Imidazole ring system

The imidazole ring system provides the nucleus for two diuretic agents with structures unusual for that activity. Reaction of the N-cyanoaniline 140 (obtainable from the aniline (139) and cyanogen bromide) with N-methylchloroacetamide leads to the heterocycle 142. The sequence can be rationalized by... 

Conversion of the S=C—NH moiety in the 2//-imidazolethiones 13 to X—C=N, where X is a single-bonded group, generates the 2H-imidazole ring system. This has been accomplished in a number of ways, generally in high yields. 

Histamine, an important mediator of inflammation, gastric acid secretion and other allergic manifestations, contain an imidazole ring system. Thiamine, an essential vitamin, possesses a quaternized thiazole ring. 

Although several different rate laws have been drawn for different substrates, the kinetic equations are generally consistent with a mechanism involving an electrophilic attack by I2 on an anionic imidazole ring system, followed by proton abstraction from the sigma complex as the rate-determining step. 

The location of the maverick proton on the pyrrolo[ 1,2-a ]imidazole ring system is on carbon. NMR spectral evidence favors the methylene and not the NH form <77HC(30)l). 

The synthesis of naphthimidazo[2,l-fe]thiazol-3(2//)-ones, in which a 4-thiazolidinone nucleus has fused to both naphth[2,3-d]imidazole and naphth[l,2-c/]imidazole ring systems, has been reported. 

The photosensitivity of this active ingredient is attributable to its imidazole ring system and nitro moiety. Photolysis results in increased concentrations of nitrite. Studies have shown that the effects of temperature and pH are more significant than those of UV-VIS radiation (19,20). 

Microcyclamide 342, isolated from the cultured cyanobacterium Microcystis aeruginosa, is a cytotoxic cyclic hexa-peptide alkaloid containing an imidazole ring system <2000JNP1315>. It showed moderate cytotoxicity against P388 murine leukemia cells. 

Benzimidazole is a fused aromatic imidazole ring system where a benzene ring is fused to the 4 and 5 positions of an imidazole ring. Benzimidazoles are also known as benziminazoles and 1,3-benzodiazoles [1,2]. They possess both acidic and basic characteristics. The NH group present in benzimidazoles is relatively strongly acidic and also weakly basic. Another characteristic of benzimidazoles is that they have the capacity to form salts. Benzimidazoles with unsubstituted NH groups exhibit fast prototropic tau-tomerism, which leads to equihbrium mixtures of asymmetrically substituted compounds [1]. 

Considerable parallelism emerges from an examination of the major methods for the construction of oxazole, thiazole and imidazole ring systems. 

IR values of the carbonyl groups present in pyrrolo[l,2-a]imidazole ring systems are used to explain structural features e.g., in the case of 5-oxopyrrolo[l,2-a]imidazole (41), the carbonyl group showed a strong absorption in the IR at 1760 cm which indicates that normal delocalization of the lone pair in the ring junction nitrogen atom is severely impaired <87JCS(Pi)653>. 

This technique has rarely been applied to the systems covered in this chapter. In the imidazo[2,l-i]thiazole and imidazo[l,2-a]imidazole ring systems, the bridgehead nitrogen is more shielded than the other ring nitrogens <89MI 804-01, 86JHC54l>. 

Compounds that bear an imidazole ring system can have many pharmacological properties and play important roles in biochemical processes [67]. Balalaie et al. synthesized these species under MW conditions by three-component condensation ofbenzil, benzaldehyde derivatives, and 2 equiv NH4OAC (Scheme 17.22) [68]. The reaction vas catalyzed by zeolite HY or silica gel under solvent-free conditions. After MW irradiation for 6 min in a domestic oven at 850 W the desired triarylimi-dazoles 31 vere obtained in good yields (80-94%) by use of zeolite HY slightly lower yields (54-89%) were obtained for the reactions on silica gel. 

Many biologically active therapeutic agents contain five-membered heterocycles.92 The imidazole ring system is of particular interest since it is a component of histidine and its decarboxylation metabolite histamine. The wide applicability of the imidazole pharmacophore can be attributed to its hydrogen bond donor-acceptor capability as well as its high affinity for metals which are present in many protein active sites (e.g. Zn, Fe, Mg). Furthermore, improved pharmacokinetics and bioavailability of peptide-based protease inhibitors have been observed by replacing an amide bond with an imidazole. 

Imidazole alkaloids. A group of natural products of plant and animal (especially marine oiganisms) origin containing the imidazole ring system. 

In the cyazofamid synthesis (Scheme 13.2.5), a nice all-in-one reaction can be used to convert 5 into 6 it involves a dehydration, two deoxygenations and a chlorination at the imidazole ring system in an one-pot reaction [104]. 

Another pharmaceutically important fused-imidazole ring system is the popular sleeping aid medication zolpidem. Bromination of 4-methylacetophenone and condensation with methylated 2-amino pyridine provides the fused-imidazole in good overall yield. Note that the ring nitrogen on the aminopyridine reaction reacts with the bromide carbon. Mannich-type alkylation at the unsubstituted 5-position provides the dimethylaminomethyl substituent in good yield. Further elaboration yields zolpidem. ... 

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