Conformational study of some N-Nitroso-2r, 6c-diphenylpiperidin-4-one oximes using NMR spectra

Article abstract of DOI:10.1016/j.molstruc.2018.11.068

Stereochemistry of N-nitroso-2r,6c-diphenylpiperidin-4-one oxime (1), N– nitroso -3t-methyl-2r,6c-diphenylpiperidin-4-one oxime (2), N– nitroso-3t-isopropyl -2r,6c-diphenylpiperidin-4-one oxime (3), N– nitroso-3t-ethyl-2r,6c-diphenylpiperidin-4-one oxime (4) has been studied using ¹H, ¹³C and two-dimensional NMR spectra. Analysis of the spectral data shows that in 2, 3 and 4 the NOH group is anti to the alkyl group at C-3. All the four compounds seem to exist largely in boat conformations with one phenyl group in the flagpole position. Analysis on the reported spectral data on N– nitroso -2r,6c-diphenylpiperidin-4-ones suggests that these compounds also largely exist in boat conformations with one phenyl group in the flagpole position. Chair conformation with axial phenyl groups may contribute to some extent. The relative populations of the boat and chair conformations have been supported by the observed NOEs in their NOESY spectra.

Full text of DOI:10.1016/j.molstruc.2018.11.068

Accepted Manuscript
Conformational study of some N-Nitroso-2r, 6c-diphenylpiperidin-4-one oximes using
NMR spectra
G. Muthukumaran, K. Pandiarajan
PII:
S0022-2860(18)31381-4
DOI:
https://doi.org/10.1016/j.molstruc.2018.11.068
MOLSTR 25897
Reference:
To appear in: Journal of Molecular Structure
Received Date: 26 September 2018
Revised Date: 21 November 2018
Accepted Date: 22 November 2018
Please cite this article as: G. Muthukumaran, K. Pandiarajan, Conformational study of some N-
Nitroso-2r, 6c-diphenylpiperidin-4-one oximes using NMR spectra, Journal of Molecular Structure
(2018), doi: https://doi.org/10.1016/j.molstruc.2018.11.068.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical abstract
O
NH OH.HCl
HO
2
O
Dil.HCl
NaNO2
N
CH COONa.3H O
R
3
2
R
Ethanol (Reflux)
R
Chloroform
Ph
Stirred
Ph
N
N
Ph
Ph
N
H
Ph
N
N
Ph
O
O
-
4-one oximes
Synthesis of N-Nitroso piperidin
R= H or Me or iPr or Et

1
ACCEPTED MANUSCRIPT
Conformational study of some
N-Nitroso-2r, 6c-diphenylpiperidin-4-one
oximes using NMR spectra
a
b
G. Muthukumaran , K. Pandiarajan
a-Department of Chemistry, Krishnasamy College of Engineering and
Technology, Cuddalore, Tamil Nadu 607 109, India
b-Department of Chemistry, Annamalai University, Annamalainagar,
Tamil Nadu 608 002, India
Abstract
Stereochemistry of N-nitroso-2r,6c-diphenylpiperidin-4-one oxime (1),
N- nitroso -3t-methyl-2r,6c-diphenylpiperidin-4-one oxime (2), N- nitroso-3t-
isopropyl -2r,6c-diphenylpiperidin-4-one oxime (3), N- nitroso-3t-ethyl-
1
13
2
r,6c-diphenylpiperidin-4-one oxime (4) has been studied using H, C and
two-dimensional NMR spectra. Analysis of the spectral data shows that in 2, 3
and 4 the NOH group is anti to the alkyl group at C-3. All the four compounds
seem to exist largely in boat conformations with one phenyl group in the
flagpole position. Analysis on the reported spectral data on N- nitroso -2r,6c-
diphenylpiperidin-4-ones suggests that these compounds also largely exist in
boat conformations with one phenyl group in the flagpole position. Chair
conformation with axial phenyl groups may contribute to some extent. The
relative populations of the boat and chair conformations have been supported
by the observed NOEs in their NOESY spectra.
1
13
1,3
Keywords: H NMR; C NMR; NOESY, A strain; Conformation.

