2,1 -Benziso thiazole

Oxidation of 5-chlorobenzo[6]thiophene-2,3-quinone with hydrogen peroxide in the presence of ammonia gives 5-chloro- 1,2-benziso-thiazole-3-carboxamide (179d).m... 

The cycloaddition of l-methoxy-3-trimethylsilyoxy-1,3-butadiene with 3-methyl-1,2-benziso-thiazole 1,1-dioxide (107) (R = Me) affords the pyridone (108) <84H(22)67l>. An improved synthesis of 1,2-benzisothiazole 1,1-dioxide has led to the preparation of the benzothiazepine (109) (R = H) by cycloaddition of the ynamine followed by ring expansion <83CC520>. Addition of yV,7V-diaikylprop-l-ynamines to 3-substituted 1,2-benzisothiazole 1,1-dioxide (107) (R = SMe, SPh, SePh) gives mainly the imine-vinylamine (110) with only small amounts of the benzothiazepine (109) <85CC845>. 

This review, intended to continue the earlier review of benzisothiazoles1 and of benzisosulfonazoles (Saccharin and related compounds),2 covers the period between about 1970 and early 1984. In general, attention has been focused on new results however, an attempt has been made to be comprehensive. Some parts of this review have received attention elsewhere. For example, a review has appeared on the biological activity of 1,2-benziso-thiazole derivatives,3 thus that topic has received less attention. 

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- 1,2-benziso-thiazole (79GEP2734866). 

The action of nucleophiles (MNuc M = H or Na) on 3-alkoxy-l,2-benziso-thiazole 1,1-dioxides (62 R = Me or Pr ) yields either 3-substituted 1,2-benziso-thiazole 1,1-dioxides (63) or saccharin (61) as main products. The nature of the nucleophile determines which pathway predominates. ... 

Sections VI,A, B, D, and E give information about indazoles, oxazole, benzoxazole, isoxazole, benzisoxazoles, isothiazole, benziso-thiazoles, and benzothiazole. In addition, Sections II and VI,F,1 refer to quaternization reactions of isoxazole and benzisothiazoles, respectively. 

Electrophilic substitution reactions of substituted 2,1-benziso-thiazoles have already been discussed. The only other functionally substituted compound so far studied in any detail is the 3-amino derivative (87). This compound is readily diazotized and the dia-zonium salt formed (88) couples with tertiary aromatic amines yielding azo dyes.117,119-121 The salt (88) also undergoes the usual Sandmeyer reactions, and other 3-substituted derivatives, such as the cyano compound (89) may be prepared.111 Acylation of the amine (87) yields diacyl derivatives which appear to possess the 3-acylimino structure (90).111... 

As mentioned earlier in Section III,C, 6, 3-amino-2,l-benziso-thiazole displays reactions which yield fixed products of the tautomeric 3-imino form. Ross has prepared a number of 3-alkylimino and 3-arylimino derivatives.103... 

Only very mild conditions are required to convert 2,2 -dithiobis(benzonitrile) 396 into 3-amino-l,2-benziso-thiazoles 397 using secondary amines and CUCI2 as the oxidant <19978871 >. 

Isothiazole (1) was first described comparatively recently, in 1956, whilst the benzisothiazoles have been known for a long time, the most widely known, saccharin (2) having been originally prepared in 1879. There are two series of benzisothiazoles, 1,2-benzisothiazole (3) and 2,1-benziso-thiazole (4). 

Synthesis. - From ortho-Halobenzoyl Compounds, Aqueous Ammonia, and Elemental Sulphur. Treating a mixture of 2,5-Cl(N02)C6H3CH0 and sulphur in DMF at 70 C with 25% aqueous NH3 gives 95% of 5-nitro-l, 2-benziso-thiazole (38) (Scheme 4). Other compounds (39 = H, aliphatic, cyclo-... 

Nitration of 2,1-benzisothiazole affords mainly 5-nitro-2,l-benziso-thiazole, with smaller quantities of the 7-nitro- and 4-nitro-isomers. Monosubstituted 2,1-benzisothiazoles give nitro-derivatives, the orientation of which indicates that the substituent in the benzenoid ring is the decisive directing influence. 

Isothiazoles, Isoselenazoles, and Isotellurazoles Synthesis.—Several new methods for the synthesis of isothiazoles and benziso-thiazoles have been reported. Nitrile sulphides are probable intermediates in one such synthesis they are produced by the thermolysis of l,3,4-oxathiazol-2-ones... 

Thus, the synthesis of 2,1-benzisothiazoles by the action of thionyl chloride on o-toluidines (see Vol. 2, p. 576) has found further application. o-Benzylaniline affords 3-phenyl-2,l-benzisothiazole (72 R = Ph) nearly quantitatively, but < -toluidines functionally substituted in their methyl group yield only tars or iV-sulphinyl-derivatives. o-Ethylaniline gives several products 3-methyl-2,l-benzisothiazole (72 R = Me) may first be formed, but is rapidly chlorinated at its methyl group, to produce, after hydrolysis, 2,l-benzisothiazole-3-carboxylic acid (30%) (72 R = COaH). Another product, previously erroneously regarded as 3-methyl-2,l-benzisothiazole (72 R = Me), appears to be 2-(2,l-benziso-thiazol-3-yl)-7-ethylbenzothiazole. More highly substituted o-alkyl-anilines produce, apart from traces of 2,1-benzisothiazoles, merely A-sulphinyl-amines. ... 

Diazonium salts derived from 7-aminobenzisothiazole (43) similarly yield l,2,3-benzothiadiazole-7-carbaldehyde and analogues (44) on decomposition under Sandmeyer conditions. Reduction of the diazonium group by hypophosphorous acid produces, without rearrangement, the benziso-thiazole (45). ... 

---