Crystal structure of 2,6-diphenyl-3-methyl-N-nitrosopiperidin-4-one

Article abstract of DOI:10.1016/j.molstruc.2009.10.021

The structure of the 2,6-diphenyl-3-methyl-N-nitrosopiperidin-4-one (C₁₈H₁₈N₂O₂) has been investigated in solution and in the solid state by IR, NMR and X-ray methods. The crystal belongs to the monoclinic space

Full text of DOI:10.1016/j.molstruc.2009.10.021

Journal of Molecular Structure 963 (2010) 111–114
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Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Crystal structure of 2,6-diphenyl-3-methyl-N-nitrosopiperidin-4-one
*
T. Hemalatha, S. Nagarajan
Department of Chemistry, Annamalai University, Annamalainagar, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 August 2009
Received in revised form 13 October 2009
Accepted 14 October 2009
Available online 21 October 2009
The structure of the 2,6-diphenyl-3-methyl-N-nitrosopiperidin-4-one (C18H18N2O2) has been investi-
gated in solution and in the solid state by IR, NMR and X-ray methods. The crystal belongs to the mono-
clinic space group P21/n with a = 7.7134(6), b = 14.7754(14), c = 27.321(3) Å and b = 94.617(3)°. In crystal
structure, the piperidine ring adopts a boat conformation with a slight distortion. One of the phenyl
groups is in axial orientation, while the other phenyl and methyl groups are in equatorial orientations.
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
Piperidone
N-Nitrosopiperidone
Conformations
Crystal structure
1. Introduction
dered rotation around the N–N bond in N-nitroso group. Due to the
restricted rotation of N N O bond, the N-nitrosopiperidones are
Nitrogen based heterocyclic compounds are very important in
the field of medicinal chemistry. Compounds including 2,6-disub-
stituted derivatives have been reported as tranquillizers and pos-
ses hypotensive activity as well as bactericidal, fungicidal and
herbicidal activities. The nitroso group introduced at the nitrogen
atom profoundly affects the biological activity and conformation
of the piperidone ring and the orientation of substituents [1–3].
Many nitrosoamines are known to possess antitumour activity
and are used as antitumour agents or antibiotics.
The preferred conformation of all the piperidine and piperidone
precursors has been shown to be the chair conformation with a
slight flattening or distortion of the ring depending upon the posi-
tion and size of the substituents [4]. The introduction of nitroso
group at the nitrogen position is known to exert a large influence
on the conformation of the piperidine ring and orientation of the
ring substituents [5]. In this investigation, we report here the crys-
tal structure of 2,6-diphenyl-3-methyl-N-nitrosopiperidin-4-one
(NOMPO).
unsymmetrical and exist in syn and anti forms (Fig. 2).
The 1H NMR spectrum shows two sets of signals corresponding
to syn and anti isomers. The two forms arise due to the restricted
rotation of planar N N O group around C2–N–C6 plane. These
two sets of signals are selectively separated with the help of
NMR peak integration values. The signals with high integration
values correspond to anti isomer and those with low integration
values correspond to syn isomer. In syn form, the nitroso group
experiences steric interference with ring protons. Hence the energy
of syn form is higher, thus leading to smaller populations and thus
low integration values are obtained in 1H NMR spectrum. On the
other hand, in anti form, the nitroso group is far from the ring pro-
tons, here there is no pseudoallelic strain between the heterocon-
jugate group (N N O) and the anti side proton. Hence the energy
of anti form is lower, thus leading to higher populations and thus
higher integration values are obtained in 1H NMR spectrum.
The crystal structure shows the bond lengths and bond angles
of the molecule, the values are in agreement with the values re-
ported for 3,5-dimethyl-2,6-diphenylpiperidin-4-one oxime and
other related structures [7–10]. The carbonyl oxygen bond length
(C@O) 1.213(3) Å is comparable with the average value of
1.218(3) Å reported elsewhere [11,12]. As expected, it is known
from the conformation angles and least-square planes that the
piperidine ring adopts a distorted boat conformation. C2 and C5
atoms deviate in the same direction from the best plane of the
piperidine rings N1, C1, C3 and C4 in contrast to the parent piperi-
done (without nitroso group).
2. Results and discussion
The 4-piperidone is prepared from benzaldehyde, ethyl methyl
ketone and ammonium acetate in ethanol. 2,6-Diphenyl-3-methyl-
N-nitrosopiperidin-4-one (Fig. 1) was obtained by nitrosation
using sodium nitrite [6]. In the N-nitroso compounds the partial
double bond character between two nitrogen atoms results in hin-
The methyl group in the third position is in the equatorial posi-
tion. The corresponding torsion angle is (N1–C1–C2–C18)
166.6°(2). The phenyl rings at C5 in axial and C1 in the equatorial
* Corresponding author. Tel.: +91 94430 46272.
E-mail address: nagarajan.au@gmail.com (S. Nagarajan).
0022-2860/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2009.10.021

