Reactions of substituents involving ring transformations

Reactivity of Five-membered Rings with Two or More Heteroatoms 

A somewhat similar type of ring interconversion involving attack on sulfur has been postulated in the 1,2,4-thiadiazole series, e.g. (485— 486). Such reactions are common in the 1,2,4-dithiazolium series, e.g. (487- 488). 

In compounds with a fused benzene ring, electrophilic substitution on carbon usually occurs in the benzenoid ring in preference to the heterocyclic ring. Frequently the orientation of substitution in these compounds parallels that in naphthalene. Conditions are often similar to those used for benzene itself. The actual position attacked varies compare formulae (489)-(494) where the orientation is shown for nitration sulfonation is usually similar. 

Substituents on the benzene rings exert their usual influence on the orientation and ease of electrophilic substitution reactions. For example, further nitration (H2S04/S03/HN03) of 4-nitro-benzofuroxan (496) gives the 4,6-dinitro derivative, the first nitro group direct meta as expected. 

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The reactions of the homocyclic ring are considered in three parts attack by electrophiles attack by nucleophiles and transformations involving substituent groups, together with miscellaneous reactions. Unless otherwise stated common behaviour is assumed for benzofurazans and benzofuroxans. 

Beyond the well-defined substitutions of the heterocyclic ring systems, numerous other transformations have been carried out that cannot be simply classified into the substitution category. These transformations involve side chain alkylations, exchange of substituents by more sophisticated methods, or ring closures carried out on the side chains. A set of such reactions are summarized in Table 3. 

Concerning the transformation of substituents, a special note should be made on a series of ring-closure reactions carried out on the side chain of some [l,2,4]triazolo[4,3-r]benzo[l,2,3]triazines published by Moustafa <2001SC97>. The results are summarized in Scheme 18. This scheme shows that by transformation of the R group attached to the sulfur atom of derivative 97 a fairly large set of cyclic products - involving thiazolidone 97a, [l,2,4]triazole 97b, coumarone and its imine 97c and 97d, respectively, benzoxazylpyrane, 97e, thiophene 97f, and cyclopenta- or cyclohexa-fused protected pyrone 97g substituents - have been obtained. 

Most reactions of this type were found to involve acyclic 1,4-dipolar intermediates which cydize to four-membered heterocydes or are intercepted by isocyanate or C=X components, such as C=N, C=S, and CR2, to form a six membered ring. This group of reactions is illustrated in Figure 1. Depending on the nature of the isocyanate and the double-bond system, any of the products shown in Figure 1 can be obtained. Variations in the component ratio or judicious choice of reagents are noted to have pronounced control of product type. Additional reaction details, as well as a description of the multiple transformations involving adjacent substituents, have been summarized (28). 

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