Facile One‐Pot Synthesis of <i>N</i>‐Alkylated Benzimidazole and Benzotriazole from Carbonyl Compounds

Meng, Xu; Li, Xiaolong; Chen, Wenlin; Zhang, Yuanqing; Wang, Wen; Chen, Jinying; Song, Jinli; Feng, Huijie; Feng, Bo

doi:10.1002/jhet.1616

Cited by 7 publications

(3 citation statements)

References 51 publications

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“…Further exploration on the reactivity of benzylic halides with benzimidazoles was undertaken due to their prevalence in medicinal compounds. Numerous protocols for the synthesis of benzyl benzimidazoles have been developed, which typically require the use of excess base and elevated temperatures. − Further, some reports indicate that debenzylation can lead to loss of products under similar conditions in the presence of a base. , Other catalytic procedures for the synthesis of benzyl benzimidazoles require transition-metal catalysts. ,,, A base-free and transition-metal-free procedure, however, has yet to be reported.…”

Section: Resultsmentioning

confidence: 99%

Transition-Metal-Free and Base-Free Electrosynthesis of 1H-Substituted Benzimidazoles

Dissanayake

Vannucci

2017

ACS Sustainable Chem. Eng.

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A direct electrochemical synthesis of 1H-substituted benzimidazoles is described. Benzimidazole is a commonly used nitrogen heterocycle in U.S. FDA approved drugs; therefore, a direct and sustainable approach that limits chemical waste for the synthesis of substituted benzimidazoles is appealing. The electrosynthetic approach described within is able to synthesize a variety of 1H-substitubed benzimidazoles while concurrently producing H 2 , without a transition-metal catalyst or added bases. Furthermore, the procedure works efficiently with only simple carbon electrodes, thus avoiding commonly employed platinum and gold electrodes. This electrochemical procedure also exhibited good functional group tolerance. Desired products were achieved with up to 88% yield, illustrating the range and possible sustainability of this approach.

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Section: Resultsmentioning

confidence: 99%

Transition-Metal-Free and Base-Free Electrosynthesis of 1H-Substituted Benzimidazoles

Dissanayake

Vannucci

2017

ACS Sustainable Chem. Eng.

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“…On the other hand, in a study of anticancer compounds, an inseparable mixtures of 2 regioisomers were obtained from 6-[ N -(2- t -butyldimethylsilyloxyethyl)- N -methylamino]-2-bromo-3-methoxy-1,4,5,8-triptycenetetraone; and 6-[ N -(4-hydroxybutyl)- N -methylamino]-2-bromo-3-methoxy-1,4,5,8-triptycenetetraone by silica gel column chromatography [ 36 ]. In addition, Meng et al reported the synthesis of a regioisomer mixture (1:1 ratio) of 5(6)-methyl-1-(1-phenylethyl)-1 H -benzo[d]imidazole [ 37 ].…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of 2-(2-Amino-5(6)-nitro-1H-benzimidazol-1-yl)-N-arylacetamides as Antiprotozoal Agents

et al. 2017

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Parasitic diseases are a public health problem affecting millions of people worldwide. One of the scaffolds used in several drugs for the treatment of parasitic diseases is the benzimidazole moiety, a heterocyclic aromatic compound. This compound is a crucial pharmacophore group and is considered a privileged structure in medicinal chemistry. In this study, the benzimidazole core served as a model for the synthesis of a series of 2-(2-amino-5(6)-nitro-1H-benzimidazol-1-yl)-N-arylacetamides 1–8 as benznidazole analogues. The in silico pharmacological results calculated with PASS platform exhibited chemical structures highly similar to known antiprotozoal drugs. Compounds 1–8 when evaluated in silico for acute toxicity by oral dosing, were less toxic than benznidazole. The synthesis of compounds 1–8 were carried out through reaction of 5(6)-nitro-1H-benzimidazol-2-amine (12) with 2-chlroactemides 10a–h, in the presence of K2CO3 and acetonitrile as solvent, showing an inseparable mixture of two regioisomers with the -NO2 group in position 5 or 6 with chemical yields of 60 to 94%. The prediction of the NMR spectra of molecule 1 coincided with the experimental chemical displacements of the regioisomers. Comparisons between the NMR prediction and the experimental data revealed that the regioisomer endo-1,6-NO2 predominated in the reaction. The in vitro antiparasitic activity of these compounds on intestinal unicellular parasites (Giardia intestinalis and Entamoeba histolytica) and a urogenital tract parasite (Trichomonas vaginalis) were tested. Compound 7 showed an IC50 of 3.95 μM and was 7 time more active against G. intestinalis than benznidazole. Compounds 7 and 8 showed 4 times more activity against T. vaginalis compared with benznidazole.

