Synthesis and conformational study of some r(2),c(4)-bis(isopropoxycarbonyl)-t(3)-aryl-c(5)-hydroxy-t(5)-methylcyclohexanones using NMR spectra

Article abstract of DOI:10.1016/j.molstruc.2007.04.033

Seven r(2),c(4)-bis(isopropoxycarbonyl)-t(3)-aryl-c(5)-hydroxy-t(5)-methylcyclohexanones 7-13 (aryl = C₆H₅, p-ClC₆H₄, p-FC₆H₄, p-OMeC₆H₄, p-Me₂NC₆

Full text of DOI:10.1016/j.molstruc.2007.04.033

Available online at www.sciencedirect.com
Journal of Molecular Structure 875 (2008) 226–234
www.elsevier.com/locate/molstruc
Synthesis and conformational study of some
r(2),c(4)-bis(isopropoxycarbonyl)-t(3)-aryl-c(5)-hydroxy-
t(5)-methylcyclohexanones using NMR spectra
a,
a
a
b
K. Pandiarajan *, R.T. Sabapathy Mohan , K. Murugavel , R. Hema
a
Department of Chemistry, Annamalai University, Annamalainagar 608 002, India
Department of Chemistry, Seethalakshmi Ramasamy College, Trichy 620 002, India
b
Received 18 January 2007; received in revised form 13 April 2007; accepted 20 April 2007
Available online 27 April 2007
Abstract
Seven r(2),c(4)-bis(isopropoxycarbonyl)-t(3)-aryl-c(5)-hydroxy-t(5)-methylcyclohexanones 7–13 (aryl = C6H5, p-ClC6H4, p-FC6H4, p-
OMeC6H4, p-Me2NC6H4, m-O2NC6H4 and m-C6H5OC6H4) have been synthesized by condensing isopropyl acetoacetate with aromatic
aldehydes in the presence of methylamine. For all these compounds 1H and 13C NMR spectra have been recorded. For 7, HOMOCOSY,
NOESY, HSQC and HMBC spectra also have been recorded. The spectral data suggest that compounds 7–13 exist in chair conforma-
tion with axial orientation of the hydroxy group and equatorial orientations of all the other substituents. Long range coupling is
observed between OH proton and H(6a) in all cases suggesting that OH group is anti to C(5)AC(6) bond. In all cases four distinct dou-
blets are observed for the methyl protons of the two isopropyl groups. In 7 and 13 four separate, closely spaced signals are observed for
the methyl carbons of the two isopropyl groups. All signals could be assigned unambiguously in the case of 7. The protons of one methyl
group of the isopropoxycarbonyl group at C-4 seems to be highly shielded. This suggests that these protons lie above the plane of the aryl
group at C(3). This conclusion is in accordance with the structure of 7, determined by X-ray crystallography. MOPAC calculations on 7
suggest that the chair conformation with OH group anti to C(5)AC(6) bond is more stable than the chair conformation with OH bond
anti to C(5)ACH3 bond by 1.5 kcal molꢀ1
Ó 2007 Elsevier B.V. All rights reserved.
.
Keywords: 1H NMR; 13C NMR; Cyclohexanones; Conformation
1. Introduction
yl)-t(3)-aryl-c(5)-hydroxy-t(5)-methylcyclohexanones (1–6)
has been reported. These compounds have been shown to
adopt chair conformations 1C–6C with axial orientation
of OH group and equatorial orientations of all other sub-
stituents. Also the OH bond has been shown to be anti
to C(5)AC(6) bond. Also the structure of r(2),c(4)-bis(iso-
propoxycarbonyl)-t(3)-phenyl-c(5)-hydroxy-t(5)-methyl-
cyclohexanone (7) has been determined by X-ray
crystallography [15]. It has been found that 7 adopts chair
conformation 7C. In 1–6 two separate triplets were
observed for the methyl protons of the two carbethoxy
groups. However, only one signal was found for the two
methyl carbons of the carbethoxy groups. In order to
throw light on this and to compare the results from
NMR spectroscopy is a powerful tool in determining the
structure and stereochemistry of organic compounds [1–
12]. From the vicinal proton–proton coupling constants
the torsional angles between the protons could be deter-
mined using DAERM [13] and Altona’s [14] equation.