112
T. Hemalatha, S. Nagarajan / Journal of Molecular Structure 963 (2010) 111–114
C2
O
C5
C3
-0.7(4)
6.1(3)
C4
N
N1
C1
NO
Fig. 3. The conformational angles (°) of the piperidine ring.
Fig. 1. 2,6-Diphenyl-3-methyl-N-nitrosopiperidin-4-one.
position (Fig. 4) with their torsion angles C3–C4–C5–C12 and C3–
C2–C1–C6 being equaled to À83.2(3)° and 166.5(2)°, respectively.
The piperidine ring system offers a wide variety of conformational
flexibility such as chair, boat and twist conformations [13,14].
However, the chair or slightly distorted chair conformation has
been found to be the most favoured [15,16]. The conformational
angle (°) of the piperidine ring is shown in Fig. 3.
A literature survey on the conformation of 2,6-dialkyl-N-nitros-
opiperidines and related compounds suggested two possibilities
for the conformation of N-nitroso-2,6-diphenylpiperidine, in which
the phenyl group might have occupied the axial positions when the
nitroso group is coplanar to the best plane of the piperidine ring (I).
The phenyl ring could occupy the equatorial positions and the ni-
troso group would then have to adopt a perpendicular orientation
to avoid steric interaction (II). The 2,6-diphenyl-3-methyl-N-
nitrosopiperidin-4-one falls in neither category I nor II but forms
a unique conformation with axial and equatorial substituted phe-
nyl groups.
Due to delocalization of lone pair of electrons of nitrogen atom
with hetero p-electron system of the carbonyl and nitroso groups,
a partial double bond character at the N–C and N–N bonds is devel-
oped. This double bond character restricts the N–C and N–N free
rotation resulting in two different orientations [17,18] namely, pla-
nar and perpendicular (syn and anti) with respect to the best plane
of the piperidine ring, irrespective of the nature and size of substit-
uents at second and sixth positions [19–22].
The ORTEP of the molecule is shown in Fig. 4 and powder XRD
of NOMPO is shown in Fig. 5. Packing of the molecules viewed
along b-axis and c-axis is shown in Figs. 6 and 7, respectively.
2,6-Diphenyl-3-methyl-N-nitrosopiperidin-4-one, the nitroso
group is oriented syn to the C1 (C1–N1–N2–O1) = À3.7(4)°) and
anti to the C5 (C5–N1–N2–O2 = À176.2(2)°) atoms of the piperi-
dine ring. This can be termed as a syn–anti conformation of the ni-
troso group. In this study, the torsion angles, asymmetry
parameters and least-square planes show that the piperidine ring
adopts a boat conformation with a slight distortion.
Fig. 4. ORTEP of the molecule.
3. Experimental
IR spectrum was recorded with AVATAR 330 FT-IR spectrometer
using KBr pellet. The frequencies corresponding to the functional
groups are assigned. The 1H and 13C NMR spectra were recorded
on a Bruker 400 MHz instrument in CDCl3 solution with TMS as
an internal standard.
3.1. Crystal structure determination and refinement
The compound is crystallized in ethanol by slow evaporation
method at room temperature. The intensity data were collected
on a Bruker AXS (Kappa Apex II) X-ray diffractometer, equipped
O
O
O
N
N
N
N
N
N
O
O
R
R
Ph
N
Ph
O
N
Ph
Ph
N
N
syn
O
anti
Fig. 2. N–NO partial double bond character: syn and anti forms.