2
ACCEPTED MANUSCRIPT
1.Introduction
NMR spectroscopy has been used as a powerful tool in studying the
conformations of six-membered ring compounds in solution [1–8]. Vicinal
proton–proton coupling constants have been widely used in deriving
information about the conformations of heterocyclic compounds [1– 7].
2r,6c-Diarylpiperidin-4-ones [4] and their oximes [5] have been shown to
exist largely in chair conformation with equatorial orientations of the
substituents.
Substituted piperidines adopt chair conformation with equatorial
orientations of the bulky substituents because in these compounds nitrogen is
3
in sp -hybridized state and adopts tetrahedral geometry. However, in N-acyl
piperidines and N-nitrosopiperidines the nitrogen of the piperidine ring should
2
be in sp -hybridized state so that there could be resonance between the
nitrogen lone pair and the p-electrons of the CO or NO group. Hence, in N-
acylpiperidines and N-nitrosopiperidines the nitrogen of the piperidine ring
should adopt trigonal planar geometry. In such cases there will be a steric
interaction between the N-nitroso group and the adjacent equatorial substituent
1
,3
(
Fig. 1). This interaction introduces a strain in the molecule called A strain.
1
,3
This A strain is relieved in chair con-formation with axial orientations of the
substituents and in boat conformation with one substituent in the flagpole
position ( Fig. 2). It is of interest to investigate the conformations of N-nitroso
piperidines with substituents at C-2 and C-6.

3
ACCEPTED MANUSCRIPT
H
N
H
H
1
OH
R
H
O
N
H
1
N
R
H
1
,3
Fig. 1. A strain in chair conformation with equatorial substituents.
1
1
H
R
R
1
N
H
R
H
H
N
OH
H
H
1
H
H
O
N
R
H
N
H
H
H
H
H
N
O
1
,3
Fig. 2. Chair and boat conformations without A strain
Indeed several conformational studies [2,3,7,9–15] have been made on
such compounds. This subject has been reviewed [16]. However, the vicinal
proton–proton coupling constants of N-nitroso-2r,6c-diphenylpiperidin-4-ones
[
13,14] and N-nitroso-2r,6c-diphenyl-piperidin-4-ones oximes [15] have not
been analysed in detail in terms of their conformational behaviour in solution.
In N-nitroso compounds [13–15] there is complication due to the observation
of separate signals for syn and anti forms. This is due to a higher energy
barrier for rotation of N–NO moiety compared to a N-acyl moiety. In order to
understand the conformational behaviour of the more complex N-nitroso
compounds it is desirable to study some more simple compounds in detail

4
ACCEPTED MANUSCRIPT
using NMR spectroscopy. This paper reports the conformational study of N-
nitroso-2r,6c-diphenylpiperidin-4-one oxime (1), N- nitroso -3t-methyl-2r,6c-
diphenylpiperidin-4-one
diphenylpiperidin-4-one
oxime
oxime
(2),
(3),
N-
N-
nitroso-3t-isopropyl-2r,6c-
nitroso-3t-ethyl -2r,6c-
diphenylpiperidin-4-one oxime (4) using NMR spectra.
2
2
. Experimental
.1. Preparation of compounds
Compounds 1–4 were prepared from the corresponding N-nitroso
piperidine-4-ones 1a–4a, which were prepared following the procedure of
Krishna Kumar and Krishna Pillay [17]. They were recrystallized from
suitable solvents. The melting points of the N-nitroso piperidin-4-ones are as
follows: 1a (104°C); 2a (124 - 125°C); 3a (119°C); 4a (87-88°C);. These are
in excellent agreement with those reported in the literature [17].
The appropriate N-nitroso piperidin-4-one (50 mmol) and sodium acetate
trihydrate (156 mmol) were dissolved in boiling ethanol and hydroxylamine
hydrochloride (60 mmol) was added.After removing the precipitated NaCl by
filtration the reaction mixture was heated under reflux for 15 min. The
reaction mixture was then poured into water. The separated N-nitroso
piperidin-4-one oxime was recrystallized from ethanol. The yield was 70–
8
-
0%.The melting points are as follows 1 (183-186°C); 2 (172 - 174°C); 3 (120
124°C); 4 (136°C);.

