Isothiazol-5-one

The exoeyelie earbonyl group of isothiazol-3-ones absorbs in the region 1610-1660 em <7lJHC59l). 2-Methylisothiazol-3-one itself has the C=0 and C=C bands at 1660 and 1629 em respeetively, in CCI4 solution <64TL1477). The low earbonyl frequeney is due in part to eontributions from the resonanee form (20b). The earbonyl frequeney inereases in sulfoxides (1660-1730 em ) and 1,1-dioxides (1690-1740 em ) where sueh forms are not favourable. Sulfoxides (1060-1190 em ) and sulfones (1330-1360 and 1150-1190 em ) absorb in the regions expeeted (e.g. saeeharin, 1353 and 1162 em ), but resonanee forms related to (13) eause a reduetion of the frequeney of the asymmetrie SO2 vibration to near 1280 em (70CB3166). A similar situation arises in 3-amino-1,2-benzisothiazole 1-oxides. 

Few isothiazoles undergo simple cycloaddition reactions. 4-Nitroisothiazoles add to alkynes (see Section 4.17.7.4). With 5-thiones (84) and dimethyl acetylenedicarboxylate, addition to both sulfur atoms leads to 1,3-dithioles (85) (77SST(4)339, 80H(14)785, 81H(16)156, 81H(16)595). Isothiazol-3-one 1-oxide and the corresponding 1,1-dioxide give normal adducts with cyclopentadiene and anthracene (80MI41700), and saccharin forms simple 1 1 or 1 2 adducts with dimethyl acetylenedicarboxylate (72IJC(B)881). 

Cephalosporin 5-oxides and penicillin 5-oxides (221) can be converted into isothiazol-3-ones (222) by the action of bases. These reactions proceed via an intermediate azetidinonesulfenic acid (223 Scheme 37) (77SST(4)339). Attempts to prepare /3-lactam compounds from isothiazoles have, as yet, been unsuccessful (81X2181). 

Dichloro-22 2-octyl-4-isothiazol-3-one, biocide for antifouling coatings,... 

The reaction of 2-substituted-5-aroyl-isothiazol-3-ones (214) with hy-droxylamine or arylhydrazines gives the 1,2,5-oxathiazoles 216 (Z = O) or 1,2,3-thiadiazoles 216 (Z = NAr ), as a result of a spontaneous rearrangement of unisolated oximes 215 (Z = O) or arylhydrazones 215... 

Isothiazolo[5,4-c]pyridines have been prepared by a Diels-Alder reaction (Scheme 68) (90HCA69). The regioselective [4 + 2] addition of the dienophile 2-(t-butyl)isothiazol-3-one 1,1-dioxide (538) with 5-ethoxy-4-methyloxazole (537) in benzene at room temperature gave a 5 3 mixture of the exo to endo adducts (539) and (540) in an overall 85% yield. The two adducts (539) and (540) were surprisingly stable and separable by fractional crystallization from a methylene chloride/hexane mixture. Bubbling a stream of anhydrous hydrochloric acid into an ethanolic solution of these adducts (539) and (540) gave the isothiazolo[5,4-c]pyridine (541) as its hydrochloride in 63% yield. 

The general structures of cyclic sulfoximines are reported in CHEC-II(1996) <1996CHEC-II(3)319> (see p. 348). Very few examples of sulfoximines were reported in the decade under review. The preparation of cyclic sulfilimides 165 and 173 from (R)-l-/>-tolyl-lA-isothiazol-3-ones 164 and diazoalkanes and cyclic dienes, respectively, have been reported (see Section 4.05.5.11). Furthermore, studies on the alkylation of a-sulfonimidoyl carbanions and on their use as chiral ligands in copper reagents were reported (see compounds 227 and 228, Section 4.05.6.3.4). 

Another application of the well-known cyclization of ortV o-substituted benzenesulfonamides consists in the treatment of 415 (R =NR2, R = Me) with Et30Bp4 followed by aqueous H2SO4 affording good yields of benz-isothiazol-3-one 1,1-dioxides 416. Their alkaline hydrolysis afforded 415 (R = OH, R = R = H), which is stable at neutral pH but recyclizes to 416 under even mild acidic conditions (pH <4) <1999T237>. 

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