1H and 13C NMR spectral study of some 3-aryl-5r-aryl-6t-carbethoxycyclohex-2-enones - A study of four-bond 1H-1H couplings

Article abstract of DOI:10.1002/mrc.2724

Nine 3-aryl-5r-aryl-6t-carbethoxycyclohex-2-enones 2a-2i have been synthesized. For all these compounds, ¹H and ¹³C NMR spectra have been recorded. For two compounds, 2D spectra have been recorded. The spectral data suggest that thes

Full text of DOI:10.1002/mrc.2724

MRC Letters
Received: 8 September 2010
Revised: 24 November 2010
Accepted: 13 December 2010
Published online in Wiley Online Library: 28 January 2011
(wileyonlinelibrary.com) DOI 10.1002/mrc.2724
1H and 13C NMR spectral study of some 3-aryl-
5r-aryl-6t-carbethoxycyclohex-2-enones – a
study of four-bond 1H–1H couplings
C. Yuvaraj and K. Pandiarajan∗
Nine 3-aryl-5r-aryl-6t-carbethoxycyclohex-2-enones 2a–2i have been synthesized. For all these compounds, 1H and 13C NMR
spectra have been recorded. For two compounds, 2D spectra have been recorded. The spectral data suggest that these
compounds adopt sofa conformation in solution with H-5, H-6 and H-4t occupying axial-like positions and H-4c occupying
equatorial-like positions. In 3-phenyl-5r-(o-chlorophenyl)-6t-carbethoxycylohex-2-enone (2b), the o-chlorophenyl group is
oriented such that the chlorine atom is in between H-4c and H-5. Allylic coupling of H-2 is observed only with H-4t. Evidence has
c
been obtained for four-bond coupling between 1,3-diaxial and 1,3-axial–equatorial protons. Copyright ꢀ 2011 John Wiley &
Sons, Ltd.
Keywords: cyclohex-2-enones; 1H NMR; 13C NMR; four-bond 1H–1H coupling
Introduction
Cyclohex-2-enones are useful in the synthesis of orga-
nic compounds.[1–5] Cyclohex-2-enone derivatives exhibit
antifungal[6] and anticancer[7] activities. However, to our knowl-
edge only two NMR spectral studies[8,9] have been reported on
In the IR spectra, the C O stretching of the ester carbonyl
cyclohex-2-enones. Though it has been established by theory and
group is observed in the range 1734–1739 cm−1 and that of the
experiments that the vicinal coupling between two protons de-
keto carbonyl group is observed in the range 1654–1600 cm−1
.
pend on the torsional angle between them, the dependence of
allylic coupling with the relative positions of the coupling protons
has not been investigated. This is probably due to the lack of
suitable compounds for this study. In the 1H NMR spectra of 5-aryl-
3-methylcyclohex-2-enones (1)[9] the olefinic proton H-2 has been
found to give rise to a singlet though there can be allylic coupling
with the methyl protons and protons at C-4. Probably, the signal
of H-2 is not well resolved due to too many small couplings.
Four-bond coupling between 1,3-diequatorial protons, which
are in W conformation, has been well demonstrated.[9–11]
However, such couplings involving 1,3-diaxial protons and 1,3-
equatorial–axial protons have not been demonstrated. Herein
we report the NMR spectral study of nine 3-aryl-5r-aryl-6t-
carbethoxycyclohex-2-enones2a–2i. Thisstudyrevealsthatallylic
couplingpreferentiallyoccurswithprotonparalleltothe p-orbitals
involved in the formation of the π-bond. Also evidence has been
obtainedfor1,3-diaxialand1,3-equatorial–axial 1H–1Hcouplings.
All compounds gave molecular ion peaks corresponding to their
molecular formulae. For the chloro compounds, 2b, 2c and 2d (M
+ 2)+ peak also was observed. For 2a–2f the experimental values
of elemental analysis are in good agreement with those calculated
for the molecular formulae. The structures of 2b and 2g have been
determined using X-ray crystallography.[12,13]
The 1H NMR signals were assigned based on their positions,
multiplicities and integral values. The 13C NMR signals were
assigned based on their positions and intensities. In 2b–2i the
signals for the aromatic carbons and protons were assigned using
knowneffectsof substituents.[14] Theassignmentswereconfirmed
1
for 2b using H–1H COSY, HSQC and HMBC spectra and for 2c
using 1H–1H COSY and HSQC spectra. Though the methylene
protons of the COOCH2CH3 group are diastereotopic only for 2b
and 2c, a multiplet was observed for them. In all other cases
only a quartet was observed for them. However, in all cases only
the center of the signal was taken as chemical shift of these
protons.
