Synthesis of 1,2,4- and 1,3,4-oxadiazoles from 1-aryl-5-methyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole-4-carbonyl chlorides

5-Substituted 2-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-1,3,4-oxadiazoles were synthesized by reaction of 1-aryl-5-methyl-1H-1,2,3-triazole-4-carbonyl chlorides with the corresponding 5-substituted 1H-tetrazoles. 5-Methyl-1-phenyl-1H-1,2,3-triazole-4-carbonyl chloride reacted with N′-hydroxybenzimidamides to give 3-aryl-5-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazoles. Reactions of 4-(5-methyl-1H-1,2,3-triazol-1-yl)benzoic acid with N′-hydroxybenzimidamides resulted in the formation of 3-aryl-5-[4-(5-methyl-1H-1,2,3-triazol-1-yl)phenyl]-1,2,4-oxadiazoles.     

Synthesis of 1,2,4-triazole, 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine derivatives of benzotriazole

A novel series of 1-(1-carbonylmethyl-1H-benzotriazole) thiosemicarbazides 3a-e was synthesized and then cyclized with sodium hydroxide to afford 1-(4-substituted-4H-1,2,4-triazole-3-thion-5-yl)methyl-1H-benzotriazoles 4a-e , which were alkylated with ethyl iodide to l-(3-ethylthio-4-substituted-4H-1,2,4-triazol-5-yl)-methyl-1H-benzotriazoles 5b-e . The reaction of 1H-benzotriazol-1-acetic acid hydrazide ( 2 ) with carbon disulphide and potassium hydroxide followed by hydrazine hydrate gave 1-(4-amino-4H-1,2,4-triazole-3-thion-5-yl)methyl-1H-benzotriazole ( 6 ). Its subsequent condensation with carboxylic acids in the presence of phosphorus oxychloride or with phenacyl bromides afforded two series of fused heterocycles namely; 6-substituted-3-[1-(1H-benzotriazole)methyl]-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles 7a-e and 6-substituted phenyl-3-[1-(1H-benzotriazole)methyl]-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines 8a-e respectively. The structure of the newly synthesized compounds was elucidated by elemental analyses, ir and nmr spectra.     

Synthesis of ethyl 2-[(1-aryl-1H-1,2,4-triazol-3-yl)oxy]propionates and related derivatives

Alkylation of 1-aryl-1H-1,2,4-triazol-3-ols with ethyl 2-bromopropionate under basic conditions resulted in the formation of 2-[(1-aryl-1H-1,2,4-triazol-3-yl)oxy]propionic acid, ethyl esters. No N-alkylated products were detected. Similar alkylation of 2-oxo-5-phenyl-1,3,4-thiazole and the corresponding 1,3,4-oxadiazole gave only N-alkylated derivatives. With 4-hydroxy-6-phenylpyrimidine and 2-oxo-4-phenylthiazole, both O- and N-alkylation occurred. Structure assignments were based on ir and ¹³C nmr spectral data.     

Oxidative addition of N-aminophthalimide to 2-alkenyl-1,3,4-oxadiazoles. Synthesis of aziridinyloxadiazoles

Oxidation of N-aminophthalimide with lead tetraacetate in the presence of 2-[(E)-2-arylethenyl]-5-phenyl-1,3,4-oxadiazoles gives the corresponding 2-(3-aryl-1-phthalimidoaziridin-2-yl)-5-phenyl-1,3,4-oxadiazoles. From 2-phenyl-5-[(1E,3E)-4-phenylbuta-1,3-dien-1-yl]-1,3,4-oxadiazole only the addition product at both C=C bonds was obtained, while in the reaction with 2,5-bis[(E)-2-phenylethenyl]-1,3,4-oxadiazole both mono- and bis-adducts were isolated.     

