Microwave-assisted synthesis of 3-substituted-6-ferrocene methylene-1,2,4-triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]-1,3,4-thiadiazoles

A series of triazolo-thiadiazole derivatives containing ferrocene were synthesized under microwave assistance. Compared with the phosphorus oxychloride method, the microwave method has the advantages of simple operation, short reaction time, fast reaction rate and high yield. The effects of different reaction conditions were explored, and under the optimized conditions, the products were obtained in good yields (up to 80%).     

Synthesis of 3-methyl-6-r-6h-thiazolo-[4,3-<Emphasis Type="Italic">b</Emphasis>]-1,2,4-triazolo[4,3-<Emphasis Type="Italic">d</Emphasis>]-1,3,4-thiadiazoles

A one-reactor method has been developed for the synthesis of 3-methyl-6-R-6H-thiazolo[4,3-b]-1,2,4-triazolo[4,3-d]-1,3,4-thiadiazoles by the condensation of aromatic aldehydes, thioglycolic acid, and 4-amino-5-methyl-1,2,4-triazole-3(2H)-thione in a sulfuric acid medium.     

New Synthesis of Pyrano[4,3-<Emphasis Type="Italic">d</Emphasis>]pyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]pyridines

A new efficient method has been developed for the synthesis of highly biologically active pyrano-[4,3-d]pyrazolo[3,4-b]pyridines on the basis of Smiles rearrangement of ethyl [(8-alkyl(aryl)-5-cyano-3,3-dimethyl-3,4-dihydro-1H-pyrano[3,4-c]pyridin-6-yl)oxy]acetates. Intermediate acetohydrazides have also been isolated. The proposed procedure is advantageous due to the possibility of avoiding experimentally difficult chlorination stage.     

A facile synthesis of novel pyrrolo[3,4-<Emphasis Type="Italic">b</Emphasis>]quinolin-1-one derivatives

A simple and concise construction of a series of new quinoline-based isoindolin-l-ones, namely N-substituted-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-ones, wherein the benzene moiety of isoindolin-l-one is replaced by a quinoline ring has been achieved via a two-step procedure, involving the one-step synthesis of ethyl 2-chloromethyl-quinoline-3-carboxylate followed by its one-pot reaction with various amines in a refluxing EtOH–AcOH (v/v, 10:1) solvent system. These newly synthesized compounds could be good candidates for the development of lead compounds for use in medicinal chemistry.     

Synthesis and antimicrobial activity of novel fused [1,2,4]triazino[5,6-<Emphasis Type="Italic">b</Emphasis>]indole derivatives

Synthesis of new fused systems of triazino[5,6-b]indole starting with preparation of 3-amino[1,2,4]-triazino[5,6-b]indole 1 by reaction of isatin with 2-aminoguanidinium carbonate in boiling acetic acid is presented [1]. Intermediate compound 1 reacted with aldehyde, ethyl chloroformate, triethyl orthoformate, and ninhydrine and gave new heterotetracyclic nitrogen systems, such as 3-(N ²-guanidinylimino)indole-2(1H)-one 2, 3-(N-ethoxycarbonylamino)-4H-[1,2,4]triazino[5,6-b]indole 3, 3-(N-ethoxymethyleneamino)-4H-[1,2,4]-triazino[5,6-b]indole 4, 3-(hydrazinothiocarbonylamino)-4H-[1,2,4]triazino[5,6-b]indole 5, respectively. N-(1,3-dioxoindene-2-ylidene)-4H-[1,2,4]triazino[5,6-b]indol-3-amine 6 was synthesized by reaction of compound 1 with aldehyde, ethyl chloroformate, triethyl orthoformate, and ninhydrine. New fused indole systems, pyrimido[2′,1′:3,4][1,2,4]triazino[5,6-b]indol-3(4H)-one 8, 9, 11, 12 and 1H-imidazo[2′,1′:3,4][1,2,4]triazino-[5,6-b]indol-2(3H)-one 10, were synthesized in the reaction of the intermediate 1 with bifunctional compounds. Structures of the products were elucidated from their elemental analysis and spectral data (IR, ¹H and ¹³C NMR and mass spectra). Antimicrobial activity of some synthesized compounds was tested.     

