Nitrogen inversion in cyclic amines and the bicyclic effect

Anatoly M. Belostotskii, Hugo E. Gottlieb, Michael Shokhen

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


The hitherto unsolved problem of the origin of the unusually high nitrogen inversion - rotation (NIR) barriers in 7-azabicyclo[2.2.1]heptanes (the bicyclic effect) was examined using the natural bond orbital (NBO) approach. Reinvestigating the NIR barrier for tropane by DNMR, we found that NIR barriers increase smoothly on going from nitrogen-bridged bicyclic systems of a larger ring size to the smaller ring homologous systems. The experimental NIR barriers are reproduced with good accuracy using the MP2/6-31G* level of theory. The NBO analysis for these and other azabicycles led to the conclusion that the height of these barriers is mostly determined by the energy of the σ-orbitals of the Cα-Cβ bonds as well as the nitrogen lone pair. Thus, the bicyclic effect is actually an extreme case of a common Cα-N - Cα tripyramid geometry - NIR barrier dependence for N-bridged bicyclic amines. By establishing the rate-determining role of the Cα-N - Cα tripyramid fragment for NIR, we have derived the first sufficiently accurate quantitative correlations amine geometry - NIR barrier for monocyclic as well as bicyclic N-H and N-Me amines (i.e., for an amine set which also includes the bicyclic effect systems).

Original languageEnglish
Pages (from-to)9257-9266
Number of pages10
JournalJournal of Organic Chemistry
Issue number26
StatePublished - 27 Dec 2002


Dive into the research topics of 'Nitrogen inversion in cyclic amines and the bicyclic effect'. Together they form a unique fingerprint.

Cite this