However, such torsional angles, determined from the vici-
nal coupling constants, have not been compared with those
determined by X-ray crystallography. Recently [10], 1H
and 13C spectral study of six r(2),c(4)-bis(ethoxycarbon-
*
Corresponding author.
E-mail address: profkprajan@yahoo.co.in (K. Pandiarajan).
0022-2860/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2007.04.033

K. Pandiarajan et al. / Journal of Molecular Structure 875 (2008) 226–234
227
O
ROOC
MeNH2
OH
2CH3COCH2COOR
+
ArCHO
Ethanol /
Δ
CH3
Ar
COOR
R = i-Pr
Ar = C6H5
R = Et
Ar = C6H5
7,
8,
9,
1,
2,
3,
4,
5,
6,
p
Ar = -ClC6H4
p
Ar = -ClC6H4
p
Ar = -FC6H4
p-
Ar = MeOC6H4
p-
10,
p-
Ar = MeOC6H4
Ar = O2NC6H4
11,
12,
13,
p
Ar = -Me2NC6H4
m
Ar = -O2NC6H4
m
Ar = -O2NC6H4
m
Ar = -C6H5OC6H4
m
Ar = -C6H5OC6H4
H
O
O
H C
3
ROOC
COOR
Ar
R = Et
R = i-Pr
1C,
2C,
3C,
4C,
5C,
6C,
7C,
8C,
9C,
Ar = C6H5
Ar = C6H5
p
p
Ar = -ClC6H4
Ar = -ClC6H4
p-
p
Ar = MeOC6H4
Ar = -FC6H4
p-
Ar = MeOC6H4
10C,
11C,
12C,
13C,
p-
Ar = O2NC6H4
m
p
Ar = -Me2NC6H4
Ar = -O2NC6H4
m
m
Ar = -O2NC6H4
Ar = -C6H5OC6H4
m
Ar = -C6H5OC6H4
Scheme 1. Synthesis of cyclohexanones.
NMR and X-ray crystallography, H NMR, 13C NMR,
HOMOCOSY, NOESY, HSQC and HMBC spectra have
been recorded for 7. Compounds 1–7 were synthesized by
condensing aromatic aldehydes with alkyl acetoacetates
in presence of methylamine (Scheme 1). Six substituted
aldehydes were condensed with isopropyl acetoacetate in
presence of methylamine. Compounds 8–13 should be
formed during this condensation. In order to confirm the
structures of 8–13 and to determine their conformations
1H and 13C NMR spectra have been recorded for 8–13.
The preferred conformation of 7 also has been deduced
using MOPAC calculations.
anol. The physical data for compounds 7–13 are given in
1
Table 1.
2.2. Recording of spectra
IR spectra were recorded on AVATAR 330 FT-IR
Thermo Nicolet spectrometer in KBr pellets.
All NMR measurements were made using 5 mm tubes.
1D NMR spectra were recorded for 7 on a Bruker DRX
1
500 NMR spectrometer operating at 500.03 MHz for H
and 125.75 MHz for 13C. For 8–13 these spectra were
Table 1
2. Experimental
Physical data for compounds 7–13
Compound
Yield (%)
Mp (°C)
2.1. Preparation of compounds
7
8
80
70
72
68
60
65
75
171
158
167
158
154
162
137
A mixture of isopropyl acetoacetate (100 mmol), aro-
matic aldehyde (50 mmol) and methylamine (50 mmol) in
ethanol (50 ml) was heated to boiling. The reaction mixture
was kept at room temperature for one day. The separated
solid was filtered and purified by recrystallisation from eth-
9
10
11
12
13

228
K. Pandiarajan et al. / Journal of Molecular Structure 875 (2008) 226–234
recorded on Bruker AMX 400 NMR spectrometer operat-
The carbon atoms in the cyclohexanone ring are num-
bered as shown in Fig. 1. The numbering of aromatic car-
bons is shown in Fig. 2 taking m-phenoxyphenyl group as
the example. The numbering of the other carbon atoms and
oxygen atoms in 7 is shown in Fig. 3. The hydrogen atoms
on the carbons are numbered accordingly. Thus hydrogen
on C(2) is denoted as H(2) and that at C(20) is denoted as
H(20).
