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Density functional and spectroscopic studies of nitrogen inversion in substituted dizocilpines
Author(s) -
Aliev Abil E.,
Sinclair Alex J.,
Zhou Shen,
Wilden John D.,
Caddick Stephen,
Kullmann Dimitri M.,
Rusakov Dmitri A.
Publication year - 2009
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.1490
Subject(s) - chemistry , nitrogen inversion , nitrogen , inversion (geology) , density functional theory , computational chemistry , organic chemistry , paleontology , structural basin , biology
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 (Δ G ≠ ) 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‐ d 6 . 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.