Imidazole ring

An imidazole ring is a structural unit m the ammo acid histidine (Section 27 1) and is involved m a large number of biological processes as a base and as a nucleophile... 

When the proportion of acid to amine groups is reversed-namely, l 2--a process rather similar to reaction (5.II) yields a polymer which ultimately contains the five-membered imidazole ring. This reaction is also carried out in the stages listed below and illustrated by reaction (5.JJ) ... 

ReceptorAg onists. In the histamine molecule there are two principal stmctural elements an imidazole moiety and an ethylamine side chain (16). Only the N -position is absolutely necessary for agonism. The imidazole ring can be replaced, eg, 2-pyridylethylamine,... 

At Merck Research Laboratories, the imidazole ring ia losartan (81, K = n — butyl), a novel clinical candidate against hypertension, was replaced with a pyrazole ring (52). Some of the best compounds are represented by formula (82), where K = n — butyl and R = 2,6-dichlorophenyl, 2-chlorophenyl, or... 

Imidazole rings also survive most oxidation conditions, but photosensitized oxidation of imidazoles can give diarylbenzamidines through a hydroperoxide (136) (70AHC(12)103). 

A -Bridgehead compounds have been obtained from the photochemical cyclization of cfi-1-styrylimidazoles. For example, irradiation of the imidazole (532) in methanol in the presence of I2 resulted in cyclization at the 2-position of the imidazole ring with the formation of an imidazo[2,l-a]isoquinoline (533) (76JCS(Pl)75). Isomerization of the trans-to the c/i-styrylimidazole was followed by photodehydrocyclization, trans- 1-Styrylbenzimidazole (534) was isomerized under Pyrex-filtered light in the presence of one molar equivalent of I2. The resulting cis isomer on irradiation through quartz gave the benzimidazo[2,l-a]isoquinoline (535) in 53% yield. 

The imidazole ring of the histidine side chain acts as a proton acceptor in certain enzyme-catalyzed reactions. Which is the more stable protonated form of the histidine residue, A or B Why ... 

Electrons from cytochrome c are transferred to Cu sites and then passed to the heme iron of cytochrome a. Cu is liganded by two cysteines and two histidines (Figure 21.18). The heme of cytochrome a is liganded by imidazole rings of histidine residues (Figure 21.18). The Cu and the Fe of cytochrome a are within 1.5 nm of each other. 

Histidine, one of the 20 natural amino acids, contains an imidazole ring. 

Compare the electrostatic potential map for heptapeptide glyglyglyhis glyglygly to that of imidazole. Would you expect the imidazole ring in this molecule to be more or less basic than free imidazole Explain. 

The 5H-imidazole ring (37) possesses two nitrogen atoms with lone pairs e,vailable for quaternary salt formation, but unlike those in the... 

The main conclusion on the influence of substituents in the imidazole ring on the state of the tautomeric equilibria 14a 14b is that electron-withdrawing groups favor the 4-position, i.e., the tautomers 14a with = Hal, NO2, and so on, are the energetically preferable species. Application of Charton s equation, Kt = [4-R Im]/[5-R Im] = 3.2 was discussed in detail [76AHC(S1) 96CHEC-II(3)77]. The equation was found to be in a qualitative agreement with the experimental data presented in Table III. 

MO studies (AMI and AMI-SMI) on the tautomerism and protonation of 2-thiopurine have been reported [95THE(334)223]. Heats of formation and relative energies have been calculated for the nine tautomeric forms in the gas phase. Tire proton affinities were determined for the most stable tautomers 8a-8d. Tire pyrimidine ring in the thiones 8a and 8b has shown a greater proton affinity in comparison with the imidazole ring, or with the other tautomers. In solution, the thione tautomers are claimed to be more stabilized by solvent effects than the thiol forms, and the 3H,1H tautomer 8b is the most stable. So far, no additional experimental data or ab initio calculations have been reported to confirm these conclusions. 

Most frequently the synthetic routes to imidazoquinolines involve the ring closure of pyridine ring starting from aminobenzimidazoles. Ring closure of the imidazole ring is preferred when starting from o-diaminoquinolines. 

In addition to the intramolecular effects, steric factors are of considerable influence. The most usual one consists of steric hindrance to attack on the lactam nitrogen atom. Certain examples of this will be given. By comparison with uracil, it would be expected that uric acid (10) would be iV-methylated in the pyrimidine ring, but that in the imidazole ring 0-methylation should also be possible. However, the experiments of Biltz and Max show that all uric acid derivatives which carry a hydrogen atom in the 9-position are converted by ethereal diazomethane into l,3,7-trimethyl-8-methoxyxanthine (11). The following are examples uric acid and its 1-methyl, 3-methyl, 7-methyl, 1,3-dimethyl, 1,7-dimethyI, 3,7-dimethyl, and 1,3,7-trimethyl derivatives. Uric acid derivatives which arc substituted by alkyl groups in the 3- and 9-positions (e.g., 3,9-dimethyl-, 1,3,9-trimethyl-, and 3,7,9-trimethyl-uric acid)do not react at all with diazomethane, possibly because of insufficient acidity. Uric acids which are alkylated... 

The influence of an ort/io-imidazole substituent on the bond dissociation energy of the O—H bond in phenol was studied by DFT calculations [00IJQ714]. The imidazole ring is twisted with respect to the phenol ring by 59° and causes a decrease of the bond dissociation energy by about -1 kcal/mol with respect to the unsubstituted molecule only. 

There are five possible classes of compounds which can be drawn under this heading of imidazoquinolines. Examples of imidazo[l,2-u]quinoline, imidazo[l,5-u]quinoline and imidazo[4,5,l-(/]quinoline (Fig. 6) are found in literature. The respective isomers having the imidazole ring fused on face j are not so far known. 

The imidazole ring can be constructed on the quinoline by reaction with bromomethyl phenacyl hydrazones to afford 493 (91H2373). On the other... 

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