Conformational and structural analysis of exocyclic olefins and ketimines by multinuclear magnetic resonance

Article abstract of DOI:10.1002/mrc.2259

The ¹H, ¹³C, and ¹⁵N NMR spectra of 5 exocyclic alkenes and 15 different ketimines obtained from cyclohexanone and derivatives using benzyl bromide and primary amines - are analyzed. Relative stereochemical and preferentia

Full text of DOI:10.1002/mrc.2259

Research Article
Received: 11 January 2008
Revised: 24 April 2008
Accepted: 25 April 2008
Published online in Wiley Interscience: 3 June 2008
(www.interscience.com) DOI 10.1002/mrc.2259
Conformational and structural analysis
of exocyclic olefins and ketimines
by multinuclear magnetic resonance
a
b
´
´
´
´
Ruben Montalvo-Gonzalez, J. Ascencion Montalvo-Gonzalez and
Armando Ariza-Castolob∗
The 1H, 13C, and 15N NMR spectra of 5 exocyclic alkenes and 15 different ketimines obtained from cyclohexanone and
derivatives using benzyl bromide and primary amines – are analyzed. Relative stereochemical and preferential conformations
are determined by analyzing both the homonuclear coupling and the chemical shifts of the protons and carbon atoms in
the aliphatic rings, which are directly related to the geometry of the double bond and the steric and electronic effects of the
exocyclic group. In addition, the racemic mixture of the N-(4-methylcyclohexylidene)pyridine-3-amine derivative is resolved.
c
Copyright ꢀ 2008 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: NMR; 1H; 13C; 15N; chiral axis; conformation; alkenes; ketimines
Introduction
1H–1H (COSY) and heteronuclear 1H–13C (HETCOR) correlation
spectroscopy. The selected pulse sequence was applied because a
high resolution in 13C is necessary due to the fact that the chemical
shift differences of some resonances are less than 0.02 ppm (<2 Hz
at 75.47 MHz). Also, J-modulated spectra attached proton test,
(APT) were recorded to distinguish between the C, CH, CH2, and
CH3 groups in compounds 1b–e, 2b–e, 3b–e, and 4b–e.
The exocyclic substituent (R2) effect on the atoms of the
cyclohexenyl moiety of alkenes and imines was based on the
change in the chemical shift of the equatorial/axial protons of C2
and C6 in olefins and imines derived from symmetric ketones (1a,
1d, 1e, 2a, 2d, 2e, 3a, 3d, and 3e).
Chiral conformers (1a, 2a, 3a, and 4a) were derived from
cyclohexanone exchange because of the fast ring inversion at
20 ◦C.[4] In contrast, compounds with a methyl or tert-butyl group
on the aliphatic ring have a conformational preference for the
structure with the alkyl group at the equatorial position. Alkenes
and imines derived from symmetric ketones are asymmetric
compounds obtained as pairs of enantiomers (Ra and Sa) in a
racemic mixture. This fact was demonstrated by the addition of a
chemical shift reagent to the imine compound 3d, which allowed
separation of the enantiomer in the proton spectra.
The NMR is a powerful tool in determining the preferred
conformation, the stereochemistry of a compound, and the
stereoselectivityofreactions.[1] Severalworkshavebeenpublished
regarding both nucleophilic attacks on an exocyclic double bond,
namely C N, and the effects that the N-group may have on
the regioselectivity (axial/equatorial) of imine compounds similar
to those reported herein.[2] However, in order to determine the
preferential conformation, a more detailed analysis is required.
Saito and Nukuda determined the geometry of the exocyclic
C
N double bond of compound 1a, and the preferential
orientation of the phenyl group with respect to the double bond,
by using 1H NMR and UV spectroscopy.[3] In this article, we
describe the preferential orientations of aryl groups with respect
to an exocyclic C C or C N double bond and the orientations
and effects of the cyclohexenyl substituents on the chemical shifts
and coupling constants of the aliphatic ring.