Synthesis of substituted 4-([1,2,4]triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]-[1,3,4]thiadiazol-6-yl)quinolines

4-Amino-5-R¹-4H-1,2,4-triazole-3-thiols react with 2-R²-6-R³-quinoline-4-carboxylic acids in phosphoryl chloride to give 2-R²-6-R³-4-(3-R¹-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)quinolines.     

Synthesis and antimicrobial evaluation of some 1,3-thiazole, 1,3,4-thiadiazole, 1,2,4-triazole,and 1,2,4-triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]-thiadiazine derivatives including a 5-(benzofuran-2-yl)-1-phenylpyrazole moiety

Abstract  Potassium hydrazinecarbodithioate were prepared by treatment of acid hydrazides with carbon disulfide in the presence of potassium hydroxide. Reaction of this potassium salt with hydrazine hydrate, phenacyl bromide, or hydrazonoyl chlorides afforded 1,2,4-triazole, 1,3-thiazole, and 1,3,4-thiadiazoles. Reaction of 1,2,4-triazole with phenacyl bromide or hydrazonoyl chlorides afforded the corresponding 1,2,4-triazolo[3,4-b][1, 3, 4]-thiadiazines. All these new compounds were screened for antibacterial and antifungal activity. Some had promising activity. Graphical abstract        

Synthesis and X-ray study of 6<Emphasis Type="Italic">H</Emphasis>-chromeno[3,4-<Emphasis Type="Italic">e</Emphasis>][1,3,4]triazolo[2,3-<Emphasis Type="Italic">a</Emphasis>]pyrimidine

2-Dimethylamino methylenechromanone 1 reacted with 4H-1,2,4-triazol-3-amine in acetic acid to give only one isolated product which was identified by X-ray study as 6H-chromeno[3,4-e][1,3,4]triazolo[2,3-a]-pyrimidine. The molecular structure of 3, C₁₂H₈N₄O, was determined to be monoclinic, P2₁/c, a = 16.3875(5), b = 8.8378(3), c = 13.8392(5) Å, β = 101.190(1)°, V = 1966.22(11) ų, Z = 8.     

Synthesis of 3-aminopyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]pyridine-4-carbonitriles

Annulation of 2-chloropyridine-3,4-dicarbonitriles with hydrazine hydrate and N,N-dimethylhydrazine afforded 3-aminopyrazolo[3,4-b]pyridine-4-carbonitriles and 3-amino-1-methylpyrazolo[3,4-b]pyridine- 4-carbonitriles, respectively.     

Fluorinated [1,2,4]triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidines and [1,2,4]triazolo[5,1-<Emphasis Type="Italic">c</Emphasis>][1,2,4]triazines*

The reaction of 3-R-5-amino-1,2,4-triazoles with the ethyl ester of 2-fluoroacetoacetic acid gave 2-R-fluoro[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-ones. The reaction of a 3-R-1,2,4-triazolyl-5-diazonium salt with the ethyl ester of 2-fluoroacetoacetic acid and subsequent cyclization of the triazolylhydrazones lead to 7-R-3-fluoro[1,2,4]triazolo[5,1-c][1,2,4]triazin-4(1H)-ones.     

Synthesis of naphtho[1,2-<Emphasis Type="Italic">e</Emphasis>]-pyrazolo[5,1-<Emphasis Type="Italic">b</Emphasis>][1,3]oxazines

The previously unknown heterocyclic system naphtho[1,2-e]pyrazolo[5,1-b][1,3]oxazine was synthesized by the condensation of 1-dimethylaminomethyl-2-naphthols with bromopyrazoles. It is proposed that the highly reactive o-methylenequinone of the naphthalene series is formed as an intermediate.     

