UNUSUAL MEDIUM EFFECT ON THE DISTRIBUTION OF 1,2,3-SELENADIAZOLE REGIOISOMERS IN THE REACTION OF N-BENZYL-4-HOMOPIPERIDINONE SEMICARBAZONE WITH SELENIUM DIOXIDE

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%) than ''distal'' isomer (b; ca. 30%), 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 > 96%) 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 90-95%, and HOAc (at 23-degrees-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. 85%) was experienced, but water now had little effect on the isomer ratio. Se-77 NMR measurements were employed to distinguish and quantitate selenadiazole regioisomers.