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[摘要]：Protonation of typical unstrained amides and lactams is heavily distorted lactam 1-azabicyclo[2.2.2]octan-2-one is heavily favored at nitrogen. What structures occupy "crossover boundaries" where N- and O-protonation are nearly equienergetic? Density function theory calculations at the B3LYP/6-31G* level, as well as QCISD(T)/6-31G* calculations, predict that 1-azabicyclo[3.3.1]nonan-2-one favors N-protonation at nitrogen only very slightly (<2.0 kcal/mol; "gas phase") over O-protonation. H-1 and C-13 NMR as well as ultraviolet (UV) studies of this lactam, in its combination with sulfuric acid, confirm predominant protonation at nitrogen. Although the calculations very slightly favor the N-protonated chair chair conformation, experimental spectra clearly support the N-protonated boat-chair. Broadened resonances in the C-13 NMR spectrum suggest an exchange phenomenon. Variable-temperature studies of the C-13 NMR spectra support dynamic exchange between the major tautomer (N-protonated) and the minor tautomer (O-protonated) in a roughly 4:1 mixture. The findings also support the published prediction that a twisted bridgehead lactam with the nitrogen lone pair (n(N)) as HOMO will protonate at nitrogen. |
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