The Effect of Long-range Circumannular Non-bonding Orbital Interaction on the Inversion of Groups on Nitrogen in 2,2,4,4-Tetramethyl-3-imino-1-cyclobutanones

Article abstract of DOI:10.1021/ol0102693

matrix presented The free energy of activation, ΔG*, for nitrogen inversion was calculated from the coalescence temperature for the methyl signals obtained via variable temperature NMR for a series of imino derivatives of the title compounds. There was a

Full text of DOI:10.1021/ol0102693

ORGANIC
LETTERS
2002
Vol. 4, No. 7
1059-1061
The Effect of Long-Range
Circumannular Non-Bonding Orbital
Interaction on the Inversion of Groups
on Nitrogen in
2,2,4,4-Tetramethyl-3-imino-1-cyclobutanones
Arati Naik, Michelle Ferro, and James Worman*
Department of Chemistry, Rochester Institute of Technology,
85 Lomb Memorial DriVe, Rochester, New York 14623
jjwsch@rit.edu
Received November 19, 2001
ABSTRACT
The free energy of activation, ∆G*, for nitrogen inversion was calculated from the coalescence temperature for the methyl signals obtained
via variable temperature NMR for a series of imino derivatives of the title compounds. There was a direct correlation between the long-range
nonbonding circumannular orbital interactions between the heteroatoms in the 1,3-positions and the ∆G* for inversion of groups on nitrogen.
Values of ∆G* range from 26 kcal/mol on systems with maximum interaction in the transition state (I and II) to 17 kcal/mole on those systems
with minimal interaction (III and IV).
Synthesis, spectroscopy, and chemistry of simple imines is
well documented,1 and inversion through nitrogen is a
common theme. Similar studies on the title compounds are
available and include spectroscopy2,3 and circumannular and
transannular orbital interactions. Photoelectron spectroscopy
clearly established that the nonbonding lone pair orbitals
interact to give a symmetric and asymmetric pair of distinct
nonbonding molecular orbitals.4 This discovery of two
different nonbonding energy levels was a significant finding
and explained the observed ultraviolet absorption spectros-
copy. There is no previous evidence in the literature on
whether the long-range nonbonding orbital interactions affect
physical or chemical behavior of the title compounds. In
recent work we described the affect of these orbital interac-
tions on the chemistry of the carbonyl chromophore in the
monoimines, and depending on the magnitude of the non-
bonding interaction, the carbonyl behavior was altered. The
greater the interaction, the more the carbonyl group deviates
from normal chemical behavior.5
* Phone: (585) 475-2545. Fax: (585) 475-7800.
(1) Patai, S. The Chemistry of the Carbon-Nitrogen Double Bond;
Interscience Publishers: London, 1970.
(2) Rozeboom, M. D., M.S. Thesis, Preparation and Spectral Properties
of Monoimines of Tetramethyl-1,3-Cyclobutanedione, South Dakota State
University, Brookings, SD, 1977.
(3) Worman, J. J.; Schmidt, E. A. J. Org. Chem. 1970, 35, 2463-2464.
(4) Behan, J. M.; Johnstone, A. W.; Worman, J. J. J. Mol Struct. 1977,
40, 151-152.
(5) Naik, A.; Ferro, M.; Worman, J. J. 217th National Meeting of the
American Chemical Society, San Francisco, March 1999, Abstract 0198.
Naik, A., M.S. Thesis, The Study of Circumannular Orbital Interactions in
the Imine DeriVatiVes of 2,2,4,4-Tetramethyl-1,3-cyclobutanedione, Roch-
ester Institute of Technology, Rochester, NY, 1998.
10.1021/ol0102693 CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/06/2002