1
ing at 400.13 MHz for H and 100.62 MHz for 13C. For
1
recording H NMR spectra, solutions were prepared by
dissolving 10 mg of the material in 0.5 ml of CDCl3. For
recording 13C NMR spectra, solutions were prepared by
dissolving 50 mg of the material in 0.5 ml of CDCl3. The
number of data points was 32 K.
HOMOCOSY, phase-sensitive NOESY, HSQC and
HMBC spectra were recorded on a Bruker DRX 500
NMR spectrometer using standard parameters. For
recording 2D spectra solutions were made by dissolving
50 mg of the material in 0.5 ml of CDCl3. The number of
data points was 1 K. For NOESY spectrum mixing time
was one thousand milliseconds.
The mass spectrum of 7 was recorded on a JEOL DX-
303 mass spectrometer. Elemental analysis was performed
on a Perkin-Elmer CHNS/O analyser. Semiempirical calcu-
lations were performed for 7 using MOPAC programme
available in CHEMDRAW version.
3.2. Analysis of spectra
The 1H NMR signals for the protons in the cyclohexane
ring, OH proton and the methyl protons at C-5 were
assigned by comparison with those made for the biscar-
bethoxy compounds 1–6, earlier [10]. For 7 these assign-
ments were confirmed by HOMOCOSY and NOSEY
spectra. The observed correlations in these spectra are
given in Table 3. The 13C signals for the cyclohexane ring
carbons and carbonyl carbons of the ester groups were
assigned by comparison with the assignments made earlier
3. Results and discussion
O
O
3.1. Characterisation of compounds 7–13
1
(H3C)2HCO
2
3
6
For all compounds the purity was checked by TLC. For
7 the percentages of carbon and hydrogen were found as
66.7 and 8.20, respectively. The percentages of carbon
and hydrogen, calculated for C21H28O6 are 67.02 and
7.50, respectively. The molecular mass of 7 was found as
376 which agrees with the proposed formula.
The IR spectrum of 7 showed a medium band at
3460 cmꢀ1 due to OH stretching. There were three
strong bands at 1729, 1716 and 1692 cmꢀ1 due to the
three kinds of carbonyl groups. The band at
1692 cmꢀ1 should be due to keto carbonyl group.
Among the two ester carbonyl groups that at C-4
should have a lower stretching frequency due to hydro-
gen bonding with OH. Hence, the band at 1716 cmꢀ1
should be due to the stretching vibration of ester car-
bonyl group at C-4. The band at 1729 cmꢀ1 should be
due to the ester carbonyl group at C-2. The stretching
frequencies for compounds 7–13 are given in Table 2.
For 11 the bands due to keto carbonyl group and the
ester carbonyl group at C-4 merged.
OH
5
4
Ar
CH3
COOCH(CH3)2
Fig. 1. Numbering of carbon atoms in cyclohexanone ring.
2''
'
2
O
'
1''
6''
1
3''
4''
'
3
'
4
'
6
5''
'
5
Fig. 2. Numbering of aromatic carbons in the m-phenoxyphenyl group.
(2)
(7)
(1)
O
O
C
(10)
H3C
H3C
C
(8)
CH
(3)
O
Table 2
OH
(6)
IR stretching frequencies of compounds 7–13
(9)
Compound
Stretching frequencies (cmꢀ1
Carbonyl groups
)
Ph
(15)
CH3
OH group
(11)
(5)
7
8
1729,1716,1692
1729,1711,1700
1729,1716,1698
1730,1712,1699
1733,1705
3460
3491
3481
3483
3496
3489
3476
(4)
O
O
9
(13)
CH3
(12)
CH
(14)
10
11
12
13
H3C
1729,1716,1700
1732,1716,1689
Fig. 3. Numbering of carbons and oxygen in 7.