Synthesis of pyrazolo[4,3-<Emphasis Type="Italic">e</Emphasis>][1,2,4]triazolo[4,3-<Emphasis Type="Italic">c</Emphasis>]pyrimidines

Starting from 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones, a synthesis pathway to the tricyclic pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines is described. Reaction of 1,5-dihydro-4H-pyrazolo[3,4-d] pyrimidin-4-ones with phosphoryl chloride afforded the corresponding 4-chloro-1H-pyrazolo[3,4-d]pyrimidines. Treatment of these compounds with hydrazine hydrate at reflux temperature gave the hydrazino derivatives, which were subsequently cyclized to the titled compounds on heating with orthoesters in ethanol. Correspondence: Abolghasem Davoodnia, Department of Chemistry, School of Sciences, Islamic Azad University, Mashhad Branch, Mashhad 91735-413, Iran.     

Synthesis and properties of cyanomethyl derivatives of imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyridine,imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine,and imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>]thiazole

2-Cyanomethyl derivatives were obtained of imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine, and imidazo[2,1-b]thiazole, and their reactivity was investigated by an example of imidazo[1,2-a]pyridine: It was subjected to nitration, bromination, azo coupling and nitrosation. Acylation of the methylene group effected by amino acids esters with a subsequent addition of the amino group to the cyano group resulted in the formation of 5-amino-4-imidazo[1,2-a]-pyridin-2-yl-1-phenyl-1,2-dihydro-3H-pyrrol-3-one and 2-amino-1-ethyl-3-imidazol[1,2-a]pyridin-2-yl-4(1H)-quinolinone.     

Halocyclization of 3-allylthio-5H-[1,2,4]triazino[5,6-<Emphasis Type="Italic">b</Emphasis>]indole

The synthesis of 3-allylthio-5H-[1,2,4]triazino[5,6-b]indole has been carried out by the reaction of 3-mercapto-5H-[1,2,4]triazino[5,6-b]indole with allyl bromide in the NaOH–H₂O–DMSO system and in a one-pot synthesis from isatin-β-thiosemicarbazide. Halocyclization of allylthio-5H-[1,2,4]-triazino[5,6-b]indole synthesized the 3-halomethyl-3,10-dihydro-2H-[1,3]thiazolo[3',2':2,3][1,2,4]-triazino[5,6-b]indolium halides.     

New general synthesis of benzo[4,5]imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine and benzo[4,5]imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>]quinazoline derivatives

The reactions of benzene-1,2-diamine with 5-substituted 2-(alkylsulfanyl)-4-methylpyrimidin-6(1H)-ones and 2-(propylsulfanyl)- and 5-iodo-2-(propylsulfanyl)-3,4-dihydroquinazolines at 175–185°C under solvent-free conditions unexpectedly afforded benzo[4,5]imidazo[1,2-a]pyrimidine, benzo[4,5]imidazo[2,1-b]-quinazoline, and 2,2′-(benzene-1,2-diyldiimino)bis[pyrimidin-4(3H)-ones]. The described reaction is the first example of synthesis of these heterocyclic systems by fusion of benzimidazole to pyrimidine or quinazoline and is likely to follow ANRORC mechanism.     

Synthesis and biological activity of 3-guanidino-6-R-imidazo[1,2-<Emphasis Type="Italic">b</Emphasis>]- and 6-guanidino-3-R-[1,2,4]triazolo[4,3-<Emphasis Type="Italic">b</Emphasis>][1,2,4,5]tetrazines

The reaction of azoloannulated [1,2,4,5]tetrazines with guanidine was studied. New 3-guanidinoimidazo[1,2-b]- and 6-guanidino[1,2,4]triazolo[4,3-b] [1,2,4,5]tetrazines were synthesized using the nucleophilic substitution methodology. Compounds with high antibacterial and antiglycation activity were revealed.     

Ring-Chain Transformations of Dihydroisoxazolo[4,5-<Emphasis Type="Italic">b</Emphasis>]quinoxaline

Ring-chain transformation of 3-hydroxyiminomethyl-1-methylquinoxalinium iodide into 9-methyl-9,9a-dihydroisoxazolo[4,5-b]quinoxaline was studied. The isoxazole ring in the latter was cleaved by the action of alcohols.