CH/π Interaction on the structure of N-substituted-4- phenyltetrahydroisoquinoline derivatives

Article abstract of DOI:10.1246/bcsj.20090307

Rotational barriers about the CN bonds and differences of ground state energies of tert-butyl 4-phenyltetrahydroisoquinoline- 2-carboxylate derivatives were determined by NMR spectroscopy. The results are discussed assuming characteristic intramolecular C

Full text of DOI:10.1246/bcsj.20090307

8
02
Bull. Chem. Soc. Jpn. Vol. 83, No. 7, 802–808 (2010)
© 2010 The Chemical Society of Japan
CH/³ Interaction on the Structure of N-Substituted-
4
-phenyltetrahydroisoquinoline Derivatives
1
2
2
2
2
Hiroko Suezawa,* Tomoaki Yuzuri, Yuji Kohno, Yoshitaka Yamaguchi, and Masatoshi Asami*
1Ministry of Education, Culture, Sports, Science and Technology, Kasumigaseki, Chiyoda-ku, Tokyo 100-8959
2Department of Advanced Materials Chemistry, Graduate School of Engineering, Yokohama National University,
Tokiwadai, Hodogaya-ku, Yokohama 240-8501
Received November 24, 2009; E-mail: m-asami@ynu.ac.jp
Rotational barriers about the C­N bonds and differences of ground state energies of tert-butyl 4-phenyl-
tetrahydroisoquinoline-2-carboxylate derivatives were determined by NMR spectroscopy. The results are discussed
assuming characteristic intramolecular CH/³ interactions accompanied by results of X-ray structure analysis, ab initio
MO, and DFT calculations. The calculated values with MP2/6-31G(d,p) level are in good agreement with the
experimental results of X-ray structure analysis and NMR measurements.
Non-covalent interactions have been known to play impor-
double bond character. Therefore, these potential energy
barriers are affected very sensitively by the conjugative
properties of their hydrocarbon moieties with the carbonyl
tant roles in understanding conformational preferences and
behaviors of organic molecules. These interactions are very
often attractive but far weaker than those of covalent bonds.
group. Previously we reported the rotational barriers about the
1
14,15
Among weak attractive forces, the hydrogen bond is one of the
C­N bonds of several arenecarboxamides
and N-acyl-N-
1
6
most significant.
alkylamino acids.
During the course of
An ordinary hydrogen bond, i.e., X­H£Y, is an interaction
working between hard acid (XH) and hard base (Y), while a
a
synthetic investigation of
(6S*,10bR*)-6-phenyl-1,2,3,5,6,10b-hexahydrobenzo[g]indoli-
2
17
hydrogen bond such as CH/³ interaction can be regarded
dine, we encountered an interesting structure of tert-
as weak interaction, which occurs between a soft acid (CH)
and soft base (³-system). The enthalpy of CH/³ interaction
butyl trans-1-allyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline-2-
carboxylate (trans-1). Namely, an N-Boc group is directed to
a phenyl group on C-4 of an isoquinoline ring and one of the
methyl groups on tert-butyl is as close as possible to interact
with the phenyl group by CH/³ interaction. (Figure 1)
We then prepared some analogs of trans-1 (X = allyl, Y =
¹
1
has been estimated by NMR to be at most 9 kJ mol for
intermolecular interacting CH-donor/aromatic ³-base sys-
3
tems. Although the CH/³ interaction is weak, it can some-
times play an important role because many CH groups can
participate simultaneously without considerable loss of entropy.
Similarly, intramolecular CH/³ interaction often affects con-
formational properties because it can interact without a large
loss of entropy. Therefore the CH/³ interaction is important
factor in the fine tuning of organic and biochemical reactions
and molecular recognition. Previously, we reported the CH/³
interaction in determining the conformation of aromatic amides
t
t
Ph, R = O Bu), trans-1¤ (X = allyl, Y = Ph, R = CH2 Bu),
i
17
trans-2 (X = allyl, Y = Ph, R = O Pr), trans-3 (X = allyl,
1
7
t
Y = Ph, R = OEt), cis-1 (X = allyl, Y = Ph, R = O Bu),
cis-3 (X = allyl, Y = Ph, R = OEt), 4 (X = H, Y = Ph, R =
1
7
t
t
O Bu), 4¤ (X = H, Y = Ph, R = CH Bu), 5 (X = H, Y = Ph,
2
i
R = O Pr), 6 (X = H, Y = Ph, R = OEt), 6¤ (X = H, Y = Ph,
R = CH Et), 7 (X = H, Y = H, R = O Bu), and 7¤ (X = H,
Y = H, R = CH Bu) (Table 1), and measured the rotational
t
2
4
t
and ketones by spectroscopy, and the crystal packing of
2
clathrates, the relative stability of diastereomeric salts6 by
5
barriers about their C­N bonds by NMR in order to clarify
the effect of CH/³ interaction on conformations of those
compounds. Furthermore, we carried out quantum chemical
calculations of these conformations.