5
ACCEPTED MANUSCRIPT
2.2. Recording of spectra
1
For 1,2 and 3 H NMR spectra were recorded on a Bruker DRX 500 NMR
1
spectrometer operating at 500.03 MHz for H with the following spectral
parameters; acquisition time = around 3.0s,number of scans = 100,number of data
points=32 K and spectral width =5000Hz.Solutions
were prepared by dissolving about 10 mg of the compound in 0.5 ml of
CDCl3.
1
For 4, H NMR spectra were recorded on a Bruker DRX 400 NMR
1
spectrometer operating at 400.03 MHz for H with the following spectral
parameters; acquisition time = around 3.0s,number of scans = 100,number of data
points=32 K and spectral width =5000Hz.Solutions
were prepared by dissolving about 10 mg of the compound in 0.5 ml of
CDCl3.
13
For 2 and 3, C NMR spectra were recorded on a Bruker DRX 500 NMR
1
3
spectrometer operating at 125.75 MHz for C.
1
3
For 1 and 4 C NMR spectrum was recorded on a Bruker AMX-400 NMR
1
3
spectrometer operating at 100.62 MHz for C. The following spectral
parameters were used: acquisition time = around 0.5 s; number of scans =
around 1000; number of data points = 32 K; spectral width = around 30000
Hz. Solutions were prepared by dissolving about 50 mg of the compound in
0.5 ml CDCl3.
1
1
H– H COSY, phase-sensitive NOESY and HMBC spectra were recorded

6
ACCEPTED MANUSCRIPT
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 mol of CDCl . The number of data points was 1 K. For NOESY spectra
3
the mixing time was 800 ms.
All NMR measurements were made using 5 mm tubes.

7
ACCEPTED MANUSCRIPT
RESULTS AND DISCUSSION
Synthesis of Compounds:
Compounds 1,2,3 and 4 were synthesized following Scheme -1
O
O
Dil.HCl
NaNO2
R
R
Chloroform
Stirred
Ph
N
N
Ph
Ph
N
H
Ph
O
NH OH.HCl
2
CH COONa.3H O
3
2
Ethanol (Reflux)
HO
N
R
Ph
N
N
Ph
O
R= H or Me or iPr or Et
4-one oximes
-
Scheme-1 :Synthesis of N-Nitrosopiperidin
S.NO
Name of compound
N-nitroso-2r,6c-diphenylpiperidin-4-one oxime
N- nitroso -3t-methyl-2r,6c-diphenylpiperidin-4-one oxime
R
H
1
2
3
4
(1)
(2)
Me
iPr
Et
N- nitroso-3t-isopropyl -2r,6c-diphenylpiperidin-4-one oxime (3)
N- nitroso-3t-ethyl-2r,6c-diphenylpiperidin-4-one oxime (4)