Unfixed (R1 = H) and fixed (R1 = methyl or tert-butyl) com-
pounds were used for the structure analyses. These compounds
had either an aryl (1a–e, 2a–e, and 3a–e) or an alkyl (4a–e)
substituent bonded to the exocyclic atom of the C C (alkenes)
or C N (imines) double bond (Scheme 1). Assignment of the 1H
spectra of olefin and imine derivatives obtained from symmetric
ketones (1a, 1d, 1e, 2a, 2d, 2e, 3a, 3d, 3e, 4a, 4d, and 4e) was car-
ried out based on simulations. Furthermore, the two enantiomers
of 3d were resolved using the lanthanide shift reagent ytterbium
tris[3-(trifluoromethylhydroxymethylene)-(+)-camphorate].
Derivatives of 3- or 2-methylcyclohexanone have two pairs of
geometric isomers (namely, ER, ES, ZR, and ZS). The ratio between
∗
´
Correspondence to: Armando Ariza-Castolo, Centro de Investigacion y de
´
Estudios Avanzados del IPN, Apartado Postal, 14-740, 07000, Mexico
D.F., Mexico. E-mail: aariza@cinvestav.mx
Results
´ ´ ´
Unidad Academica de Ciencias Químico Biologicas y Farmaceuticas Universi-
a
´
´
dad Autonoma de Nayarit, Mexico
Assignment of the 1H and 13C spectra of alkenes and imines
was based on one- and two-dimensional NMR experiments.
The connectivities were established by means of homonuclear
b
Departamento de Química, Cinvestav. Apartado postal, 14-740, 07000 Mexico
D.F., Mexico
c
Magn. Reson. Chem. 2008, 46, 907–912
Copyright ꢀ 2008 John Wiley & Sons, Ltd.

R. Montalvo-Gonza´lez, J. A. Montalvo-Gonza´lez and A. Ariza-Castolo
Scheme 1. Structure of olefins (1a-1e) and imines (2a-4e).
Scheme 2. Preferential orientation of the aryl group (a) in olefins and (b) in imines.
Scheme 3. Aliphatic region of the 1H NMR spectrum of the imine compound 3d. From top to bottom spectra with ytterbium tris[3-
(triflouromethylhydroxymethylene)-(+)- camphorate]) in relation 1 : 9, simulated and experimental spectra with the corresponding assignments.
c
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Copyright ꢀ 2008 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2008, 46, 907–912

Exocyclic olefins and ketimines by multinuclear magnetic resonance
Table 1. 1H NMR chemical shifts of olefins (1) and ketimines (2, 3, and 4)
HC
2
3
4
5
6
7
8
9
10
11
12
Me
eq
ax
eq
ax
eq
ax
eq
ax
eq
ax
1a
6.22
6.18
6.20
6.23
6.21
–
2.25
–
2.25
o
1.54
o
1.54
o
1.59
o
1.59
o
1.64
o
1.64
o
2.37
o
2.37
o
–
–
–
–
–
–
–
–
–
7.19
o
7.29
o
7.16
o
7.29
o
7.19
o
–
1bZ
1bE
1d
1e
1.20
1.15
0.92
0.86
–
–
2.26
2.22
2.19
2.46
2.45
2.42
2.45
2.48
2.38
2.36
2.28
2.24
1.83
1.83
1.84
1.83
2.02
2.12
1.84
2.04
1.97
2.08
1.73
1.88
1.25
1.12
1.16
1.83
1.40
1.44
1.84
1.43
1.36
1.41
1.73
1.24
1.76
–
1.41
1.60
1.22
1.62
1.77
1.40
1.61
1.56
1.71
1.36
1.64
1.73
1.68
1.75
1.92
1.64
1.84
1.95
1.65
1.81
1.78
1.89
1.64
1.87
1.51
1.01
1.05
1.64
1.15
1.18
1.65
1.45
1.10
1.14
1.64
1.10
2.73
2.86
2.96
2.16
2.43
2.50
2.16
2.46
2.45
2.54
2.29
2.77
1.96
1.92
1.84
2.16
1.98
1.92
2.16
1.88
1.88
1.83
2.29
1.83
7.19
7.19
7.20
8.07
8.06
8.07
6.72
7.30
7.29
2.29
–
7.13
7.17
7.16
8.29
8.31
8.31
7.03
7.30
7.29
7.29
7.20
7.22
7.23
7.27
7.19
7.19
7.20
7.06
7.07
7.08
6.72
2.33
2.38
2.46
2.56
2.62
2.45
–
2a
1.62
–
2d
2e
–
–
0.98
0.89
–
–
–
–
3a
–
1.61
1.61
–
7.27
3bZ
3d
3e
1.22
0.95
0.90
–
–
–
–
–
2.54
2.59
2.28
2.35
–
6.70
6.72
1.58
1.58
7.25
7.27
0.93
0.93
7.01
7.03
–
7.25
7.27
–
6.70
6.72
–
–
–
4a
1.64
–
3.26
3.19
3.16
3.27
3.23
4d
–
–
–
0.95
4e
–
2.41
2.22
1.96
1.29
–
1.34
1.97
1.15
2.86
1.75
1.63
0.93
–
–
–
0.88
o, overlapped.
