Five-membered ring systems oxazoles

Ring expansion of five- to six-membered rings such as oxazole —> pyridine derivatives via a Diels-Alder reaction is a well-established procedure. However, the conversion of a six-membered heterocycle into a five-membered ring system has not been exploited to any great extent, and those systems that have been studied usually involve a cationic species. 

Several other syntheses of this ring system were accomplished by annulation of the triazine ring onto a five-membered ring, either oxazole (69C303) or thiazole (71JCS(C)1615), with concurrent ring opening and reclosure to form the imidazo[2,l-c][l,2,4]triazine system. For example, treatment of 2-amino-3-phenacyl-5-phenyloxazolium bromide (598) with phenyl-hydrazine produced (599). 

It is evident from the structure of the oxazol-5(4//)-one, also sometimes called an azlactone or oxazolinone, why it is so susceptible to epimerization. Removal of the a-proton generates a five-membered ring with six n-electrons, an aromatic system according to the Hiickel 4n + 2 rule (Scheme 5). 

Oxazole, imidazole and thiazole systems contain a five-membered ring and two hetero-atoms, one of which is a nitrogen atom. The hetero-atoms are separated by a carbon atom in the ring. The second hetero-atoms are oxygen, nitrogen and sulphur for oxazole, imidazole and thiazole systems, respectively. 

When sulfur or oxygen atoms are present in a five-membered ring, they provide the pyrrole-like lone pair and any nitrogen atoms are necessarily pyridine-like. The four most important systems are oxazole 17 and thiazole 18 with 1,3-related heteroatoms and isoxazole 19 and isothiazole 20 with an N-0 or N-S bond. 

As shown in Scheme 2, two heteroatom-carbon bonds are constructed in such a way that one component provides both heteroatoms for the resultant heterocycle. By variation of X and Z entry is readily obtained into thiazoles, oxazoles, imidazoles, etc. and by the use of the appropriate oxidation level in the carbonyl-containing component, further oxidized derivatives of these ring systems result. These processes are analogous to those utilized in the formation of five-membered heterocycles containing one heteroatom, involving cyclocondensation utilizing enols, enamines, etc. 

The diazotization of heteroaromatic amines is basically analogous to that of aromatic amines. Among the five-membered systems the amino-azoles (pyrroles, diazoles, triazoles, tetrazoles, oxazoles, isooxazoles, thia-, selena-, and dithiazoles) have all been diazotized. In general, diazotization in dilute mineral acid is possible, but diazotization in concentrated sulfuric acid (nitrosylsulfuric acid, see Sec. 2.2) or in organic solvents using an ester of nitrous acid (ethyl or isopentyl nitrite) is often preferable. Amino derivatives of aromatic heterocycles without ring nitrogen (furan and thiophene) can also be diazotized. 

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. ... 

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