6682 J . Org. Chem., Vol. 66, No. 20, 2001
Garcia et al.
Sch em e 1
taken into account to propose a reasonable hypothesis
about the motion which is more likely to be observed by
NMR spectroscopy.
Both the crystal and computed structures indicate that
in 1 the pyramid of the aryl-bonded sp3 nitrogen atom is
quite flat, the degree of pyramidalization being 5.8° (X-
9
ray) or 8° (ab initio ), i.e., values that are much closer
to the 0° of a planar sp2-hybridized nitrogen atom than
to the 27° of the truly pyramidal sp3 nitrogen of trim-
ethylamine.16 Owing to this situation, the N-inversion
barrier of 1 is presumably too low to be amenable to NMR
observation, and this is confirmed by our ab initio
9
calculations that predict an N-inversion barrier in 1
equal to 2.7 kcal mol-1. It has also to be stressed that
N-inversion processes sufficiently high (i.e. >4 kcal mol-1
)
to be measurable by dynamic NMR spectroscopy have
never been reported for arylamines.17 On the other hand,
ring inversion of six-membered heterocycles, comprising
an endocyclic double bond, have barriers accessible to
NMR detection, since a number of derivatives were
found18 to display free energies of activation in the range
7-11 kcal mol-1. The asymmetry resulting from the
“frozen” inversion of the six-membered ring creates a
second source of chirality, in addition to the mentioned
Ar-N stereogenic axis. As a consequence two stereolabile
diastereoisomers, each entailing a pair of enantiomers,
are expected to occur in these derivatives. The ab initio
computation9 for compound 1 predict that, in addition to
the conformation depicted in Figure 1, the restriction of
the ring inversion process should lead to a second
minimum of energy, corresponding to a minor conformer.
The two conformers were labeled anti (1b), when the CH2
moiety in position 5 is on the opposite side of the chlorine
atom, and syn (1a ) when on the same side (Scheme 1).
The corresponding energy difference was computed9 to
be 1.5 kcal mol-1, thus indicating that the proportion of
the less stable conformer syn-1a should be very small
(about 1%) in the temperature range where the ring
inversion becomes sufficiently slow for NMR observation.
For this reason it is unlikely that the spectrum of the
minor conformer is directly visible.
F igu r e 6. 13C signals (75.5 MHz in CHF2Cl) of the three
methylene carbons of 1 at different temperatures. At -127 °C
the central line broadens more than the other two, but
sharpens again at -147 °C, indicating the occurrence of an
exchange process involving an invisible species (see text).
process between two species experiencing a very biased
equilibrium.19
The relationship k ) 2π∆ω, where ∆ω represents the
20
maximum incremental width (in the case of 1 ∆ω was
found 14 ( 1 Hz at 75.5 MHz), allows one to obtain the
rate constant, hence the ∆Gq value (7.0 ( 0.2 kcal mol-1
)
for the ring inversion process. An estimate of the signal-
to-noise ratio indicates that the amount of the minor
conformer 1a is certainly lower than 10%, in agreement
with the theoretical prediction. As shown in Table 1
similar results were obtained for 2 and 3.
It should be also noticed that in 1-3 the topomeriza-
tion and ring inversion barriers (Table 1) are equal within
the experimental errors. This might be due to an ac-
cidental coincidence, even though the possibility that
these equal values are the consequence of a correlated
motion cannot be, in principle, excluded. If so, the
measured ∆Gq values would be the manifestation of an
unique dynamic process. A definite evidence, however,
is not available to support this hypothesis which remains,
therefore, rather speculative.
Actually, in the low temperature 13C spectrum of 1 the
signals of the minor conformer were not detected, but its
presence could be nonetheless established in an indirect
manner. For it was observed that one CH2 broadens at
low temperature considerably more than the other two
CH2 lines, reaches a maximum width at -127 °C, and
sharpens again on further cooling to -147 °C (Figure 6).
This is the typical feature expected for an exchange
With the purpose of achieving direct evidence for the
presence of two conformers, we searched for a compound
(19) Anet, F. A. L.; Yavari, I.; Ferguson, I. J .; Katritzky. A. R.;
Moreno-Man˜as, M.; Robinson, M. J . T. J . Chem. Soc., Chem. Commun.
1976, 399. Cerioni, G.; Piras, P.; Marongiu, G.; Macciantelli, D.;
Lunazzi, L. J . Chem. Soc., Perkin Trans. 2 1981, 1449. Lunazzi, L.;
Placucci, G.; Chatgilialoglu, C.; Macciantelli, D. J . Chem. Soc., Perkin
Trans. 2 1984, 819. Casarini, D.; Lunazzi, L, Macciantelli, D. J . Chem.
Soc., Perkin Trans. 2 1985, 1839. Lunazzi, L.; Placucci, G.; Macciantelli,
D. Tetrahedron 1991, 47, 6427. Grilli, S.; Lunazzi, L.; Mazzanti, A. J .
Org. Chem. 2000, 65, 3563.
(16) The degree of piramidalization is defined as 360° - Σ RNR,
see: Ganguly, B.; Freed, D. A.; Kozlowski, M. C. J . Org. Chem. 2001,
66, 1103.
(17) (a) Brand, J . C. D.; Williams, D. R.; Cook, T. J . J . Mol. Spectrosc.
1966, 20, 359. (b) Lambert, J . B.; Stec, D. Org. Magn. Reson. 1984,
22, 301. (c) Davalli, S.; Lunazzi, L.; Macciantelli, D. J . Org. Chem. 1991,
56, 1739.
(18) Oki, M. Applications of Dynamic NMR Spectroscopy to Organic
Chemistry; VCH: Deerfield Beach, 1985; p 306.
(20) Anet, F. A. L.; Basus, V. J . J . Magn. Reson. 1978, 32, 339.