The methylene protons at C-4 form an AB system and their
chemical shifts were calculated using second-order analysis.[15]
The chemical shifts of H-5 and H-6 were determined by first-
order analysis in 2b. Since H-5 and H-6 from an XY system in
Results and Discussion
Compounds 2a–2i were synthesized as racemates using the
reaction shown in Scheme 1. The physical and analytical data
are given in Table 1. The numbering of the carbon atoms is also
shown in the scheme. The protons are numbered accordingly.
Thus, protons at C-2 is denoted as H-2 and that at C-2ꢁ is denoted
as H-2ꢁ. Among the two methylene protons at C-4, proton cis to
H-5 is denoted as H-4c and that trans to H-5 is denoted as H-4t.
∗
Correspondence to: K. Pandiarajan, Department of Chemistry, Annamalai
University, Annamalainagar 608 002, India. E-mail: profkprajan@yahoo.co.in
Department of Chemistry, Annamalai University, Annamalainagar 608 002,
Tamil Nadu, India
c
Magn. Reson. Chem. 2011, 49, 253–257
Copyright ꢀ 2011 John Wiley & Sons, Ltd.

C. Yuvaraj and K. Pandiarajan
Scheme 1. Synthesis of compounds 2a–2i.
Table 1. Physical and analytical data of 2a–2i
IR (cm−1
)
Found
Calculated
Compound
Yield (%)
m.p. (◦C)
Ester C
O
Keto C
O
% C
% H
% C
% H
2a
2b
2c
2d
2e
2f
65
70
69
73
72
63
65
71
72
103
116
112
130
146
112
86
1735
1739
1736
1737
1738
1734
1736
1739
1739
1659
1654
1659
1660
1660
1659
1657
1662
1659
78.66
70.98
70.99
71.00
78.94
74.47
–
6.25
5.35
5.32
5.30
6.56
5.59
–
78.73
71.08
71.08
71.08
79.08
74.54
–
6.29
5.40
5.40
5.40
6.63
5.66
–
2g
2h
2i
108
115
–
–
–
–
–
–
–
–
2c, 2d and 2f their chemical shifts were calculated using second-
order analysis in these cases. In the other cases, H-5 and H-6
probably form an XXꢁ system and their chemical shifts were
taken as the center of the two most intense lines observed for
them. In 2c, 2e, 2f, 2h and 2i the chemical shifts of the 5-
aryl protons were calculated using second-order analysis. The
1H chemical shifts and 1H–1H coupling constants are given in
Tables 2 and 3, respectively. The 13C chemical shifts are furnished
in Table 4.
Figure 1. Conformation of 2a–2i.
2a–2i the torsional angles about C(1)–C(2) and C(2)–C(3) bonds
should be in this range. Thus, atoms C(1), C(2), C(3), C(4) and
C(6) should be almost coplanar, whereas atom C(5) can be above
or below this plane. These two arrangements represent the sofa
conformations of the two possible enantiomers. The conformation
of one enantiomer with C-5 above the plane containing the other
carbon atoms is shown in Fig. 1.
For 2b the vicinal coupling constants J4c,5 and J4t,5 were
calculated using second-order analysis and are true values.
These values are characteristics of equatorial–axial and diaxial
couplings. Also the value of J5,6 is the characteristic of diaxial
coupling. In the earlier studies,[12,13] the torsional angle for
segments involving hydrogens has not been reported. From
X-ray crystallographic data we have found that in 2b the
torsionalanglesH(4c)–C(4)–C(5)–H(5), H(4t)–C(4)–C(5)–H(5)and
H(5)–C(5)–C(6)–H(6)are−56.05,173.66and177.86◦,respectively.
These torsional angles and the vicinal 1H–1H coupling constants
The chemical shifts and coupling constants are quoted to two
decimal points less than those obtained directly from the spectral
data. Thus, 13C chemical shifts were obtained to three decimal
points but are rounded off and quoted to one decimal point.
