Isothiazole ring opening

Woodward (1963) plan for colchicine isothiazole ring opened via reduction with Raney Ni... 

Thus quaternized thiazoles (170) consume two equivalents of OH on titration because the pseudo bases (171) ring open to (172), which form anions (173). Quaternized oxazoles (174) are readily attacked by hydroxide to give open-chain products such as (175) (74AHC(17)99), and quaternized 1,3,4-oxadiazoles behave similarly. Quaternary isothiazoles (e.g. 176) are cleaved by hydroxide (72AHC(l4)l), as are 1,2,4-thiadiazolium salts (177 178). 

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... 

To further illustrate the diversity of hydrolytic opening reactions, we turn our attention to an isothiazole ring as found in the antipsychotic agent ziprasidone (11.129). This drug is subject to various reactions of oxidation and reduction, but also undergoes hydrolytic cleavage of the C=N bond of the isothiazole ring. Evidence for this reaction was afforded by detection of radioactive metabolite 11.130, a sulfonamide, in the urine of patients dosed... 

Thienooxazines can also be made from 3-hydroxyisothiazoles (365) by a process involving ring opening of the isothiazole ring, followed by two ring closures (Scheme 27) <85JHC1497>. 

Practical syntheses of 5a or N-substituted 3-aminobenz[d]isothiazole-1,1 -dioxides are mostly based on the following procedures (iv) Refluxing saccharin with an excess of a monoalkyl or aryl amine above 130°, presumably via ring opening, by analogy with 75.161,189,248... 

Ring expansion of the bicyclic isothiazole (698) occurred upon treatment with cyanide ion to give the imidazo[l,2-c][l,3]thiazine (699). The mechanism involves initial ring opening by attack on sulfur, and then ring closure. The anion of methyl propiolate also causes the same type of rearrangement (79TL1281). 

Treatment of aminoisothiazolopyrimidine 136 with chloroacetone gave an unexpected transformation. A thienopyrimidine formed, apparently, through the intermediate opening of the isothiazole ring and the formation of the corresponding nitrile (1988JCR(S)46). 

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