Five-membered ring heterocycles imidazole

Pyrazole and Imidazole. These are five-membered ring heterocycles containing two nitrogens, one basic and one neutral. Two common forms are pyrazole (1,2-diazole) and imidazole (1,3-diazole) both are prone to aromatic hydroxylation. 

Five-Membered Ring Heterocycles with Two Hetero Atoms Imidazoles, Benzimidazoles, 1H-pyrazoles, Oxazoles, Isoxazoles, Thiazoles, and Indazoles... 

Five-membered ring heterocycles are common in numerous pharmaceuticals. In particular, the imidazole core structure, an element of histidine and its decarboxylation metabolite histamine, is often found [53]. The exceptional properties and wide applicability of the imidazole pharmacophore are due to its hydrogen-bond donor/acceptor capabilities and its high affinity for metals (present in many protein active sites, e.g., Zn, Fe, Mg) [54-58]. In addition, peptide-based protease inhibitors with improved pharmacokinetics and bioavailability have been obtained by replacing an amide bond with an imidazole [59]. 

Among the five-membered ring heterocyclics with more than one hetero-atom, the derivatives of imidazole, oxazole, thiazole and 1,2,4-triazole are particularly important. 

Pyrrole is the five-membered ring heterocycle containing one nitrogen. There are two five-membered ring molecules with two nitrogen atoms—imidazole (1,3 N) and pyrazole (1,2 N) 1, 2, 3, 41, 42. 

Five-membered ring heterocyclic compoxmds containing nitrogen are one of the most common heterocycles. In fact, the synthesis of a great variety of that such as pyrrole, pyrazole, imidazole, triazole, tetrazole, lactams, and imides involving porous catalytic systems have been investigated. 

Imidazole is another aromatic five-membered ring heterocycle that has two nitrogens. These nitrogens, however, have different properties. The one with its lone pair in a p-orbital uses those electrons to complete the aromatic sextet and this nitrogen, as in pyrrole, is neutral. The other nitrogen has its lone pair contained within an sp orbital and those electrons are therefore in the plane of the ring, do not interact with the Jt-system, and can act as a base (Figure 1.39). 

Figure 2.19) exhibited the most potent antiviral activity among the evaluated five-membered ring heterocycles (1,2,4-triazole and imidazole) carbocychc nucleosides (Figure 2.20 and Table 2.12). 

Details of bond lengths and bond angles for all the X-ray structures of heterocyclic compounds through 1970 are listed in Physical Methods in Heterocyclic Chemistry , volume 5. This compilation contains many examples for five-membered rings containing two heteroatoms, particularly pyrazoles, imidazoles, Isoxazoles, oxazoles, isothlazoles, thlazoles, 1,2-dlthloles and 1,3-dlthloles. Further examples of more recent measurements on these heterocyclic compounds can be found in the monograph chapters. 

Other common five-membered heterocyclic amines include imidazole and thiazole. Imidazole, a constituent of the amino acid histidine, has two nitrogens, only one of which is basic. Thiazole, the five-membered ring system on which the structure of thiamin (vitamin Bt) is based, also contains a basic nitrogen that is alkylated in thiamin to form a quaternary ammonium ion. 

The azoles (oxazole, imidazole, and thiazole) are five-membered aromatic heterocycles that have two heteroatoms in the ring. One of the heteroatoms in each of these heterocycles is an sp2-hybridized nitrogen that contributes one electron to the 6n aromatic system and has a basic nonbonded lone pair. The other heteroatom (oxygen, nitrogen, or sulfur) contributes two electrons to the 6n system. The imidazole skeleton is present in the amino acid histidine. The thiazole ring occurs in thiamin (vitamin B. ... 

The heterocyclic five-membered ring systems such as pyrrole, furan, thiophene, thiazole, imidazole, etc., deserve special attention. 

Most diazotized heterocyclic amines undergo normal coupling reactions with common aromatic coupling components, as well as with some C—H acidic compounds . This pertains for five-membered ring systems such as pyrrols 46 pyrazoles imidazoles 45 , l,2,4-(49) and 1,2,3-triazoles 50... 

Grimmett, M. R., Advances in Imidazole Chemistry, 12,103 27,241 Electrophilic Substitution in the Azines, 47, 325 Halogenation of Heterocycles /. Five-membered Rings, 57,291 ... 

The 1,3- and 1,2-azoles, five-membered rings with two heteroatoms, present a fascinating combination of heteroatom types - in all cases, one heteroatom must be of the five-membered heterocycle (pyrrole, thiophene, furan) type and one of the imine type, as in pyridine imidazole with two nitrogen atoms illustrates this best. Contributor 39 is a particularly favourable one. 

Proline, histidine, and tryptophan are heterocyclic amino acids. Proline has its nitrogen incorporated into a five-membered ring—it is the only amino acid that contains a secondary amino group. Histidine is an imidazole-substituted alanine. Imidazole is an aromatic compound because it is cyclic and planar and has three pairs of delocalized tt electrons (Section 21.11). The pA a of a protonated imidazole ring is 6.0, so the ring will be protonated in acidic solutions and nonprotonated in basic solutions (Section 23.3). 

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