8
ACCEPTED MANUSCRIPT
N-Nitroso-r(2),c(6)-diphenylpiperidin-4-one oxime (1)
N-Nitroso-r(2),c(6)-diphenylpiperidin-4-one
oxime
has
been
synthesized and the following NMR spectra have been recorded for it.
1
(
(
(
(
(
i)
ii)
H NMR spectrum at 500 MHz
C NMR spectrum at 100.62 MHz
1
3
iii) HOMOCOSY spectrum at 500 MHz
iv)
v)
NOESY spectrum at 500 MHz
HMQC spectrum at 500 MHz
1
In the H NMR spectrum of 1 two signals are obtained for the
hydroxylic proton at 8.25 and 8.21 ppm. Four signals are observed for the
benzylic protons at 6.46, 6.36, 6.15and 5.61 ppm. There are seven signals for
the methylene protons in the range 2.50 – 4.00 ppm. The signal centered at
about 2.7 ppm seems to contain two overlapped signals. Thus, there are eight
signals for the methylene protons. This suggests that the compound exists in
two forms. The integral values of the signals show that the two forms are
present in the ratio 7:3.
The rotation about N-N bond in N-nitroso compounds is slow on the
NMR time scale due to high energy barrier for rotation about the N-NO bond.
Hence, in solution N-nitroso compounds exist in two forms and both forms
will give rise to different spectra [21]. The two forms of 1 are 5 and 6.

9
ACCEPTED MANUSCRIPT
In 5 the nitroso group is syn to the hydroxylic group and in 6 the
nitroso group is anti to the hydroxylic group. The atoms in the heterocyclic
ring are numbered so that the benzylic carbon anti to OH group is taken as
C-2.
Based on integral values among the four signals for the benzylic
protons, the signals at 6.46 and 5.61 ppm are due to the major form and the
signals at 6.36 and 6.15 ppm are due to the minor form.
1
In the H NMR spectrum of 1 two doublet of doublets appear at 3.80
and 3.52 ppm. The signal at 3.80 ppm is due to the major form and that at 3.52
1
9
ppm is due to minor form. Generally, in piperidin-4-one oximes one of the
methylene protons syn to the hydroxylic group appears downfield in the range
of 3.5 to 3.9 ppm. Therefore, two doublet of doublets at 3.80 and 3.52 ppm
must be due to one of the protons at C-5.
In the HOMOCOSY spectrum (Plate-1) of 1 the doublet of doublet at
3.80 ppm has cross peaks with the benzylic proton signal at 6.46 ppm and the
methylene proton signal at 3.14 ppm. Hence, the signals at 6.46, 3.80 and 3.14
ppm are respectively, due to H-6, H-5 and H-5′in the major form (Among the
two methylene protons at C-5 that appearing at a downfield is designated as
H-5 and the other proton is designated as H-5′). The benzylic proton at C-2
(H-2) of the major form appears at 5.61 ppm. This signal has cross peaks with

1
0
ACCEPTED MANUSCRIPT
the signals at 2.94 and 2.78 ppm. Hence, the signals at 5.61, 2.94 and 2.78
ppm are, respectively, due to H-2, H-3 and H-3′of the major form (Among the
two methylene protons at C-3 that appearing at a downfield is designated as
H-3 and the other proton is designated as H-3′). It should be noted that the
signals at 2.78 ppm is a merged signal due to one proton in the major form and
another proton in the minor form.
In the case of minor form, the doublet of doublet at 3.52 ppm has cross
peaks with the benzylic proton signal at 6.36 ppm and with the merged signal
at 2.78 ppm. Therefore, the signals at 6.36, 3.52 and 2.78 ppm are,
respectively, due to H-6, H-5 and H-5′ in the minor form. The benzylic proton
at C-2 (H-2) of the minor form appears at 6.15 ppm. This signal has cross
peaks with the signals at 3.32 and 2.98 ppm. Hence, the signals at 6.15, 3.32
and 2.98 ppm are, respectively, due to H-2, H-3 and H-3′of the minor form.

