Reaction Of Triazoles Research Articles

A regioselective and convenient one-pot multicomponent synthesis of 9-amino-3,5-diaryl-4,9-dihydro-5H-[1,2,4]triazolo[5,1-c][1,2,4]triazepine-8-thiol

ABSTRACTAn efficient and environment-friendly procedure for the synthesis of a new series of nitrogen bridge-head [1,2,4]triazolo[5,1-c][1,2,4]triazepine derivatives through one-pot three-component reaction of polyfunctional triazole with aromatic aldehydes and acetophenone derivatives using alcoholic sodium hydroxide solution. The same new products were prepared in classical route through reaction of triazole with the corresponding chalcones under the same conditions.

Synthesis and anticancer activity of novel aza-artemisinin derivatives

Three series of aza-artemisinin derivatives were synthesized for studies of anticancer activity. The first series of compounds were prepared via copper(I)-catalyzed azide alkyne cycloaddition, so called “click reaction”, starting from propargyl derivatives of 11-aza-artemisinin and various azides, whereas the second and third series of compounds were prepared by triazolization reaction starting from enolizable ketones and primary amines connected to artemisinin. In vitro studies of the 23 synthesized artemisinin derivatives unveiled that 9 compounds displayed antiproliferative activity in the low micromolar range, with 5d being the most promising compound showing 50% inhibition of Cem and HeLa cell growth at 0.92 and 1.2µM, respectively.

Application of the Triazolization Reaction to Afford Dihydroartemisinin Derivatives with Anti-HIV Activity.

Artemisinin and synthetic derivatives of dihydroartemisinin are known to possess various biological activities. Post-functionalization of dihydroartemisinin with triazole heterocycles has been proven to lead to enhanced therapeutic potential. By using our newly developed triazolization strategy, a library of unexplored fused and 1,5-disubstituted 1,2,3-triazole derivatives of dihydroartemisinin were synthesized in a single step. All these newly synthesized compounds were characterized and evaluated for their anti-HIV (Human Immunodeficiency Virus) potential in MT-4 cells. Interestingly; three of the synthesized triazole derivatives of dihydroartemisinin showed activities with half maximal inhibitory concentration (IC50) values ranging from 1.34 to 2.65 µM.

Force-induced retro-click reaction of triazoles competes with adjacent single-bond rupture.

The highly controversial force-induced cycloreversion of 1,2,3-triazole, its well-known retro-click reaction, is shown to be possible only for 1,5-substituted triazoles, but competes with rupture of an adjacent single-bond. We draw this conclusion from both static and dynamic calculations under external mechanical forces applied to unsubstituted and 1,4- and 1,5-substituted triazoles. The JEDI (Judgement of Energy DIstribution) analysis, a quantum chemical tool quantifying the distribution of strain energy in mechanically deformed molecules, is employed to identify the key factors facilitating the force-induced retro-click reaction in these systems. For 1,4-substituted triazoles it is shown to be impossible, but the parallel alignment of the scissile bond in 1,5-substituted triazoles with the acting force makes it generally feasible. However, the weakness of the carbon-nitrogen bond connecting the triazole ring to the linker prevents selective cycloreversion.

Two-Step Synthesis of Fluorescent 3-Arylated 1,3a,6a-Triazapentalenes via a Three-Component Triazolization Reaction.

Novel 3-arylated 1,3a,6a-triazapentalenes were synthesized using a metal-free three-component triazolization reaction followed by a triflate based cyclization step. This method starts from simple commercial starting materials and provides an easy functionalization strategy for the 3-position of the triazapentalenes. By introducing electron-withdrawing groups onto this position, stable and highly fluorescent dyes could be synthesized.

Cobalt-catalyzed amination of triazoles with dioxazol-5-ones through triazole-directed ortho C[sbnd]H activation

Cobalt-catalyzed reactions of triazoles and dioxazol-5-one involving nitrene transfer were described. A number of amidated 1,2,3-trizole derivatives have been obtained in moderate to excellent yields.

ChemInform Abstract: Synthesis of 3‐Pyrazolyl‐1,2,4‐triazoles via One‐Pot Multicomponent Reaction in Phosphoric Acid.

A high-yielding synthetic route towards pyrazolyl-[1,2,4]triazole derivatives has been developed via one-pot multicomponent reaction of polyfunctionalized triazoles, DMF–DMA, acetophenone, ethyl cyanoacetate, and/or 3-oxo-3-phenylpropanenitrile in ortho-phosphoric acid (85%). In the same manner, a new series of 2-triazolyl-tetrahydro-indazol-4-ones and pyrazolo[3,4-d]pyrimidines has been synthesized by reaction of triazoles, DMF–DMA and 1,3-cyclohexanediones and/or barbituric acid, respectively. The same products were prepared a classical manner via reaction of triazoles with the corresponding enaminones in ortho-phosphoric acid (85%).

