Benzoisothiazoles

Singlet oxygen adds in a [4+ 2] fashion to the thiazole nucleus forming adducts similar to those of oxazoles (cf. 395). Ethyne-dicarboxylate esters add to 2,1-benzoisothiazole to generate quinoline esters 399, and benzyne reacts to yield acridine. 

There is only one way in which a benzene ring can be fused to each of the three 1,3-azoles, generating 17 -benzimidazole, benzothiazole, and benzoxazole. Indazole is the only possibility for the analogous fusion to a pyrazole it exists as a -H tautomer - the 2-7 -tautomer cannot be detected, though 2-substituted 2// -indazoles are known. Two distinct isomers each are possible for the other two 1,2-azoles 1,2-benzoisothiazole and 2,1-benzoisothiazole, and 1,2-benzisoxazole and 2,1-benzisox-azole," respectively. 

To date, only the parent benzoisotellurazole 9 has been obtained. For its synthesis, methods similar to those used for the preparation of benzoisothiazole andben-zoisoselenazole were employed. The reaction of 2-bromotellurenylbenzaldehyde with ammonia affords 9 in 74% yield, whereas cyclization of the oxime of o-butyltellurobenzaldehyde catalyzed by PPA gives 9 in 40% yield (78JHC865). In contrast to the reaction of 2-bromoselenenylacetophenone with ammonia, which leads to 3-methylbenzoisoselenazole (73JHC267), 2-bromotellurenylacetophe-none reacts with ammonia to give telluroindoxyl (78JHC865). 

Few racemic alkyl p-tolyl sulphoxides were prepared in rather low yields (16—40%) by the reaction of Grignard reagents with mixed anhydrides 108, 109 and compound HO formed in situ from p-toluenesulphinic acid and 3-phthalimidoxy-l,2-benzoisothiazole 1, 1-dioxide167 (equation 59). The mixed anhydrides 109 or 110 when reacted with cyclopen-tene and cyclohexene enamines 111 gave the corresponding a-ketocycloalkyl sulphoxides 112 in low yields (10-41%) along with small amounts of several by-products such as disulphides and thiosulphonates167 (equation 60). 

In contrast with the reaction of the chloropyridine, but in keeping with its observed reactions with diethyl malonate under classical procedures, 3-chloro-l,2-benzoisothiazole produces not only the SNAr products, (1) and (2) (Scheme 2.3), but also products arising under the basic conditions from ring opening of the isothiazole... 

Reaction of 3-chloro-1,2-benzoisothiazole with diethyl malonate... 

Benzoisothiazole-2,2-dioxides undergo autoxidation under basic conditions in the presence of TBA-Br to yield 2-aroylaniline derivatives (Scheme 10.6) and the more simple diarylmethylsulphones produce diaryl ketones (Table 10.29) [1],... 

Benzoisothiazole dioxides undergo [2+2] cycloaddition with 1-diethylaminopropyne followed by ring expansion to give 3-diethylamino-l,2-benzothiazepine 1,1-dioxides (378 R1 = Me, R = Et) (76H(5)95). JV-Tosylsulfimines, e.g. (386), are converted into 1,2-benzothiazepines (388) in high yield when treated with triethylamine in benzene under reflux. In the absence of base the intermediate (387) can be isolated (80JCS(Pl)2830, 81JCS(P1)1037). 

The 1,4- and 1,5-benzothiazepines (421) and (423) have been prepared by the photochemical reactions of the benzoisothiazole (420) and the benzothiazole (422) respectively with ethyl vinyl ether (81TL529, 2081). The mechanisms of these reactions are not fully established but it is interesting to note that the reactions of (422) with cis- and trans-but-2-ene are stereospecific. 

Fluoro-3,3-dimethyl-2,3-dihydro-l,2-benzoisothiazole 1,1-dioxide ()V-fluoro-2,oc-... 

We make no comment about benzoisothiazole, ( -X-Y- = -CH=N-, Z = -S-) (XXXVI), 1,2,3-benzoxadiazole (XXXVII), 1,2,3-benzothiadiazole (XXXVIII), or 1,2,3-benzotriazole (XXXIX) ( -X-Y- = -N=N-, Z = -NH-,-0- and -S-) since we lack experimental measurements for the enthalpy of formation of these species in the gas phase and also for their reference species. Estimations can be made for the enthalpy of formation of all of these species, but this seems ill-advised in the current context. 

TV-Substituted 2,3-dihydrobenzo-TAs 157 were obtained by cyclization of benzyl-(o-carbamoyl)phenyl sulfoxides 156. However, this reaction is not characteristic of other sulfoxides 156 (when R + Ph and R = H), which afford either 2-acetyl-l,2-benzoisothiazol-3-one 158 or 1,3-benzothioxan-4-ones 159 (74T2641) (Scheme 53). 

Few examples of photochemical transformations of the 10n heterocycles in this series have been reported. Notable is the conversion of thieno[2,3-c]isothiazoles (33) to thiophenes (37) by homolytic cleavage of the nitrogen-sulfur bond (Scheme 4). The enedithione (34) which arises from the initial diradical may undergo (a) cyclization via the bicyclic thiirane (35) or (b) electrocyclization to the 1,2-dithiine (36) <88H(27)2539>. Since similar rearrangements do not occur with isothiazoles, benzoisothiazoles, or the isomeric thieno[3,2-d]isothiazoles, this unique transformation is a direct consequence of the thieno[2,3-c]annelation. However, substituent effects on the efficiency of the transformation have not been explored. 

A-Tosylsulfimines, e.g., 250, are converted into 1,2-benzothiazepines 252 by triethylamine (Scheme 142). In the absence of base the intermediate 251 can be isolated <1981J(P1)1037>. 1,2-Benzothiazepine 1,1-dioxides 254 are prepared by ring expansion of the 1,2-benzoisothiazole derivatives 253 upon treatment with 1-diethylamino-l-propyne (Scheme 143) <1996T3339, CHEC-III(13.07.4.2)241>. 

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