these isomers (E : Z) was 10 : 1 for the 2-methylcyclohexanone
derivatives (1b, 2b, 3b, and 4b). The signals of both isomers
overlapped, which complicated the assignment of the minor
isomer. The isomer relation for the 3-methylcyclohexanone
derivatives was 10 : 9 (E : Z) (1c, 2c, 3c, and 4c). The spectra
showed overlapped resonances for both isomers, which made
complete assignment difficult. The assignment of the atoms in the
cyclohexenyl moiety was based on the cis/trans-to-lone-pair and
the exocyclic substituent effects.
is such that the diamagnetic current shifts the protons at high
frequency, the corresponding orientation in the imine group shifts
protons at a lesser frequency, which is only possible when the
orientation of the phenyl group is on the same plane in olefins but
perpendicular in imines (Scheme 2).
The coupling constant data listed in Table 2 for protons
3
bonded to C4 (3JH4ax,H3ax = 12.1 0.7; JH4ax,H3ec = 3.0 0.5;
3
3JH4ax,H5ec = 2.8 0.8; and JH4ax,H5ax = 12.9 1.8) make it
possible to determine the chair conformation of the six-atom ring.
The magnitude of the methyl group coupling constant of the 2b
isomer Z (3JH,H = 7.2 Hz), as well as its 13C chemical shift, allows
the determination of the axial preference.
Discussion
1H NMR
The enantiomers Ra and Sa became nonequiva-
lent as
a result of the addition of ytterbium tris[3-
(trifluoromethylhydroxymethylene)-(+)-camphorate]) to com-
pound 3d. Consequently, the resonance of 5-methyl could be
distinguished and the chemical shift effect observed was at-
tributed to the fact that the chemical shift reagent coordinated
only one of the two enantiomers. This result could be deduced
because the methyl signal was enhanced upon increasing the
concentration of the chemical shift reagent (Scheme 3).
In the present work, it was necessary to simulate the proton
spectra[5] of the compounds (1a, 1d, 1e, 2a, 2d, 2e, 3a, 3d, 3e,
4a, 4d and 4e) in order to correctly assign the compounds giving
rise to the NMR data obtained. This was due to the complexity of
the results, which arose from the similarity of the chemical shifts
and the complicated coupling patterns – the signals of most of
the protons reveal up to five different couplings to other protons.
The assignment was performed considering the chemical shifts,
the multiplicity, and the connectivity.
13C NMR
The data shown in Table 1 indicate that the proton chemical
shifts of methylene C2 and C6 are similar for alkenes (1a, 1d, and
1e) and aliphatic imines (4a, 4d, and 4e), and that the inductive
effect of nitrogen is similar to that corresponding to a phenyl
group (C2 methylene). The same behavior is observed for the
steric interaction and diamagnetic protection (C6 methylene). The
ꢀδ of protons bonded to C2 between alkenes (1a, 1d, and 1e) and
imines derived from aromatic amines (2a, 2d, 2e, 3a, 3d, and 3e)
is 0.19 0.02 ppm (being greater for imines), whereas for protons
bonded to C6, the ꢀδ is about 0.43 0.03 ppm for equatorial
protons (being greater for the corresponding alkenes). There are
no significant differences between axial protons. The preceding
data show that while in olefins the orientation of the phenyl group
The complete assignments of the 13C NMR spectra for all the
isomers of the olefins (1a–e) and imines (2a–e, 3a–e, and
4a–e) are shown in Table 3. These assignments were made con-
sidering the effects of the substituents, the orientations, the
connectivity, and the isomeric abundances for the 2- and 3-
methylcyclohexanone derivatives (1b, 1c, 2b, 2c, 3b, 3c, 4b, and
4c).