When the coupling constants could be determined from several
spacings the reported values are the average of all the observed
spacings. For example, the value of J4c,4t can be obtained from the
spacing between lines 1 and 3 and that between lines 2 and 4 in
the signal for H-4c. This value can also be obtained from the signal
for H-4t. The reported J4c,4t values are the averages of the several
values obtained from the signals of H-4c and H-4t. The individual
values differ from the average value by 1–3% when Jobs > 6 Hz
and by 2–5% when Jobs < 6 Hz.
X-ray crystallographic studies[12,13] have shown in 2b and 2g
that the torsional angles about C(1)–C(2) and C(2)–C(3) bonds
are in the range 0.3–3.8◦. Since m- or p-substituents cannot have
a significant effect on the ring torsional angles in compounds
c
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Magn. Reson. Chem. 2011, 49, 253–257

1H and 13C NMR spectral study of 3-aryl-5r-aryl-6t-carbethoxycyclohex-2-enones
Table 2. 1H NMR chemical shifts (ppm) of 2a–2i
Compound
2a
2b
2c
2d
2e
2f
2g
2h
2i
H-2
6.57
3.11a
3.00a
3.81
3.81
4.06
1.03
7.55
7.43
7.43
7.33
6.57
3.20
2.86
4.39
3.97
4.08
1.07
7.55
7.42
7.42
7.41
6.56
3.07
2.96
3.80
3.74
4.08
1.09
7.55
7.43
7.43
7.33
6.57
3.08
2.97
3.78
3.75
4.09
1.09
7.55
7.42
7.42
7.33
7.22
7.27
6.56
3.08
2.97
3.77
3.77
4.07
1.07
7.55
7.42
7.42
7.21
6.56
3.08
2.96
3.80
3.76
4.07
1.07
7.55
7.43
7.43
7.20
6.54
3.05
2.97
3.79
3.79
4.05
1.04
7.55
7.41
–
6.53
3.04
2.94
3.75
3.75
4.07
1.07
7.55
7.40
–
6.51
3.04
2.94
3.75
3.75
4.07
1.07
7.55
7.10
–
H-4c
H-4t
H-5
H-6
C(8)H2
C(9)H3
H-2ꢁ, H-6ꢁ
H-3ꢁ, H-5ꢁ
H-4ꢁ
H-2ꢁꢁ, H-6ꢁꢁ
7.21
7.20
7.20
H-3ꢁꢁ, H-5ꢁꢁ
7.33
7.33
7.37
7.29
7.23
7.26
–
7.15
–
7.04
–
7.28
7.21
7.15
–
7.15
–
H-4ꢁꢁ
7.22
a Calculated assuming J4c,4t as 18.0 Hz.
Table 3. 1H–1H coupling constants (Hz) of 2a–2i
Compound
2a
2b
2c
2d
2e
2f
2g
2h
2i
J2,4t
2.18
1.96
18.12
4.52
2.25
18.10
4.20
2.24
18.37
3.98
2.34
18.15
3.00
2.23
18.29
4.26
2.27
18.09
4.00
2.24
18.13
3.04
2.29
18.32
3.03
a
J4c,4t
d J4c,5
d J4t,5
J5,6
e J6,4t
e J6,4c
3.28
a
11.02
10.16
13.24
9.58
6.99
b
10.41
12.69
6.68
b
6.46
b
6.39
b
b
a
c
12.97
c
13.09
1.18
c
2.01
c
4.26
0.84
0.81
c
4.46
0.33
4.66
0.85
4.92
0.94
c
a The frequencies of only four lines of the AB part where given by the computer and these values could not be determined.
b Could not be determined since H-6 and H-5 form an XXꢁ system.
c Not observed.
d Except for 2b the reported values are only apparent values.
e Apparent values.
suggestthatthepositionsofH-5,H-6andH-4t areequivalenttothe
axial positions of the chair conformations of cyclohexanone. Also,
the positions of Arꢁ, COOEt and H-4c are equivalent to equatorial
positions of the chair conformation of cyclohexanone.
