Oxazole ring thiazole

In addition to the reactions described in the preceding section, alkyl groups in the 2-positions of imidazole, oxazole and thiazole rings show reactions which result from the easy loss of a proton from the carbon atom of the alkyl group which is adjacent to the ring (see Section 4.02.3.1.2). 

In general, methyl groups in the 4- and 5-positions of imidazole, oxazole and thiazole do not undergo such deprotonation-mediated reactions, even when the ring is cationic. 

Selenazole is the selenium-containing compound in the series of heterocyclic 5-membered ring azoles with two different hetero atoms, of which the first two members are oxazole and thiazole. The numbering of the ring system is according to the scheme given (1). 

In NRPs and hybrid NRP-PK natural products, the heterocycles oxazole and thiazole are derived from serine and cysteine amino acids respectively. For their creation, a cyclization (or Cy) domain is responsible for nucleophilic attack of the side-chain heteroatom within a dipeptide upon the amide carbonyl joining the amino acids [61]. Once the cyclic moiety is formed, the ring may be further oxidized, to form the oxazoline/thiazoline, or reduced, to form oxazolidine/thiazolidine (Figure 13.20). For substituted oxazoles and thiazoles, such as those... 

The very broad structural requirements for NSAIDs that allow replacement of the benzene ring by a pyrrole or an oxazole ring have been noted earlier in this chapter. Thiazoles, too, it has been found, can substitute for the central benzene ring. 

Details of bond lengths and bond angles for 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, isothiazoles, thiazoles, 1,2-dithioles and 1,3-dithioles. Further examples of more recent measurements on these heterocyclic compounds can be found in the monograph chapters of CHEC and CHEC-II. 

Aryl-5,6-dihydrobenzo[4,5]imidazo[l,2-C]-quinazolines Isatoic anhydride could also be reacted with amino-, hydroxyl- or thiolanilines to form 2-(2-aminophenyl)benz-imidazoles, oxazoles or thiazoles, Scheme 5.38. In the case of 2-(2-aminophenyl)benzimidazoles (X=N), the product was formed after 3 min at 150°C in acetic acid. The products could subsequently be further elaborated 6-aryl-5,6-dihydrobenzo[4,5]imidazo[l,2-C]quinazolines, a four ring system, was formed by treatment of the 2-(2-aminophenyl) benzimidazole (X=N) with different aldehydes in acetic acid at 150°C for 5 min (J. Westman, and K. Orrling, Personal Chemistry, Uppsala, Sweden, unpublished results). Fifteen compounds were synthesised in 20-75% overall yield. This 3 + 5 min procedure should be compared to the conventional heating protocol developed by Devi and co-workers57, where each reaction step was run overnight to eventually afford the products in only 30-50% yield. 

Superacid-promoted dicationic species containing heteroaromatic rings, where positive charge centres migrate through consecutive deprotonation-reprotonation steps, undergo cyclization reactions followed by aromatization and superacid-promoted elimination of benzene (Scheme 10).31 The process leads to the synthesis of aza-polycyclic aromatic compounds in moderate to good yields. Seven examples include pirazole, oxazole, and thiazole heterocycles. 

Phenylthiazole, like 2-phenyloxazole, is also nitrated (and brominated) at the 5-position of the heterocyclic ring. The thiazole is less reactive than the oxazole ring. In nitration of the protonated thiazole, the predominant product is 2-(4-nitrophenyl)-thiazole (85CS295), in contrast to the nitration of 2-phenyloxazole, which gives predominantly 2-(3-nitrophenyl)oxazole (84CHE713). 

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

Anthraquinoneazoles. In contrast to the older yellow Algol dyes, which contain two thiazole rings (e g., 2,2-bisanthra [2,1 d thiazole-6,11-quinonyl), the red to blue oxazoles and thiazoles derived from l-aminoanthraquinone-2-carboxylic acid and 3-amino-2-hydroxy- or -mercaptoanthraquinones exhibit good lightfastness. The good fastness to atmospheric conditions and chlorine of the blue deriv-... 

Chart 3 Ring systems formed by fusion of oxazole or thiazole with pyridine (Z = O, S)... 

Fused ring systems can be prepared either from an azine precursor or from an oxazole or thiazole precursor. In the sections on the synthesis of these compounds the former method is grouped under Azine approach , the latter under Azole approach . 

The fully conjugated oxazole and thiazole ring systems possess aromatic stability, which is higher in the latter due to better electron-releasing properties of sulfur. In fused dihydroazole systems the resistance towards nucleophilic opening of the azole ring is less. 

The oxazole ring possesses less aromatic stabilization than a thiazole ring and is readily opened in many of its fused derivatives, especially in oxazolium salts. In the pyridazinium derivative (191) the oxazole ring is opened by oxygen, sulfur or carbon nucleophilic attack at the C-8a ring junction (77YZ422). In the mesoionic pyridine (192) an amine attacks at C-2, which is a pseudocarbonyl carbon atom (70JCS(C)1485). 

The ending -ole is systematic and refers to a five-membered heterocyclic ring. All the flve-membered aromatic heterocycles with nitrogen in the ring are sometimes called the azoles. Strictly speaking, pyrrole is "azole, pyrazole is 1,2-diazole", and imidazole is 1,3-diazole. These names are not used but oxazole and thiazole are used for the oxygen and sulfur analogues of imidazole. 

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