Reactions Involving Cleavage of the Isothiazole Ring

Cleavage of isothiazoles during lithiation was discussed in Section III,B, and a related example is provided by the fission of the isothiazole ring of an isothiazolo[5,4-6][l,4]benzothiazine during alkylation with sodium hydride and alkyl halide.123 

The synthesis of 3-hydroxyisothiazoles by cyclization of 3-thio-cyanatoacrylamide is reversible (see Section I,D), and Crow and Gosney have demonstrated that 2-alkyl-3-isothiazolones are particularly vulnerable to nucleophilic attack [Eq. (17)].132 134 In the 

5-Dimercaptoisothiazoles on standing in the dark in ethanolic solution for several days49,80 or by acid treatment47 give high yields of cyclic disulfides [Eq. (18)]. 

Treatment of quaternary isothiazoles with hydrazine or phenyl-hydrazine gives pyrazoles [Eq. (19)].145 

Lee and Volpp85 observed that although diazotized 5-aminoiso-thiazoles gave good yields of disulfides on treatment with thiourea, 4-aminoisothiazoles under the same conditions gave 1,2,3-thiadiazoles [Eq. (20)]. During discussion of the mechanism of this reaction, Lee 

---