Metal-free C–H functionalization of 2H-imidazole 1-oxides with pyrrolyl fragments in the design of novel azaheterocyclic ensembles

Вараксин, Михаил В.; Moseev, Timofey D.; Чупахин, О. Н.; Charushin, Valery N.; Трофимов, Б. А.

doi:10.1039/c7ob01999h

Cited by 19 publications

(7 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reaction of 2Н-imidazole-N-oxides ImNO(1-5)H with polyphenols Phl, Pyr, Hyd proved to proceed in the presence of AcCl, thus leading to a series of previously unknown 2H-imidazole-derived phenolic compounds, such The design and synthesis of water-soluble bifunctional molecular systems, bearing both 2H-imidazole and polyphenolic building blocks, for the study of their antioxidant activity as challenging drug candidates with a combined mechanism of action, was carried out in accordance with the established synthetic methodology [44]. The synthetic strategy is based on the pot and atom economy methodology of C-H functionalization of non-aromatic azaheterocyclic substrates that was realized as reactions of nucleophilic substitution of hydrogen (S N H ) in 2H-imidazole 1-oxide [45][46][47][48][49]. The targeted synthesis of arylimidazoles bearing functional groups in the para-position of the aryl fragment was carried out to assess at the next step the effects of various substituents on antiradical properties of the investigated bifunctional compounds.…”

Section: Resultsmentioning

confidence: 99%

Design and Antioxidant Properties of Bifunctional 2H-Imidazole-Derived Phenolic Compounds—A New Family of Effective Inhibitors for Oxidative Stress-Associated Destructive Processes

et al. 2021

Self Cite

View full text Add to dashboard Cite

The synthesis of inhibitors for oxidative stress-associated destructive processes based on 2H-imidazole-derived phenolic compounds affording the bifunctional 2H-imidazole-derived phenolic compounds in good-to-excellent yields was reported. In particular, a series of bifunctional organic molecules of the 5-aryl-2H-imidazole family of various architectures bearing both electron-donating and electron-withdrawing substituents in the aryl fragment along with the different arrangements of the hydroxy groups in the polyphenol moiety, namely derivatives of phloroglucinol, pyrogallol, hydroxyquinol, including previously unknown water-soluble molecules, were studied. The structural and antioxidant properties of these bifunctional 5-aryl-2H-imidazoles were comprehensively studied. The redox transformations of the synthesized compounds were carried out. The integrated approach based on single and mixed mechanisms of antioxidant action, namely the AOC, ARC, Folin, and DPPH assays, were applied to estimate antioxidant activities. The relationship “structure-antioxidant properties” was established for each of the antioxidant action mechanisms. The conjugation effect was shown to result in a decrease in the mobility of the hydrogen atom, thus complicating the process of electron transfer in nearly all cases. On the contrary, the conjugation in imidazolyl substituted phloroglucinols was found to enhance their activity through the hydrogen transfer mechanism. Imidazole-derived polyphenolic compounds bearing the most electron-withdrawing functionality, namely the nitro group, were established to possess the higher values for both antioxidant and antiradical capacities. It was demonstrated that in the case of phloroglucinol derivatives, the conjugation effect resulted in a significant increase in the antiradical capacity (ARC) for a whole family of the considered 2H-imidazole-derived phenolic compounds in comparison with the corresponding unsubstituted phenols. Particularly, conjugation of the polyphenolic subunit with 2,2-dimethyl-5-(4-nitrophenyl)-2H-imidazol-4-yl fragment was shown to increase ARC from 2.26 to 5.16 (104 mol-eq/L). This means that the considered family of compounds is capable of exhibiting an antioxidant activity via transferring a hydrogen atom, exceeding the activity of known natural polyphenolic compounds.

show abstract

Section: Resultsmentioning

confidence: 99%

Design and Antioxidant Properties of Bifunctional 2H-Imidazole-Derived Phenolic Compounds—A New Family of Effective Inhibitors for Oxidative Stress-Associated Destructive Processes

