Methylthiazoles, basicity

The easier elimination of pyridine compared to quinoline-4 may be related to the pK value of 4-methylthiazole, which is between those of lepidine and 2-picoline (25. 55). This reaction explains also why a neutrodimethine cyanine is obtained with such good yields when reacting together a quaternary salt, ketomethylene, and o-ester in a basic medium. As the reaction proceeds, the trimethine cyanine is attacked by the ketomethylene. The resulting 2-methyl quaternary salt is transformed into trimethine cyanine, consuming the totality of the ketomethylene (1, p. 512 661). The mesosubstituted neutrodimethine cyanine is practically pure. 

With the exception of the nuclear amination of 4-methylthiazole by sodium amide (341, 346) the main reactions of nucleophiles with thiazole and its simple alkyl or aryl derivatives involve the abstraction of a ring or substituent proton by a strongly basic nucleophile followed by the addition of an electrophile to the intermediate. Nucleophilic substitution of halogens is discussed in Chapter V. 

NMR data for 4-methyloxazole have been compared with those of 4-methylthiazole the data clearly show that the ring protons in each are shielded. In a comprehensive study of a range of oxazoles. Brown and Ghosh also reported NMR data but based a discussion of resonance stabilization on pK and UV spectral data (69JCS(B)270). The weak basicity of oxazole (pX a 0.8) relative to 1-methylimidazole (pK 7.44) and thiazole (pK 2.44) demonstrates that delocalization of the oxygen lone pair, which would have a base-strengthening effect on the nitrogen atom, is not extensive. It must be concluded that not only the experimental measurement but also the very definition of aromaticity in the azole series is as yet poorly quantified. Nevertheless, its importance in the interpretation of reactivity is enormous. 

Base catalysis is another area which has received a recent stimulus from developments in materials science and microporous solids in particular. The Merk company, for example, has developed a basic catalyst by supporting clusters of cesium oxide in a zeolite matrix [13]. This catalyst system has been developed to manufacture 4-methylthiazole from acetone and methylamine. 

Under basic conditions thiamine degrades to 5-(2-hydroxyethyl)-4-methylthiazole (45, sulfurol) and the pyrimidine derivative 46 [71]. Sulfurol is used in compounded flavourings in the flavour industry. It is almost odourless as such [73] however, it can decompose giving rise to thiazole and its derivatives such as 4-methylthiazole (47), 4,5-dimethylthiazole (48), 4-methyl-5-ethylthiazole (49) and 4-methyl-5-vinylthia-zole (50) ]71, 74], which possess nutty, green notes [75]. 

Zeolites function as Bronsted or Lewis acid catalysts or (less frequently) as basic catalysts. Examples of the former are alkylation and isomerization of aromatics, such as the isomerization of xylenes an example of the latter is the use of cesium zeolite in the synthesis of the key intermediate, 4-methylthiazole, used in the preparation of the anthelmintic, thiabendazole. 

The same trend in basicity has been observed by Haake and Bausher27 300 among 4-methyl-l,3-heteroazoles. Thus, 4-methyloxazole (piCa 1.07) is about 100 times less basic than 4-methylthiazole (3.07), and about 10° times less basic than 4-methylimidazole (7.61).301... 

Base-catalyzed and bifiinctional (acid/base) applications of zeolites have been reported for bulk chemicals, but they are not as numerous as the acid-catalyzed applications (15), However, base catalysis may play a major role in the synthesis of fine and specialty chemicals. For example, in the synthesis of 4-methylthiazole, a systemic fungicide, basic sites of the Cs zeolite catalyst are... 

---