Azoles Five-membered ring heterocycles with

We have looked at the five-membered aromatic heterocycles pyrrole, furan and thiophene in Section 11.5. Introduction of a second heteroatom creates azoles. This name immediately suggests that nitrogen is one of the heteroatoms. As soon as we consider valencies, we discover that in order to draw a five-membered aromatic heterocycle with two heteroatoms, it must contain nitrogen A neutral oxygen or sulfm atom can have only two bonds, and we cannot, therefore, have more than one of these atoms in any aromatic heterocycle. On the other hand, there is potential for having as many nitrogens as we like in an aromatic ring. 

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. 

The ending -ole is systematic and refers to a five-membered heterocyclic ring. All the five-membered aromatic heterocycles with nitrogen in the ring are sometimes called the azoles. Oxazole and thiazole are used for the oxygen and sulfur analogues of imidazole. 

N-Substituents in hetarylazomethine ligands are represented by three-and five-membered rings with one heteroatom as well as azole and azine heterocycles. They may not always participate in the formation of metallacycles and thus play the role of coordination-active or inactive constituents of the hetarylazomethine ligands. A great majority of coordination compounds includes mononuclear complexes, although di- and oligonuclear structures are also known. 

Electrophilic substitution in the azoles is intermediate in facility between pyridine and pyrroles, thiophene and furans the presence of the electron-with-drawing azomethine unit has an effect on the five-membered aromatic heterocycles just as it does when incorporated into a six-membered aromatic framework, i.e. the comparison is like that between benzene and pyridine (chapter 4). The order of reactivity - pyrrole > furan > thiophene - is echoed in the azoles, though the presence of the basic nitrogen complicates such comparisons. The regiochemistry of electrophilic attack can be seen nicely by comparing the character of the various ring positions - those that are activated in being five-membered in character and those that are deactivated by their similarity to a-and y-positions in pyridine. 

As it has been already mentioned in the Introduction, aminoazoles besides the role of 1,3-binucleophiles can take part in the MCRs as 1,1-binucleophiles with participation of exclusively exocyclic NH2-group. Usual products of such multi-component interaction are five-membered heterocycles having azole ring as a substituent. 

Heterocyclic compounds are ubiquitous in biology, medicine, and biochemistry, and the azoles form an important class of nitrogen heterocyclic compounds with five-membered aromatic rings that can contain one to five nitrogen atoms (other heteroatoms can also be present). Many drugs and pharmaceuticals are derived from azole structures. The structures of representative azoles are shown in Figure 6.1. Note that some of these compounds exist in tautomeric equilibrium in solution. 

---