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The same substrate 7 can be used as an electrophile rather than as a nucleophile. Our group reported the cross-coupling reaction of 2H-imidazole 1-oxides (7a-c) with electron-rich heteroarenes, such as indoles (90), 24 pyrroles (92) 51,52 and thiophenes (93) (Schemes 26-28). 52 The coupling of these partners can be done in two different ways.…”

Section: Organic and Biomolecular Chemistry Reviewmentioning

confidence: 99%

C(sp²)–H functionalization in non-aromatic azomethine-based heterocycles

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…NaHCO 3 in aqueous ethanol was utilized to convert the salts into resulting heterocyclic bases (Scheme 140). [157] …”

Section: C−h Functionalization Of Pyrrolesmentioning

confidence: 99%

Recent Advances in Functionalization of Pyrroles and their Translational Potential

Hunjan

Panday

Gupta

et al. 2021

The Chemical Record

View full text Add to dashboard Cite

Among the known aromatic nitrogen heterocycles, pyrrole represents a privileged aromatic heterocycle ranging its occurrence in the key component of “pigments of life” to biologically active natural products to active pharmaceuticals. Pyrrole being an electron‐rich heteroaromatic compound, its predominant functionalization is legendary to aromatic electrophilic substitution reactions. Although a few excellent reviews on the functionalization of pyrroles including the reports by Baltazzi in 1963, Casiraghi and Rassu in 1995, and Banwell in 2006 are available, they are fragmentary and over fifteen years old, and do not cover the modern aspects of catalysis. A review covering a comprehensive package of direct functionalization on pyrroles via catalytic and non‐catalytic methods including their translational potential is described. Subsequent to statutory yet concise introduction, the classical functionalization on pyrroles using Lewis acids largely following an ionic mechanism is discussed. The subsequent discussion follows the various metal‐catalyzed C−H functionalization on pyrroles, which are otherwise difficult to implement by Lewis acids. A major emphasize is given on the radical based pyrrole functionalization under metal‐free oxidative conditions, which is otherwise poorly highlighted in the literature. Towards the end, the current development of pyrrole functionalization under photocatalyzed and electrochemical conditions is appended. Only a selected examples of substrates and important mechanisms are discussed for different methods highlighting their scopes and limitations. The aromatic nucleophillic substitution on pyrroles (being an electron‐rich heterocycle) happened to be the subject of recent investigations, which has also been covered accentuating their underlying conceptual development. Despite great achievements over the past several years in these areas, many challenges and problems are yet to be solved, which are all discussed in summary and outlook.

show abstract

Metal-free C–H functionalization of 2H-imidazole 1-oxides with pyrrolyl fragments in the design of novel azaheterocyclic ensembles

Cited by 19 publications

References 38 publications

Design and Antioxidant Properties of Bifunctional 2H-Imidazole-Derived Phenolic Compounds—A New Family of Effective Inhibitors for Oxidative Stress-Associated Destructive Processes

Design and Antioxidant Properties of Bifunctional 2H-Imidazole-Derived Phenolic Compounds—A New Family of Effective Inhibitors for Oxidative Stress-Associated Destructive Processes

C(sp²)–H functionalization in non-aromatic azomethine-based heterocycles

Recent Advances in Functionalization of Pyrroles and their Translational Potential

Contact Info

Product

Resources

About

Metal-free C–H functionalization of 2H-imidazole 1-oxides with pyrrolyl fragments in the design of novel azaheterocyclic ensembles

Cited by 19 publications

References 38 publications

Design and Antioxidant Properties of Bifunctional 2H-Imidazole-Derived Phenolic Compounds—A New Family of Effective Inhibitors for Oxidative Stress-Associated Destructive Processes

Design and Antioxidant Properties of Bifunctional 2H-Imidazole-Derived Phenolic Compounds—A New Family of Effective Inhibitors for Oxidative Stress-Associated Destructive Processes

C(sp2)–H functionalization in non-aromatic azomethine-based heterocycles

Recent Advances in Functionalization of Pyrroles and their Translational Potential

Contact Info

Product

Resources

About

C(sp²)–H functionalization in non-aromatic azomethine-based heterocycles