Density functional and spectroscopic studies of nitrogen inversion in substituted dizocilpines |
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| Authors: | Abil E. Aliev Alex J. Sinclair Shen Zhou John D. Wilden Stephen Caddick Dimitri M. Kullmann Dmitri A. Rusakov |
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| Affiliation: | 1. Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK;2. Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK |
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| Abstract: | While developing a synthesis towards tagged dizocilpine (MK‐801) analogues, we observed highly restricted inversion of a nitrogen centre in a number hydroxylamines obtained as key intermediates. These compounds are shown to possess some of the structural elements which are expected to significantly hinder the nitrogen inversion, potentially leading to hydroxylamines with a chiral nitrogen centre. Free energy barriers (ΔG≠) of the nitrogen inversion were estimated to be ca. 22 kcal mol?1 at temperatures near 420 K using variable temperature NMR measurements in DMSO‐d6. Further density functional studies of a number model systems were undertaken in order to better rationalize the measured inversion barriers and follow the role of various structural factors in raising the barrier height of the nitrogen inversion process. Copyright © 2008 John Wiley & Sons, Ltd. |
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| Keywords: | dizocilpine hydroxylamines nitrogen inversion chiral nitrogen energy barrier transition state NMR spectroscopy DFT calculations |
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