K. Pandiarajan et al. / Journal of Molecular Structure 875 (2008) 226–234
229
Table 3
Correlations in the COSY and NOESY spectra of 7
Signal
Correlations in the COSY spectrum
Correlations in the NOESY spectrum
7.25 (m, 5H)
4.86 (m, 1H)
4.74 (m, 1H)
3.96 (t, 1H)
3.79 (d, 1H)
3.61 (d, 1H)
2.99 (d, 1H)
2.69 (d, 1H)
2.48 (dd, 1H)
1.33 (s, 3H)
1.08 (d, 3H)
1.03 (d, 3H)
0.97 (d, 3H)
0.57 (d, 3H)
None
3.96, 3.61, 2.99, 1.03, 0.57
2.69, 0.97, 1.03
2.48, 0.57, 1.08
7.25, 3.79, 3.61, 2.99
1.33, 3.96
7.25, 3.96, 2.99, 2.48
7.25, 3.96, 3.61, 2.48, 1.33
3.79 (weak) 2.48, 1.33
3.61, 2.99, 2.69, 1.33
3.79, 2.99, 2.69, 2.48
7.25, 4.74
0.97, 1.03
0.57, 1.08
3.61, 2.99
2.48
3.96
3.96
2.48
3.96, 3.79, 3.61, 2.69
3.79
4.74, 0.57
4.86
4.86
4.74, 1.08
4.86
4.86
7.25, 4.74
Table 4
Correlations in the HSQC and HMBC spectra of 7
13C chemical shifts (ppm)
Correlations in the HSQC spectrum
Correlations in the HMBC spectrum
2a, H6e, H(6a) and CH3 at C-5
CH of COOi-Pr at C-4, H3a, H(4a), H6e
CH of COOi-Pr at C-2, H3a, H2a, H6e
Aromatic, H2a, H3a, H(4a)
Aromatic protons, H3a
CH3 at C-5, H(6a), H6e, H(4a), H3a, OH at C-5
CH3 of COOi-Pr at C-2
201.3
173.4
167.1
138.0
127.6–128.5
73.0
None
None
None
None
H
Aromatic protons
None
CH proton of COOi-Pr at C-2
68.8
68.6
CH proton of COOi-Pr at C-4
CH3 of COOi-Pr at C-4
62.6
H2a
H3a, H(4a), H6e, OH at C-5
56.9
H(4a)
H3a, H2a, H6e, CH3 at C-5
52.6
45.2
28.5
21.6, 20.7
21.5, 21.4
H(6a), H6e
H3a
CH3 proton at C-5
CH3 protons of COOi-Pr at C-4
CH3 protons of COOi-Pr at C-2
OH at C-5, CH3 at C-5
Aromatic, H2a, H(4a)
H6e
CH proton of COOi-Pr at C-4
CH proton of COOi-Pr at C-2
[10] for 1–6. For 7 these assignments were confirmed by
HSQC and HMBC spectra. The observed correlations in
the HSQC and HMBC spectra are given in Table 4.
In all cases the methine protons of the two isopropyl
groups give two distinct multiplets. Also, the four methyl
groups appear as four doublets. From the correlations in
the HOMOCOSY, NOSEY and HMBC spectra of 7 it is
seen that the signals at 4.74, 1.08 and 0.57 ppm are due
to the isopropyl group of the ester group at C-4 and those
at 4.86, 1.03 and 0.97 ppm are due to the other isopropyl
group of the ester group at C-2.
By analogy, in all the other compounds, among the two
signals for the isopropyl methine proton, that at a lower
frequency was assigned to the isopropoxycarbonyl group
at C(4). Also, among the four doublets for the methyl pro-
tons, those appearing at the lowest and highest frequencies,
were assigned to the methyl protons of the isopropoxycar-
bonyl group at C(4).
positions, multiplicities and integral values of the signals.
In 9 coupling with 19F was observed.
The proton chemical shifts of 7–13 are given in Table 5.
The various proton coupling constants are given in Table 6.
In the 13C NMR spectrum of 7 two signals at 68.8 and
68.6 ppm were observed for the two isopropylmethine car-
bons. From the correlations in the HMBC spectrum of 7
the signal at 68.8 ppm can be assigned to the isopropylme-
thine carbon of the isopropoxycarbonyl group at C(2). By
analogy, in all the other cases, among the two signals
observed for the isopropyl methine carbons, that at higher
frequency was assigned to isopropylmethine carbon of the
isopropoxycarbonyl group at C(2).