1
1
ACCEPTED MANUSCRIPT
Plate-1: HOMO COSY Spectrum of compound 1
The proton chemical shifts for the major and minor forms of 1 are
given in Table-1.
Table-1
The proton chemical shifts of 1, ppm
a
Form H-2
H-3 H-3′ H-5 H-5′ H-6
OH
Aromatic
Major 5.61 2.94 2.78 3.80 3.14 6.46
Minor 6.15 3.32 2.98 3.52 2.78 6.36
8.25
8.21
7
.45-6.84
a
For both forms

1
2
ACCEPTED MANUSCRIPT

1
3
ACCEPTED MANUSCRIPT

1
4
ACCEPTED MANUSCRIPT

1
5
ACCEPTED MANUSCRIPT
The geminal and vicinal coupling constants for the major and minor
forms of
Table-2.
1
were calculated and the values are given in
Table-2
The coupling constants of 1, Hz
Form
Major
Minor
J2,3
J ′
J ′
J5,6
3.14
4.49
J ′,
J ′
2,3
3,3
5 6
5,5
5.89
5.63
9.70
6.41
a
6.63
6.73
18.93
17.81
16.07
a Could not be determined
The possible conformations for the syn form 5 are 5A, 5B, 5C, 5D, 5E,
F, 5G and 5H. For the anti form 6, the possible conformations are 6A, 6B,
C, 6D, 6E, 6F, 6G and 6H. For the syn form 5 conformations 5A, 5C and
G have allylic strain between the nitroso group and one phenyl group. Hence,
5
6
5
these conformations need not be considered for 5. Similarly for 6
conformations 6A, 6E and 6G have allylic strain between nitroso group and
one phenyl group. These conformations need not be considered for 6.

1
6
ACCEPTED MANUSCRIPT
Plate-2: NOESY Spectrum of compound 1
In the NOESY spectrum (Plate-2) of 1, for the major form
H-6 benzylic proton at C-6 shows NOE with H-5, H-5′ and H-3′.
This shows that there is significant NOE between H-6 and one methylene
proton at C-3. Such a NOE is possible only in 5C and 6C. However, 5C is not
a probable conformation (ruled out due to severe allylic strain). However, in
6C there is no severe allylic strain and this can make significant contribution.
This is a probable conformation for 6. Therefore, the major form should be 6,
in which the NO group is anti to NOH group.

1
7
ACCEPTED MANUSCRIPT
H
H
N
Ar
R
N
2
Ar
H
3
2
Ar
4
H
OH
4
3
6
OH
5
H
6
N
H
1
Ar
H
5
N
H
N
R
H
1
O
N
H
O
XA
XB
R
H
Ar
H
3
6
3
6
H
H
H
Ar
R
H
O
4
4
5
5
N
OH
H
H
N
OH
H
Ar
N
1
2
N
2
1
O
Ar
N
H
N
XC
XD
H
H
H
Ar
5
2
R
3
5
2
H
H
Ar
H
H
4
4
HO
H
HO
Ar
3
N
H
N
R
6
N
1
6
N
1
Ar
O
N
H
O
N
XE
XF
N
N
O
4
N
N
OH
N
Ar
H
1
O
4
OH
N
H
R
1
2
3
H
2
3
Ar
H
R
H
H
Ar
H
6
5
6
5
H
H
Ar
H
XG
XH
Compound
Number
Syn Form
Ar
R
(X)
5
7
9
11
1
2
3
4
Ph
Ph
Ph
Ph
H
Me
i Pr
Et

1
8
ACCEPTED MANUSCRIPT
H
H
N
Ar
R
N
2
Ar
H
3
2
Ar
4
H
OH
4
3
6
OH
5
H
6
O
N
H
1
Ar
H
O
5
N
H
N
R
H
1
N
H
YA
YB
R
H
Ar
H
3
6
3
6
H
H
H
Ar
R
H
4
4
5
5
N
OH
H
H
N
OH
H
Ar
N
2
N
2
1
1
Ar
N
H
H
N
O
O
YC
YD
H
H
Ar
5
2
R
5
2
H
H
Ar
H
H
4
4
HO
H
3
HO
Ar
3
N
H
N
R
N
6
1
6
N
1
Ar
N
O
H
N
O
YE
YF
O
N
N
O
N
N
4
OH
N
1
Ar
2
H
4
OH
N
H
R
1
3
H
2
3
Ar
H
R
H
H
Ar
H
6
5
6
5
H
H
Ar
H
YG
YH
Anti
Form
Compound
Number
Ar
R
(Y)
1
2
3
4
6
8
10
12
Ph
Ph
Ph
Ph
H
Me
i Pr
Et