In 2b H-5 and H-4c are deshielded but C-4, C-5 and H-4t are
shielded relative to the other compounds. These observations
suggest that the chlorine atom of the o-chlorophenyl group lies
in between H-4c and H-5. In such a conformation, the chlorine
atom can interact with the C–H(4c) and C–H(5) bonds so that
H-4c and H-5 get partial positive charge, whereas C-4 and C-5
get partial negative charge. Interestingly, X-ray crystallographic
study[12] has shown that in 2b the o-chlorophenyl group adopts
such a conformation.
Obviously, H-4c couples with H-4t and H-5 whereas H-4t couples
with H-4c, H-5 and H-2.
In all the other cases, the signal for H-4t showed additional
splittings due to coupling with H-6 also. In 2c, 2d and 2f the value
of this coupling varies from 0.81 to 2.01 Hz. In these compounds
H-4t, H-6 and H-5 form an AXY system. The values of J4t,6 and J4t,5
obtained directly from the spectral data are only apparent values.
The observed value of J4t,6 should be greater than the real value
and the observed value of J4t,5 should be less than the real value.
In 2e, 2g, 2h and 2i the observed value of J4t,6 is greater than
4 Hz. In these compounds H-4t, H-6 and H-5 form an AXXꢁ system
causing an increase in the observed value of J4t,6 and a decrease
in the observed value of J4t,5
.
In all cases, H-2 appeared only as a doublet. In the 1H–1H
COSY[16] spectra of 2b and 2c there was correlation between H-2
and H-4t. The AB part of the 1H NMR spectrum of 2b, containing
the signals for H-4c and H-4t, is shown in Fig. 2. The signal due to
H-4c is a double-doublet, whereas that of H-4t contain eight lines.
In the cases of 2e, 2h and 2i additional splitting occurs in the B
part also. The AB part of 2e is also shown in Fig. 2. The apparent
value for the four bond coupling J4c,6 is around 0.84–0.94 Hz. The
real value of this coupling should be small. Indeed in these cases
the value of J4c,5 decreases apparently to 3.00–3.04 Hz.
c
Magn. Reson. Chem. 2011, 49, 253–257
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C. Yuvaraj and K. Pandiarajan
Table 4. 14C NMR chemical shifts (ppm) of 2a–2i
Compound
2a
2b
2c
2d
2e
2f
2g
2h
2i
C-1
194.0
124.1
158.6
36.1
193.6
124.1
158.3
34.5
193.4
124.0
158.3
35.8
193.5
124.1
158.3
35.8
194.0
124.1
158.5
36.2
193.6
124.2
158.3
36.2
193.8
124.3
157.1
36.0
193.8
124.4
157.1
36.0
193.8
124.0
C-2
C-3
157.2
C-4
36.3
C-5
44.1
40.2
43.4
43.7
43.7
43.5
44.0
43.6
43.7
C-6
59.6
58.1
59.3
59.3
59.7
59.8
59.5
59.6
59.6
C-7
169.2
60.9
168.8
61.0
168.9
60.9
168.9
61.1
169.2
60.8
169.1
61.0
169.0
61.0
169.0
60.9
169.1
C-8
60.8
C-9
13.9
13.9
13.9
14.0
13.9
14.0
13.9
13.9
13.9
C-1ꢁ
137.7
126.2
128.8
130.5
141.0
127.3
128.8
127.5
–
137.7
126.2
128.8
130.5
138.4
134.0, 127.3
128.5, 127.6
130.3
–
137.5
126.1
128.8
130.5
139.5
128.6
128.8
133.2
–
137.5
126.2
128.9
130.6
143.0
127.6, 125.5
134.6, 130.1
127.7
–
137.8
126.1
128.7
130.4
138.0
127.1
129.4
137.8
126.2
128.9
130.5
136.9
128.9
115.7 (21 Hz)a
136.5
128.8
132.1
124.9
140.8
127.3
127.7
127.6
–
137.2
129.5
132.1
124.9
137.9
127.1
127.7
136.7
20.9
134.0
C-2ꢁ, C-6ꢁ
C-3ꢁꢁ, C-5ꢁ
C-4ꢁꢁ
128.2
115.9 (21 Hz)a
164.1 (250 Hz)a
138.0
C-1ꢁꢁ
C-2 , C-6ꢁꢁ
C-3ꢁꢁ, C-5ꢁꢁ
C-4ꢁꢁ
129.5
127.1
137.0
20.9
162.1 (245 Hz)a
137.1
CH3
–
20.9
a Values of 13C–19F coupling constants.