Synthesis and selected transformations of 1-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)ethanones and 1-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl]ethanones

By cycloaddition of arylazides to acetylacetone are obtained derivatives of 1,2,3-triazole. In the reaction of 1-[5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] ethanones (IIa–IIe) and 1-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl] ethanones (VIIa-VIIe) with isatin are obtained 2-[1-(R-phenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-4-quinolinecarboxylic acids (IIIa–IIIe) and 2-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl] -4-quinolinecarboxylic acids (IXa, IXb), respectively. We found that 1-[5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] ethanones (IIa–IIe) readily transform into [5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] acetic acids (IVa–IVc) by the method of Wilgerodt-Kindler. The (5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)acetic acid reacts with 5-phenyl-4-amino-4H-1,2,4-triazol-3-thiol affording 6-[(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl) methyl]-3-phenyl[1,2,4] triazolo[3,4-b] [1,3,4] thiadiazole (VI). Original Russian Text ? N.T. Pokhodylo, R.D. Savka, V.S. Matiichuk, N.D. Obushak, 2009, published in Zhurnal Obshchei Khimii, 2009, vol. 79, no. 2, pp. 320–325.     

Anodic formation of 3,6-diaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and 2(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles

3,6-Disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles together with the unknown systems 2-(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles were obtained by anodic oxidation, under aprotic conditions, of aryl aldehyde N-(5-aryl-1,3,4-thiadiazol-2-yl) hydrazones. Mechanistic proposals are given.     

Synthesis and in-vitro antioxidant activities of some coumarin derivatives containing 1,2,3-triazole ring

A new green protocol was developed for the S-alkylation of 2-mercapto-1,3,4-oxadiazole by the reaction of 5-substituted-2-mercapto-1,3,4-oxadiazole with propargyl bromide in sodium bicarbonate in water. The newly synthesized 5-[(substitutedphenoxy)methyl]-2-[(prop-2-yn-1-yl)sulfanyl]-1,3,4-oxadiazole when reacted with azidomethyl coumarins underwent regioselective reaction yielding 4-(((4-((5-((substitutedphenoxy)methyl)-1,3,4-oxadiazol-2-yl)sulfanylmethyl)-1H-1,2,3-triazol-1-yl)methyl)-6-methyl)-2H-chromene-2-one or 1-((4-((5-((substitutedphenoxy)methyl)-1,3,4-oxadiazol-2-yl)sulfanylmethy)-1H-1,2,3-triazol-1-yl-)methyl)-3H-benzo[f]chromene-3-one. Structures of the newly synthesized compounds were confirmed by spectral and analytical data. The compounds were screened for their in-vitro antioxidant property.     

Oxidative addition of <Emphasis Type="Italic">N</Emphasis>-aminophthalimide to styryl-1,2,4-oxadiazoles

The oxidation of N-aminophthalimide with lead tetraacetate in the presence of 5-[(E)-2-arylethenyl]-3-(4-methylphenyl)-1,2,4-oxadiazoles and 5-(4-methylphenyl)-3-[E)-2-phenyl-ethenyl]-1,2,4-oxadiazole led to the formation of the corresponding (3-aryl-1-phthalimidoaziridin-2-yl)-(4-methylphenyl)-1,2,4-oxadiazoles. In the reaction with 3,5-distyryl-1,2,4-oxadiazole a mixture was obtained of two regioisomeric monoadducts and a diadduct in the ratio 80 : 15: 5; at the use of 3 equiv of the aziridinating reagents only diadduct was isolated as a mixture of two diastereoisomers in the ∼3 : 2 ratio that were separated by recrystallization.     

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.     

Ring transformations of heterocycles. Part 1. Transformation of 4-amino-Δ2-1,2,4-oxadiazolines into 1,3,4-oxadiazoles

3-Aryl-4-amino-δ²-1,2,4-oxadiazolines 3 and their N-chloroacetyl derivatives 4 , upon treatment with chloroacetic anhydride in refluxing toluene, afford 2-chloromethyl-5-aryl-1,3,4-oxadiazoles 5 , suggesting the conversion sequence 3 → 4 → 5 . The generality of the new ring transformation 4 → 5 is supported similar conversion of other 4-(acylamino)-1,2,4-oxadiazolines 8 to 1,3,4-oxadiazoles 9 .     

Synthesis of [5-(1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-4-yl)-1,3,4-oxadiazol-2-yl]pyridines

2-, 3-, and 4-[5-(1-Aryl-5-R-1H-1,2,3-triazol-4-yl)-1,3,4-oxadiazol-2-yl]pyridines were synthesized from the corresponding 1-aryl-5-R-1H-1,2,3-triazole-4-carbonyl chlorides and 2-, 3-, and 4-(1H-tetrazol-5-yl)-pyridines.     

