3- Phenyl-1,2-benzisothiazoles

Furthermore, chloride 109b reacted with substituted phenols and thiophenols 364 to yield primarily the 3-phenoxy- or the corresponding 3-phenylthio-l, 2-benzisothiazoles 366. When the attack of salts 109b occurred at the aromatic ring of phenol, the 3-phenyl-1,2-benzisothiazoles 368 were produced (74CB1667, Scheme 122). 

Photodecomposition of 1,2-benzisothiazole (17) affords the ring-opened disulfide 7.40 If the 3-position is blocked by substitution, then more interesting products may result. Photocycloaddition reactions of 3-phenyl-1,2-benzisothiazole (23) with alkenes afford excellent yields of 2,3-dihydro-1,4-benzothiazepins such as 24.41 With electron-rich alkynes, thiazabicyclohep-tadienes (25) are produced, but no reaction occurs with 2-butyne, 1-phenylpropyne, or dimethyl acetylenedicarboxylate.42 An analogous S—N bond fission occurs with 2-aryl-1,2-benzisothiazolinones.43... 

Phenyl-1,2-benzisothiazole (71) gives a 1,4-benzothiazepin on irradiation with ethyl vinyl ether, consistent with initial S—N bond cleavage rather than... 

Reactions. - Photoreactions. 3-Phenyl-1,2-benzisothiazoles (21 X=H, Cl) and electron-rich alkynes (ethoxyacetylene, ethoxy-propyne, and diethylaminopropyne) undergo photocycloaddition to give substituted 3>4-benzo-2,6-thiazabieyclo[3 2.0Jhepta-3,6-dienes (22 R=H,CHj,R =0Et R=NEt2,R =CH, respectively), and smaller amounts of other products. 1,4-Benzothiazepine... 

A soln. of startg. N,N-diphenylarenesulfonamide in THF at —78° treated under N2 with 1.1 eqs. 1.6 M BuLi in hexane, stirred for 1 h, neat benzonitrile added via syringe, after 1 h the mixture allowed to warm to room temp., stirred overnight, and hydrolyzed with satd. aq. NH4CI - 3-phenyl-1,2-benzisothiazole 1,1-dioxide. Y 75%. F.e.s. D. Hellwinkel, R. Karle, Synthesis 1989, 394-5. 

Synthesis.—A series of 4-substituted 6-carboxy-3-phenyl-1,2-benzisothiazole 1,1-dioxides (58) has been produced in almost quantitative yields by the thermolysis of 3-substituted 4-benzoyl-5-sulphamoylbenzoic acids (57). The diuretic... 

Isothiazole behaves as a typical stable aromatic molecule. Thermolysis of substituted isothiazoles at 590 °C leads to the formation of thioketenes (80MI41700) and phenyl-isothiazoles undergo photoisomerism (Section 4.17.6.2) (73BSF1743, 81T3627). 1,2-Benzisothiazole boils at 220 °C without appreciable decomposition, and the 2,1-isomer... 

Both 1,2- and 2,1-benzisothiazoles react with electrophiles to give 5- and 7-substituted products (see Section 4.02.3.2). The isothiazole ring has little effect on the normal characteristics of the benzene ring. C-Linked substituents react almost wholly normally, the isothiazole ring having little effect except that phenyl substituents are deactivated (see Section 4.17.2.1). There are, however, considerable differences in the ease of decarboxylation of the carboxylic acids, the 4-isomer being the most stable (see Section 4.02.3.3). 

Benzisothiazoles can be prepared by the reaction of aromatic chloro compounds with sulfur and ammonia. Thus, 2,6-dichlorobenzylidene chloride gives 4-chloro-l,2-benzisothiazole (72AHC(14)43), and 2-chlorobenzophenone gives 3-phenyl-l,2-benziso-thiazole (79GEP27 34866). 