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“…Isolated using flash column chromatography (silica gel, 10% EtOAc in isohexane) yielding 2-(cyclohex-1-en-1-yl)-1H-benzo[d][1,2,3]triazole as a pale yellow oil (67 mg, 48%) and 2-(cyclohex-1-en-1-yl)-2H-benzo[d][1,2,3]triazole as a white solid (44 mg, 32% yield) from 1H-benzotriazole 1g (83 mg, 0.70 mmol) and cyclohexanone 2a (206 mg, 2.10 mmol). [1,2,3]triazole, (3g′) 48 [1,2,3]triazole, (3g″) 48 49 CAS 1451090−71−3. Synthesized according to the general procedure A.…”

Section: -(Cyclohex-1-en-1-yl)-1h-benzo[d][123]triazole (3g′) and 1-(...mentioning

confidence: 99%

Synthesis of N-Alkenylated Heterocycles via T₃P-Promoted Condensation with Ketones

Balestri,

Beveridge,

Gising

et al. 2024

J. Org. Chem.

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Herein, we describe a convenient protocol for the synthesis of N-alkenylated heterocycles using abundant ketone electrophiles and T 3 P as a water scavenger under microwave irradiation. The method can be applied to a diverse range of NHheterocycles and ketones with good to excellent yields (up to 94%). This procedure is particularly attractive, as it is metal-and basefree, tolerates a variety of functional groups, and offers ease of product purification. The utility of the protocol was exemplified by synthesizing pharmaceutically relevant scaffolds containing the N-alkenyl motif and was further extended to a one-pot reductive amination sequence.

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Facile One‐Pot Synthesis of N‐Alkylated Benzimidazole and Benzotriazole from Carbonyl Compounds

Cited by 7 publications

References 51 publications

Transition-Metal-Free and Base-Free Electrosynthesis of 1H-Substituted Benzimidazoles

Transition-Metal-Free and Base-Free Electrosynthesis of 1H-Substituted Benzimidazoles

Design, Synthesis and Biological Evaluation of 2-(2-Amino-5(6)-nitro-1H-benzimidazol-1-yl)-N-arylacetamides as Antiprotozoal Agents

Synthesis of N-Alkenylated Heterocycles via T₃P-Promoted Condensation with Ketones

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Facile One‐Pot Synthesis of N‐Alkylated Benzimidazole and Benzotriazole from Carbonyl Compounds

Cited by 7 publications

References 51 publications

Transition-Metal-Free and Base-Free Electrosynthesis of 1H-Substituted Benzimidazoles

Transition-Metal-Free and Base-Free Electrosynthesis of 1H-Substituted Benzimidazoles

Design, Synthesis and Biological Evaluation of 2-(2-Amino-5(6)-nitro-1H-benzimidazol-1-yl)-N-arylacetamides as Antiprotozoal Agents

Synthesis of N-Alkenylated Heterocycles via T3P-Promoted Condensation with Ketones

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Synthesis of N-Alkenylated Heterocycles via T₃P-Promoted Condensation with Ketones