetrahydrobenzo[c]-1,5-naphthyridine ( 5a ) was prepared by a novel synthetic route involving the rearrangement of (±)-(Z)-1,10a-dihydropyrrolo[1,2-b]isoquinoline-3,10(2H,5H)-dione oxime to afford 1,4-dihydrobenzo[c]-1,5-naphthyridin-2(3H)-one, which was reduced to 5a. The cholinomimetic activity observed with 5a prompted the synthesis and biological evaluation of additional analogues.     

Methyl imidazo[1,2-b]pyridazine-2-carbamates and related compounds as potential antifilarial agents

A series of imidazo[1,2-b]pyridazines have been synthesized for antifilarial evaluation. The compounds prepared include methyl 6-benzoylimidazo[1,2-b]pyridazine-2-carbamate ( 12 ), 6-benzoyl-2-t-butylimidazo[1,2-b]pyridazine ( 13 ), methyl 6-(4-fluorobenzoyl)imidazo[1,2-b]pyridazine-2-carbamate ( 14 ), and methyl 6-(2-thienylcarbonylcarbonyl)imidazo[1,2-b]pyridazine-2-carbamate ( 15 ) which are aza analogs of the anthelmintic agents mebendazole, flubendazole and nocadazole. In addition, the preparation of a series of 2-t-butylimidazo[1,2-b]-pyridazine-6-carboxylic acid derivatives is described. Electrophilic bromination and iodination substitutions of 2-t-butyl-6-methylimidazo[1,2-b]pyridazine afforded 3-halo derivatives. Methyl 6-(4-fluorobenzoyl)pyridazine-3-carbamate was also prepared for antifilarial evaluation. None of these compounds possessed significant antifilarial activity against Brugia pahangi or Acanthocheilonema viteae infections in jirds.     

Naphthyridine chemistry: Ring enlargement to a pyrido[2,3-b] azepine

The boron trifluoride-catalyzed rearrangement of the epoxide derived from 3-benzylidene- 7-methyl-2,3-dihydro-1,8-naphthyridin-4-(1H)one (II) is described. The structure of the obtained 8-methyl-4-phenyl-1,2,3,4-tetrahydro-5H-pyrido[2,3,-b]-azepin-3, azepin-3,5-dione (X) has been elucidated with aid of chemical and spectral evidence.     

The synthesis of benzo[b]phenanthro[d]thiophenes and anthra[b]benzo[d]thiophenes

The synthesis of benzo[b]phenanthro[2, 3-d]thiophene ( 5 ), benzo[b]phenanthro[4, 3-d]thiophene ( 6 ), benzo-[b]phenanthro[2, 1-d]thiophene ( 9 ), benzo[b]phenanthro[3, 2-d]thiophene ( 14a ), anthra[1, 2-b]benzo[d]thiophene ( 24 ), anthra[2, 3-b]benzo[d]thiophene ( 29 ) and anthra[2, 1-b]benzo[d]thiophene ( 30 ) is described as well as the preparation of 13-methylbenzo[b]phenanthro[3, 2-d]thiophene ( 14b ).     

Synthesis of 4-hydrazino-5H-pyrimido[5,4-b]indole and related compounds

This paper describes the synthesis of two 4-amino-5H-pyrimido[5,4-b]indoles 5 , 4-hydrazino-5H-pyrimido[5,4-b]indole 6 , two 1,2,4-triazolo[4,3-c]pyrimido[5,4-b]indoles 8 , and tetrazolo[4,5-c]pyrimido[5,4-b]indole 10 . Starting with ethyl 3-aminoindole-2-carboxylate 1 , 5H-pyrimido[5,4-b]indol-4-one 2 was obtained (80%) by condensing with formamide. Reactions of 2 with phosphorus oxychloride and phosphorus pentasulfide gave respectively, 4-chloro-5H-pyrimido[5,4-b]indole 3 (70%) and 5H-pyrimido[5,4-b]indole-4-thione 4 (80%). Compound 3 reacted with amines (morpholine, piperidine) to give the respective 4-amino-5H-pyrimido[5,4-b]-indoles 5 , and compound 4 reacted with hydrazine to give 4-hydrazino-5H-pyrimido[5,4-b]indole 6 (80%). Two hydrazones of 6 (benzylidene, isopropylidene) 7 were also prepared (90%). Compound 6 reacted with formic and acetic acids to give (65–75%) the respective 1,2,4-triazolo[4,3-c]pyrimido[5,4-b]indoles 8 and with nitrous acid to give tetrazolo[4,5-c]pyrimido[5,4-b]indole 9 (85%). All the new compounds 2 to 9 were characterized by elemental analysis and spectral data (ir, nmr).     