using a crystallographic database (CSD), and the conformation
7
of alcohols, the diastereofacial selectivity in a reaction of
8
chiral acyclic ketones by ab initio MO calculation. Further-
more, high-level ab initio MO calculations supported the
concept.
9
Results and Discussion
On the other hand, dynamic nuclear magnetic resonance
spectroscopy has supplied much useful information on the
dynamic behaviors of molecules. Amides and related nitrogen
compounds have been most extensively investigated by this
In order to investigate the effect of CH/³ interaction on the
conformational preference and on the rotational barrier heights
of N-substituted-4-phenyltetrahydroisoquinoline derivatives,
their dynamic behaviors were examined by NMR. Changes
in relative energies and structures during the process of rotation
about the C­N bond of those compounds are illustrated in
method because their NMR spectra show coalescence phenom-
ena near ambient temperature.1
0­13
Rotational barriers about the
‡
C­N bonds of the amides are directly related to the partial
Figure 1. The rotational barriers (¦G ), the conformational free
Published on the web June 30, 2010; doi:10.1246/bcsj.20090307

H. Suezawa et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 7 (2010)
803
0
TS
energy differences (¦G ) between the conformers about the
1
C­N bond, the conformational population (P and P ), and H
A
B
chemical shift (¤ and ¤ ) of R in N-COR are given in Table 1.
A
B
0
Effect of CH/³ Interaction on ¦G .
In a series of
alkyl trans-1-allyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline-2-
1
carboxylate (trans-1, -2, and -3), H NMR signals (¤ and
A
∆
G
¤
B) of the two conformers in ground state were observed
unequivocally at room temperature. Conformer A is more
¹1
stable than conformer B (about 2.5 kJ mol ) in the ground state
GB
G0
(Table 1). The CH/³ interaction between CH(CH ) in N-COR
∆
3
GA
and phenyl substituent of the isoquinoline ring is illustrated
in Figure 2a. The CH/³ interaction is assumed to stabilize
0
conformer A, and the value of ¦G is the same without regard
0
H X
O
H X
R
to R (trans-1, -2, and -3). In the case of trans-1¤, ¦G became
¹1
larger (4.5 kJ mol ) than that of trans-1 because CH/³
N
R
N
O
interaction occurred between the 4-phenyl ring and CH in
3
∆
G
∆G
t
t
Bu as well as CH in N-COCH Bu as shown in Figure 2b.
2
2
The CH/³ interaction is supported also by chemical shifts;
1
the H chemical shift of CH of R in conformer A revealed
3
H Ph
Conformer A
H Ph
Conformer B
high-field shift of 0.30, 0.37, and 0.44 ppm corresponding to
t
i
R = O Bu, O Pr, and OEt for trans-1, -2, and -3, respectively.
These characteristic phenomena should originate from the
phenyl ring magnetic anisotropy (³), which was not observed
Figure 1. The rotational barrier and the conformational-
energy difference between the conformers of N-substituted-
in conformer B. The high-field shift was more obvious for CH
2
t
4
-phenyltetrahydroisoquinolines.
in N-COCH Bu, that is, ¤ (¤ in conformer A) was 1.36 ppm
2
A
and ¤B (¤ in conformer B) was 2.23 ppm. It meant that the
t
CH/³ interaction between CH in CH of N-COCH Bu and the
2
2
‡
0
Table 1. The Rotational Barrier (¦G ), the Conformational Free Energy Difference (¦G ), the Conformational
1
Population (P), and H Chemical Shift (¤) of N-Substituted-4-phenyltetrahydroisoquinolines in CDCl3
H X
O
G
H X
R
∆
G0
N
R
N
O
∆
∆G
H Y
H Y
Conformer A
Conformer B
‡
¦G0
/kJ mol
¦
G
PA
/%
PB
/%
1
Compd.