In the 13C NMR spectrum of 7, for the methyl carbons
of the isopropyl groups, four signals were observed at 21.6,
21.5, 21.4 and 20.8 ppm. From the HMBC spectrum the
signals 21.6 and 20.8 ppm could be assigned to the methyl
carbons of the isopropoxycarbonyl group at C(4). By anal-
ogy, among the signals for the four methyl carbons, those
with the highest and lowest chemical shifts, were assigned
to the methyl carbons of the isopropoxycarbonyl group
at C(4).
The methoxy protons in 10 appeared as a singlet at
3.76 ppm. In 11 the protons of the NMe2 group appeared
as a singlet at 2.88 ppm. In 10, 11, 12 and 13 individual
assignments of the aromatic protons were made based on

230
K. Pandiarajan et al. / Journal of Molecular Structure 875 (2008) 226–234
Table 5
Proton chemical shifts in 7–13
Compounds Chemical shifts, d (ppm)
H-2a H-3a H(4a) OH
H(6a) H-6e CH3 at C-5 Others
7
8
3.61
3.55
3.55
3.55
3.55
3.62
3.55
3.96
3.97
3.97
3.93
3.86
4.14
3.96
2.99
2.97
2.96
2.95
2.94
3.07
2.94
3.79 2.48
3.70 2.47
3.72 2.47
3.75 2.43
3.78 2.44
3.62 2.53
3.75 2.45
2.69
2.69
2.70
2.68
2.66
2.74
2.68
1.33
1.33
1.33
1.32
1.32
1.30
1.32
(0.97, 1.03, 4.86)a, (0.57, 1.08, 4.74)b, (7.24)c
(1.02, 1.08, 4.87)a, (0.66, 1.11, 4.77)b, (7.19, 7.27)c
9
(1.00, 1.07, 4.87)a, (0.65, 1.10, 4.78)b, [6.98 (30,50), 7.23 (20,60)]c
(1.06, 1.00, 4.87)a, (0.65, 1.10, 4.77)b, [6.80, (30,50), 7.15 (20,60)]c
(1.02d, 4.88)a, (0.65, 1.10, 4.77)b, [6.62 (30,50), 7.16 (20,60)]c
(1.01d, 4.87)a, (0.60, 1.09, 4.77)b, [8.14 (20,40), 7.49 (50), 7.61 (60)]c
(1.05, 1.08, 4.92)a, (0.75, 1.13, 4.83)b, [7.32 (30 0,50 0), 7.25 (50), 7.22 (60),
6.94 (20,20 0,60 0), 6.86 (40), 7.11 (40 0)]
10e
11f
12
13
a
b
c
d
e
f
Protons of the COOi-Pr group at C-2.
Protons of the COOi-Pr group at C-4.
Aromatic, the numbers in the parenthesis give the positions of the protons.
Centres of overlapped signals.
OCH3 protons appeared at 3.75 ppm.
N(CH3)2 protons appeared at 2.88 ppm.
Table 6
In compounds 8–13 the vicinal coupling constant
between H(2) and H(3) is either 12.4 or 12.5 Hz. Also the
coupling constant between H(3) and H(4) is either 12.2
or 12.3 Hz. Moreover, long range coupling is observed
between OH proton and H(6a) in all cases. Hence, com-
pounds 8–13 should adopt chair conformations 8C–13C.
The 13C chemical shifts of C(2), C(3), C(4), C(5) and C(6)
in 7 can be calculated by adding the effects of the various sub-
stitutents to the 13C chemical shifts of the corresponding car-
bons in cyclohexanone. Only a-, b- and c-gauche effects are
important. The chemical shifts of C(2), C(3) and C(4) in
cyclohexanone have been reported as 41.9, 26.6 and
24.6 ppm, respectively [17]. The effects of phenyl, methyl
and hydroxyl group, have been reported [18]. The a- and
b-effects of equatorial COOCH(CH3)2 group may be taken
as those of COOMe group, reported by Pehk and Lippma
[19]. The calculated chemical shifts of C(2), C(3), C(4),
C(5) and C(6) are 64.7, 41.1, 61.6, 70.8 and 56.1 ppm, respec-
tively. These values are in good agreement with the observed
values. The chemical shifts of the cyclohexanone ring car-
bons in 8–13 are close to those of the corresponding carbons
in 7. Thus, the 13C chemical shifts of 7–13 are in agreement
with the proposed conformation for them.