Analysis of the substituent effects on the atoms of the aliphatic
ring was performed considering the chemical shifts of the
compounds derived from cyclohexanone (1a, 2a, 3a, and 4a).
The inductive effect on the cyclohexenyl atoms is greater
for imines than for alkenes, with the order being N-3-pyridyl
c
Magn. Reson. Chem. 2008, 46, 907–912
Copyright ꢀ 2008 John Wiley & Sons, Ltd.
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R. Montalvo-Gonza´lez, J. A. Montalvo-Gonza´lez and A. Ariza-Castolo
Table 2. 1H NMR coupling constants of selected olefins and imine derivatives
2JHH
1bE
1d
1e
2d
2e
3bE
3d
3e
4d
4e
2,2
–
13.2
13.1
–
13.3
12.4
–
13.4
12.8
–
13.4
12.4
–
–
13.4
12.8
–
13.4
13.1
–
13.4
13.1
–
14.0
13.0
–
3,3
13.4
12.5
12.8
13.7
–
12.1
11.8
11.4
12.7
–
4,4
5,5
12.8
13.4
–
12.4
13.5
–
13.4
13.7
–
12.2
13.9
–
12.9
13.7
–
12.1
13.4
–
13.4
13.4
11.9
13.4
14.0
11.9
6,6
7,7
3JHH
H,CH3
2ax,3ax
2ax,3eq
2eq,3ax
2eq,3eq
3ax,4ax
3ax,4eq
3eq,4ax
3eq,4eq
4ax,5ax
4ax,5eq
4eq,5ax
4eq,5eq
5ax,6ax
5ax,6eq
5eq,6ax
5eq,6eq
7,8
6.5
13.2
4.4
–
6.5
13.2
4.4
3.6
3.4
11.4
–
–
12.5
4.6
3.9
3.1
12.0
–
6.5
13.1
5.5
3.2
4.5
11.4
–
–
14.0
5.2
3.7
3.1
12.4
–
6.7
13.1
4.3
0.5
–
6.6
13.1
5.3
4.0
3.2
11.1
–
–
13.8
5.2
3.7
3.2
12.1
–
6.6
13.2
5.2
4.4
3.6
11.2
–
–
13.1
5.5
4.2
3.6
12.8
–
–
11.4
3.6
4.8
2.9
11.8
3.6
4.7
3.7
11.9
4.9
4.4
4.1
–
12.8
3.0
3.5
4.0
11.1
3.6
3.5
4.5
11.1
4.7
3.1
3.0
–
3.1
–
2.3
–
3.0
–
2.5
–
3.0
–
2.5
–
3.1
–
2.6
–
11.1
3.1
–
13.5
2.0
–
11.1
2.8
–
14.1
2.7
–
11.1
2.8
–
14.7
2.8
–
11.8
2.9
–
12.5
2.7
–
–
–
–
–
–
–
–
–
13.2
3.3
4.8
4.1
–
13.1
4.2
4.0
2.0
–
13.2
4.0
4.7
3.0
–
13.6
3.7
5.1
2.6
–
13.2
4.0
4.7
3.0
–
13.5
4.2
5.2
2.6
–
13.2
3.8
5.1
3.1
7.5
7.5
–
13.7
3.4
5.2
3.4
7.5
7.5
–
8,9
7.4
7.6
–
7.3
7.4
–
7.3
7.4
–
–
–
7.3
7.3
–
7.9
7.4
–
7.9
7.3
–
9,10
–
–
10,11
4.8
8.0
4.8
8.0
–
–
11,12
–
–
–
–
–
–
–
–
4JHH
HC ,2ax
HC ,2eq
HC ,6ax
HC ,6eq
2eq,6eq
2eq,6ax
3eq,5eq
3eq,5ax
4eq,6eq
4eq,6ax
4ax,6ax
7,9
1.3
–
2.0
0.5
1.8
1.5
2.4
0.5
2.3
n.d.
n.d.
n.d.
0.5
–
1.8
n.d.
2.0
n.d.
2.2
0.5
2.4
n.d.
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
1.8
1.4
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
2.3
n.d.
2.9
0.5
n.d.
n.d.
n.d.
–
2.3
0.3
3.0
n.d.
–
–
2.3
0.3
2.9
0.5
n.d.
n.d.
n.d.
