Imidazole delocalization

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

Electron delocalization can dictate the site of chemical reaction within a molecule. Consider, for example, two alternative acid-base reactions for imidazole ... 

Compare atomic charges and electrostatic potential maps for imidazole NH protonated and imidazole Nprotonated. In which ion is the positive charge more delocalized Compare carbon-nitrogen bond distances in each ion to those in imidazole as a standard. Are these distances consistent with the bonding patterns shown above for each ion Draw whatever Lewis structures are needed to describe each ion s geometry and charge distribution. 

Bis-imidoyl chloride 187 reacts with A -methyl imidazole 188 to give bis-cationic diimidazo[l,2- 2, T-c]pyrazine 189 (Equation 46) <2006T731>. The charges are believed to be delocalized over the ring system. 

In isocytosine and anthranilic acid it seems that any given molecule is always of the same tautomeric form in the crystal that is, the proton is not moving from site to site in the hydrogen bond. In general, however, the question of whether the proton is localized or not was difficult to answer until the advent of solid-state NMR Thus, for example, there has been much controversy as regards imidazole, 48. On the one hand there were the proponents of delocalization on this basis Zimmerman introduced his controversial theory of proto-merism (106). Others argued for localization. Recently evidence from high-resolution l3C NMR of the solid has provided evidence in support of the latter (107). A similar situation exists for pyrazole, 49 (107). 

Two factors are responsible for the high reactivity of the imidazolides as acylating reagents. One is the relative weakness of the amide bond. Because of the aromatic character of imidazole, there is little of the N —> C=0 delocalization that stabilizes normal amides. The reactivity of the imidazolides is also enhanced by protonation of the other imidazole nitrogen, which makes the imidazole ring a better leaving group. 

Extensive analysis of the EPR and redox behavior of this unusual copper protein led to the hypothesis that the protein might contain a Cu(A) site similar to that in cytochrome oxidase (Riester et ai, 1989) and that the unusual seven-line EPR is due to the Cu(A)-type site. An alternative interpretation of this EPR is based on electron spin-echo spectroscopy as well, and that is that the seven-line EPR is due to a half-met Cu—Cu pair and to unusual type I sites (Jin et ai, 1989). Three sets of spin-echo peaks can be attributed to nitrogens on imidazole ligands to a CuA-type site and to another imidazole on the half-met site. The electron spin-echo spectra of cytochrome oxidase are similar, although there is not enough copper in cytochrome oxidase for a half-met site. Conceivably, the property of delocalization of the paramagnetic electron could be effected by the proposed bridging between Cub and heme as (nomenclature summarized by Capaldi, 1990), which are proposed to be 3-4 A apart. 

Most recorded mass spectra show a parent ion (1 89,90 major fragmentation process, as with 2//-imidazoles, is loss of RCN, which can and frequently does occur in two different ways this often leads to the base peak. Loss of a 4-substituent to give a delocalized cation can also compete as the primary process ... 

A thermodynamic analysis (86UP1) of the effect of annelation on the acid-base properties of the couples imidazole/benzimidazole and pyra-zole/indazole in aqueous solution has shown that this effect is essentially determined by the enhanced electronic delocalization in the case of the anions of the benzazoles. The differential steric hindrance to solvation, on the other hand, does not seem to play a significant role. 

These compounds are isomeric with the 1,2-azoles, e.g. isoxazole, pyrazole and iso thiazole. The aromatic characters of the oxazole, imidazole and thiazole systems arise from delocalization of a lone pair of electrons from the second hetero-atom. 

TT-Electron delocalization in isoxazole seems to be more effective than in oxazole however, isothiazole is less aromatic than thiazole thus it is not a general rule that 1,2-diazoles possess higher aromaticity in comparison with 1,3-diazoles. Oxygen-containing heterocycles are always less aromatic than their sulfur and nitrogen counterparts, e.g. thiazole > imidazole > > oxazole. At the same time, the relative aromaticity of S- and N-containing heterocycles can interchange (pyrazole > isothiazole > isoxazole). 

Magnetic criteria have received wide application mainly as a qualitative test for aromaticity and antiaromaticity. The values of the exaltation of diamagnetic susceptibility (in 10-6A cm-3 mol-1), and therefore aromaticity, decrease in the sequence thiazole (17.0) > pyrazole (15.5) > sydnone (14.1). The relative aromaticity of heterocycles with a similar type of heteroatom can be judged from values of the chemical shifts of ring protons. The latter reveals paramagnetic shifts when Tr-electron delocalization is weakened. For example, in the series of isomeric naphthoimidazoles aromaticity decreases in the sequence naphthof 1,2-djimidazole (8 = 7.7-8.7 ppm) > naphtho[2,3- perimidine (8 = 6.1-7.2 ppm). This sequence agrees with other estimates, in particular with energetic criteria. 

TT-delocalization in carbenes is diminished relatively to imidazolium cations. The last conclusion is supported by the upheld shift of the imidazole ring protons in carbenes (from near 7.9 —< 6.9 ppm). Other NMR chemical shifts are given in Table 41. 

Diazole (imidazole) is a planar molecule with substantial delocalization (resonance) energy. 

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