Five-membered ring systems thiazoles

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

A more widely applied approach to modifying the terpyridine system so as to reduce the field has been to replace one or more of the pyridine rings with five-membered rings. The effects of replacement are much more pronounced for the central ring, because of the steric and electronic features mentioned above, and the [Fe N6]2+ derivative of l,3-bis(pyridin-2-yl)pyra-zole 47, for example, is high spin [64]. This effect is revealed further by the drastically different properties of the [Fe N6]2+ derivatives of the isomeric tridentate ligands 2,4-bis(pyridin-2-yl)thiazole 48 (Dq(Ni2+) 1125 cm-1) and 6-(thiazol-2-yl)-2,2/-bipyridine 49 (Dq(Ni2+) 1230 cm-1). 

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. 

Examples of five-membered heterocyclic systems having more than one heteroatom, the derivatives of which have been selected to illustrate some important methods of ring formation, are pyrazole (36), pyrazolone (37), hydan-toin (38), oxazolone (39), thiazole (40), benzimidazole (41) and benzotriazole (42). 

The spin-coupled method has now been applied to a large number of aromatic systems benzene and naphthalene azobenzenes, such as pyridine, pyridazine, pyrimidine and pyrazine five-membered rings, such as furan, pyrrole, thiophen, and thiazole and inorganic heterocycles, such as borazine ( inorganic benzene ) and boroxine, for which we find little evidence of aromaticity. Structural formulae are collected in Fig. 1. For all of these molecules we have included the effects of electron correlation for the Jt electrons but not for the a framework. This a-n separation is an approximation whose utility rests upon the chemistry of aromatic systems — to abandon it would be to ignore this entire body of experience. Furthermore, very extensive calculations [4] have demonstrated that rc-electron only correlation affords an excellent description of ground and excited states of benzene. 

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). 

In an attempt to synthesize fused aromatic systems of a pentalene-like structure, Boekelheid and Fedoruk (332) submitted the dicyanomethyl ylide of thiazole (77) to the addition reaction with dimethyl acetylenedi-carboxylate (DMA). They unexpectedly observed the formation of a fused six-membered (80) rather than a five-membered-ring (78). This ylide (77) was readily afforded by the reaction of thiazole (73) with tetracyanoethylene oxide and then put into reaction with DMA. The initially formed thiazolopyrrole derivative (78) is strongly polarized by the gcm-dicyano group, and its pyrrole ring is spontaneously cleaved with proton elimination. The ring dosure of the intermediate (79) leads to the final stable derivative of 5-FT-thiazolo[3,2-a]pyridine (80). More recently. 

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. 

In contrast to 6-substituted-bipyridine systems such as 49, attachment of a five-membered heterocycle to the 2-position of 1,10-phenanthroline, which is a structural modification similar to the replacement of one of the terminal rings of terpyridine, does generally bring the ligand field into the crossover region and spin transitions have been observed for such systems when the heterocycle is thiazole 51 [74], imidazoline [75], triazole [76], pyrazole [77] and oxadiazole [78]. 

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. ... 

Nuclear Overhauser enhancements (NOE) were used to measure the nuclear relaxation rates of C as a function of temperatures for neat thiazole <84MP141i>. A study of the spin-spin coupling between C nuclei in five-membered heteroaromatic ring systems showed the high aromaticity of thiazole <94MRC62>. 

Five-membered aromatic ring compounds with two or more hetero atoms are deprotonated more easily than the one-hetero atom systems [1], The ease of this proton removal is in part due to inductive electron withdrawal by the additional hetero atom(s), and in some cases coordination of the lithiating reagent by (sp2) nitrogen may contribute (e.g. in 1,3-thiazole and 1-substituted imidazoles). Some examples of aromatic systems with more hetero atoms are ... 

Thiazole (28) may be considered to be derived from benzene by replacing a CH group with a nitrogen atom and a CH=CH group with a sulfur atom. Hence, the chemistry of thiazole shows similarities to those of five- and six-membered aromatic rings. The closest system is thiophene. The donor-acceptor concept which has been successfully applied to 1,3-diazoles <92H(33)ll29> can be extended to thiazole (28) in order to predict both reactivity and regioselectivity. 

In this review an aromatic compound is any five- or six-membered cyclic structure that is formally aromatic or that one of its tautomers or resonance forms is aromatic (76M11), that is, not only p nidine but also pyridones, and not only thiazole but also thiazolinethiones. We will include systems, like phthalimide, that although nonaromatic have all its ring atoms in a plane or close to it, that is, the critical condition is the absence of sp atoms in the ring, thus 3,5-dihydrox5 yrazoles will be considered but their tautomers pyrazolidine-3,5-diones will not. 

---