Reactions of acetylimidazole and acetylimidazolium ion with nucleophilic reagents. Structure-reactivity relations

Jencks, William P.; Oakenfull, David

doi:10.1021/ja00730a031

Cited by 43 publications

(2 citation statements)

References 4 publications

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“…Cleavage of acetylimidazole with hydroperoxide anion at neutral pH has a half-life of -75 sees. 101 The mechanism for peroxide hydrolysis may proceed as is depicted in Scheme 3. 10 The nucleophilicity of the hydrogen peroxide anion compared to hydroxide is attributed to the alpha effect.…”

Section: Peroxide As a Nucleophilementioning

confidence: 99%

Biomimetic Oxygenations Related to Cytochrome P450: Metal-Oxo and Metal-Peroxo Intermediates

McLain

Lee

Groves

2000

Biomimetic Oxidations Catalyzed by Transition Metal Complexes

123

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Oxometalloporphyrin Intermediates in Enzymatic ProcessesMetalloenzymes catalyze a host of biological oxidation reactions that are crucial to life processes. The cytochromes P450, an important family of heme-iron metalloenzymes, are oxidoreductases that activate molecular oxygen (O2) and incorporate one of the oxygen atoms into a wide variety of biological substrates, with concurrent two-electron reduction of the other oxygen atom to H 2 0.' The structure, biochemistry, molecular biology and the chemistry of cytochrome P450 and related model systems was extensively reviewed recently. 1 Cytochrome P450 enzymes have been isolated from numerous mammalian tissues (e.g. liver, kidney, lung, intestine and adrenal cortex), as well as insects, plants, yeast and bacteria, 2 and are known to catalyze hydroxylations, epoxidations, N-, S-and O-dealkylations, N-oxidations, sulfoxidations, and dehalogenations. 1 These oxygenation reactions play a central role in carcinogen activation, drug and xenobiotic detoxification, and steroid and prostaglandin metabolism. Surprisingly, the active site of the enzyme, known in detail from several X-ray crystal structures, is extraordinarily simple, with an iron protoporphyrin IX (3.1; Fig. 3.1) buried deep in a hydrophobic, substrate-binding pocket of 91 Biomimetic Oxidations Catalyzed by Transition Metal Complexes Downloaded from www.worldscientific.com by KAINAN UNIVERSITY on 02/20/15. For personal use only.

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Section: Peroxide As a Nucleophilementioning

confidence: 99%

Biomimetic Oxygenations Related to Cytochrome P450: Metal-Oxo and Metal-Peroxo Intermediates

McLain

Lee

Groves

2000

Biomimetic Oxidations Catalyzed by Transition Metal Complexes

123

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“…This is an unusually large degree of charge development on the base for a general based-catalyzed reaction. For comparison, the Brønsted β values for the general base-catalyzed hydrolysis of acetylimidazole, acetylimidazolium ion, and ethyl dichloroacetate are +0.55, +0.34, and +0.47, respectively. , The later transition state for the hydrolysis of the β-sultam is indicative of a much greater selectivity on the general base than that observed with acyl transfer.…”

Section: Resultsmentioning

confidence: 96%

An Activated Sulfonylating Agent That Undergoes General Base-Catalyzed Hydrolysis by Amines in Preference to Aminolysis

et al. 2008

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Activated sulfonyl derivatives, similar to acyl ones, usually undergo aminolysis with amines in water as nucleophilic attack by the amine is preferred to hydrolysis. However, despite being active sulfonyl derivatives, four-membered heterocyclic sulfonamides, beta-sultams, do not undergo aminolysis in aqueous solution but preferentially react to give hydrolysis products only. The rate of the reaction of beta-sultams in buffered solutions of simple primary amines shows a first-order dependence on amine concentrations attributed to general base-catalyzed hydrolysis by the amine. Even N-benzyl-4,4-dimethyl-3-oxo-beta-sultam, which is both a beta-sultam and a beta-lactam, undergoes hydrolysis at the sulfonyl center rather than aminolysis at either the sulfonyl or acyl center. The solvent kinetic isotope effects (SKIE, k(H(2)O)/k(D(2)O)) for the amine-catalyzed hydrolyses are 1.4 and 1.9 for the hydrolysis of N-benzoyl-beta-sultam and N-benzyl-4,4-dimethyl-3-oxo-beta-sultam, respectively, compatible with a general base-catalyzed mechanism. The amine-catalyzed hydrolysis gives a Bronsted beta value of +0.9 for both N-benzoyl beta-sultam and N-benzyl-4,4-dimethyl-3-oxo-beta-sultam, indicating that the general base amine is almost fully protonated in the transition state. A general base-catalyzed mechanism for hydrolysis rather than nucleophilic attack was also deduced for the reaction of N-benzyl-4,4-dimethyl-3-oxo-beta-sultam with carboxylate anions based on a SKIE of 1.7-1.9 and rate constants which fit the Bronsted plot for amines. In contrast to acyl transfer reactions, those for sulfonyl transfer appear to show an inverse reactivity-selectivity relationshipthe most active compounds being the most selective. The lack of reactivity of beta-sultams toward amine nucleophiles appears to be related to the mechanism of ring opening of beta-sultams with a decreased reactivity toward amines relative to hydroxide ion, probably related to the expulsion of the relatively poor leaving group amide anion.

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The Importance of Methyl Positioning and Tautomeric Equilibria for Imidazole Nucleophilicity

Campos

Menezes

Barison

et al. 2016

Chemistry A European J

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Imidazole (IMZ) rings catalyze many biological dephosphorylation processes. The methyl positioning effect on IMZs reactivity has long intrigued scientists and its full understanding comprises a promising tool for designing highly efficient IMZ-based catalysts. We evaluated all monosubstituted methylimidazoles (xMEI) in the reaction with diethyl 2,4-dinitrophenyl phosphate by kinetics studies, NMR analysis and DFT calculations. All xMEI showed remarkable rate enhancements, up to 1.9×10 fold, compared with spontaneous hydrolysis. Unexpectedly, the electron-donating methyl group acts to decrease the reactivity of the xMEI compared to IMZ, except for 4(5)methylimidazole, (4(5)MEI). This behavior was attributed to both electronic and steric effects. Moreover, reaction intermediates were monitored by NMR and surprisingly, the reactivity of the two different 4(5)MEI tautomers was distinguished.

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Reactions of acetylimidazole and acetylimidazolium ion with nucleophilic reagents. Structure-reactivity relations

Cited by 43 publications

References 4 publications

Biomimetic Oxygenations Related to Cytochrome P450: Metal-Oxo and Metal-Peroxo Intermediates

Biomimetic Oxygenations Related to Cytochrome P450: Metal-Oxo and Metal-Peroxo Intermediates

An Activated Sulfonylating Agent That Undergoes General Base-Catalyzed Hydrolysis by Amines in Preference to Aminolysis

The Importance of Methyl Positioning and Tautomeric Equilibria for Imidazole Nucleophilicity

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