Unusual Medium Effect on the Distribution of 1,2,3-Selenadiazole Regioisomers in the Reaction of N-Benzyl-4-homopiperidone Semicarbazone with Selenium Dioxide

Article abstract of DOI:10.1021/jo00017a038

Four 7-membered ring, unsymmetrical semicarbazones (1, 4-6) were reacted with selenium dioxide to give 1,2,3-selenadiazole products.Special interest was directed to the regiochemical control obtained.Carbocycle 6 and carbamate 4 provided slightly more "proximal" isomer (a; ca. 70 percent) than "distal" isomer (b; ca. 30 percent), and the ratios were unaffected by the presence of water.Thioether 5 showed a significant bias toward the proximal isomer (8a:8b = ca. 7:1); again, there was essentially no water dependence.Amino compound 1 behaved like 4 and 6 in relatively nonpolar solvents, but the proximal isomer 2a was much more prevalent (75 to >96percent) in polar, protic media.For the case of 1, water dramatically amplified the amount of proximal isomer 2a in ether solvents, from 60-65 to 90-95percent, and HOAc (at 23 deg C) gave 2a almost exclusively.When the HCl salt of 1 was reacted with selenium dioxide in anhydrous ether solvents, an enhancement of proximal isomer 2a (from 60-65 to ca. 85percent) was experienced, but water now had little effect on the isomer ratio. 77Se NMR measurements were employed to distinguish and quantitate selenadiazole regioisomers.