Benzothiadiazole analogs

Amino-2,l,3-benzothiadiazole treated under similar conditions afforded, re-gioselectively, an analogous angularly annelated ester 68 and acid 69, both to be tested for inhibition of the DNA synthesis (74MI1). Subsequent alkylation of the... 

Somewhat less common is the preparation of the analogous. S -oxidcs and. S, .S -dioxidcs. Recently, l,3-dihydro-2,l,3-benzothiadiazole 2,2-dioxides 201 <1999JA10281> and 202 <2004BML5045> were prepared from the corresponding 1,2-diamines using sulfamide (Equation 44). 

The mononitro-2,1,3-benzothiadiazoles are the sulfur analogs of the similarly substituted benzofurazans. They display less tendency to form a-adducts than benzofurazans as indicated by indirect evidence based on stopped-flow kinetic experiments.213... 

The electronegative influences of the thiadiazole system greatly increases the acidity of substituents (Table 15). The effect is further enhanced in the 1-monoxide and 1,1-dioxide analogs. The ionization constants of 4- and 5-hydroxy-2,l,3-benzothiadiazoles were determined in water (70AC(R)80l). 

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>. 

A large body of information on the methods of synthesis, application, structure, and properties of all known five-membered nitroazoles - pyrazoles, imidazoles, triazoles, tetrazoles, oxazoles, isoxazoles, oxadiazoles, thiazoles, isothiazoles, thiadiazoles, selenazoles, selenadiazoles, and their benzo analogs - indazoles, benzimidazoles, benzoxazoles, benzisoxazoles, benzoxadiazoles, benzothiazoles, benzoisothiazoles, benzothiadiazoles, benzotriazoles, benzoselenazoles, and ben-zoselenadiazoles has been systematized, summarized, and critically discussed in this monograph. 

The synthesis of 1,2,5-thiadiazoles from a-diamines was studied as early as 1897 when Michaelis attempted the preparation of the parent compound by reaction of ethylenediamine with sulfur dioxide. The product, however, was bissulfimic acid (28) which readily lost sulfur dioxide to form the betaine (28a). Later Shew reported that 3,4-dicyano-l,2,5-thiadiazole (30) results from the reaction of cis-diaminomaleonitrile (29, HCN tetramer) with thionyl chloride, a reaction which is analogous to 2,1,3-benzothiadiazole formation from o-phenylenediamines. The synthesis of the parent 1,2,5-thiadiazole and some alkyl analogs (32) was accomplished by reaction of salts of... 

Benzoselenadiazole (128) behaves as a heterodiene toward dimethyl acetylenedicarboxylate, with which it gives the quinoxaline 124 and selenium. But 128 reacts differently with benzyne (generated from 4 or from 9) to give the 1,2-benzisoselenazole derivative 132 (88%) and a small amount of a cis,trans stereoisomer of 132.82 The analogous adduct 131 is obtained in lower yield from benzyne and 2,1,3-benzothiadiazole (127). The structure of these benzyne adducts is strikingly reminiscent of 135, which is obtained from a photochemical addition of dimethyl acetylenedicarboxylate to 126 via a nitrile oxide intermediate.84 However, for reasons given elsewhere,82 a nitrile selenide is unlikely to be an intermediate in the formation of 132, which is better explained by the mechanism outlined in Scheme 16. As in the case of thiophen (Section V,B), this is a 1,3-cycloaddition (in one or two steps) of benzyne to the heterocycle, enabled by the use of d orbitals on the sulfur or selenium atom. 

Fig. 1. Salicylic acid and its synthetic functional analogs. Salicylic acid and its derivative acetyl salicylic acid (aspirin) induce expression of the PR genes and enhance resistance to pathogens. The two synthetic compounds, 2,6-dichloroisonicotinic acid (INA) and benzothiadiazole S-methyl ester (BTH) show structural similarities to salicylic acid and like salicylic acid induce expression of the PR genes and enhance resistance to pathogens.

Isothiazolo[5,4-c]-2,l,3-benzothiadiazole (502) has been prepared by two methods. In the first, 5-nitro-2,l-benzoisothiazole (498) was converted to the nitroamine (499) by treatment with hydroxyl-amine in basic solution this was reduced with iron and acetic acid, and the o-diamino product (500) cyclized to (502) with thionyl chloride. In a second approach, treatment of 5-amino-4-methyl-2,l,3-benzothiadiazole (501) with iV-sulfinylmethanosulfonamide also led to (502). The isothiazolo[4,5-c]-2,l,3-benzothiadiazole (504) has been synthesized from 4-amino-5-methyl-2,l,3-benzothiadiazole (503) by an analogous procedure (Scheme 39) <80JHC537>. 

The sulfur analogs of these selenium compounds react less efficiently with benzyne. Thus the yield of396 (S in place of Se) was only 5% from the benzothiadiazole. However, with the parent thiadiazoles 406 the yields are improved. Thus 1,2-benzoisothiazoles 409 are formed in 25-75% yield, depending on probably by the mechanism shown. Selenium... 

The ring system has been the subject of quantum-chemical calculations. The outstanding feature of the mass spectra of the 2,1,3-benzothiadiazoles (35 examples) is the occurrence of molecular ions of very great abundance. Fragmentations analogous to the benzyne formation postulated in the case of the 2,1,3-benzoselenadiazoles are not encountered. The polarographic behaviour of a large number of 2,1,3-benzothiadiazoles, of 2,1,3-benzoselenadiazole, and of several fused 1,2,5-thiadiazoles has been examined. ... 

Diazotization of 7-aminobenzothiazole (37), followed by hydrolysis, yields 7-aminO l,2,3-benzothiadiazole (39), presumably by the electrophilic intramolecular attack of the diazonium cation at the sulphur. 7-Amino-6-halogenobenzothiazoles react analogously. The isolation (95%) of intermediate 7-formamido-l,2,3-benzothiadiazoles (38) suggests that the mechanism may be depicted as in Scheme 2. ... 

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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