1
9
ACCEPTED MANUSCRIPT
Furthermore, in 6C among the two methylene protons at C-3 only that
cis to H-2 can have NOE with H-6. Therefore, the proton at 2.72 ppm should
be cis to H-2 and the signal at 2.94 ppm is due to the proton trans to H-2.
From the data for the signal at 2.94 ppm the coupling constant between H-2
and this proton is found to be 9.70 Hz. Therefore, for 6 among the two vicinal
couplings about C(2)–C(3) bond the value of 9.70 Hz must correspond to the
coupling of H-2 with the methylene proton trans to it. In other words, it is
Jtrans value and that of 5.89 Hz must correspond to the coupling of
H-2 with the methylene proton cis to it. In other words it is J value.
cis
However, in 6C these coupling constants should have values about 2-6
Hz since the torsional angle between the hydrogens is around 60° for both the
couplings. Moreover, in 6C among the two vicinal coupling constants about
C(5)–C(6) bonds one should have a value of about 10-12 Hz and the other
should have a value of about 2-6 Hz. Hence, the observed vicinal coupling
constants could not be accounted exclusively by 6C. The probable values for
the various couplings in the various conformations of 6 are given in Table-3.

2
0
ACCEPTED MANUSCRIPT
a
Table-3
Probable values for various vicinal coupling constants
for 6, Hz
About C(2) – C(3) bond
About C(5) – C(6) bond
Conformations
Jcis
2-6
Jtrans
2-6
Jcis
2-6
2-6
2-6
2-6
10-12
b
Jtrans
2-6
6B
6
C
D
2-6
2-6
10-12
2-6
6
2-6
10-12
2-6
6F
2-6
10-12
4-6
6H
10-12
5.89
4-6
Observed
9.70
b
a
Jcis refers to coupling between the corresponding benzylic proton and the
methylene proton cis to it. Jtrans refers to coupling between the
corresponding benzylic proton and the methylene proton trans to it
b Is not possible to assign individual coupling and they are 3.14 and
.63 Hz
6
It is not possible to establish among the two vicinal coupling constants
about C(5)-C(6 )bond which corresponds to J . Hence, information about the
cis
conformations contributing significantly to 6 has to be obtained only using the
vicinal coupling constants about C(2)–C(3) bond. In order to account for the
observed vicinal coupling constants it is essential to include the contribution
of conformation 6D.
Since the Jtrans value about C(2)-C(3) bond is quite high conformation
6D should be the major conformation for 6. If one assumes that the Jtrans value
is 12 Hz in 6D and 6 Hz in any other conformation, the contribution of 6D can
be calculated using the following relation in which x is the mole fraction of
6D.

2
1
ACCEPTED MANUSCRIPT
9.70 = 12x + 6 (1-x)
The value of x comes as 0.62.
In conformation 6C one phenyl group is in the boat–equatorial position
and the other phenyl group is in boat–axial position. In 6D one phenyl group
is in boat–equatorial position and the other phenyl group is in flagpole
position. Since 6D is more stable than 6C it can be inferred that for phenyl
group prefers flagpole position over boat–axial position. In conformations 6B,
6F and 6H the Jtrans value about C(2)-C(3) bond should be low. Therefore,
these three conformations cannot significantly contribute to 6. Thus, this may
be concluded that 6 exist as an equilibrium mixture of 6C and 6D.
Conformation 6D is more stable than 6C.
Minor form should be 5. The conformations 5B, 5D, 5E, 5F and 5H,
which do not have severe allylic strain, are considered for 5. The probable
values for the various couplings in the various conformations of 5 are given in
Table-4.