X
Y
R
¤A
¤B
Obsd. H (R)
¹1
¹1
/
kJ mol
t
t
trans-1
trans-1¤
allyl
allyl
Ph
Ph
O Bu
64.4
73.5
2.5
4.5
75
88
25
12
1.06
0.76
1.36
1.00
2.23
1.13
1.19
Me ( Bu)
t
t
CH2 Bu
Me ( Bu)
t
1
.36
CH2- Bu
i
i
trans-2
trans-3
cis-1
cis-3
4
allyl
allyl
allyl
allyl
H
Ph
Ph
Ph
Ph
Ph
Ph
O Pr
65.0
65.3
68.9
68.4
63.9
72.5
2.5
2.5
0
0
1.6
1.9
75
75
50
50
67
70
25
25
50
50
33
30
0.76
0.75
Me ( Pr)
OEt
Me (Et)
t
t
O Bu
1.48
1.28
Me ( Bu)
OEt
Me (Et)
t
t
O Bu
1.21
0.93
1.45
Me ( Bu)
t
t
4¤
H
CH2 Bu
1.01
2.34
1.27
Me ( Bu)
t
1
.83
CH2- Bu
i
i
5
H
Ph
O Pr
62.7
1.2
63
37
1.02
Me ( Pr)
6
6
H
H
Ph
Ph
OEt
CH2Et
64.2
72.6
0.8
1.9
59
70
41
30
1.01
0.66
1.27
0.86
2.90
Me (Et)
Me (Et)
CH2-Et
¤a)
2
.22
t
t
7
7
H
H
H
H
O Bu
61.0
70.5
0
0
50
50
50
50
1.49
1.08
.34
Me ( Bu)
t
t
¤
CH2 Bu
Me ( Bu)
t
2
CH2- Bu
a) Solvent: DMSO-d6.

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04
Bull. Chem. Soc. Jpn. Vol. 83, No. 7 (2010)
CH/³ Interaction on the Structure
H
H
H
O
N
O
N
O
H
N
O
H
H
H
C
H
H
C
H
H
H
H
H
H
H
CH/π interaction
CH/π interaction
CH/π interaction
(a) trans-1
(b) trans-1'
Figure 2. CH/³ interactions in (a) trans-1 and (b) trans-1¤.
-
-
O
O
O
O
O
O
+
N
C
:N
∆G
C
: N
∆G
C
amide
conjugation
ester
conjugation
∆
G
R'
R'
R'
+
structure (I)
structure (II)
Figure 3. Cross conjugation in urethane.
4
-phenyl ring was rather strong in conformer A of trans-1¤.
the C­N bond, the rotational barrier about the C­N bond
becomes lower in urethane compared with the corresponding
1
On the other hand, H NMR signals of the two ground state
conformers in cis-1 and -3 were observed equivalently
t
amide. Consequently, the rotational barriers of the N-COO Bu
¹1
(
¤ = ¤ ). In cis-form, the two ground state energies are
series (trans-1, -4, and -7) were lower by about 9 kJ mol than
A
B
t
almost the same (G = G ) and the stabilization by CH/³
those of the corresponding N-COCH Bu series (trans-1¤, -4¤,
A
B
2
‡
interaction in conformer A was not observed because CH(CH3)
in R could not be directed to and close to the phenyl ring due to
the steric hindrance of the cis-1-allyl substituent. In the series
of N-substituted-4-phenyl-1,2,3,4-tetrahydroisoquinoline 4, 4¤,
and -7¤). The lowering of ¦G implies a decrease of the
contribution of structure (I) in the amide conjugation.
CH/³ Interaction as Evidenced Using X-ray Crystallo-
graphic Analysis. Crystal structures of trans-1 and 4 are
given in Figures 4 and 5. Hydrogen atoms of molecule 4 were
located from difference Fourier maps and refined isotropically.