Reaction of 4,5-diamino-3-methyl-1-phenylpyrazole with 3-dimethylaminopropiophenones. Synthesis of new 4-aryl-6-methyl-8-phenyl-2,3-dihydropyrazolo[3,4-b]diazepines and 4-aryl-8-methyl-6-phenyl-2,3-dihydropyrazolo[4,3-b]diazepines

New 4-Aryl-6-methyl-8-phenyl-2,3-dihydropyrazolo[3,4-b]diazepines and 4-aryl-8-methyl-6-phenyl-2,3-dihydropyrazolo[4,3-b]diazepines were obtained from the reaction of 4,5-diamino-3-methyl-1-phenylpyrazole 1 with one equivalent of the 3-dimethylaminopropiophenones 2 in absolute ethanol. The structures of 4-aryl-6-methyl-8-phenyl-2,3-dihydropyrazolo[3,4-b]diazepines 3 and 4-aryl-8-methyl-6-phenyl-2,3-dihydropyrazolo[4,3-b]diazepines 4 were determined by detailed nmr measurements.     

Photoelectron spectroscopy of heterocycles. Azaindenes and azaindolizines

The HeI photoelectron (PE) spectra of indole ( 1 ), benzimidazole ( 2 ), indazole ( 3 ), 3-chloro-indazole ( 4 ), imidazo[1,2-b]pyridazine ( 5 ), 6-chloroimidazo[1,2-b]pyridazine ( 6 ), 2-phenyl-imidazo[1,2-b]pyridazine ( 7 ), 2-phenyl-6-chloroimidazo[1,2-b]pyridazine ( 8 ), tetrazolo[1,2-a]-pyridine ( 9 ) and 8-cyanotetrazolo[1,5-a]pyridine ( 10 ) have been recorded. The spectra of 2–10 are of special interest for studying lone pair interactions. The assignment of the PE spectra submitted here, conjointly with the electronic structure of the studied compounds is discussed on the basis of molecular orbital calculations.     

Studies on the Synthesis of New 3-(3,5-Diamino-1-substituted-pyrazol-4-yl)azo-thieno[2,3-b]pyridines and 3-(2-Amino-5,7-disubstituted-pyrazolo[1,5-a]pyrimidine-3-yl)azothieno[2,3-b]pyridines

Coupling the diazonium salt of 3-amino-2-cyano-4,6-dimethylthieno[2,3-b]pyridine 1 with malononitrile 2 gave 2-cyano-3-(hydrazonomalononitrile)-4,6-dimethylthieno[2,3-b]pyridine 3 which then reacted with hydrazine compounds 4a-4h to yield corresponding 2-cyano-3-(3,5-diamino-1-substituted-pyrazol-4-yl)azo-4,6-dimethylthieno[2,3-b]pyridines 5a-5h. The 2-cyano-3-(2-amino-5,7-disubstituted-pyrazolo-[1,5-a]pyrimidine-3-yl)azo-4,6-dimethylthieno[2,3-b]pyridines 7a-7f were obtained in good yield by the cyclocondensation reaction of 2-cyano-3-(3,5-diamino-pyrazol-4-yl)azo-4,6-dimethylthieno[2,3-b]pyridine 5a with the appropriate 1,3-diketones 6a-6f under acidic condition.     