Synthesis of 5-aryl-3-carbazoyl-1,3,4-oxadiazol-2(3H)-one. Derivatives and their ring transformation into 5-benzamido-1,2,4-triazolidine-3,5-dione derivatives

Some 5-aryl-3-carbazoyl-1,3,4-oxadiazol-2(3H)-one derivatives 6 and 9 have been synthesized in two ways. The expected thermal ring transformation into 2,5-disubstituted 1,3,4-oxadiazoles did not occur but, by acid hydrolysis of 5-aryl-3-[3-benzylidene-2-methyl(or phenyl)carbazoyl]-1,3,4-oxadiazol-2(3H)-ones 6 , a new ring transformation took place and the corresponding 4-benzamido-1-methyl(or phenyl)-1,2,4-triazolidine-3,5-dione derivatives 11 were formed. The 4-amino-1-phenyl-1,2,4-triazolidine-3,5-dione ( 19 ) has been prepared and its structure was confirmed by some reactions.     

3,3-Dinitrobutyl-1,2,4-oxadiazoles

The syntheses of 3,5-bis(3,3-dinitrobutyl)-1,2,4-oxadiazole and a series of 3-aryl-5-(3,3-dinitrobutyl)-1,2,4-oxadiazoles were accomplished by treating 4,4-dinitropentanoyl chloride with the appropriate amidoximes to yield the intermediate O-(4,4-dinitropentanoyl)amidoximes, which were dehydrated to the 1,2,4-oxadiazoles.     

Synthesis of novel 1-benzyl/aryl-4-{[(1-aryl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-4-yl)methoxy]methyl}-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole derivatives and evaluation of their antimicrobial activity

A series of 1-benzyl/aryl-4-{[(1-aryl-1H-1,2,3-triazol-4-yl)methoxy]methyl}-1H-1,2,3-triazole derivatives were synthesized via Cu(I) catalyzed reaction between terminal alkyne and substituted aryl or benzyl azides. The synthesized triazoles were characterized by 1H NMR, 13C NMR, IR, and mass spectral techniques. All the synthesized compounds were screened for their antimicrobial activity.     

新型1,2,4-三唑[3,4-b]-1,3,4-噻二嗪的合成及表征

以3-(2-苯基-1,2,3-三唑-4-基)-4-氨基-5-巯基-1,2,4-三唑(1)为原料分别与ω-溴代芳基乙酮、ω-溴代-ω-(1H-1,2,4-三 唑-1-基)芳基乙酮反应, 合成了一系列新的1,2,4-三唑[3,4-b]-1,3,4-噻二嗪类化合物2a～2e和3a～3e. 其结构经IR, ¹H NMR和MS及元素分析确证.     

Studies on Condensed Heterocyclic Compounds XVII. Synthesis of 6-(1-Aryl-5-methyl-1,2,3-triazol-4-yl)-3-phenyl-s-triazolo[3,4-b]-1,3,4-thiadiazoles

Treatment of 4-amino-5-mercapto-3-phenyl-1,2,4-triazole 2 with 1-aryl-4-carboxy-5-methyl-1,2,3-triazoles 1a-1j in a one-step reaction yielded several 6-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-3-phenyl-s-triazolo[3,4-b]-1,3,4-thiadiazoles 3a-3j . The structures of all the products were established on the basis of elemental analyses and spectral data. The fragmentation of the mass spectra of 3a-3j under electron impact was discussed.     

含三唑基的新型咪唑[2,1-b]-1,3,4-噻二唑的合成及表征

以2-(2-苯基-1,2,3-三唑-4-基)-5-氨基-1,3,4-噻二唑(1)为原料分别与ω-溴代芳基乙酮、ω-溴代-ω-(1H-1,2,4-三唑-1-基)芳基乙酮反应, 合成了一系列新型咪唑[2,1-b]-1,3,4-噻二唑类化合物2a～2e和3a～3e. 其结构经IR, ¹H NMR和MS及元素分析确证.     