Generally, the positions of hydrogen atoms obtained from
neutron diffraction are more reliable than those from X-ray
diffraction. However, it is assumed that the parameters of
hydrogen atoms obtained from X-ray analysis can be equiv-
5
, and 6, with no substituent at C-2 of the isoquinoline ring, the
t
predominant conformers were stabilized by 1.6 (R = O Bu),
1
compared to the other conformer, respectively. All these results
are explained similarly as in the case of trans-1 by assuming
CH/³ interaction between CH(CH ) in N-COR and 4-phenyl
ring. High-field shift of CH of R was also observed in those
compounds. However, the strength of CH/³ interaction in
those compounds seemed to be weaker than those of trans-1,
t
i
¹1
.9 (R = CH Bu), 1.2 (R = O Pr), and 0.8 (R = OEt) kJ mol
2
3
1
9
alent to those from neutron data. As is easily understood from
3
2
Figures 4 and 5, the short CH­³(C(sp )) hydrogen bonds were
observed in short intramolecular through space distances;
2.8813(18) and 2.9390(17) ¡ in trans-1, and 3.02(3) and
-1¤, -2, and -3 because values of both the differences of the
t
ground state energies of the two conformers and high-field
shifts were not as large as those of trans-1, -1¤, -2, and -3.
3.05(3) ¡ in 4 between the proton of CH donor group ( Bu) and
2
C(sp ) (4-phenyl ring), in addition, 2.8277(16) ¡ in trans-1
‡
2
Effect of Steric Hindrance on ¦G . Since the rotational
between CH (cis-1-allyl substituent) and C(sp ) (isoquinoline)
barrier was estimated as the energy difference between the
more stable conformer A and the transition state (TS), steric
effects on ¦G should originate from the steric congestion in
(Figure 4). As the difference of the intramolecular distance and
0
a number of CH­³ hydrogen bonds may relate to each ¦G ,
‡
0
¹1
the stabilization of trans-1 (¦G = 2.5 kJ mol ) by CH/³
0
¹1
the more stable conformer A. As the rotational barriers of cis-1
interaction is larger than that of 4 (¦G = 1.6 kJ mol ).
CH/³ Interaction as Evidenced Using Ab Intio MO and
DFT Calculations. At first, we carried out a full geometry
optimization for the isolated trans-1 and 4 molecules using
MP2 (second-order Møller­Plesset perturbation) (Figures 6
and 7) in comparison with the experimental values as shown in
Figures 4 and 5.
¹
1
and -3 were higher by 5.0­4.2 kJ mol than those of 4 and 6,
the transition state of cis-1 and -3 were labilized by steric
hindrance of the cis-1-allyl substituent on the C­N bond
rotation.
‡
Effect of Resonance on ¦G . Cross conjugation between
amide and ester was permitted in compounds having urethane
moiety, as shown in Figure 3. The relatively high rotational
barrier in amides comes from the partial double bond character
of the C­N bond due to the mesomeric contribution of the
dipolar canonical structure (I).18 As the structure (II) by ester
conjugation has no influence on the rotational barrier about
As seen by comparing the experimental data to the
theoretical results at MP2/6-31G(d,p) level, the optimized
CH/³ hydrogen bond distances were in good agreement
with experimental values of the crystalline state. However,
there was a considerable difference in the optimized CH/³

H. Suezawa et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 7 (2010)
805
C
C
C
C
C
C
C
C
2
.882 Å
2.8813(18) Å
2.9390(17) Å
C
C
C
2
.8277(16) Å
2.868 Å
C
C
C
2
.823 Å
C
C
C
C
C
C
C
C
Figure 4. ORTEP drawing of trans-1 with thermal ellip-
soids drawn at the 30% probability level. Selected C£H
distances are shown in the Figure and values in parentheses
are estimated standard deviations.
Figure 6. Optimized molecular structure of trans-1 at
MP2/6-31G(d,p) level.
C
C
C
C
3.02(3) Å
3.05(3) Å
2
.755 Å
C
2
.842 Å
C
C
C
C
C
C
C
C
C
C
C
C
C
C
Figure 5. ORTEP drawing of 4 with thermal ellipsoids
drawn at the 30% probability level. Selected C£H
distances are shown in the Figure and values in parentheses
are estimated standard deviations.
Figure 7. Optimized molecular structure of 4 at MP2/
6-31G(d,p) level.
hydrogen bonds distances at HF/6-311++G(d,p) and B3LYP/
N-substituted-4-phenyltetrahydroisoquinoline derivatives were
estimated by NMR. The short CH/³ hydrogen bond distances
were observed in trans-1 and 4 between the proton of CH
donor ( Bu) and C(sp ) (4-phenyl ring) from X-ray structure
analysis, and the experimental values were in good agreement
with the theoretical results at MP2/6-31G(d,p) level, the
optimized CH/³ hydrogen bond distances.