The purpose of this study was to show that the nonbonding
orbital interactions have an effect on the free energy of
activation for the inversion of the group attached to nitrogen
on the monoimines.
cyclohexyl group can be explained by less repulsion in the
transition state as a result of resonance stabilization. If the
R group on nitrogen inverts mainly via a translational
mechanism, the transition state will have the nonbonding
orbitals on nitrogen change from sp2 hybrid orbitals to p
orbitals and back to sp2 (Figure 1).
All compounds were prepared by a standard synthetic
technique of refluxing the diketones in toluene with a slight
excess of the amine, in the presence of a catalytic amount
of p-toluene sulfonic acid,; water is azeotroped off using a
Dean Stark trap. Evaporation of toluene in vacuo followed
by sublimation and recrystalization gives most products in
60% yield. Synthesis, spectral properties, and elemental
analysis for compounds I-IV were consistent with the
structures and identical to those reported in the literature.5-7
At room temperature the methyl groups on the monoimines
gave two distinct singlet resonances that gradually coalesce
as the temperature is increased. All NMR spectra were
observed in d6-DMSO on a Bruker 300-MHz spectrometer.
The temperature was increased from 20 to 190 °C, and the
NMR spectra were observed at 10° intervals until coalescence
was attained. The original data and spectra can be found
elsewhere.5
Figure 1.
When the substituent is phenyl the lone pair on nitrogen
will be delocalized into the ring, thus decreasing the orbital
repulsion with the lone pair on oxygen. The ∆G* of
activation for nitrogen inversion should be less for the phenyl
derivatives and greater when R ) cyclohexyl where maxi-
mum repulsion is predicted, and this is observed.
The free energy of activation, ∆G*, for compounds I-IV
was calculated using the following formula:
To further support the hypothesis, the carbonyl was
converted to a methylene group; this would preclude lone
pair interaction in the transition state and the free energy of
activation should decrease, which is consistent with the
observed results. Electron-withdrawing and -donating groups
on the phenyl rings are presently being examined, and the
data supports the hypothesis that long-range nonbonding
orbital interactions affect the inversion of groups on nitrogen
in the title compounds. The results from this study were
presented recently.8 One might argue that there is also a
rotational component to the inversion. We examined the
magnitude of this interaction by preparing the N-oxide of
the cyclohexyl imino cyclobutanone9,10 and observing the
methyl coalescence where the only component to the
inversion mechanism would be rotation. The coalescence
temperature was not measurable within the limits of the
instrument. An extrapolated Tc value allowed us to calculate
∆G* and conclude that a minimum of 30 kcal/mol would
be required for rotation.9 This is far above that observed for
the free imine, and at best would only play a minimum role
in the overall inversion mechanism.
∆G* ) 2.3RTc(10.32 + log Tc/k)
where ∆G* is the free energy of activation, R is the universal
gas constant, Tc is the temperature of coalescence, and k is
the rate of inversion at slow exchange.
Values of ∆G* for the imine derivatives are listed in Table
1.
Table 1. Free Energy of Activation (∆G*) Values for the
Various Imine Derivatives
∆G* (kcal/mol)
I
26.13
II
22.17
Another point of discussion could reflect on the trans-
annular interaction via the p-π orbitals. However, for the
most part the interaction of the p-π orbitals with the
orthogonal nonbonding orbitals should be non-existent or at
least constant since all compounds examined contain 2p-
2p type π bonds.
III
IV
17.71
17.36
(6) Hasek, R. H.; Elam, E. U.; Martin, J. C. J. Org. Chem. 1961, 26,
4340-4342.
(7) Lee-Ruff, E. Can. J. Chem. 1972, 50, 952-955.
(8) Chong, A.; Worman, J. J. 222nd National Meeting of the American
Chemical Society, Chicago, August, 2001, Abstract 245.
(9) Mitchell, R., Undergraduate Senior Thesis, Variable Temperature
NMR Studies of 2,2,4,4-Tetramethyl Cyclobutanedione Imine DeriVatiVes,
Department of Chemistry, Dartmouth College, Hanover, NH, 1995.
(10) Boyd, D. et al. J. Chem. Soc., Perkins Trans. 1 1990, 301-306.
The fact that phenyl imine derivatives require less activa-
tion energy for nitrogen inversion than those containing the
1060
Org. Lett., Vol. 4, No. 7, 2002

Long-range nonbonding orbital interactions in 2,2,4,4-
tetramethyl-3-iminocylcobutanones affect the free energy of
activation for inversion of substituents on the nitrogen atoms.
Lone pair-lone pair repulsion in the transition state can
account for the observed results.
Mitchell, ’95 Dartmouth College, for preparing the N-oxide
of compound I for his senior thesis requirement. In addition
the authors thank Brenda Mastrangelo for helping prepare
the manuscript.
Supporting Information Available: Synthesis and char-
acterization data of compounds I-IV and the N-oxide of I.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. The author wishes to thank Rochester
Institute of Technology for financial support through a
Dean’s Summer Dean’s Fellowship 1998 and for providing
matching funds for a SmithKline-Beecham (Glaxowelcome)
award for undergraduate summer support. Thanks to Rick
OL0102693
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