1.2.3- benzothiadiazole, nitration

Like naphthalene, 1,2,3-benzothiadiazoles react with electrophiles. Nitration of 1,2,3-benzothiadiazole affords predominately the 4-isomer (equation 19). Bromination of compound (28) yields the expected ortho-para product, directed by the hydroxy group (equation 20) (B-61MI42400). 

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. 

Unlike 1,2,3-benzoxadiazoles the existence of which is open to question [208-210], 1,2,3-benzothiadiazoles are well known and their nitration has been described in the literature. On nitration of 1,2,3-benzothiadiazoles with sulfuric-nitric mixture Overberger et al. [211] have obtained 4-nitro-l,2,3-benzothiadiazole. 

Freis and Reitz, using potassium nitrate in sulfuric acid on heating, have obtained two mononitrated products and assigned to them the structures of 4- and 7-nitro isomers [212], Later, this structure has been proved by a secondary synthesis [213], and the other isomer turned out to be 5-nitro-l,2,3-benzothiadiazole [214, 215], On a more careful study all three isomers were found among the reaction products, as shown in Scheme 2.18 [216],... 

Substituted 1,2,3-benzothiadiazoles are nitrated to the position 5 or 7 if they are vacant [197, 217-219], The data [218] on the synthesis of 4-nitro-substituted 1,2,3-benzothiadiazoles need to be checked. 

Electron-donating substituents at the C-4 atom direct the incoming nitro group to the position 5 or 7 however, the amount of 7-nitro isomer is higher than that of 4-nitro isomer [222-234], The direction of the nitration of di- and tri-substituted 2,1,3-benzothiadiazoles is determined by the position and electron nature of substituents [223, 227, 229, 230, 232, 235-239], Ipso-nitration of 4,7-dibromo-2,l,3-benzothiadiazole to form 4-bromo-7-nitroderivative has been reported [235],... 

Table 3.82 Mass spectra of nitrated 2,1,3-benzothiadiazoles Compound m/z (Relative intensity, %)...

Synthesis of the benzo[l,2-c 3,4-c ]bis[l,2,5]thiadiazole (509) required cyclization of diamine (508). Nitration of (505) led to 4-nitro-2,1,3-benzothiadiazole (506) in 95% yield. Amination of (506) with hydroxylamine in basic medium led to compound (507), immediately reduced to the diamino derivative (508). Ring closure of (508) with thionyl chloride and pyridine led to the benzo[l,2-c 3,4-c ]bis[l,2,5]thiadiazole (509) in 89% yield. Compound (509) has been successfully used in the synthesis of several fused tetracyclic compounds (Scheme 40) <75JHC829>. 

Amino-2,1,3-benzothiadiazole (237) is convertible into its anthranilic acid derivative (238), which is cyclized by phosphorus oxychloride to 6-chloro-[l,2,5]thiadiazolo[3,4-c]acridine (239). Replacement of its 6-halogeno-substituent produces derivatives such as (240). An analogous series of reactions provides 7,8,9,10-tetrahydro-analogues. The condensation of (237) and alkyl 2-oxocyclopentanecarboxylate yields derivatives of the [1,2,5]-thiadiazolo[3,4-h]quinoline ring system such as (241)—(243). Electrophilic substitutions of naphtho[l,2-d][2,l,3]thiadiazole (244) have been studied in some detail. Nitration produces a mixture of the 6- and... 

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