Isothiazoles from nitrile sulfides

Phenyl-l,3,4-oxathiazol-2-one (370), prepared from primary amides and tri-chloromethanesulfenyl chloride, undergoes a ready thermal elimination of carbon dioxide with the formation of the nitrile sulfide ylide (371). This can be trapped by a wide variety of unsaturated dipolarophiles, and with an alkyne provides a ready route to isothiazoles (372) (see Chapter 4.17). Applications to 1,2,4-thiadiazole synthesis are described in Chapter 4.25. Thermolysis of l,3,4-oxadiazolin-5-ones (500 C/10 mmHg) results in the loss of CO2 and generation of the corresponding nitrilimine (78JOC2037). 

Nitrile sulfides are well suited for the synthesis of isothiazoles incorporating the C=N-S unit via their 1,3-dipolar cycloaddition reactions with double or triple-bonded dipolarophiles. Benzonitrile sulfide 210 is readily prepared from decarboxylation of oxathiazolone 209 using microwave irradiation <05SC807>. Subsequent cycloadditions to dimethyl acetylene-dicarboxylate (DMAD) and dimethyl fumarate afford 211 and 212, respectively. In the case of ethyl propiolate, a 1 1 regioisomeric mixture of phenylisothiazoles 213 and 214 is obtained. 

Franz and Black539 have studied the thermolysis and photolysis of l,3,4-oxathiazol-2-one (l).530 This compound is thermally labile and yields benzonitrile and sulfur instead of the expected phenyl isocyanate and carbonyl sulfide. It is probable that benzonitrile sulfide (3) is an intermediate and this appears to be confirmed by formation of the adduct 4 in 90% yield when 1 is heated with 2 moles of DMAD at 130° in chlorobenzene. Heating a mixture of benzonitrile and sulfur with DMAD gave tetramethyl thiophenetetracarboxylate (6), also obtained without the nitrile. The formation of the isomeric isothiazoles 7 and 8 from 1 and EP531 is similar to the production of the corresponding... 

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