Triazoles and Fused Triazoles II: Synthesis of Certain Substituted s-Triazoles,s-Triazolo[3,4-b]-1,3,4-Thiadiazoles and s-Triazolo [3,4-b]-1, 3,4-Thiadiazines

The synthesis of a certain series of s-triazoles and fused s-triazoles namely: 3-(3,4-dimethoxyphenyl)-4-arylideneamino-5-mercapto-s-triazoles 3.8 , 3-(3,4-dimethoxyphenyl)-6-substituted-s-triazolo[3,4-b]-1,3,4-thiadiazoles 11-17 , 3-(3,4-dimethoxyphenyl)-6-substituted thio-s-triazolo[3,4-b]-1,3,4-thiadiazoles 19, 20 and 3-(3,4-dimethoxyphenyl)-6-substituted-7H-s-triazolo[3,4-b]-1,3,4-thiadiazines 21, 22 , is described.     

Systèmes aromatiques à 10 électrons π dérivés de l'aza-3a penlalène. VIII. Recherches dans la série du pyrazolo[3,2-c]-s-triazole

It has been shown that the reaction of β-ketoesters with 1,2-diamino-1,3,4-triazoles affords pyrazolo[3,2-c]-s-triazoles. These results induces us to propose a 7,8-dihydro-9H-s-triazolo[4,3–6]-[1,2,4] triazepin-8-one structure for the intermediate in this synthesis.     

Synthesis and antibacterial activity of 1-(2,4-dichlorobenzoyl)-4-substituted thiosemicarbazides, 1,2,4-triazoles and their methyl derivatives

A series of 1-(2,4-dichlorobenzoyl)thiosemicarbazides, s-triazoles and their methyl derivatives have been synthesised by condensation of 2,4-dichlorobenzoyl hydrazine with aryl isothiocyanates. Subsequent ring closure of the substituted thiosemicarbazides yielded the s-triazoles, and reaction with methyl iodide resulted methyl derivatives. All the compounds were subjected to in vitro testing against two gram-positive and two gram-negative bacteria. Antibacterial activity was found to be moderate to good in most of the compounds.     

A new synthesis of s-triazoles from 1H-2,3-benzoxazine 4-hydrazones

Aliphatic and aromatic aldehydes react with 4-hydrazino-1H-2,3-benzoxazines (I) to form the corresponding 1H-2,3-benzoxazine hydrazones (II). Compounds II when heated in the presence of an acid catalyst rearrange to form substituted s-triazoles (III) in high yields. In particular, the hydrazones containing one imino hydrogen undergo the same rearrangement by refluxing in xylene. Structure III, in agreement with the analytical and spectroscopic data, was confirmed by univocal syntheses. The N-acylation and N-alkylation of some unsymmetrically 3,5-sub-stituted s-triazoles were also investigated and the mechanism of formation of III is briefly discussed.     

Novel syntheses of thiazolo[3,2-b]-s-triazoles

The reaction of 2-amino-and 2-acylaminothiazoles with O-mesitylenesulfonylhydroxylamine resulted in the ready formation in the corresponding 3-aminium salts, which were converted into thiazolo[3,2-b]-s-triazoles in high yields.     

Triazoles and fused triazoles,III: Facile and efficient synthesis of 2,5-disubstituted-s-triazolo[3,4-b]-1,3,4-thiadiazoles

Summary The development of a facile and efficient method for the synthesis of 2,5-diaryl-s-triazolo[3,4-b]-1,3,4-thiadiazoles4 a–e from the corresponding 3-aryl-4-amino-5-mercapto-s-triazole (2), is described. 3-Aryl-4-arylideneamino-5-mercapto-s-triazoles (3 a–e) were cyclized to compounds4 a–e by heating in nitrobenzene for a few minutes.Part II: See Ref. [11]     

Synthesis of heterocycles. Part VII Synthesis and antimicrobial activity of some 7H-s-triazolo[3,4-b][1,3,4]thiadiazine and s-triazolo[3,4-b][1,3,4]thiadiazole derivatives

The cyclization of 4-amino-5-aryl-3-cyanomethylthio-1,2,4-triazoles II in the presence of concentrated sulfuric acid yields 7H-6-amino-s-triazolo[3,4-b][1,3,4]thiadiazines III . Cyclization of 4-amino-5-aryl-1,2,4-tria-zole-3-thiones I with phenacyl chloride yields 7H-3-aryl-6-phenyl-s-triazolo[3,4-b][1,3,4]thiadiazines IV . Similarly, compounds I condensed with cyanogen bromide, phenyl isothiocyanate and carbon disulfide to give the corresponding cyclized products 6-amino-3-aryl-s-triazolo[3,4-b][1,3,4]thiadiazoles V , 3-aryl-6-phenyl-amino-s-triazolo[3,4-b][1,3,4]thiadiazoles VI and 3-aryl-striazolo[3,4-b][1,3,4]thiadiazol-6(5H)thiones VII , respectively. Also in the presence of phosphoryl chloride, compounds I underwent cyclization with monocarbo-xylic acids and oxalic acid to 3,6-diaryl-s-triazolo[3,4-b][1,3,4]thiadiazole VIII and 6,6′-bis(3-aryl-s-triazolo-[3,4-b][1,3,4]thiadiazoles) IX . The above compounds were screened for their antimicrobial activity.     

