2.1.3- Benzothiadiazole 7-nitro

Although derivatives of 2,1,3-benzoxadiazole have been used extensively to make quinoxalines (see Section 1.6.7), the corresponding selena and thia systems have been paid scant attention for that purpose. However, 5-chloro-4-nitro-2,l,3-benzoselenadiazole (456) has been used as a convenient source of 4-chloro-3-nitro-1,2-benzenediamine (457) (HCl + HI, 20°C, 2 h 88%), which was then converted into 6-chloro-5-nitro-2,3(l//,4//)-quinoxalinedione (458) (oxalic acid, 2M HCl, reflux, 2.5 h 23%). ° In addition, irradiation of 2,1,3-benzoselenadiazole (460, X = Se) or 2,1,3-benzothiadiazole (460, X = S) with dimethyl acetylenedicarboxy-late afforded, among other products, dimethyl 2,3-quinoxalinedicarboxylate (459)... 

Nitro-substituted 1,2,3-benzothiadiazoles undergo an interesting reaction with methyl (trimethyl-silyl)acetate (Scheme 6) <86JOC1704>. The benzothiadiazole is also stable to the conditions used to reduce the nitro group to the amine. 

The reaction of 4-nitro-2,1,3-benzothiadiazole with methoxide ion leads to 2,l,3-benzothiadiazole-4,7-dione monoxime as the final product. 

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],... 

The synthesis, structure, and superoxide dismutase mimetic activity in vitro and the protection against reactive oxygen species in vivo of mononuclear copper complexes with 2-(4-methylphenylsulfamoyl)-6-nitrobenzothiazole have been reported [602], Like 1,2,3-benzoxadiazoles, nitroderivatives of 1,2,3-benzothiadiazoles were obtained on diazotization of the corresponding or/Zzo-aminothiophcnolcs [213, 218, 583], The initial or/Zzo-thiophcnols for this reaction were synthesized by nucleophilic substitution of halogen in ort/zo-halogenoanilines. It turned out that 4-nitro- and... 

An attempt to synthesize 5- or 7-nitro-l,2,3-benzothiadiazoles in this way was unsuccessful. mefrz-Nitroaniline reacts with sulfur monochloride (Herz s reaction), while 1,2,3-benzothiazathiolium chloride reacts with nitrous acid to give a small amount of 5-nitro-l,2,3-benzothiadiazole, according to Scheme 2.112 [218, 603], Different derivatives of 2,1,3-nitrobenzothiadiazole (earlier called nitropiazthiole)... 

The NMR spectra of nitro-l,2,3-benzothiadiazoles have been considered in [810-813] and those of nitro-2,l,3-benzothiadiazoles in [352, 813-816], For the identification of... 

The radical anions of five isomers of nitrobenzothiazole (4-N02-, 5-N02-, 6-N02-, 7-N02- and 2-N02-) have been obtained by electrochemical reduction in DMSO and easily characterized by ESR spectroscopy [889], To the contrary, the chemical reduction in alkaline solution (t-BuOK in DMSO or glucose and MeOK in MeOH) presented some problems with 6-N02- and 4-N02-benzothiazoles, and 2-N02-benzothiazole did not provide any detectable paramagnetic species [889], Copper(II) complexes of 6-nitrobenzothiazole-A-sulfonamides as protective agents against superoxide anion have been investigated by ESR spectroscopy [890], The ESR spectrum of 5-nitro-2,l,3-benzothiadiazole RA obtained by electrochemical generation in DMF was reported [886], Unfortunately, the HFS constants of this radical anion are absent and we estimated the HFS constants from simulated spectrum (Table 3.40). 

Table 3.40 Simulated splitting constants (mT) in ESR spectra of 5-nitro-2,1,3-benzothiadiazole RA (DMF)a ...

Nitro-2,l,3-benzothiadiazole and 4-nitro-2,1,3-benzosclcnadiazolc in DMF are reduced into half by the one-electron and reversible waves (Scheme 3.43) [1008, 1009],... 

The authors [1259] managed to determine the position of the absorption maximum of 4-nitro-2,l,3-benzothiadiazole however, because of poor solubility of the substance (n-hexane) its concentration and extinction factor remained unknown. 

Mass spectra of the following series of nitro derivatives of 2,1,3-benzothiadiazole have been studied [1360] (Table 3.82). Their mass spectra are characterized by an intense peak of the molecular ion. The fragments N02, NO, H, HCN, and NS are the most important elimination fragments. The nitro group position does not affect much the fragmentation outcome the spectra of 4-nitro- and 5-nitro-2,l,3-benzothiadiazoles are nearly the same [1360],... 

The mass spectral characteristics of 4,7-dibromo-5,6-dinitro-2,l,3-benzothiadiazoles and 4-bromo-5-nitro-6,7-(2, l, 3 -oxadiazole)-2,l,3-benzothiadiazole have been considered [1361],... 

Benzothiadiazole is oxidized by ozone, potassium permanganate,and chromic acid which all lead to the dicarboxylic acid (8). In the ozonolysis the intermediate crystalline ozonide is decomposed to l,2,5-thiadiazole-3,4-dicarboxaldehyde (isolated as the semicarbazone) as well as 8. Permanganate oxidation has been applied to a number of derivatives of 7, among them being the 5-methyl, 4-nitro, and 4,7-dichloro derivatives. In some cases, particularly in the permanganate oxidation of 4-nitro-2,l,3-benzo-thiadiazole, the yield of 8 is much higher than in the oxidation of the unsuhstituted compound (7). 

Reduction of 4-nitro-5-amino-2,l,3-benzothiadiazole 1505 with Sn/HCl in the presence of a carboxylic acid having a C(l)-C(3) chain yields the corresponding 2,5-dialkylbenzo[l,2-i7 3,4-,7 ]diimidazoles 1506 (Scheme 389) <1998H(48)113>. 

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