3- Phenylisothiazole, from irradiation

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. 

This symmetry is removed in the case of 2-deuterio-5-phenylthiazole 52-2d, and hence deuterium labeling expands the dyad into a tetrad. As expected from this analysis, irradiation of 2-deuterio-5-phenylthiazole 52-2d resulted in the formation of 4-deuterio-5-phenylthiazole 52-4d, the product of a Pg permutation process not observed in the absence of deuteration, and to 5-deuterio-4-phenylisothiazole 48-5d and 3-deuterio-4-phenylisothiazole 48-3d, formed via P5 and P7 pathways respectively. Again, these observations are entirely consistent with the electrocyclic ring closure heteroatom migration mechanism shown in Scheme 10. 

Reinvestigation of these reactions, however, gave substantially different results. Thus Pavlik and coworkers observed that 3-phenylisothiazole 47 is formed with deuterium incorporation at C-4 upon irradiation of either 2-phenylthiazole 50 or 5-phenylisothiazole 49 but with approximately twice the extent of incorporation from the latter reactant. Furthermore, although Maeda... 

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