1,2,3-Benzothiadiazole, 5-6-dichloro

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). 

Chlorination of 2,1,3-benzothiadiazoles can take place either by addition or substitution, depending on the reaction conditions, the nature of the substituents in the benzene ring, and the catalyst employed. The uncatalyzed reaction of (1) with chlorine is exothermic and produces an isomeric mixture of tetrachloro addition products, which form 4,7-dichloro-2,l,3-benzothiadiazole on treatment with base <70RCR923>. In the presence of an iron catalyst, chlorine substitution in the 4,7-positions predominates. 

It is apparent from extensive reviews of the induction of monooxygenase activity by xenobiotics that many compounds other than methylenedioxyphenyl compounds have the same effect. It may be that any synergist that functions by inhibiting microsomal monooxygenase activity could also induce this activity on longer exposure, resulting in a biphasic curve as described previously for methylenedioxyphenyl compounds. This curve has been demonstrated for NIA 16824 (2-methylpropyl-2-propynyl phenylphosphonate) and WL 19255 (5,6-dichloro-l,2,3-benzothiadiazole), although the results were less marked with R05-8019 [2,(2,4,5-trichlorophenyl)-propynyl ether] and MGK 264 [A-(2-ethylhexyl)-5-norbomene-2,3-dicarboximide],... 

BENZOTHIADIAZOLE, 5-CHLORO-4- (2-IMIDAZ0LIN-2-YL)-BENZOTHIAZOLE, 6- ((p- (DIETHYLAMINO)PHENYL AZO-BENZOTHIAZOLE, 2-AMINO-5.6-DICHLORO-... 

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). 

Wen found that A-sulfamoyloxamic acid (12), a by-product formed during the permanganate oxidation of 2,1,3-benzothiadiazole (Section II,A,1), can be converted into 3,4-dichloro-l,2,5-thiadiazole-1,1-dioxide (53) by reaction with phosphorus pentachloride. Other thiadiazole-1,1-dioxides that were derived from 12 by methylation of its disilver salt include 2-methyl-3-oxo-4-methoxy-l,2,5-thiadia-zoline-1,1-dioxide (54) and 2,5-dimethyl-3,4-dioxo-l,2,5-thiadia-zolidine-1,1-dioxide (55). 

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