The real value of J4t,6 can be calculated from the spectral
data of 2c, 2d and 2f using second-order analysis. However, the
frequencies of all the lines of the XY part were given by the
computer only for 2c. Calculations suggested that the real value
of J4t,6 in 0.33 Hz. In 2c, 2d and 2f the observed values of J4t,6
are greater than this real value due to second-order effect. Since
no such second-order effect is in 2b, the long-range coupling
between H-4t and H-6, being really small, is not observed in it.
In 2c the value of JAY (J4t,5) was calculated as 11.01 Hz. However,
thiscannotbetherealvalueofJ4t,5 becauseH-4t,H-4candH-5form
an ABY system. Further second-order analysis suggested that in 2c
the real values of J4t,5 and J4c,5 are 11.24 and 3.98 Hz, respectively.
Thus, in compounds 2a–2i the real values of J4t,5 should be around
11.0 Hz and that of J4c,5 should be around 4.0 Hz. Hence, all these
compounds must adopt sofa conformation shown in Fig. 1.
alcohol (50 ml) was refluxed for 14 h. After cooling, the reaction
mixture was neutralized with 0.1 N HCl. It was then extracted
with diethyl ether (3 × 20 ml). The organic layer was dried over
anhydrous sodium sulfate, filtered and the solvent was removed
in a rotary evaporator. The solid mass obtained was recrystallized
from ethanol.
IR spectra
IR spectra were recorded on an Avatar Nicholet FT-IR spectrometer
in KBr pellets.
Mass spectra
MassspectrawererecordedonaVARIANSATURN2200GC–MS/MS
spectrometer.
Elemental analysis
Conclusions
Elemental analyses were performed on an Elemental Vario EL III
CHNS/O analyzer.
In solution 3-aryl-5r-aryl-6t-carbethoxycyclohex-2-enones adopt
sofa conformation with H-4t, H-5 and H-6 occupying axial-like
positions and the 5-aryl group, carbethoxy group and H-4c occu-
pying equatorial-like positions. In 3-phenyl-5r-(o-chlorophenyl)-
6t-carbethoxycyclohex-2-enone, the o-chlorophenyl group is ori-
ented such that the chlorine atom is in between H-4c and H-5.
Allylic coupling occurs preferentially with a proton parallel to
the p-orbitals involved in the formation of π-bond. Evidence is
obtained for four-bond coupling between 1,3-diaxial and 1,3-
axial–equatorial protons.
NMR spectra
1H and 13C NMR spectra were recorded on a Bruker AMX 400 NMR
spectrometer operating at 400.23 MHz for 1H and 100.62 MHz
for 13C. Solutions were prepared by dissolving 10 mg of the
compound in 0.5 ml of CDCl3. All NMR measurements were made
in5 mmNMRtubes.Thespectralparametersfor1Hwereasfollows:
spectral width 8223.6859 Hz; acquisition time 3.98 s; number of
data points 16K; digital resolution 0.3 Hz; number of scans 16.
For 13C the spectral parameters were as follows: spectral width
25 000 Hz; acquisition time 1.31 s; number of data points 32K;
digital resolution 5 Hz and number of scans 80. 2D NMR spectra of
2b and 2c were recorded on a Bruker DRX 500 NMR spectrometer
using standard parameters. The number of data points were 1K.
Experimental
Preparation of cyclohex-2-enones 2a–2i
A mixture of chalcone ArCOCHCHArꢁ (0.015 mol), ethyl acetoac-
etate (0.015 mol) and sodium ethoxide (0.015 mol) in absolute
c
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1H and 13C NMR spectral study of 3-aryl-5r-aryl-6t-carbethoxycyclohex-2-enones
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Figure 2. 1H NMR spectra of 2b and 2e (inset – expanded spectra of H-4c
and H-4t).
Acknowledgement
The authors are thankful to SIF, Indian Institute of Science,
Bangalore, India for recording the NMR spectra.
c
Magn. Reson. Chem. 2011, 49, 253–257
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