Thiazole, fused mesoionic

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). 

Mesoionic systems may be readily substituted by electrophiles. Thus the thiazolo mesoion (342) will couple with diazonium salts despite their relatively weak electrophilicity (80KGS621). Substitution in a fused heteroaromatic betaine azine ring, e.g. (343), also takes place with ease. The resonance form (344) of the mesoion (343) shows that the electrophile will attack at C-6. The substitution in this position is also predicted by MO calculations (73JHC487). Similarly the pyridine ring in pyridinium olates is active towards electrophiles and is substituted in the positions ortho and para to the olate function. Bromination of the 5-methyl derivative (321 R = Me) occurs exclusively in the 7-position which is rationalized via the intermediate (345). In the absence of a 5-substituent, attack in either the 5- or 7-position occurs the dibromide is readily formed. No bromination in the thiazole ring is observed. The 2-bromo derivative (346) has been made, however, by condensation between the appropriate mercaptopyridine and 1,1,2,2-tetrabromoethane. 

Numerous structures containing the thiocarbonyl ylide dipole are conceivable. Incorporation of the thiocarbonyl ylide dipole into a bicyclic heterocyclic system is possible by the conversion of the cyclic thione (203) into the ring-fused mesoionic system (204). The thiocarbonyl ylide dipole (205) undergoes cycloaddition with both alkenic and alkynic electron-poor dipolarophiles in refluxing benzene or xylene so that, after extrusion of hydrogen sulfide or sulfur, respectively, from the initial 1 1 cycloadducts (206) and (207), a ring-fused pyridinone is formed. The method has been used for the annelation of pyridinones to the imidazole, 1,2,4-triazole, thiazole and 1,3,4-thiadiazole systems... 

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