Imidazole resonance structures

Protonation of imidazole yields an ion that is stabilized by the electron delocalization represented in the resonance structures shown... 

The resonance structures of the 3-substituted imidazole 1-oxides 245 are discussed in Section 1.1.1. According to IUPAC nomenclature, structure 245 is a 1-substituted lH-imidazole 3-oxide since the rules dictate that when R=H the indicated hydrogen position takes numbering precedence. Other names found in the literature are 1-substituted imidazole 3-oxides or 1-substituted 3-oxo-lH-imidazoles. Frequently the numbering is switched to give the names 3-substituted 2H-imidazole 1-oxide, 3-substituted imidazole 1-oxides, or 3-substituted 1 -oxo-3H-imidazoles. In the present review the most commonly used naming, which is accepted by IUPAC, Chem. Abstr. Autonom., is used calling structure 245 a 3-substituted imidazole 1-oxide. Consistently, structure 245 (R=OH, OAlk, or NH2) is named 3-hydroxy, 3-alkoxy, or 3-aminoimidazole 1-oxide, respectively. 

The conclusion from these studies is that the stability of the imidazol-2-ylidene-type systems, 102, results mainly from the presence of the two a-nitrogen atoms which stabilize the metallylene by electron donation from the nitrogen lone-pair to the empty p orbital on M, as shown in resonance structure 104a. The calculations predict a stabilizing... 

The valence bond approach allows resonance structures to be drawn for imidazole (7-12 Scheme 1), among which are a number of dipolar structures. Certainly such dipolar contributors will be much more important than in the case of benzene. They correctly compute the amphoteric nature of the molecule and its susceptibility to electrophilic attack at N-3, C-4 and C-2. When tautomerism is taken into account, electrophilic attack at C-5 could also be expected. There is also an indication in structure (11) that nucleophiles will be attracted to C-2. A structure such as (12) can have real meaning only in the presence of very strong bases. 

The best known of the potential mercaptoimidazoles are the imidazoline-2- and benz-imidazoline-2-thiones, which resemble imidazolin-2-ones in that the tautomeric form (53 X = S) is the preferred form. The crystal structure and the HNMR spectrum of 1,3-dimethyl-3H-imidazoline-2-thione have been interpreted as showing partial double bond character in the N—C—N system, but no aromaticity (70CC56). However, the preference for a betaine structure (56) rather than (57) or (58) should be accepted with caution since it is really only a resonance structure similar to others which undoubtedly contribute to the overall structures of oxo-, thio- and amino-imidazoles. Measurement of the piSTa values for a series of imidazoline-2-thiones substituted variously on C-4, C-5, N-1 and N-3 by hydrogen, phenyl or methyl shows that all of the values are similar. Approximate Kr values calculated show that these compounds exist even more in the thione forms (53, X = S 58) than do the corresponding thiazoline-2-thiones and oxazoline-2-thiones. The UV spectra in aqueous solution support thione structures, as do dipole moment and X-ray studies (76AHC(S1)280, p. 400). 

The selective UV absorption of imidazole-4-carbaldehyde has been referred to resonance structures such as (92), which are improbable in the cation. In addition, a hydroxymethylene form can be excluded. 

When the imidazole ring is considered to be something resembling a pyrrole-pyridine combination (1) it would appear that any electrophilic attack should take place preferably at C-5 (pyrrole-or, pyridine-j8). Such a model, though, fails to take account of the tautomeric equivalence of C-4 and C-5 (Section 4.06.5.1). The overall reactivities of imidazole and benzimidazole can be inferred from sets of resonance structures in which the dipolar contributors have finite importance (Section 4.06.2) or by mesomeric structures such as (2). These predict electrophilic attack in imidazole at N-3 or any ring carbon atom, nucleophilic attack at C-2 or C-1, and also the amphoteric nature of the molecule. In benzimidazole the acidic and basic properties, the preference for nucleophilic attack at C-2 and the tendency for electrophiles to react at the fused benzene ring can be readily rationalized. 

Attempts to correlate reaction mechanisms, electron density calculations and experimental results have met with only limited success. As mentioned in the previous chapter (Section 4.06.2), the predicted orders of electrophilic substitution for imidazole (C-5 > -2 > -4) and benzimidazole (C-7>-6>-5>-4 -2) do not take into account the tautomeric equivalence of the 4- and 5-positions of imidazole and the 4- and 7-, 5- and 6-positions of benzimidazole. When this is taken into account the predictions are in accord with the observed orientations of attack in imidazole. Much the same predictions can be made by considering the imidazole molecule to be a combination of pyrrole and pyridine (74) — the most likely site for electrophilic attack is C-5. Furthermore, while sets of resonance structures for the imidazole and benzimidazole neutral molecules (Schemes 1 and 2, Section 4.06.2) suggest that all ring carbons have some susceptibility to electrophilic attack, consideration of the stabilities of the expected tr-intermediates (Scheme 29) supports the commonly observed preference for 5- (or 4-) substitution. In benzimidazole attack usually occurs first at C-5 and a second substituent enters at C-6 unless other substituent effects intervene. 

Probably the most important property of these compounds is the propensity of iV-acyl-imidazoles and -benzimidazoles (as well as other azoles) to become involved in reactions which result in acylation of an attacking nucleophile. The compounds are unlike other tertiary amides in that there is little or no contribution from resonance structures of type (251) to the hybrid (Scheme 142) hence the positive nature of the carbonyl carbon is undiminished. The electron pair on the annular nitrogen is part of the aromatic sextet. The compounds are known as azolides generally, and more specifically as imidazolides . Because the annular nitrogens are not directly adjacent imidazolides are more reactive than the corresponding pyrazolides. 

In solution, resonance stabilization (R) is commonly the predominant structural driving force of a reaction. Gas-phase proton-transfer equilibria offer a striking contrast, in which the R effects are frequently found to be secondary to a predominant combination of I and P effects. However, it is recognized that for aromatic compounds, such as, for instance, imidazole, resonance stabilization of the protonated form is the predominant contribution determining the relatively high basicity of imidazole and its congeners in the class of five-membered heteroaromatic compounds. 

Structure of imidazole resonance contributors (mesomeric structures)... 

Imidazole and its derivatives form an interesting and important class of heterocyclic aromatic amines. Imidazole is approximately 100 times more basic than pyridine. Protonation of imidazole yields an ion that is stabihzed by the electron delocalization represented in the resonance structures shown ... 

Additionally, a hydroxyl or thiol substituent at the 2-position of imidazole may exhibit reactivity of the ketone or thione as illustrated in the resonance structures below. 

The imidazole ring system has a great deal of aromatic character. Can you formulate two resonance structures that account for this characteristic ... 

Imidazole is a weak acid, and thus reacts with strong bases to form the corresponding anion. Show this reaction, and draw resonance structures that account for the stability of the conjugate base. Suggest a mechanism for the dehydration involved in the last step in the synthesis of benzimidazole. 

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