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1-Azabicyclo[3.3.1]nonan-2-one: nitrogen versus oxygen protonation
Brian Sliter1, Jessica Morgan, Arthur Greenberg
1Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, United States.
The Journal of Organic Chemistry
|March 12, 2011
Summary
Protonation of amides typically occurs at oxygen. However, this study found that a specific distorted lactam, 1-azabicyclo[3.3.1]nonan-2-one, predominantly protonates at nitrogen, confirmed by NMR and UV studies.
Area of Science:
- Organic Chemistry
- Computational Chemistry
- Physical Chemistry
Background:
- Amide and lactam protonation typically favors the oxygen atom due to its higher electronegativity.
- Highly strained cyclic amides, or lactams, can exhibit altered protonation preferences.
- Understanding protonation sites is crucial for predicting reactivity and molecular properties.
Purpose of the Study:
- To investigate the protonation site preference of the strained lactam 1-azabicyclo[3.3.1]nonan-2-one.
- To identify structures at the crossover boundary between N- and O-protonation.
- To reconcile computational predictions with experimental observations for lactam protonation.
Main Methods:
- Density Functional Theory (DFT) calculations (B3LYP/6-31G* and QCISD(T)/6-31G*).
- Nuclear Magnetic Resonance (NMR) spectroscopy ((1)H and (13)C) in combination with sulfuric acid.
- Ultraviolet (UV) spectroscopy.
Main Results:
- Computational methods predict a slight preference for N-protonation over O-protonation (<2.0 kcal/mol) for 1-azabicyclo[3.3.1]nonan-2-one.
- Experimental NMR and UV studies confirm predominant N-protonation.
- Variable-temperature (13)C NMR indicates a dynamic exchange between N- and O-protonated tautomers in a 4:1 ratio.
- The N-protonated boat-chair conformation is favored experimentally over the calculated chair-chair.
Conclusions:
- 1-azabicyclo[3.3.1]nonan-2-one represents a structural "crossover boundary" favoring nitrogen protonation.
- Experimental evidence supports computational predictions of altered protonation sites in strained lactams.
- Dynamic tautomerism plays a role in the observed protonation behavior of this lactam.
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