A single-step acid catalyzed reaction for rapid assembly of NH-1,2,3-triazoles

Thomas, Joice; Jana, Sampad; Liekens, Sandra; Dehaen, Wim

doi:10.1039/c6cc03744e

Cited by 71 publications

(32 citation statements)

References 39 publications

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“…As an effective method of functionalizing dihydroartemisinin with triazole heterocycle, we implemented our recently developed triazolization strategy [ 27 , 28 , 29 ]. The method generally involves the reaction of a primary amine and an enolizable ketone 6 in the presence of 4-nitrophenyl azide 7 as a source of dinitrogen.…”

Section: Resultsmentioning

confidence: 99%

“…The widespread applications of 1,2,3-triazoles have triggered the demand for metal free and easier access to this privileged scaffold. Herein we disclose the implementation of our recently developed triazolization strategy [ 27 , 28 , 29 ] in which dihydroartemisinin scaffold was joined with variety of interesting heterocyclic moieties. We presume that this strategy could help in synthesizing a series of compound with minimal effort to obtain various fused and 1,5-disubstituted triazole derivatives of dihydroartemisinin.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…An elegant and facile synthetic protocol for NH‐1,2,3‐triazoles was also developed by the same group . Their methodology uses enolizable ketones and ammonium acetate to synthesize the triazoles with high regioselectivity.…”

Section: Synthesis Of Chiral Fused 123‐triazolesmentioning

confidence: 99%

Chiral Fused 1,2,3‐Triazoles: A Synthetic Overview

2020

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Triazoles have always occupied a pivotal position in the field of medicinal and pharmaceutical chemistry. Recently, the area of chiral fused triazoles has gained attention. The synthetic routes to access chiral fused triazole may involve either a natural or synthetic chiral starting material with a suitably functionalized azide and alkyne component or isomer resolution to achieve chirality. Asymmetric synthesis methods using chiral complexes and organocatalysis have also emerged for obtaining chiral fused triazoles. Herein, we have described an up-to-date overview of different synthetic protocols applied to construct chiral fused 1,2,3-triazoles. Scheme 1. Basic methodologies for triazole construction. 2 3 4 5 6 7 8 . Yanai's stereo-divergent synthesis of ido-triazole ent-6 a and gluco-triazoles 7 a. Scheme 3. Yanai's diastereo-divergent synthesis of manno-, gulo-, galacto-and altro-triazoles. . Konda's synthesis of tricyclic triazolo-oxazepines 62. Scheme 15. Cobb's synthesis of spirocyclic triazolooxazine nucleosides 67. Scheme 16. Sen's synthesis of tetracyclic triazolo-oxazepines 69. to azide group and protected amine was propargylated to access azido-alkynes 122 c-h for triazole formation 124 (Scheme 29). The copper catalyzed version of this step was also carried out that gave almost approximately same yields in lesser Scheme 25. Chrandrasekaran's synthesis of triazolo-pyrazines and pyrazinones from amino acid derived sulfamidates. Scheme 26. Chrandrasekaran's synthesis of triazolo-pyrazinone 110 having pendant amino acid.structural features of triazoles, the authors carried out one pot hydrogenation and insitu Boc-protection of 155 a, followed by azidation and propargylation to afford azido-alkyne 160. Subsequently, thermal azide-alkyne cycloaddition furnished the triazole product 161 in good yield (Scheme 34).Allenyl silanes are extensively used in synthetic organic transformations and provide ready access to enantiopure pyrroles, oxiranes, furans and vinyl silanes. In lewis acid assisted reaction, allenyl silanes work as propargyl anion equivalents. Allenyl silane forms regioselective homopropargylic alcohol when treated with aldehyde and ketone. The stabilization is Scheme 31. Thomas's synthesis of steroidal fused 1,2,3-triazoles.Scheme 32. Thomas's synthesis of steroidal fused NH-1,2,3-triazoles and steroidal 4,5-fused triazolo-alkynes.

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“…Kuang developed a palladium‐catalyzed reaction for the preparation of 4‐aryl‐1 H ‐1,2,3‐triazoles from anti‐3‐aryl‐2,3‐dibromopropanoic acids and sodium azide (path VI) . Furthermore, there are other efficient synthetic strategies that give access to NH ‐1,2,3‐triazoles in one‐pot procedures . Despite these advances, these methods share a limitation in that inorganic azides are not good substrates.…”

Section: Figurementioning

confidence: 99%

Iodine‐Mediated Condensation–Cyclization of α‐Azido Ketones with p‐Toluenesulfonyl Hydrazide for Synthesis of 4‐Aryl‐NH‐1,2,3‐Triazoles

Ren

Wang

et al. 2020

Eur J Org Chem

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A molecular iodine mediated condensation-cyclization reaction for the synthesis of 4-aryl-NH-1,2,3-triazoles has been developed from readily available α-azido acetophenones NH-1,2,3-triazoles are an important class of nitrogen-containing heterocyclic compounds, and their derivatives exhibit widespread potent biological and pharmaceutical activities, such as inhibition of IDO, hMetAP2, HER2, and VIM-2, and anticancer activity ( Figure 1). [1] [a] azido ketone was not tolerated in this annulation reaction, and we could not gain the corresponding product 3t. Encouraged by the results described above, the scope of αazido ketones was further examined (Scheme 3). To our delight, when α-substituent was an electron-donating methyl or phenyl group, the corresponding products 3u-3w were obtained in moderate-to-good yields (58-82 %). Unfortunately, the substrate with an electron-withdrawing ester at α position was not tolerated in this cyclization reaction, and we could not obtain the corresponding product 3x.Scheme 3. Scope of α-azido ketones.In order to gain insight into the reaction mechanism, we performed a series of control experiments, as shown in Scheme 4. Initially, α-azido phenylethanone (1a) reacted with p-toluenesulfonyl hydrazide (2) in CH 3 CN at room temperature for 48 h leading to α-azido N-tosylhydrazone 1a′ with 68 % yield. If this reaction was carried out in the presence of iodine, the yield increased to 85 %, and the reaction time was shortened to 6 hours. Later, compound 1a′ could be transformed into the target product 3a in 89 % yield in the presence of TBHP in DMSO at 100°C for 3 h. These results indicated that iodine promoted the first condensation process, and 1a′ is a possible intermediate for this reaction. Scheme 4. Control experiments.Based on the abovementioned experimental results, a possible reaction mechanism for this reaction is proposed, as shown in Scheme 5 (using 3a as the example). Initially, α-azido phenyl-

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A single-step acid catalyzed reaction for rapid assembly of NH-1,2,3-triazoles

Cited by 71 publications

References 39 publications

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

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

Chiral Fused 1,2,3‐Triazoles: A Synthetic Overview

Iodine‐Mediated Condensation–Cyclization of α‐Azido Ketones with p‐Toluenesulfonyl Hydrazide for Synthesis of 4‐Aryl‐NH‐1,2,3‐Triazoles

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