INFLUENCE OF THE 2-ARYL GROUP ON THE IPSO ELECTROPHILIC SUBSTITUTION PROCESS OF 2-ARYLIMIDAZO[l,2-A]PYRIDINES

Salgado-Zamora, Héctor; Velázquez, Manuel Ricardo; Mejía, Daniel; Campos-Aldrete, Ma. Elena; Jiménez, Rogelio; Cervantes, Humberto

doi:10.1515/hc.2008.14.1-2.27

Cited by 8 publications

(3 citation statements)

References 7 publications

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“…An analysis of mesomeric structures [16] (Scheme 1), suggests that two major contributors to the imidazo[1,2-a]pyridine resonance hybrid are those in which both, the six-membered and the five-membered rings have aromatic character (mesomeric structures 1a and 1b). The latter also suggests that position 3 is rich in electron density, a structural argument put forward to account for the high reactivity of this position towards electrophiles [17-19]. The introduction of an electron-withdrawing group (cyano, nitroso, nitro, carbonyl) at position 3, contributes to the stabilization of the π electron density by placing a charge on the electronegative atom of the electron-withdrawing group (structures 2c–d), and in doing so a long distance mesomeric effect develops a positive charge on C-5 (structure 2e).…”

Section: Resultsmentioning

confidence: 99%

Intramolecular H-bonding interaction in angular 3-π-EWG substituted imidazo[1,2-a]pyridines contributes to conformational preference

Velázquez-Ponce

Salgado-Zamora

Jiménez‐Vázquez

et al. 2013

Chemistry Central Journal

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BackgroundThe proton at position 5 of imidazo[1,2-a]pyridines substituted with an angular electron withdrawing group (EWG) at position 3, shows an unusual downfield chemical shift, which is usually explained in terms of a peri effect. However usage of this term is sometimes confusing. In this investigation, it is proposed that the aforementioned shift is in fact a combination of several factors: Anisotropy, long-distance mesomerism and an attractive intramolecular interaction of the electrostatic hydrogen bond type.ResultsTheoretical calculations were performed aimed to obtain evidence of the existence of an intramolecular non-bonding interaction between H-5 and the oxygen atom of the EWG. Results derived from conformational and vibrational analysis at the DFT B3LYP/6-311++G(d,p) level of theory, the determination of Bond Critical Points derived from AIM theory, and the measurement of some geometrical parameters, support the hypothesis that the higher stability of the prevailing conformation in these molecules (that in which the oxygen of the EWG is oriented towards H-5) has its origin in an intramolecular interaction.ConclusionComputational calculations predicted correctly the conformational preferences in angular 3-π-EWG-substituted imidazo[1,2-a]pyridines. The existence of an electrostatic hydrogen bond between H-5 and the oxygen atom of the π-EWG was supported by several parameters, including X-ray crystallography. The existence of such structural array evidently impacts the H-5 chemical shift.

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Section: Resultsmentioning

confidence: 99%

Intramolecular H-bonding interaction in angular 3-π-EWG substituted imidazo[1,2-a]pyridines contributes to conformational preference

Velázquez-Ponce

Salgado-Zamora

Jiménez‐Vázquez

et al. 2013

Chemistry Central Journal

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“…A variety of synthetic methods have been reported for the preparation of C‐3 halogenated imidazo[1,2‐ a ]pyridines. At present, the main strategy is to use NXS, [ 26‐28 ] NaX, [ 29‐30 ] tetra‐ n ‐butyl ammonium halide, [ 31 ] I 2 [ 32 ] as halogen sources and synthesize them by electrochemical oxidation, [ 33‐35 ] photochemical oxidation [ 36 ] and metal oxidation catalysis. [ 37 ] Furthermore, imidazole zwitterionic molten salt, [ 38 ] new chlorination reagent chloramine‐T [ 39 ] or pyridine tribromide [ 40 ] plasma catalytic system have also been used as halogen source or catalyst in C‐3 halogenation reaction over recent years.…”

Section: Background and Originality Contentmentioning

confidence: 99%

Synthesis and Evaluation of Photophysical Properties of C‐3 Halogenated Derivatives of 2‐Phenylimidazo[1,2‐a]pyridine

et al. 2022

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Comprehensive Summary A CuX‐mediated regioselective halogenation reaction of 2‐phenylimidazo[1,2‐a]pyridine in the presence of oxygen is introduced in this paper. This reaction provides an effective method for the production of C‐3 halogenated 2‐phenylimidazo[1,2‐a]pyridines with a yield of up to 96%. A plausible mechanism for the formation of title compounds via 2‐phenylimidazo[1,2‐a]pyridine–CuX complex intermediate is proposed. The structure of representative compounds is established by the single crystal XRD method. The electronic structure, corroborated by Hirshfeld surface analysis and DFT calculations, rationalizes characters of relevant absorptions and emission as well as large Stokes shifts.

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“…1 3-bromo-2-phenylimidazo[1,2-a]pyridine (37). 51 2phenylimidazo[1,2-a]pyridine 49,50 (0.822 g, 4.2 mmol) was dissolved in MeCN (25 mL), and NBS (0.839 g, 4.7 mmol) was added at once. The reaction mixture was stirred at room temperature in the dark until completion by TLC (1.5 h).…”

Section: Journal Of Medicinal Chemistrymentioning

confidence: 99%

Structural Determinants for the Mode of Action of Imidazopyridine DS2 at δ-Containing γ-Aminobutyric Acid Type A Receptors

Rostrup

Falk-Petersen

et al. 2021

J. Med. Chem.

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Despite the therapeutic relevance of δ-containing γ-aminobutyric acid type A receptors (GABAARs) and the need for δ-selective compounds, the structural determinants for the mode and molecular site of action of δ-selective positive allosteric modulator imidazo[1,2-a]pyridine DS2 remain elusive. To guide the quest for insight, we synthesized a series of DS2 analogues guided by a structural receptor model. Using a fluorescence-based fluorometric imaging plate reader membrane potential assay, we found that the δ-selectivity and the pharmacological profile are severely affected by substituents in the 5-position of the imidazopyridine core scaffold. Interestingly, the 5-methyl, 5-bromo, and 5-chloro DS2 analogues, 30, 35, and 36, were shown to be superior to DS2 at α4β1δ as mid-high nanomolar potency δ-selective allosteric modulators, displaying 6–16 times higher potency than DS2. Of these, 30 also displayed at least 60-fold selectivity for α4β1δ over α4β1γ2 receptor subtypes representing a potential tool for the selective characterization of δ-containing GABAARs in general.

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INFLUENCE OF THE 2-ARYL GROUP ON THE IPSO ELECTROPHILIC SUBSTITUTION PROCESS OF 2-ARYLIMIDAZO[l,2-A]PYRIDINES

Cited by 8 publications

References 7 publications

Intramolecular H-bonding interaction in angular 3-π-EWG substituted imidazo[1,2-a]pyridines contributes to conformational preference

Intramolecular H-bonding interaction in angular 3-π-EWG substituted imidazo[1,2-a]pyridines contributes to conformational preference

Synthesis and Evaluation of Photophysical Properties of C‐3 Halogenated Derivatives of 2‐Phenylimidazo[1,2‐a]pyridine

Structural Determinants for the Mode of Action of Imidazopyridine DS2 at δ-Containing γ-Aminobutyric Acid Type A Receptors

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