2
2
ACCEPTED MANUSCRIPT
a
Table-4
Probable values for various vicinal coupling constants
for 5, Hz
About C(2) – C(3) bond
About C(5) – C(6) bond
Conformations
Jcis
2-6
Jtrans
2-6
Jcis
2-6
Jtrans
2-6
5B
5
D
2-6
10-12
10-12
2-6
2-6
2-6
5
E
2-6
2-6
2-6
5
F
2-6
2-6
10-12
4-6
5H
10-12
4-6
10-12
a
Jcis refers to coupling between the corresponding benzylic proton and the
methylene proton cis to it. Jtrans refers to coupling between the
corresponding benzylic proton and the methylene proton trans to it
Conformations 5B and 6B have almost identical interactions.
Conformations 5H and 6H have almost identical interactions. Since 6B and
H are not contributing significantly to 6, conformations 5B and 5H cannot
contribute significantly to 5. So we have to consider only conformations 5D,
E and 5F for 5.
6
5
The observed vicinal coupling constants about C(2)-C(3) bond are 6.41
and 5.63 Hz. In 5D and 5E the Jtrans value about C(2)-C(3) bond is high. Only
in 5F both vicinal coupling constants about C(2)-C(3) bond will be low and
almost equal. Hence, it is obvious that the higher value (6.41 Hz) must

2
3
ACCEPTED MANUSCRIPT
correspond to Jtrans value and the low value (5.63 Hz) must correspond to Jcis
value.
The observed vicinal coupling constants about C(5)-C(6) bond are 6.73
and 4.49 Hz. In 5D and 5E both vicinal coupling constants about C(5)-C(6)
bond will be almost equal. In 5F the Jtrans value about C(5)-C(6) bond is high.
Hence, it is obvious that the higher value (6.73 Hz) must correspond to Jtrans
value and the low value (4.49 Hz) must correspond to J value.
cis
The observed Jtrans value about C(2)-C(3) bond and C(5)-C(6) bond are
almost equal. This shows that the total contribution of 5D and 5E should be
equal to that of 5F. In other words conformation 5F should be more stable
than conformations 5D and 5E.
In 5D one phenyl group is in boat-equatorial position and the other
phenyl group is in flagpole position. In conformation 5E one phenyl group is
in the boat-equatorial position and the other phenyl group is in boat-axial
position. Since, phenyl group prefers flagpole position over boat-axial position
5D should be more stable than 5E.
In 5D there should be small allylic strain between nitroso group and H-
. In 5E and 5F there should be small allylic strain between NO of NOH and
6
one proton at C-5. Such interactions are not present in 6C and 6D. Hence, the
anti isomer 6 is more populated than the syn isomer 5.

2
4
ACCEPTED MANUSCRIPT
1
3
The C NMR signals were assigned by using HMQC spectrum (Plate-3).
Plate-3: HMQC Spectrum of compound 1

2
5
ACCEPTED MANUSCRIPT
1
3
The C chemical shifts are given in Table-5.
Table-5
The carbon chemical shifts of 5 and 6, ppm
C-2 C-3 C-4 C-5 C-6 ipso
56.2 33.9 153.6 28.1 59.2 138.0 126.3, 126.5,
61.0 33.7 26.7 50.2
b
Aromatic
Major 6
Minor 5
1
1
1
1
27.2, 127.3,
a
a
27.5, 127.9,
28.3, 128.4,
28.8
a Signals were weak and could not be detected
b
For both forms
Generally, the introduction of the NO group at the amino nitrogen
2
5
causes a strong upfield shift of syn α-carbon. In 5 the benzylic carbon C-6 is
syn to the nitroso group and the benzylic carbon C-2 is anti to the nitroso
group. If the assigned configuration is correct C-6 should be shielded relative
to C-2. It is found that in 5 the chemical shifts of C-2 and C-6 are 61.0 and
50.2 ppm respectively. This is in accord with the configuration of 5.
In 6 the benzylic carbon C-2 is syn to the nitroso group and the
benzylic carbon C-6 is anti to the nitroso group. If the assigned configuration
is correct C-2 should be shielded relative to C-6. It is found that in 6 the
chemical shifts of C-2 and C-6 are 56.2 and 59.2 ppm respectively. This is in
accord with the configuration of 6.

