2.1.3- Benzothiadiazole, oxidation

Purer product can be obtained by reducing 1,2,3-benzothiadiazole 1,1-dioxide with zinc and acetic acid to 1,2,3-benzo-thiadiazoline 1,1-dioxide, which is oxidized back with lead tetraacetate.5... 

In chlorinations either a substitution or an addition process can occur with the ultimate reaction pathway(s) determined by a combination of factors, which include the reaction conditions, the positions and natures of any substituents present, and the catalyst used. Uncatalyzed chlorination of benzothiadiazole is an exothermic reaction that gives rise to a mixture of isomeric tetrachloro addition products. These are converted in basic medium into 4,7-dichloro-2,1,3-benzothiadiazole (70RCR923). When an iron(III) catalyst is present 4- and 7-chloro substitution becomes the dominant process. Chlorination of a number of 4-substituted 2,1,3-benzothiadiazoles (43) using an oxidative process gave a combination of chlorinated and oxidized products. The 4-hydroxy, 4-amino-, 4-methyl-amino, and 4-acetoxy derivatives of 43 all formed the chloroquinones (44) (40-61% yields). With the 4-aIkoxy substrates both 44 and some 5,7-dichlorinated product were obtained (88CHE96). 

However, reaction of 1,2,3-benzothiadiazole 3 with 30% hydrogen peroxide in a mixture of acetic acid and methanol for 45 days afforded product 37 (Equation 7) in 60% yield <1990CJC1950>. Oxidation of 1,2,3-benzothiadiazole 3 with a variety of other oxidizing agents (w-chloroperoxybenzoic acid, 30% hydrogen peroxide, hydrogen peroxide in methylene chloride-acetic acid mixtures, etc.) was unsuccessful. 

The naphthalene-like, aromatic stmcture of 1,2,3-benzothiadiazole imparts stability to the system that survives exposure to 20% potassium hydroxide at 150°C or 27% sulfuric acid at 200 °C. It is not oxidized by potassium permanganate, potassium ferricyanide, chromic acid, or dilute nitric acid <1996CHEC-II(4)289>. Electrophilic substitution occurs in the benzo ring, predominantly at the 4-position. Chlorine in the 6-position is displaced by a variety of nucleophiles <1975SST670>. 

The numbering systems of mononuclear 1,2,5-thiadiazole 1 and 2,1,3-benzothiadiazole 2 are given below. 2,1,3-Benzothiadiazole, also referred to as benzo[l,2,5]thiadiazole, was often called piazthiole in the early literature. 1,2,5-Thiadiazole was also referred to as 2,5-diazathiophene. Both reduced and oxidized derivatives of 1,2,5-thiadiazole are known. 7... 

Bisanilino-substituted benzothiadiazole 104 was oxidized by AgzO to afford exclusively the, 4-quinonedi-... 

Photolysis of 2,1,3-benzothiadiazole-l-oxide produces l,3-dihydro-2,l,3-benzothiadiazole-2,2-dioxide, shown by flash photolysis to be formed via hydration of the 2-oxide intermediate... 

Oxidation of 4-amino (39) or 4-acetoxy-2,l,3-benzothiadiazoles (40) to quinones (41) has been reported (Equation (8)) <88KGS114>. 

The syntheses from [4+1] atom fragments, in which the Group 16 heteroatom is introduced between two nitrogen atoms, are the most widely applicable and versatile methods available for construction of the 1,2,5-thiadiazole ring system. These methods have been applied to the synthesis of monocyclic and polycyclic aromatic forms of these ring systems in addition to the direct formation of 1-oxides and 1,1-dioxides, 2-oxides, quaternary salts, and reduced forms. The earliest use of the [4+ 1] synthesis dates back to 1889 when Hinsburg prepared 2,1,3-benzothiadiazole (I) from o-phenylenediamine and sodium bisulfite. 

Readily available allylic and benzylic hichloromethyl sulfoxides undergo an unusual base-induced /(-elimination of chloroform, with formation of the corresponding a,/ -unsaturated sulfine, under mild conditions at room temperature die procedure has been applied to form vinylthioaldehyde 5-oxides and vinylthioketone 5-oxides. 89 N-Sulfinylamines (115) have likewise been prepared by /(-elimination of chloroform from trich Ioromcthanesulfinamidcs (114).90 The reaction is promoted rapidly at room temperature by pyrrolidine and Ht N and the sulfinylamines (115) can be trapped by o-phenylenediamme (116), to give benzothiadiazole, before desulfonative hydrolysis occurs. 

In the case of quinoxalines 169a,b, benzothiadiazole 172a and benzoselenodiazole 172b the reaction exhibits a remarkable dependence on the base. Whereas in the presence of DBU all these substrates react with ethyl isocyanoacetate to yield pyrimidine Y-oxides 170 and 173 only, the use of phosphorane 164 provides pyrroles 171 and 174 predominantly (Scheme 51) (96TL8391). 

The comparative ionization potentials of various triazolopyridines and [l,2,3]-thiadiazolo-pyridines versus benzotriazole or benzothiadiazole were determined by electron-impact mass spectrometry (Table 2) <74CS222>. Since their ionization potentials are similar to the benzo-fused analogues, it infers that they have comparable aromaticity profiles. The same technique shows that the [l,2,3]oxadiazolopyridines (9a,b) occur exclusively as the ozy/zo-quinoid-like pyridodiazo-oxide tautomers (Equation (1)). 

Diazo oxides when treated with phosphorus pentasulfide also form benzothiadiazoles (equatio/T34) (b-61MI42400>. 

Photolysis of 2,1,3-benzothiadiazole 1-oxide produces l,3-dihydro-2,l,3-benzothia-diazole 2,2-dioxide, shown by flash photolysis to be formed via hydration of the 2-oxide intermediate <78ACS(B)625). Independent of this process 2-thionitrosobenzene is generated reversibly as a short-lived intermediate, analogous to the thermal and photochemical formation of a 1,2-dinitroso intermediate from benzofuroxans. Preliminary flash photolysis and spectrometric results point to a nitroselenanitroso pathway in the photolysis of 2,1,3-benzoselenadiazole 2-oxide to benzofurazan (76ACS(B)675>. 

Vigorous oxidation (e.g., with KMn04) usually degrades fused benzene rings in preference to many azole rings, especially under acidic conditions. Thus, benzimidazoles are oxidized by chromic acid or 30% hydrogen peroxide to imidazole-4,5-dicarboxylic acid, and 2,1,3-benzothiadiazole is oxidized by ozone or potassium permanganate to the dicarboxylic acid 553. 

The oxidation of 2,1,3-benzothiadiazole (7) was first examined in 1889 by Hinsberg who found that the action of potassium permanganate in acidic medium led to total destruction of the compound while chromic acid was without effect. In 1957-1958 the successful oxidation of 2,1,3-benzothiadiazoles to l,2,5-thiadiazole-3,4-dicarboxylic acid (8) was reported independently by two research groups.This... 

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