In the X-ray crystallographic study [15] of 7 the tor-
sional angles were not reported. The torsional angle
between H(2) and H(3) is 175.7° and that between H(3)
and H(4) is 176.9°. Using Altona’s equation [14] the vicinal
coupling constants for these torsional angles were calcu-
lated as 11.85 and 11.88 Hz. These values are in agreement
with the observed values 12.4 and 12.3 Hz.
In isopropyl acetate the methyl protons of the isopropyl
group absorb at 1.23 ppm [20]. It is obvious that the methyl
protons of the isopropyl groups in 7 are shielded relative to
the methyl protons in isopropyl acetate. However, in iso-
propyl acetate the chemical shift of the methyl carbons of
the isopropyl group is 21.8 ppm [21], which is close to those
of the methyl carbons of the isopropyl groups in 7.
Proton–proton coupling constants in 7–13
Compounds
Coupling constants (Hz)
J2a,3a
J3a,4a
JOH,6a
J6a,6e
7
12.4
12.5
12.4
12.5
12.4
12.5
12.2
12.3
12.3
12.3
12.3
12.2
2.5
2.5
2.6
2.4
2.5
2.5
14.3
14.3
14.3
14.3
14.3
14.3
8
9
10,11
12
13
In 10 the carbon of the methoxy group appeared at
55.2 ppm. In 11 the carbons of the NMe2 group appeared
at 40.6 ppm.
The signals for aromatic carbons were assigned based on
intensities and known substituent effects [16]. In 9 coupling
with 19F was observed for the ipso and ortho carbons. The
13C chemical shifts of 7–13 are given in Table 7. The JCF
values also have been given.
3.3. Conformational study
In 7 the vicinal coupling constant between H(2) and H(3)
is found as 12.4 Hz and that between H(3) and H(4) is found
as 12.2 Hz. Furthermore, in the NOESY spectrum of 7 the
methyl protons at C(5) show NOE with both the methylene
protons at C(6). Also there is NOE between H(2) and H(4).
One of the methylene protons at C-6 shows NOE with H(2)
and H(4). This proton has long range coupling with the OH
proton. All these observations suggest that compound 7
adopts chair conformation 7C with axial orientation of
OH group and equatorial orientations of all the other sub-
stituents. Also the OH proton should be anti to C(5)AC(6)
bond so that HOAC(5)AC(6)AH(6a) form
arrangement.
Indeed X-ray crystallographic study [15] of 7 has shown
that 7 adopts such a conformation in the solid state.
a
W

K. Pandiarajan et al. / Journal of Molecular Structure 875 (2008) 226–234
231
Hence, the shielding of the methyl protons of the isopro-
pyl groups in 7 should be due to magnetic anisotropic
effect. In order to understand these shieldings it is essential
to consider the conformations of the isopropoxycarbonyl
groups and phenyl group in 7.
According to X-ray crystallographic study [15], in 7
the carbonyl oxygens of the isopropoxycarbonyl groups
are nearly anti to the axial hydrogen on the carbon bear-
ing the isopropoxycarbonyl group. The carbonyl group
and the OAC bond are nearly coplanar and are in the
same side. In both cases one methyl group is anti to
the OACO bond. The other methyl group of the iso-
propoxycarbonyl group at C(2) is pointing towards
C(1), whereas the other methyl group of isopropoxycar-
bonyl at C(4) is pointing towards C(3). The phenyl
group is parallel to the C(3)AH bond. The conforma-
tions of the isopropoxycarbonyl groups and phenyl
group are shown in Fig. 4.
Actually in the solid state the torsional angles between
the C@O group at C-2 and C(2)AH bond is 151.5° so that
the carbonyl group is tilted towards the phenyl group at C-
3. This tilting in the solid state should be to decrease the
dipolar interaction between the C(1)@O group and the car-
bonyl group of the isopropoxycarbonyl group at C(2).
However, in solution this dipolar interaction should be less
and the CO group can be nearly anti to C(2)-hydrogen.