2
6
ACCEPTED MANUSCRIPT
However, the chemical shift difference between the syn α and anti α
benzylic carbons in 5 is higher (10.8 ppm) than that in 6
(3 ppm). This can be explained as follows.
In N-nitroso-r(2),c(6)-diphenylpiperidin-4-one [21,22] the benzylic
carbon syn to the nitroso group absorbs at 53.8 ppm and the benzylic carbon
anti to the nitroso group absorbs at 60.3ppm. This indicates that due to
nitrososation the syn α- carbon is shifted upfield by about 6 ppm.
In r(2),c(6)-diphenylpiperidin-4-one oxime [19] the benzylic carbon
(C-6) syn to the hydroxylic group absorbs at 60.6 ppm and the benzylic carbon
anti to the hydroxylic group(C-2) absorbs at 61.9 ppm. This indicates that due
to oximation the benzylic carbon syn to the hydroxylic group is shielded
slightly relative to the benzylic carbon anti to the hydroxylic group.
In 5 the C-6 benzylic carbon is syn to both hydroxylic and nitroso
groups. Therefore, the shieldings of syn-α carbon due to nitroso group and
hydroxylic groups are in the same direction. Due to this in 5 the chemical shift
difference between the syn α - and anti α-benzylic carbons is high (10.8 ppm).

2
7
ACCEPTED MANUSCRIPT
In 6, the C-2 benzylic carbon is syn to nitroso group and anti to
hydroxylic group. The C-6 benzylic carbon is anti to nitroso group and syn to
hydroxylic group. Here, the nitroso group shields the C-2 benzylic carbon and
the hydroxylic group shields the C-6 benzylic carbon. Since, the shielding
effect of nitroso group (about 6 ppm) is higher than that due to hydroxylic
group (about 1 ppm) the C-2 benzylic carbon is more shielded than C-6. Due
to the opposite directions of shielding due to nitroso and hydroxylic groups the
chemical shift difference between the syn α- and anti α- benzylic carbons in 6
is smaller (3 ppm) than that in 5 (10.8 ppm).
t(3)-Alkyl-N-nitroso-r(2),c(6)-diphenylpiperidin-4-one oximes
t(3)-Alkyl-N-nitroso-r(2),c(6)-diphenylpiperidin-4-one oximes have
been synthesized using Scheme 1. Though there is a possibility of getting two
isomers during oximation only a single compound was obtained under the
experimental conditions. Hence, the compound formed must have E-
configuration as shown in Scheme1. This assignment is substantiated by the
following observations.
Baliah et al.[26] have reported that in the preparation of oximes from
t(3)-alkyl-N-nitroso-r(2),c(6)-diphenylpiperidin-4-ones only one isomer (E-
isomer) is formed. This isomer has the OH group anti to C-3. The
configuration has been proved by Beckmann rearrangement (Scheme-2).
Further, it has been substantiated by NMR spectral study [19].

2
8
ACCEPTED MANUSCRIPT
Scheme -2
HO
N
2
R
O
H
N
Bechmann
Rearrangement
2
2
O
1
R
R
R
1
Oximation
1
R
R
Ph
Ph
N
H
Ph
Ph
N
H
Ph
N
H
Ph
HCl /H O Hydrolysis
2
2
R
1
R
NH2
NH2
PhCH=CHCOOH
+
Ph
H
Smith and Amezcua [27] have reported that in the preparation of
oxime from menthone (13) only E-isomer is formed.
HO
N
CH3
O
CH3
CH3
Oximation
CH3
H C
H C
3
3
Menthone
Methone oxime
E-isomer
(
13)