Reactions of α-ketohydrazidoyl halides with some heterocyclic amines. Facile synthesis of arylazo derivatives of fused heterocycles with a bridgehead nitrogen atom

Arylazo derivatives of imidazo[2,1-b]thiazoles, imidazo[1,2-b]pyrazoles, imidazo[1,2-b]-s-triazoles, imidazo[1,2-a]pyrimidines, and imidazo[1,2-a]pyridines were obtained in good yields from α-keto hydrazidoyl halides and 2-aminothiazole, 5-aminopyrazole, 5-aminotriazole, 2-aminopyrimidine, and 2-aminopyridine, respectively (cf. Tables I and II). The structures of the products were assigned and confirmed on the basis of their elemental analyses, spectra, and alternate synthesis wherever possible.     

Die Acylierung von 5-Amino-1 H-1, 2, 4-triazolen. Eine 13C-NMR.-Studie

The Acylation of 5-Amino-1 H-1,2,4-triazoles. A ¹³C-NMR. Study The acylation of 3-substituted-5-amino-1 H-1,2,4-triazoles (1) with methyl chloroformate or dimethylcarbamoyl chloride yielded mainly 1-acyl-5-amino-1,2,4-triazoles ( 2 and 3 ). Acylation of 3-methyl-, 3-methoxy- and 3-methylthio-5-amino-1 H-1,2,4-triazole ( 1b , 1c and 1d ) with methyl chloroformate gave up to 10% of the 1-acyl-3-amino-1,2,4-triazoles. For the unsubstituted 5-amino-1,2,4-triazole (1a) , a (1:1)-mixture of the 3- and 5-isomers 2a and 4 was obtained in dioxane in the presence of triethylamine. No 4-acylated product was detected in contrast to earlier reports. The structures of the reaction products were determined with the aid of proton coupled ¹³C-NMR. spectra using the corresponding N-methyl-1,2,4-triazoles as reference compounds.     

Synthesis of 2(5H)-Furanone Derivatives with Symmetrical and Unsymmetrical Bis-1,2,3-triazole Structure

The interesting bioactivities of 2(5H)-furanone, 1,2,3-triazole, and amino acid derivatives have promoted their combination into one multifunctional molecule. The symmetrical bis-1,2,3-triazoles and mono-1,2,3-triazoles with one free azide group are synthesized respectively by controlling the molar ratio of reactants, N-[5-alkoxy-2(5H)-furanonyl] amino acid propargyl ester and 1,4-diazidobutane. The unsymmetrical bis-1,2,3-triazoles are afforded by the subsequent reaction of mono-1,2,3-triazoles with other terminal alkynes with good to excellent yields in a short time under the same mild “click” reaction conditions. The 32 new compounds obtained in the reactions are characterized by Fourier transform infrared, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. Because of the diversity of four or five basic units in molecule, this methodology provides easy access to different chiral 2(5H)-furanone compounds with polyheterocyclic structure, especially with unsymmetrical bis-1,2,3-triazole moiety. Importantly, a simple approach is provided for the synthesis of unsymmetrical bis-1,2,3-triazoles using common diazides.     

1,2,4-Triazoles. V. Nuclear magnetic resonance study of N-Methyl derivatives of 1,2,4-triazoles

The chemical shifts of the N-methyl protons of a number of N-methylated-1,2,4-triazoles were studied. Substitution of methyl and methylthio groups in position 3 causes upfield shifts of the N-methyl signals, while substitution of α-pyridyl, γ-pyridyl, and phenyl groups causes downfield shifts. In 3,5-disubstituted 1,2,4-triazoles, substituents in positions 3 and 5 have additive effects on the chemical shifts of N-methyl groups, so that the chemical shifts of the N-methyl groups of such compounds can be calculated. In this way, it was possible to assign the peaks of mixtures of N-monomethylated derivatives obtained by methylation of 1,2,4-triazoles.     

Ring-chain-transformations : Synthesis of ω-functionalized alkylthio-1,2,4-triazoles by reaction of cyclic S-analogous N-cyano or N-aroylcarbonimidoesters with hydrazines

Cyclic N-cyanocarbonimidodithioesters 4 or N-aroylcarbonimidothioic acid esters 10 react regioselectively with arylhydrazines and methylhydrazine by a ring chain transformation reaction forming ω-functionalized 3-alkylthio-1,2,4-triazoles 8 and 11 or 5-alkylthio-1,2,4-triazoles 9 .     