Geirsson et al. [22] have reported the X-ray crystallo-
1
graphic and H NMR spectral study of 14. Compound
14 adopts chair conformation 14C in the solid state. In
the solid state the O-hydrogen is involved in hydrogen
bonding with the carbonyl group of the carbomethoxy
group at C-4. However, in CDCl3 there is long range cou-
pling between the OH proton and H-4 indicating a hydro-
gen bonding between the carbonyl group of the
carbomethoxy group at C-2. This shows that in CDCl3
the carbonyl group of COOMe group at C(2) is anti and
almost parallel to C(2)-hydrogen in 14. Hence, in CDCl3
the conformation of 7 should be as shown in Fig. 4.
However, the conformations of the isopropyl groups
about the respective CAO bonds should be close to those
observed in the solid state since there is no polar interac-
tion between the isopropyl groups and the nearby substit-
uents. The conformations of the isopropyl groups about
the OACH(CH3)2 bonds, as determined by X-ray crystal-
lography, are shown in Figs. 5a and 5b. The plane of the
phenyl group should be in between these two figures.
H
O
O
H
O
H
O
C
H3C
H3C
H3C
O
H3C
C
(10)
H
C
C
O
H
H
(9)CH3
Fig. 4. X-ray crystallographic structure of 7.

232
K. Pandiarajan et al. / Journal of Molecular Structure 875 (2008) 226–234
CO
CO
H(12)
H(8)
C(10)H3
C(12)
C(8)
C(9)H3
O
MeOOC
COOMe
H
O
R
O
MeOOC
OH
MeOOCH2C
MeOOC
(H3C)2HCHC CH
COOMe
CH2COOMe
COOMe
14C,
R = (CH3)2CHCH=CH-
14
(b)
O
C
CH3
C
O
C
H
C
(a)
H
O
H3C
O
CH3
H3C
(b)
CH3
H3C
B
A
(a)
O
C
CH3
(b)
H3C
O
C
H
H3C
C
H
O
H
O
O
O
H3C
H3C
ROOC
COOR
ROOC
COOR
Ar
Ar
7A
7B
Fig. 5. (a) Conformation of isopropyl group of the C(2)-isopropoxycarbonyl group above the CAO bond. (b) Conformation of isopropyl group of the
C(4)-isopropoxycarbonyl group above the CAO bond.
In the isopropoxycarbonyl group at C(2), the methyl
group anti to the O(3)AC(7) bond is designated as
C(9)H3 and that gauche to the O(3)AC(7) bond is desig-
nated as C(10)H3. The conformation of the
C(9)H3AC(8)HAC(10)H3 group about the O(3)AC(8)
bond is shown in Fig. 5a. The torsional angles
it is obvious that the anti methyl group C(9)H3 is slightly
tilted towards the phenyl group at C(3).
In the isopropoxylcarbonyl group at C(4), the methyl
group anti to the O(5)AC(11) bond, is designated as
C(13)H3 and that gauche to the O(5)AC(11) bond is denoted
as C(14)H3. The torsional angles C(11)AO(5)AC(12)
AH(12), C(11)AO(5)AC(12)AC(13) and C(11)AO(5)
AC(12)AC(14) are, respectively, ꢀ20.8°, ꢀ140° and 98.5°.
Thesetorsionalanglesshowthattheantimethylgroupisaway
fromthephenylgroupatC-3.TheprojectionanglesH(12)AC
(12)AC(13), C(13)AC(12)AC(14) and C(14)AC(12)AH(12)
come as 119.5°, 121.8° and 119°, respectively. These angles
correspond to a normal tetrahedral system.
C(7)AO(3)AC(8)AH(8),
C(7)AO(3)AC(8)AC(9)
and
C(7)AO(3)AC(8)AC(10) are, respectively, ꢀ44°, ꢀ161.8°
and 76.7° (negative sign indicates rotation in the anticlock-
wise direction). The projection angles H(8)AC(8)AC(9),
C(9)AC(8)AC(10) and C(10)AC(8)AH(8) come as 117.8°,
121.5° and 121.7°, respectively. These values correspond
to a normal tetrahedral system. From the torsional angles

K. Pandiarajan et al. / Journal of Molecular Structure 875 (2008) 226–234
233
Table 8
It is obvious that C(14)H3 protons should be markedly
shielded by the magnetic anisotropic effect of the phenyl
group since these protons lie above the plane of the phenyl
group. The signal at 0.57 ppm should be due to C(14)H3
protons. It is interesting to note that there is strong NOE
between the methyl protons at 0.57 ppm and aromatic pro-
tons. The signal at 1.08 ppm should be due to C(13)H3 pro-
tons. These protons do not show NOE with aromatic
protons.