Synthesis of 3-Pyrazolyl-1,2,4-Triazoles via One-Pot Multicomponent Reaction in Phosphoric Acid

A high-yielding synthetic route towards pyrazolyl-[1,2,4]triazole derivatives has been developed via one-pot multicomponent reaction of polyfunctionalized triazoles, DMF–DMA, acetophenone, ethyl cyanoacetate, and/or 3-oxo-3-phenylpropanenitrile in ortho-phosphoric acid (85%). In the same manner, a new series of 2-triazolyl-tetrahydro-indazol-4-ones and pyrazolo[3,4-d]pyrimidines has been synthesized by reaction of triazoles, DMF–DMA and 1,3-cyclohexanediones and/or barbituric acid, respectively. The same products were prepared a classical manner via reaction of triazoles with the corresponding enaminones in ortho-phosphoric acid (85%).

ChemInform Abstract: Improved Microwave‐Assisted Catalyst‐Free Synthesis of 9‐Aryl‐5,9‐dihydropyrimido[4,5‐d][1,2,4]triazolo [1,5‐a]pyrimidine‐6,8(4H,7H)‐dione Derivatives.

AbstractTitle compounds are synthesized by this new green and regioselective one‐pot reaction of triazoles, aromatic aldehydes, and barbituric acids.

ChemInform Abstract: A Reaction of Triazoles with Thioesters to Produce β‐Sulfanyl Enamides by Insertion of an Enamine Moiety into the Sulfur—Carbonyl Bond.

N-Sulfonyl-1,2,3-triazoles react with thioesters in the presence of a rhodium(II) catalyst to produce β-sulfanyl enamides in a stereoselective manner. The reaction proceeds through generation of an α-imino rhodium carbene complex, nucleophilic addition of the sulfur atom of a thioester onto the carbenoid carbon atom, and subsequent intramolecular migration of the acyl group from the sulfur atom to the imino nitrogen atom. The method is successfully applied to a ring-expansion reaction of thiolactones, thus leading to the formation of sulfur-containing lactams.

A Reaction of Triazoles with Thioesters to Produce β-Sulfanyl Enamides by Insertion of an Enamine Moiety into the Sulfur-Carbonyl Bond.

N-Sulfonyl-1,2,3-triazoles react with thioesters in the presence of a rhodium(II) catalyst to produce β-sulfanyl enamides in a stereoselective manner. The reaction proceeds through generation of an α-imino rhodium carbene complex, nucleophilic addition of the sulfur atom of a thioester onto the carbenoid carbon atom, and subsequent intramolecular migration of the acyl group from the sulfur atom to the imino nitrogen atom. The method is successfully applied to a ring-expansion reaction of thiolactones, thus leading to the formation of sulfur-containing lactams.

A Reaction of Triazoles with Thioesters to Produce β‐Sulfanyl Enamides by Insertion of an Enamine Moiety into the Sulfur–Carbonyl Bond

AbstractN‐Sulfonyl‐1,2,3‐triazoles react with thioesters in the presence of a rhodium(II) catalyst to produce β‐sulfanyl enamides in a stereoselective manner. The reaction proceeds through generation of an α‐imino rhodium carbene complex, nucleophilic addition of the sulfur atom of a thioester onto the carbenoid carbon atom, and subsequent intramolecular migration of the acyl group from the sulfur atom to the imino nitrogen atom. The method is successfully applied to a ring‐expansion reaction of thiolactones, thus leading to the formation of sulfur‐containing lactams.

Reactivity of 1,2,3-triazoles towards sulfonyl chlorides. A novel approach to 1- and 2-sulfonyl-4-azolyl-1,2,3-triazoles

The reactions of N-unsubstituted triazoles with sulfonyl chlorides afforded mixtures of regioisomeric 1- and 2-sulfonyl-1,2,3-triazoles. In some cases, pure regioisomers were obtained by crystallization of mixtures of isomers. 1,2,3-Triazoles bearing thiadiazole, isoxazole and benzene rings react with mesyl chloride and tosyl chloride to form mainly 1-substituted 1,2,3-triazoles. Conversely, reactions of triazoles 1a,b and oxadiazolyl triazole 1h with more bulky 1-(2,4-dimethylphenyl)sulfonyl chloride affords mainly 2-substitued products. Oxadiazole 1b furnishes an equal mixture of the regioisomeric products 3 and 4 as a result of the reaction with mesyl and tosyl chlorides. Higher temperatures increase the ratio of isomers in favor of the 2-substituted triazole. The ratio of isomers depends on both the nature of the azolyl ring and on the size of the substituent in the sulfonyl chloride. Based on the results of experimental and theoretical data, 1-substituted and 2-substituted 1,2,3-triazoles can be considered as the kinetic and thermodynamic products.

ChemInform Abstract: Aza‐[4 + 3] and Aza‐[3 + 2] Annulations for Synthesis of Dihydroazepines and Dihydropyrroles from Alkynes, Sulfonyl Azides, and 1,3‐Dienes.

AbstractThe reaction of triazole (I) with dienes (II) and (VI) in the presence of rhodium(II) octanoate as catalyst leads to dihydropyrroles (III) and (VII), resp., whilst the Rh2((S)‐PTAD)4‐catalyzed reaction affords dihydroazepines (V).

