More Than One Heteroatom in the Five-Membered Ring

Molecules with More Than One Heteroatom in the Five-Membered Ring 

7T Densities have been calculated for both the benzisoxazoles (8.76, 8.77) [60T( 10)81 ] and for benzoxazole (8.78) (74CHE166). These will underestimate the extent of substitution at the site (5-position in each case) furthest from oxygen, but indicate that, in general, 5- and 7-substitution 

The effects of substituents in the benzenoid ring on the rate of exchange at the 2-position of benzothiazole have also been measured (Table 8.15) (76JHC1021). These parallel those for benzimidazole (Table 8.14) and notable is the small difference between the effects at the 5- and the 6-positions. This may be attributed to the fact that only inductive effects are important in base-catalyzed exchange, and they may be transmitted through either heteroatom with comparable facility. 

Nitration of 6-methoxy- and 6-chlorobenzotriazole takes place mainly in the 7-position (together with a small amount of 5-substitution) (55CA8257h), again demonstrating bond-fixation effects (i.e., the 6,7-bond is of higher order than the 5,6-bond). 

3-Benzothiadiazole is nitrated in the 4- and 7-positions (48JCS-1006). The former result is difficult to explain without involving 8.79 as a significant contributor to the overall resonance hybrid, and thereby deactivating the 5-position. 

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