Syntheses of 1-substituted 1,2,4-triazoles,imidazoles and benzimidazoles

Substituted 2-phenethyl-1,2,4-triazoles, 1-phenethylimidazoles 3 and 1-phenethylbenzimidazoles 5 were synthesized from the reaction of compound 8 with tri-n-butyltin hydride in good yield. The reaction of substituted-2-phenethyl halide with 1H-1,2,4-triazoles, imidazoles and benzimidazoles gave a low yield. The yield was increased by the use of substituted-2-phenethyl p-toluensulfonate.     

An improved procedure for the preparation of 1-benzyl-1H-1,2,3-triazoles from benzyl azides

A procedure for the preparation of substituted 1-benzyl-1H-1,2,3-triazoles from benzyl azides under very mild conditions is described. The method provides improved yields and extends the scope of the Dimroth Reaction to other types of active methylene compound to those previously used. Benzyl azides react with active methylene compounds in dimethyl sulphoxide catalysed by potassium carbonate at 35–40° to give 1H-1,2,3-triazoles usually in good yield. Acetonitrile derivatives gave 5-amino-1H-1,2,3-triazoles whereas diethyl malonate gave 5-hydroxy-1H-1,2,3-triazoles. 1H-1,2,3-Triazole-4-carboxylate esters and 1H-1,2,3-triazole-4-ketones were obtained from ethyl acetoacetate and β-diketones respectively. Benzyl methyl ketone reacted to give a 5-methyl-4-phenyl-1H-1,2,3-triazole, but acetone and acetophenone failed to react. Other active methylene compounds which did not react under these reaction conditions included ethyl cyanoacetate, ethyl fluoroacetate and ethyl nitroacetate.     

新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物的合成及抗菌活性

通过3-取代-4-氨基-5-巯基-1,2,4-三唑(3a～3m)和2-溴-2-(1H–1,2,4-三唑-1-基)-4′-氯代苯乙酮(2)的缩合反应, 合成了13个新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物4a～4m. 化合物结构经元素分析, ¹H NMR, IR和MS进行了表征. 抗菌试验表明所合成的化合物对细菌表现出中等程度的抑制活性.     

p-Toluenesulfonic acid-promoted autocatalytic hydrolyzation of 1-tosyl-1,2,3-triazoles

The first example of autocatalytic hydrolyzation of 4-aryl-1-tosyl-1,2,3-triazoles induced by p-toluenesulfonic acid was reported, providing an effective and metal-free synthetic approach to deliver a broad range of new 4-aryl-2H-1,2,3-triazoles in good yields. The kinetic profile of this hydrolyzation suggested that this reaction has exponential autocatalytic behavior.     

Reactions of 3-amino-1,2,4-triazoles with cinnamic aldehydes

The reaction of 3-amino- and 3-amino-5-methylthio-1,2,4-triazoles with cinnamaldehyde takes two directions to form mixtures of 5-[N-(3-phenylpropenylideneamino)]-1H-1,2,4-triazoles and 5-phenyl-4,5,6,7-tetrahydro[1,2,4]triazolo[1,5-a]pyrimidin-7-ols.     

New rearrangement of benzo[d]isoxazoles: recyclization of 4-R-6-nitrobenzo[d]isoxazole-3-carbaldehyde arylhydrazones into 2-aryl-4-(2-hydroxy-4-nitro-6-R-phenyl)-1,2,3-triazoles

The previously unknown recyclization of nitrobenzo[d]isoxazoles into 1,2,3-triazoles was found. A general method for the synthesis of 2-aryl-4-(2-hydroxy-4-nitro-6-R-phenyl)-1,2,3-triazoles from 4-R-6-nitrobenzo[d]isoxazole-3-carbaldehyde arylhydrazones was developed.     

Regioselectivity in the Reactions of Bis -hydrazonoyl Halides with Pyrimidine-2-thiones

 Bis-hydrazonoyl chlorides react regioselectively with pyrimidine-2-thiones, which contain a masked thiourea residue, to give the hitherto unknown annelated 2,3-bis-arylhydrazono-thiazoles and 3,3′-bis-1,2,4-triazoles. Reaction of bis-hydrazonoyl chlorides with 2-methylthio derivatives gave only 3,3′-bis-1,2,4-triazoles.     

Heterocyclic N-glycosides. III. Synthesis of N-glycosyl-v-triazoles from glycosyl azides and phenylacetylene

A number of v-triazoles were prepared by the 1,3-dipolar cycloaddition of glycosyl azides on phenylacetylene. In all the cases studied, except when 2-O-trichloroacetyI-3,4,6-tri-O-acetyl-α-D-glucopyranosyl azide was used, the two possible v-triazoles were obtained. The assignment of structure and anomeric configuration for all N-glycosides obtained is discussed.