A reinvestigation of the synthesis of 3H-[1,2]diazepino[5,6-b]indoles. The synthesis of pyrido[4,3-b]indoles

Recently reported [1] syntheses of 6-methyl-1,2,4,5-tetrahydro-1,4-dioxo-3H[1,2]diazepino[5,6-b]indole ( 5 ) and 4-hydroxy-6-methyl-3H[1,2]diazepino[5,6-b]indole ( 12 ) were reinvestigated and shown to be in error. The correct assignments for these respective structures are 3-amino-1,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2,4(3H)-dione ( 6 ) and 3-amino-3,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2-one ( 13 ). Condensation of 6 and 13 with p-nitrobenzaldehyde produced benzylidene derivatives, which confirmed the presence of the amino groups.     

Metaboliten der 1,5-Dihydroimidazo[2,1-b]chinazolin-2(3H)-one. Synthese und Reaktionen einiger 1,5-Dihydro-3-hydroxyimidazo[2,1-b]chinazolin-2(3H)-one

Metabolites of 1,5-Dihydroimidazo[2,1-b ]quinazolin-2(3H)-ones. Preparation and Reactions of Some 1,5-Dihydro-3-hydroxyimidazo[2,1-b]quinazolin-2(3H)-ones Hydroxylated 1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-ones 2–4 and 6 were isolated as metabolites of imidazoquinazolinones 1a and 1b , respectively. The synthesis of 1,5-dihydro-3-hydroxy-3-methylimidazo[2,1-b]quinazolin-2(3H)-ones 3 , 4 , and 6 , and the preparation of some derivatives thereof is described.     

Benzofuranyl-pyran-2-ones, -pyridazines,and -pyridones from naturally occurring furochromones (visnagin and khellin)

The novel and versatile enaminones 2a,b were synthesized by treatment of visnaginone methyl ether 1a or khellinone methyl ether 1b with N,N-dimethylformamide dimethylacetal. They were reacted with hippuric acid or N-acetylglycine to yield benzofuran-5-yl-2H-pyran-2-ones 3a–d . The reaction of 2a,b with cyanoacetamide and malononitrile dimer in sodium ethoxide gave benzofuran-5-yl-pyridones 4a,b and [benzofuran-5-yl-1H-pyridine-2-ylidene] malononitrile 5a , respectively. Refluxing 2a,b with hydrazine hydrate or with hydroxyla- mine afforded benzofuran-5-yl-1H-pyrazoles 6a,b and benzofuran-5-yl-isoxazoles 7a,b , respectively. Moreover, 2a,b coupled with aryl diazonium salt in the presence of sodium hydroxide to yield 3-(benzofuran-5-yl)-2-aryl-hydrazono-3-oxo-propanals 8a,b which were excellent precursors for the synthesis of pyridazines 9–12 . © 2003 Wiley Periodicals, Inc. 15:85–91, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10219     

Methyl 2-benzoylamino-3-dimethylamonopropenoate in the synthesis of heterocyclic systems. A simple synthesis of amino derivatives of isomeric naphthopyranones and naphthodipyranones

A simple synthesis of the amino derivatives of 3H-naphtho[2,1-b]pyran-3-one 5b-d, 8,11 , and 20 , 2H-naphtho[1,2-b]pyran-2-one 14 and 19 , 2H,6H-naphtho[1,2-b:3,4-b']dipyran-2,6-dione 9 , 2H,11H-naphtho[2,1-b:3,4-b']dipyran-2,11-dione 12 , and 3H,9H-naphtho[1,2-b:5,6-b']dipyran-3,9-dione 15 from the corresponding monohydroxynaphthalenes 2c,d , dihydroxynaphthalenes 2b, 7, 10 , and 13 , and tetralones 16 and 17 with methyl 2-benzoylamino-3-dimethylaminopropenoate (3) in acetic acid is described.     

Photocyclization of 2-[1]benzothien-3-yl)-3-phenylpropenoic acids

Photocyclization of the substituted 2-([1]benzothien-3-yl)-3-phenylpropenoic acids 3a-c in the presence of iodine and air in a benzene-cyclohexane mixture afforded a separable mixture of three compounds, benzo[b]naphtho[2,1-d]thiophene-6-carboxylic acids 4a-c , 6H-benzo[b]naphtho[2,3-d]thiopyran-6-ones 5a-c , and 10-methoxy-2-methyl-6H-benzo[b]naphtho[2,3-d]pyran-6-one ( 6 ).