Raasch, and Schaumann and co-workers, have studied the reactions of bis (trifluoromethyl)thioketene (83 R1 = CF3) with alkenes, with thioketones, and with carbodiimides or Schiff-base imines. The products were, respectively, thietans, 1,3-dithietans (84 R1 = CF3), and 1,3-thiazetidines (85 R1 = CF3) (from the carbodiimide).114,115 With phenyl azide the 1,2,3,4-thiatriazoline (86 R = CF3) is formed subsequent pyrolysis yields2,l-benzisothiazole.114... 

Cycloaddition of benzyne intermediates with aminothiazadienes provide access to substituted 2,4-diamino-4//-l,3-benzothiazines 196 in high yields. The benzynes are prepared by the treatment of (phenyl)[o-(trimethylsilyl)aryl]-iodonium triflates with 1.5 equiv of tetrabutylammonium fluoride (Scheme 20). Interestingly, 3-substituted-l,2-benzisothiazoles 197 are obtained when 4 equiv of tetrabutylammonium fluoride is used <2005H(65)1615>. 

The mechanism of the photochemically induced conversion of vinylazides into 2H-azirines has been examined using ab initio MO calculations. A new approach to the elusive thionitrosobenzene system has been reported. Direct irradiation of the 3-azido-2,l-benzisothiazole (88) affords a transient 2-cyanothionitrosobenzene (89) which can be trapped as the cycloadduct (90) with cyclopentadiene. Nitrene cyclization is the preferred pathway on irradiation of the 5-formyl- or 5-benzoyl-6-azidouracils (91) and yields the isoxazolo[3,4-d]pyrimidines (92). In contrast, 5-phenyl- and 5-benzyl-6-azidouracils were converted into pyrimido[4,5-b]indoles and pyrimido[4,5-ti Jquinolines, respectively, by a pathway involving photochemically induced loss of nitrogen and intramolecular nitrene insertion. 

Phenylpropionic acid derivatives of general formula 261, functionalised at C-2 with a 3-heterosubstituted benzisothiazole, were patented for use in the treatment and/or prevention of peroxysome proliferator-activated receptor gamma (PPARgamma) mediated diseases [89]. Only the synthesis of the 3-sulfur linked compound 264 (40%) was extensively described starting from methyl 3-[4-(benzyloxy)phenyl]-2-chloropropionate (263) and benzoisothiazol-3(2H)-thione (262) operating in the presence of MeONa/MeOH (Scheme 66). 

Scheme 66 Synthesis of 2-hetero-(benzisothiazol-3-yl)(3-phenyl)propionic acids...

Oxidation of 3-piperazin-l-yl-l,2-benzisothiazole (54) (w = 0) with nitric acid or MCPBA at low temperatures gives the 1-oxide (54) (n = 1), while MCPBA at room temperature, oxone and sodium periodate afford the 1,1-dioxide (54) (n = 2) <91JMC3316>. The oxidation of 2-[(S)-l-phenyl-ethyl]isothiazolin-3-one (55) with MCPBA yields a mixture of the diastereomer 1-oxides (56) and... 

Chloro-2-ethyl-l,2-benzisothiazolium chloride 109b reacted with Ar-mono- and IV,IV-dialkylanilines 356 to give 3-phenyl 1,2-benzisothiazolium salts 357, which were converted by thermal treatment to isothiazole 358 and with hydrochloric acid to salts 359 in 70-80% yield (79CB3286, Scheme 119). The isothiazole 358 can be oxidized to 2-phenyl 1,2-benzisothiazole 1,1-dioxides. 

Lawson7 discussed the factors influencing the yields of 1,2-benzisothiazoles from 2-(alkylthio)phenyl-substituted oximes. This reaction, one of the standard synthetic methods, has been used extensively by a group at the University of Hull in their syntheses of substituted 1,2-benzisothiazoles.8 A variation involves the formation of a seven-membered heterocyclic ring (1) which is then pyrolyzed to the 1,2-benzisothiazole (2).9... 

---