ChemInform Abstract: A Rh‐Catalyzed Regio‐ and Stereoselective Route to Enamides: Benzamides as Assembling Reagents.

AbstractA novel method is elaborated for the preparation of substituted enaminones (III) and (VI) by a Rh‐catalyzed reaction of triazoles (I) and (V) with amides (II).

ChemInform Abstract: N1‐Selective Oxidative C—N Coupling of Azoles with Pyrroles Using a Hypervalent Iodine Reagent.

AbstractNo explanation is given for the changed regioselectivity in the reaction of triazole (VIII) with unsubstituted indole (XV).

Biological evaluation of some triazole and triazolothiadiazine derivatives

ABSTRACT: Triazole and triazoles fused with six-membered ring systems are found to possess diverse applications in the field of medicine, agriculture and industry. The 1,2,4-triazole and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines derivatives were synthesized as cholinesterase inhibitors. The reaction of 1H-indol-3-acetic acid with thiocarbohydrazide gave the 4-amino- 3-mercapto-5-[(1H-indol-3-yl)methyl]-4H-1,2,4-triazole. The reaction of triazole with arylaldehydes in ethanol gave the 4-arylideneamino-3-mercapto-5-[(1H-indol-3-yl)methyl]-4H- 1,2,4-triazoles. The 3-[(1H-indol-3-yl)methyl]-6-aryl-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines were obtained by condensing triazole with phenacylbromides in absolute ethanol. The chemical structures of the compounds were elucidated by IR, 1H-NMR and FAB+-MS spectral data and elemental analysis. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) using a modification of Ellman’s spectrophotometric method. Compounds 1b and 1c can be identified as promising anticholinesterase agents due to their inhibitory effect on AChE with IC50 value of 96.45±8.14 and 76.24±6.42 μM respectively when compared with Donepezil (IC50 =0.056±0.001μM). KEY WORDS: Indole, triazole, triazolothiadiazine, cholinesterase inhibitors

Synthesis of 5‐Aryl‐3‐Glycosylthio‐4‐Phenyl‐4H‐1,2,4‐Triazoles and Their Acyclic Analogs Under Conventional and Microwave Conditions

Under microwave irradiation (MWI), 4‐phenyl‐5‐substituted‐4H‐1,2,4‐triazole‐3‐thiol derivatives 7 and 8 were synthesized in a good yield by intramolecular cyclization of the aroyl phenyl thiosemicarbazides 5 and 6. The respective triazolylglycosides (Str‐glycosides) 12–17 were obtained by reaction of triazoles 7 and 8 with glycosyl halides 9–11 in dry acetone in the presence of potassium carbonate as base under both conventional and MWI conditions. Alkylation of 7 and 8 with haloalchols 18–20 in boiling ethanolic solution containing sodium ethoxide as a base gave the corresponding alkylated analogs 21–26. MWI conditions led to higher yield in shorter reaction time than the conventional method. Treatment of 26 with tosyl chloride gave the unexpected product 29 and not 27 or 28. Oxidation of 26 with sodium metaperiodate afforded triazole 8 and not the aldehyde 30. Attempted glycosylation and alkylation of the phenolic OH group in triazole 8 were unsuccessful; this was proved by theoretical calculations using the AM1 semi‐empirical method.

New triazole and triazolothiadiazine derivatives as possible antimicrobial agents

Triazole and triazoles fused with six-membered ring systems are found to possess diverse applications in the fields of medicine, agriculture and industry. The new 1,2,4-triazole and 1,2,4-triazolo[3,4- b][1,3,4]thiadiazine derivatives were synthesized as novel antimicrobial agents. The reaction of 1 H-indol-3-acetic acid with thiocarbohydrazide gave the 4-amino-3-mercapto-5-[(1 H-indol-3-yl)methyl]-4 H-1,2,4-triazole. The reaction of triazole with arylaldehydes in ethanol gave the 4-arylideneamino-3-mercapto-5-[(1 H-indol-3-yl)methyl]-4 H-1,2,4-triazoles ( I). The 3-[(1 H-indol-3-yl)methyl]-6-aryl-7 H-1,2,4-triazolo[3,4- b][1,3,4]thiadiazines ( II) were obtained by condensing triazole with phenacyl bromides in absolute ethanol . The chemical structures of the compounds were elucidated by IR, 1H NMR and FAB +-MS spectral data. Their antimicrobial activities against Micrococcus luteus (NRLL B-4375), Bacillus cereus (NRRL B-3711), Proteus vulgaris (NRRL B-123), Salmonella typhimurium (NRRL B-4420), Staphylococcus aureus (NRRL B-767), Escherichia coli (NRRL B-3704), Candida albicans and Candida glabrata (isolates obtained from Osmangazi University, Faculty of Medicine) were investigated and significant activity was obtained.

Diels-Alder Reaction of Triazoles with DMAD Catalyzed by Silica-Bound AlCl3

Diels-Alder Reaction of Triazoles with DMAD Catalyzed by Silica-Bound AlCl₃