6
-311++G(d,p) levels. These optimized CH/³ hydrogen
bonds distances were 4.056 and 3.758 ¡ in trans-1, and
.253 and 3.881 ¡ in 4 at HF/6-311++G(d,p) level, and 4.045
and 3.739 ¡ in trans-1, and 4.196 and 3.772 ¡ in 4 at B3LYP/
-311++G(d,p) level. Thus, these methods are inappropriate
t
2
4
6
for calculating the weak interactions such as CH/³ hydrogen
bonds in this paper. Weak intermolecular and intramolecular
interactions such as the dispersion force and CH/³ interaction
cannot be precisely estimated by Hartree­Fock and density
functional methods. Therefore, these computational results
except Møller­Plesset perturbation bear poor implication in the
field.
Experimental
Materials. tert-Butyl trans-1-allyl-4-phenyl-1,2,3,4-tetra-
hydroisoquinoline-2-carboxylate (trans-1), ethyl trans-1-allyl-
4-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (trans-
3), tert-butyl cis-1-allyl-4-phenyl-1,2,3,4-tetrahydroisoquino-
line-2-carboxylate (cis-1), and ethyl cis-1-allyl-4-phenyl-
Conclusion
1
,2,3,4-tetrahydroisoquinoline-2-carboxylate (cis-3) were pre-
1
7
Both the effect of CH/³ interaction on the conformational
preference and the conformational free energy differences
and the effect of resonance on the rotational barrier heights of
pared according to a reported method. Isopropyl trans-
1-allyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate
(trans-2) was also prepared in a similar manner using isopropyl

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Bull. Chem. Soc. Jpn. Vol. 83, No. 7 (2010)
CH/³ Interaction on the Structure
‡
‡
Table 2. The Line-Shape-Analysis Parameters for Determining the Rotational Barrier (¦G ) and the Calculated ¦G T
c
Values of N-Substituted-4-phenyltetrahydroisoquinolines in CDCl3
H X
O
H X
1
R
1
4
O
N
R
N
∆
G
∆G
3
3
4
H Y
H Y
Conformer B
Conformer A
‡
PA
PB
/%
¦¯
/Hz
k
/s
Tc
/°C
¦G T
c
1
Compd.
X
Y
R
Obsd. H
¹
1
¹1
/%
/kJ mol
t
trans-1
trans-1¤
trans-2
trans-3
cis-1
allyl
allyl
allyl
allyl
allyl
allyl
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
O Bu
75
88
75
75
50
50
67
70
63
59
70
50
50
25
12
25
25
50
50
33
30
37
41
30
50
50
51.3
12.2
44.6
43.2
46.0
35.7
66.0
22.0
62.4
69.7
41.6
11.7
12.0
99.5
22.2
87.8
84.0
99.5
77.1
64.3
18.3
122.6
94.8
35.0
25.0
25.7
37.7
60.8
39.7
39.8
58.8
53.0
30.2
54.0
32.5
36.3
61.7
5.8
64.4
73.5
65.0
65.3
68.9
68.4
63.9
72.5
62.7
64.2
72.6
60.7
70.5
1-H
1-H
1-H
1-H
1-H
1-H
Me ( Bu)
Me ( Bu)
3-H
Me (Et)
4-H
a)
t
CH2 Bu
i
O Pr
OEt
t
O Bu
cis-3
4
OEt
t
t
O Bu
t
t
4
5
6
6
7
7
¤
CH2 Bu
i
O Pr
OEt
¤ a)
¤
CH2Et
t
H
H
O Bu
3-H
4-H
t
H
CH2 Bu
49.5
a) Solvent: DMSO-d6.