–
2.4
0.3
3.0
n.d.
–
2.2
0.6
2.9
–
2.4
0.7
3.0
n.d.
–
0.5
0.6
n.d.
0.9
0.5
n.d.
–
0.5
2.0
n.d.
0.8
n.d.
n.d.
–
n.d.
n.d.
n.d.
0.5
–
–
–
–
–
n.d.
–
n.d.
–
n.d.
–
0.7
0.5
–
8,10
1.3
–
1.2
–
1.3
–
0.2
2.6
1.6
0.2
2.6
1.5
1.3
–
1.3
–
1.3
–
8,12
–
–
10,12
5JHH
–
–
–
–
–
–
–
–
HC ,9
HC ,11
8,11
1.0
1.0
–
1.0
1.0
–
n.d.
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
0.8
n.d., Not observed.
> N-phenyl > N-propyl > C-phenyl. The syn/anti effect of the
substituent bonded to the exocyclic atom generates a ꢀδ value
between C2 and C6 of about 8.2 0.1 ppm. The stronger steric
effect of the propyl group in compounds 4a to 4e shifts C6 to a
lower frequency compared to other compounds.
The low-frequency chemical shifts of C4 (δ = 20 1 ppm)
1 ppm) in the 2-methylcyclohexanone
derivatives (1b, 2b, 3b, and 4b) of the Z isomer are a result
of the γaxial-γgauche (ꢀδ = 4.5 1.0 ppm) effect of the methyl
substituent. The γequatorial effect on C6 of the E isomer of the
and C2 (δ = 34.5
c
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Copyright ꢀ 2008 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2008, 46, 907–912

Exocyclic olefins and ketimines by multinuclear magnetic resonance
Table 3. 13C NMR chemical shifts of olefins and imine derivatives
HC
1
2
3
4
5
6
7
8
9
10
11
Me
1a
122.14
147.48
147.73
122.31
122.39
122.25
121.83
143.63
121.98
119.66
143.05
143.10
143.23
143.55
37.87
33.64
39.19
37.32
46.17
37.21
37.79
28.83
29.05
37.03
27.70
34.77
36.93
29.43
26.89
21.03
25.64
35.32
35.20
32.86
48.43
28.08
33.24
28.55
34.15
27.00
36.20
28.74
29.65
30.80
29.22
37.85
29.06
28.91
29.48
138.60
139.04
139.04
138.59
138.66
139.18
138.60
129.12
128.85
129.23
129.12
129.12
129.13
129.13
128.19
128.25
128.18
128.20
128.20
128.20
128.20
125.97
126.01
125.91
125.97
125.97
125.98
125.97
–
–
–
–
–
–
–
1b
1c
Z
E
Z
E
18.66
19.04
22.67
22.51
22.27
32.79
27.84
1d
1e
2a
–
–
–
–
–
–
–
174.91
178.74
176.69
174.90
175.13
175.38
175.63
39.28
34.91
41.48
39.12
47.79
38.93
39.40
27.75
27.89
36.27
26.55
34.97
36.17
28.88
25.66
20.05
24.77
34.44
34.44
32.31
47.82
27.54
33.43
27.99
34.54
26.64
35.94
28.74
31.15
33.48
30.62
39.42
30.93
30.73
31.17
150.64
150.31
151.19
151.11
151.23
151.28
151.23
119.74
119.11
119.37
120.25
120.25
120.27
120.36
128.68
128.74
128.50
129.16
129.20
129.21
129.20
122.87
122.70
122.40
123.08
123.24
123.40
123.42
–
–
–
–
–
–
–
2b
2c
Z
E
Z
E
17.47
16.84
22.41
22.53
21.83
28.05
32.86
2d
2e
3a
–
–
–
–
–
–
–
176.78
181.40
178.93
176.99
177.18
177.05
178.00
39.05
35.44
42.08
39.14
47.29
38.26
39.35
27.48
28.40
36.65
26.00
34.50
35.40
28.78
25.13
20.28
25.05
33.72
33.72
31.45
47.58
27.27
33.85
28.42
34.16
26.17
35.17
28.65
31.03
34.13
31.31
38.66
31.09
30.21
31.30
146.20
146.53
147.3
141.12
141.07
141.39
141.36
141.31
141.23
141.88
144.07
144.50
144.34
144.36
144.36
144.23
144.82
123.11
123.65
123.52
123.45
123.45
123.22
123.81
127.09
126.56
127.14
127.19
127.24
126.95
127.68
3b
3c
Z
E
Z
E
17.34
17.04
21.80
21.90
20.97
32.75
27.92
146.39
146.49
146.34
146.87
3d
3e
4a
–
–
–
–
–
–
–
171.39
176.49
175.10
171.89
172.00
172.21
173.16
39.42
35.52
42.01
39.14
47.93
39.08
39.83
27.29
n.d.