T. Hemalatha, S. Nagarajan / Journal of Molecular Structure 963 (2010) 111–114
113
Fig. 5. Powder XRD of the molecule.
SHELXS-97 and SHELXL-97 modules. Molecular graphics was per-
formed by ORTEP 3 and mercury. The plot for the structures was
created with DIAMOND software. The crystal data and structure
refinement detail of 2,6-diphenyl-3-methyl-N-nitrosopiperidin-4-
one are given in Table 1. The atomic coordinates of non-hydrogen
atoms with their equivalent displacement parameters are given in
Table 2. The table in the supplementary material lists the bond
length, bond angles and some selected torsion angles of interest.
The compound was prepared by using the method proposed in
our previous research paper [6]. The compound shows strong
absorption band at 1654–1714 cmÀ1 which shows the presence
of a cyclic ketone. The peaks observed at 1654–1439, 2935 and
1601 cmÀ1 represent aromatic C–C, methyl C–H and N@O,
respectively.
1H NMR (400 MHz, CDCl3): syn isomer d (ppm) = 5.24 (d,
10.1 Hz, H-2), 6.06 (t, 6.68 Hz, H-6), 1.15 (d, 7.16 Hz, CH3); anti iso-
mer d (ppm) = 5.93 (d, 6.24, H-2), 6.39 (dd, 6.82 Hz, 3.54 Hz, H-6),
Fig. 6. Packing of NOMPO along b-axis.
Table 1
Crystal data and summary of intensity data collection and structure refinement.
Parameters
NOMPO
Empirical formula
Colour/shape
C18H18N2O2
Colourless/needle
249.34
715,906
293(2)
Formula weight
CCDC deposit No.
Temperature (K)
Crystal system
Space group
Monoclinic
P21/n
Cell constants
a (Å)
b (Å)
7.7134(6)
14.7754(14)
27.321(3)
94.617(3)
3103.6(5)
8
c (Å)
b (°)
Volume (Å3)
Molecules/cell (2)
Calculated density (mg/m3)
Absorption coefficient (mmÀ1
Crystal size (mm)
F(0 0 0)
1.260
0.083
)
0.3 Â 0.05 Â 0.05
1248
Reflections collected
Unique reflections
Parameters refined
17,851
2865
400
Fig. 7. Packing of NOMPO along c-axis.
Goodness of fit (Fo2
R1
)
1.157
0.0414
0.1086
À0.227
0.272
WR2
with a graphite monochromated Mo K
a
radiation (k = 0.71073 Å).
qmm (e/Å3)
q(max) (e/Å3)
The crystal structure of NOMPO was solved and refined by full ma-
trix least squares on F2 with Wingx software package utilizing

114
T. Hemalatha, S. Nagarajan / Journal of Molecular Structure 963 (2010) 111–114
Table 2
nyl groups in the molecule is in the axial orientation, while the
other phenyl and methyl groups are in the equatorial orientations.
Atomic coordinates (Å Â 104) and equivalent isotropic displacement parameters
(Å2 Â 103) for the non-hydrogen atoms.
Atom
X
Y
Z
U(eq)
Appendix A. Supplementary data
C1
C2
C3
C4
C5
C6
C7
C8
11,266(3)
12,922(3)
14,352(4)
14,658(4)
13,480(3)
10,022(3)
8489(4)
7385(4)
7787(5)
9297(5)
10,421(4)
13,970(4)
13,027(4)
13,362(4)
14,627(5)
15,594(5)
15,287(4)
12,500(4)
11,706(3)
10,537(4)
9075(3)
434(2)
457(2)
6196(1)
5923(1)
6163(1)
6710(1)
6958(1)
6022(1)
5756(1)
5562(1)
5631(1)
5898(1)
6093(1)
6979(1)
7266(1)
7303(1)
7048(2)
6769(1)
6739(1)
5386(1)
6731(1)
7042(1)
6846(1)
5930(1)
43(1)
44(1)
52(1)
60(1)
48(1)
45(1)
61(1)
79(1)
78(1)
75(1)
60(1)
44(1)
54(1)
64(1)
73(1)
79(1)
62(1)
67(1)
45(1)
59(1)
71(1)
75(1)
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.molstruc.2009.10.021.
À116(2)
À64(2)
580(2)
1173(2)
945(2)
1606(4)
2501(3)
2733(3)
2669(2)
1568(2)
2124(2)
3032(3)
3405(3)
2868(3)
1944(2)
213(2)
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C11
C12
C13
C14
C15
C16
C17
C18
N1
N2
O1
435(2)
252(2)
100(2)
À599(2)
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0.9140 (d, 6.72 Hz, CH3). 13C NMR (400 MHz, CDCl3): syn isomer d
(ppm) = 59.6 (C-2), 53.2 (C-6), 14.3 (CH3); anti isomer
d
(ppm) = 66.8 (C-2), 62.1 (C-6), 12.1 (CH3).
4. Conclusion
2,6-Diphenyl-3-methyl-N-nitrosopiperidin-4-one crystal is
with monoclinic space group. The crystal structure proves that
the piperidine ring adopts a boat conformation with a slight distor-
tion rather than the expected chair conformation. One of the phe-