Torsional angles determined by X-ray crystallography [15] and MOPAC
calculations
Torsional angle
Values by X-ray
(°)
Values by MOPAC
(°)
C(7)AO(3)AC(8)AH(8)
ꢀ44.0
ꢀ161.8
76.7
ꢀ20.8
ꢀ36.0
ꢀ154.7
84.6
ꢀ38.8
ꢀ157.4
81.0
C(7)AO(3)AC(8)AC(9)H3
C(7)AO(3)AC(8)AC(10)H3
C(11)AO(5)AC(12)AH(12)
C(11)AO(5)AC(12)AC(13)H3 ꢀ140.8
C(11)AO(5)AC(12)AC(14)H3
98.5
The signal at 1.03 ppm also showed NOE with aromatic
protons. Hence, this signal should be due to C(9)H3 pro-
tons. Obviously, C(10)H3 protons appear at 0.97 ppm.
Though C(10)H3 protons are not shielded by the mag-
netic anisotropic effect of the phenyl group these protons
are shielded relative to the methyl protons of the isopropyl
group in isopropyl acetate. This can be explained as fol-
lows: Three conformations A, B and C are possible for
the isopropyl group in isopropyl acetate. Conformation
C can be ignored because both the methyl groups are
gauche to the COOCH3 group. Conformations A and B
are equivalent and must contribute equally. In conforma-
tion A CH3(a) protons lie above the plane of the carbonyl
group and are shielded by the magnetic anisotropic effect of
the carbonyl group. In conformation B CH3(b) protons are
shielded by the carbonyl group. Thus, each set of methyl
protons are shielded by the magnetic anisotropic effect of
the carbonyl group to the extent of 50%. However, in 7
the C(10)H3 protons are deshielded by the ester carbonyl
group to the extent of 100%. There may be also shielding
by the magnetic anisotropy of the C(1)@O group.
In compounds 8–13 one set of methyl protons are
shielded relative to the other three sets. The chemical shifts
of all the other three sets of methyl protons are around
1.00 ppm. Hence, in compounds 8–13 the conformations
of the isopropoxycarbonyl groups should be similar to
those in 7.
In 1 the methyl protons of the carbethoxy group at C-2
absorbs at 1.04 ppm. This suggests that this methyl group
probably adopts the position of C(9)H3 in 7. In 1 the
methyl protons of the carbethoxy group at C-4 absorbs
at 0.80 ppm. This suggests that the ethyl group of the car-
bethoxy group at C-4 exists in two conformations, one with
the methyl group adopting the position of C(13)H3 in 7 and
the other with the methyl group adopting the position of
C(14)H3 in 7. The effect of the additional methyl group
on the chemical shift of the methyl protons can be ignored
because the methyl protons of ethyl acetate absorb at
1.26 ppm [23] which is close to the chemical shift of methyl
protons in isopropyl acetate.
energy-minimised conformation 7C are compared with
the torsional angles from X-ray diffraction study in Table
8. It is seen that there is good agreement between the two
sets of values.
4. Conclusion
The NMR spectral data of r(2),c(4)-bis(isopropoxycar-
bonyl)-t(3)-aryl-c(5)-hydroxy-t(5)-methylcyclohexanones
7–13 suggest that these compounds exist in chair conforma-
tion with axial orientation of the hydroxy group and equa-
torial orientations of all the other substituents. The OH
bond should be anti to C(5)AC(6) bond. In both the iso-
propyl groups one methyl group should be anti to the cor-
responding OACO bond. The other methyl group of the
isopropyl group at C(2) should be pointing towards C(2)
and that of C(4) should be pointing towards C(3). The
results obtained from NMR spectra are in good agreement
with those from X-ray crystallography and MOPAC
calculations.
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234
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