25.64
20.38
24.44
34.14
34.16
32.25
48.01
26.51
32.83
27.53
33.28
25.48
35.04
27.93
28.09
30.95
27.43
36.44
27.69
27.64
28.53
51.40
51.41
52.00
51.82
51.91
52.15
52.51
23.72
24.40
24.31
24.01
24.01
24.25
24.60
11.40
12.12
12.03
11.77
11.77
12.02
12.39
–
–
–
–
–
–
–
–
–
–
–
–
–
4b
4c
Z
E
Z
E
16.903
17.417
21.83
21.98
21.52
32.78
27.91
35.95
25.98
34.20
35.84
28.59
4d
4e
n.d., not determined.
Table 4. 15N NMR of imine derivativesa
Comp.
δ (3JN,H
)
Comp.
δ (3JN,H
)
Comp.
δ (3JN,H
)
2a
−73.32 (7.78)
−73.35
3a
3b
−74.34 (7.7)
n.d.
4a
4b(E)
4c(E or Z)
4d
−64.66 (7.03)
−64.78 (5.4)
−64.33
2b(E)
2c(E, Z)
2d
−71.62, −71.90
−73.03 (4.84)
−73.7 (7.5)
3c(E, Z)
3d
−73.71, −73.94
−73.90 (7.4)
n.d.
−63.81 (5.3)
−65.17
2e
3e
4e
a The 15N–1H three-bond coupling constant is via N C–C–H, with the hydrogen syn to lone pair.
n.d., not determined.
preceding compounds is about −0.55 0.10 ppm, whereas the
γequatorial effect of the methyl group on C5 of the E isomer (1b,
2b, 3b, and 4b) is 0.70 0.30 ppm. The equivalent effect on the
3-methylcyclohexanone derivatives (1c, 2c, 3c, and 4c) is about
−0.40 0.15 ppm for both isomers.
4-methylcyclohexanone derivatives (1d, 2d, 3d, and 4d), the
equivalent effect is about −0.55 0.20 ppm.
15N NMR
The 15N chemical shift (Table 4) showed a slight variation for
compounds 1a to 2d. Signals of both geometric isomers of the
imine (E/Z) were observed in compounds 1c and 2c. The chemical
The γequatorial effect on C3 (Z isomer) or C5 (E isomer) of
the methyl group of the 3-methylcyclohexanone derivatives
(1c, 2c, 3c, and 4c) is −1.20
0.20 ppm, whereas for the
c
Magn. Reson. Chem. 2008, 46, 907–912
Copyright ꢀ 2008 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

R. Montalvo-Gonza´lez, J. A. Montalvo-Gonza´lez and A. Ariza-Castolo
shift effect of the nitrogen atom of the pyridine group in C2 can be
neglected; however, in the compound containing the propylimine
group, a shift of about 8.5 0.5 ppm is observed.
Observation of the 15N–1H coupling constants for some of the
compounds was only possible by means of INEPT nondecoupling
pulse sequence. Splitting was greater than 4.8 Hz and was found
to be in agreement with the lone pair syn effect.[6]
1H NMR assignments
The chemical shifts and spin–spin coupling constants of the
protons of the cyclohexane rings were determined by means of
computer simulations[5] carried out considering subsystems of ten
nuclei. In the case of the methyl groups, the number of spins
was reduced by symmetry because the three hydrogen atoms are
chemically and magnetically equivalent. The root-mean-square
(r.m.s.) error between the experimental and simulated spectra was
0.11 Hz. Excellent correlation was observed with the experimental
spectrumwhenthelong-rangecouplingconstants(4JH,H and5JH,H
were taken into account.
