Benzisoxazoles, Benzoxazoles, and Benzoxadiazoles

The nature of substituent in the arylene fragment significantly influences the nitration direction. For example, 3,5-dialkyl-l,2-benzisoxazoles are nitrated into the position 4 (the data about the formation of 3,5-dimethyl-7-nitro-l,2-benzisox-azole presented in [115] turned out to be wrong [119], whereas 3-alkyl-5-nitro derivatives occupy the position 7 [119]). The nitration of 7-methoxy-2-phenylben-zisoxazole affords 7-methoxy-2-phenyl-4-nitro derivative [126], 

The mechanism of the nitration of benzisoxazoles in sulfuric-nitric acid mixture has been studied with 3-methyl-l,2-benzisoxazole [121], It has been found that at a sulfuric acid concentration of about 80-90% the substrate reacts as a free base, and at a higher concentration the conjugated acid undergoes nitration. It is worth mentioning that in 1,2-benzisoxazole and its 3-methyl derivative the higher electron density is concentrated on the C-7 atom and in the case of charge-controlled reactions the nitration would lead to 7-nitro isomers. Since 5-nitro derivatives are formed, the process of nitration seems to be of orbital-controlled character [121], 

In benzoxazoles and their 2-substituted derivatives the nitro group is presumably introduced into the position 6 [131-135], In the nitration of 2-methylbenzoxazole a mixture of 80% of 6-nitro- and 20% of 5-nitro isomer was isolated. 2-Phenylbenz-oxazole is first nitrated to the position 6 [136,137], The nitration of benzoxazolones-2 and benzoxazolthiones-2 proceeds in an analogous way [138-141], 

Substituted benzoxazoles are also nitrated with nitric-sulfuric mixture into the 6 position, if it is vacant [143, 144], In earlier publications it has been stated that benzofurazans (2,1,3-benzoxadiazoles) are nitrated exclusively to the 4(7) position 

As expected, strong electron-deficient substituents in the position 5 orient the incoming nitro group exclusively to the position 7 [ 150,151 ]. 7-Nitrobenzofurazans possess fluorescent properties and may be useful as biochemical fluorescent probes [152], Some examples of obtaining dinitrobenzofurazans by nitration are described in references [153, 154], 

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