chloroformate. tert-Butyl 4-phenyl-1,2,3,4-tetrahydroisoquino-
line-2-carboxylate (4), isopropyl 4-phenyl-1,2,3,4-tetrahydro-
isoquinoline-2-carboxylate (5), ethyl 4-phenyl-1,2,3,4-tetrahy-
droisoquinoline-2-carboxylate (6), and tert-butyl 1,2,3,4-tetra-
hydroisoquinoline-2-carboxylate (7) were prepared in a similar
manner described above starting from 4-phenyl-1,2,3,4-tetra-
hydroisoquinoline or commercially available 1,2,3,4-tetra-
hydroisoquinoline. trans-1-Allyl-2-(3,3-dimethylbutanoyl)-4-
phenyl-1,2,3,4-tetrahydroisoquinoline (trans-1¤), 2-(3,3-di-
methylbutanoyl)-4-phenyl-1,2,3,4-tetrahydroisoquinoline (4¤),
coalescence temperature (T ) was the temperature where two
c
proton peaks of conformer A and B just coalesced to one peak,
and was determined by measuring at several temperatures
from low to high beyond Tc. The difference in chemical shifts
(¦¯ in Hz) was measured at low enough temperature where
the conformer A and B exchanged very slowly. The rate of
exchange between conformers (k) was computed by the
2
0
simulation of NMR peak line shapes near T using DNMR3K
c
2
1
(General NMR Line-Shape Program) which needed ¦¯ in
Hz and the population of two site protons (P and P ). The
A
B
‡
Tc
‡
2
2
-butanoyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (6¤), and
-(3,3-dimethylbutanoyl)-1,2,3,4-tetrahydroisoquinoline (7¤)
value of ¦G was calculated by the equations, ¦G
=
Tc
¹2.303RTc{10.32 + log(Tc/k)} at Tc. These parameters and the
‡
Tc
were prepared by a reaction of the corresponding amines and
,3-dimethylbutanoyl chloride (trans-1¤, 4¤, and 7¤) or butanoyl
determined ¦G values are listed in Table 2.
3
Experimental Procedure for X-ray Crystallography.
1
7
chloride (6¤) in the presence of pyridine in a usual manner.
In every case, the resulting crude product was purified by
silica gel column chromatography or recrystallization, and the
purified compound showed satisfactory NMR and IR spectra.
NMR Measurements. Variable-temperature NMR mea-
surements were carried out by using a JEOL EX-270 NMR
Crystallographic data of trans-1 was already reported.
Suitable single crystal 4 was obtained by recrystallization from
hexane and mounted on a glass fiber. Diffraction measurement
of 4 was made on a Rigaku RAXIS RAPID imaging plate
area detector with graphite-monochromated Cu K¡ radiation
(­ = 1.54187 ¡). The data collections were carried out at
23 « 2 °C to a maximum 2ª value of 136.5°. Indexing was
performed from 3 oscillations that were exposed for 90 s.
The crystal-to-detector distance was 127.40 mm. A total of 24
oscillation images were collected. A sweep of data was done
using ½ scans from 50.0 to 230.0° in 30.0° steps, at » = 45.0°
and º = 0.0°. The exposure rate was 90.0 [s/°]. A second
sweep was performed using ½ scans from 50.0 to 230.0° in
30.0° steps, at » = 45.0° and º = 90.0°. The exposure rate was
90.0 [s/°]. Another sweep was performed using ½ scans from
50.0 to 230.0° in 30.0° steps, at » = 45.0° and º = 180.0°. The
exposure rate was 90.0 [s/°]. Another sweep was performed
using ½ scans from 50.0 to 230.0° in 30.0° steps, at » = 45.0°
0
spectrometer. The value of ¦G was calculated by the
0
0
equations, ¦G = ¹RT ln K, K = P /P = exp{¹¦G /RT} at
B
A
room temperature where PA and PB are the conformational
population for conformer A and B, respectively. The peaks A
1
and B in H NMR spectra were separated at room temperature
in most of the compounds. We adopted the coalescence
‡
Tc
temperature in order to determine ¦G values by using both
temperature-dependant NMR experiments and computer sim-
ulation. This method requires the following parameters; T (the
c
coalescence temperature), k (the rate of exchange between
conformer A and B), ¦¯ in Hz (the difference in chemical
shifts between the same proton of the two conformers). The

H. Suezawa et al.
Bull. Chem. Soc. Jpn. Vol. 83, No. 7 (2010)
807
Table 3. Summary of Crystal Data for Compound 4
We thank Prof. Shinya Matsumoto (Yokohama Natl. Univ.)
for his kind help in X-ray analysis. We also thank Prof.
Kazuyoshi Ueda of Yokohama National University for his deep
consideration of, and helpful advice on, this work. The
computations were performed using the Research Center for
Computational Science, Okazaki, Japan, in particular, a Fujitsu
VPP5000 and PRIMEQUEST.
Empirical formula
Formula weight
C20H23NO2
309.41
Crystal color, habit
colorless, needle
0.55 © 0.33 © 0.25
monoclinic
Crystal size/mm3
Crystal system
Space group
Lattice parameters
a/¡
P21/n (No. 14)
11.6624(17)
25.017(4)
6.1138(9)
102.713(13)
1740.0(4)
4
1.181
664.00
5.972
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c/¡
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8
22
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2
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