Design and synthesis of novel quinoline derivatives bearing oxadiazole,isoxazoline, triazolothiadiazole,triazolothiadiazine, and piperazine moieties

A new series of 2,3-disubstituted quinoline derivatives were synthesized from 2-chloroquinoline-3-carbaldehyde. In the reaction sequence, acetanilide was cyclized to give 2-chloroquinoline-3-carbaldehyde 1 , which was transformed to 2-(4-phenylpiperazin-1-yl)quinolin-3-carbaldehyde 2 by reaction with 4-phenylpiperazine in DMF-containing anhydrous K₂CO₃; then, compound 2 was oxidized by iodine in methanol, and methyl 2-(4-phenylpiperazin-1-yl)quinoline-3-carboxylate 3 was synthesized. The key intermediate 4 , 4-amino-5-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-4H-1,2,4-triazole-3-thiol, was prepared using the ester 3 by a series of step. Reaction of 5 with various aromatic carboxylic acids or phenacyl bromides yielded 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles 5a-c and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines 6a-c , respectively. Moreover, compound 2 condensed with o-phenylenediamine to give 2-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-1H-benzimidazole 7 . Interaction of 7 and 2-chloromethyl-5-aryl-1,3,4-oxadiazoles in the presence of K₂CO₃ led to the title compounds 8a-c . Furthermore, 4,5-dihydroisoxazoline derivatives 9a-c were obtained by the reaction of readily accessible starting materials including 2-(4-phenylpiperazin-1-yl)quinolin-3-carbaldehyde 2 , 1-phenyl-2-(triphenylphosphoranylidene)ethanone and hydroximoyl chlorides under mild conditions in the presence of Et₃N. The hydrazone intermediates 10a-c were obtained by the condensation of 2 with aroylhydrazides in ethanol, then, refluxing in acetic anhydride yielded 3-acetyl-5-aryl-2-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-2,3-dihydro-1,3,4-oxadiazoles 11a-c . Structures of these compounds were established by their elemental analysis, IR, ¹H NMR, and mass spectral data.     

Synthesis and antibacterial activities of novel imidazo[2,1-b]-1,3,4-thiadiazoles

2-Amino-5-(2-aryl-2H-1,2,3-triazol-4-yl)-1,3,4-thiadiazoles 2-4 have been synthesized by the reaction of 2-aryl-2H-1,2,3-triazole-4-carboxylic acids 1 with thiosemicarbazide. Their reaction with phenacyl (p-substituted phenacyl) bromides led to formation of the respective 6-aryl-2-(2-aryl-2H-1,2,3-triazol-4-yl)imidazo[2,1-b]-1,3,4-thiadiazoles 5. Reactivity of the latter fused ring towards reaction with different electrophilic reagents afforded the corresponding 5-substituted derivatives 6-8. The structure of the above compounds was confirmed from their spectral characteristics. Some of these compounds were found to possess slight to moderate activity against the microorganisms Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, and Escherichia coli.     

Synthesis of 1,2,4-Triazol-3-ylmethyl-, 1,3,4-Oxa-, and -Thiadiazol-2-ylmethyl-1H-[1,2,3]-triazolo[4,5-d]pyrimidinediones

1-Carbethoxymethyl-4,6-dimethyl-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5,7(4H,6H)-dione was synthesized and treated with hydrazine hydrate to give the corresponding hydrazide. The latter hydrazide was treated either with phenylisothiocyanate or with carbon disulfide/alc. KOH to afford the corresponding thiosemicarbazide and oxadiazole derivatives. Alkylation of 2-mercapto-1,3,4-oxadiazole with dimethyl sulfate or ethyl chloroacetate gave the corresponding 2-methylthio-, and 2-ethylthioglycolate derivatives. Formation of 1,3,4-thiadiazole, 5-mercapto-1,2,4-triazole, and 1,3,4-oxadiazole were carried out by treating of the latter thiosemicarbazide with conc. H₂SO₄, NaOH/HCl, and HgO. Treating of 5-mercapto-1,2,4-triazole with ethyl chloroacetate afforded the thioglycolate ester. Hydrolysis of the latter with hydrazine hydrate afforded the hydrazide derivatives. Condensation of these hydrazides with monosaccharide aldoses gave the corresponding sugar hydrazones. The novel compounds were tested for antiviral activity against hepatitis B virus and showed moderate activities.