)
Conclusions
Aryl groups have a preferential rotamer that is co-planar to the
carbon–carbon double bonds, whereas in imine compounds, the
aryl group predominates at a position that is orthogonal to the
carbon–nitrogen double bond. Cyclohexane exchanges rapidly in
compounds that do not contain a substituent, but in compounds
with a substituent it prefers the conformation with an alkyl group
at C3 or C4 (at the equatorial position). However, when the methyl
group is at C2, it prefers the axial position. To the best of our
knowledge, this is the first article that shows a chiral axis in
exocyclic ketimines.
Synthesis
Schiffbaseswerepreparedbycondensationofequimolaramounts
of the corresponding amines and cyclohexanones in methylene
chloride (4a to 4e) or toluene (2a to 3e) solutions. The reaction
was carried out under reflux (for 12 h) in a Dean-Stark water
separator.Thecompoundswerepurifiedbymeansoflow-pressure
distillation.
Alkenes (1a to 1e) were prepared through the Wittig reaction
from benzyl triphenyl phosphonium and the corresponding
cyclohexanone in a dry dimethyl sulfoxide (DMSO) solution,
using NaH as base. The compounds were purified by using a
chromatography silica gel column and hexane as eluting agent.
The physical and spectroscopic properties of 1a,[10] 2a,[11]
and 2b[12] are in good agreement with previous reports. These
properties are listed in the Supplementary Material.
Experimental Section
NMR spectra of compounds 1a to 4e were recorded at 18 ◦C
using a Bruker 300 Avance spectrometer equipped with a 5-
mm multinuclear probe. All spectra were obtained using a CDCl3
solution (0.9 mmol of the compound per 0.4 ml of solvent). The
1
chemical shifts were referenced[7] to internal (CH3)4Si (δ H = 0,
Supporting information
δ
13C = 0) and neat CH3NO2 (δ 15N for ꢁ 15N = 10.136767 MHz).
Supporting information may be found in the online version of this
article.
1H NMR spectra were recorded at 300 MHz (spectral width:
6188.1 Hz, acquisition time: 2.648 s, 16 384 data points, equivalent
30◦ pulse duration, 16 scans, recycle delay: 1 s). 13C{ H} NMR
1
spectra were recorded at 75.47 MHz (spectral width: 17 361.1 Hz,
32 768 data points, equivalent to 30◦ pulse duration, 256 scans,
recycle delay: 0.01 s). Similar conditions were used for the APT and
INEPT spectra.
References
[1] (a) W. A. Thomas, Prog. Nucl. Magn. Reson. Spectrosc. 1997,
30, 183; (b) E. Rangel-Cruz, Concepts Magn. Reson. 1996, 8,
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(d) V. I. Bakhmutov, Practical NMR Relaxation for Chemists (1st edn),
John Wiley & Sons, The Atrium, southern Gate, Chichester, West
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[2] (a) R. O. Hutchins, W. Y. Su, R. Sivakurmar, F. Cistone, Y. P. Stercho,
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Z. N. Umarova, Zh. Org. Khim. 1988, 24, 127.
15N NMR spectra of compounds 2a to 4e were recorded at
30.38 MHz by using INEPT methods[8] (spectral width: 15 151.6 Hz;
16 384 data points, from 1024 to 13 706 scans, depending on
the solubility; recycle delay: 4 s, the delays were optimized in
agreement with 3JNH).
1H–1H COSY spectra were obtained with the cosy45 pulse
sequence[9] using a 1024 × 512 data point matrix and a
751.20×751.20Hzfrequencymatrix. Therecycledelaywas2 sand
a total of 16 scans were performed. Fourier transformations were
carriedoutforF1andF2usingasinefunctionintheabsolute-value
mode.
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matrix and a 6265 × 751 Hz frequency matrix. The pulse time
intervals 1 and 2 were set as 2 × 1/4J = 1.85 ms. The recycle
delay was 2 s and a total of 16 scans were performed. Fourier
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[5] Nuts NMR Utility Transform Software, http://www.acornnmr.com.
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[11] L. A. Kayukova, K. B. Erzhanov, Z. N. Umarova, Zh. Org. Khim. 1988,
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[12] R. O. Hutchins, O. Robert, J. Org. Chem. 1983, 48, 3412.
c
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Copyright ꢀ 2008 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2008, 46, 907–912