Thiazole ring enamines

Thiazolo[4 5-d]pyriiiiidines (C3NS-C4NJ).—Like linear enamines (see Ch. 13, T5fpe B syntheses), heterocyclic enamines react with chlorocarbonyl sul-phenyl chloride, with formation of an annelated thiazole ring. Members of the thiazolo[4,5-d]pyrimidine series (199) are readily accessible by this route. ... 

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. 

When there are two different heteroatoms in a five-membered aromatic ring, questions of regio-selectivity often arise. The unsymmetrical thiazole 27 might be disconnected at the imine to give the unstable primary enamine 28 and then at the thiolester to give an acylating agent and the undoubtedly very unstable 30. Note that 30 must have SH and NH2 on the same side of the alkene for cyclisation to be possible. We want to find a better way. 

Carbonyl compounds and other dipolarophiles containing heteroatoms react with miinch-nones. Thus benzaldehyde forms the betaine (245) which suffers ring-cleavage to yield the enamine (246 equation 65). Thiocarbonyl compounds and nitrosobenzene behave in an analogous manner. The action of dipolarophiles containing cumulative double bonds results in the formation of new mesoionic systems. Thus carbon disulfide and phenyl isothiocyanate afford a zwitterionic thiazole and imidazole, respectively (Scheme 25). 

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