Synthesis, spectral and structural studies of alkyl 2-(3-alkyl-2,6-diarylpiperidin-4-ylidene)hydrazinecarboxylate derivatives: Crystal and molecular structure of methyl 2-(3-methyl-2,6-diphenylpiperidin-4-ylidene)hydrazinecarboxylate

Article abstract of DOI:10.1016/j.molstruc.2016.02.003

An efficient synthetic route with good overall yields to synthesize alkyl 2-(3-alkyl-2,6-diarylpiperidin-4-ylidene)hydrazinecarboxylates (7-14) is reported. All the synthesized compounds were characterized by their analytical and spectral (IR, ¹H, ¹³C and 2D NMR) data. Single crystal X-ray structural analysis of compound 7, evidences that the configuration about C=N double bond is syn to C5 carbon (E-form) and exists in normal chair conformation with equatorial orientations of all the substituents.

Full text of DOI:10.1016/j.molstruc.2016.02.003

Accepted Manuscript
Synthesis, spectral and structural studies of 3-alkyl-2,6-diarylpiperidin-4-
ylidene)hydrazinecarboxylate derivatives: Crystal and molecular structure of methyl 2-
(3-methyl-2,6-diphenylpiperidin-4-ylidene)hydrazinecarboxylate
C. Udhaya Kumar, A. Sethukumar, M. Velayutham Pillai, B. Arul Prakasam, C.
Ramalingan, T. Vidhyasagar
PII:
S0022-2860(16)30097-7
10.1016/j.molstruc.2016.02.003
MOLSTR 22212
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 22 July 2015
Revised Date: 1 February 2016
Accepted Date: 1 February 2016
Please cite this article as: C. Udhaya Kumar, A. Sethukumar, M. Velayutham Pillai, B. Arul Prakasam, C.
Ramalingan, T. Vidhyasagar, Synthesis, spectral and structural studies of 3-alkyl-2,6-diarylpiperidin-4-
ylidene)hydrazinecarboxylate derivatives: Crystal and molecular structure of methyl 2-(3-methyl-2,6-
diphenylpiperidin-4-ylidene)hydrazinecarboxylate, Journal of Molecular Structure (2016), doi: 10.1016/
j.molstruc.2016.02.003.
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Graphical Abstract
R''
O
O
HN
N
R'
N
H
R
R
O
CHO
R
CHO
R
R'
H3C
R''
O
+
O
NH4OAc
HN
N
R'
N
Compound 7
CH3
R
R

ACCEPTED MANUSCRIPT
Synthesis, spectral and structural studies of 3-alkyl-2,6-diarylpiperidin-4-
ylidene)hydrazinecarboxylate derivatives: Crystal and molecular structure of methyl 2-
(3-methyl-2,6-diphenylpiperidin-4-ylidene)hydrazinecarboxylate
*
C. Udhaya Kumar a,b, A. Sethukumara, M. Velayutham Pillaib, B. Arul Prakasama, C.
Ramalinganb, T. Vidhyasagara
aDepartment of Chemistry, Annamalai University, Annamalainagar, 608 002 Chidambaram,
India
bDepartment of Chemistry, Kalasalingam University, Krishnankovil, 626 126 Srivilliputtur,
India.
ABSTRACT
An efficient synthetic route with good overall yields to synthesize 3-alkyl-2,6-
diarylpiperidin-4-ylidene)hydrazinecarboxylates (7-14) is reported. All the synthesized
1
compounds were characterized by their analytical and spectral (IR, H, 13C and 2D NMR)
data. Single crystal X-ray structural analysis of compound 7, evidences that the configuration
about C=N double bond is syn to C5 carbon (E-form) and exist in normal chair conformation
with equatorial orientations of all the substituents.
Keywords: Hydrazinecarboxylate, HSQC, HMBC, Single crystal XRD
1. Introduction
Heterocyclic systems have been used as an important scaffold for designing new
molecules. It is well known that molecules containing nitrogen and sulphur hetero atoms
exhibit a variety of biological activities [1-3]. Piperidine heterocycles play an important role
in the field of medicinal chemistry.[4] Among the enormous number of biologically relevant
piperidones, the 2,6-diaryl substituted piperidine nucleus has emerged as one of the most
* Corresponding author. Tel.: +91 9786616333.
E-mail address: udkchemist@gmail.com (C. Udhaya Kumar).

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widely studied molecular substructures. Along with the related 2,6-diarylpiperidin-4-one
systems, these heterocycles represent architectures found in many important nitrogen and
oxygen containing natural products. Functionalized piperidones have enormous medicinal
properties. Piperidones are important synthetic construction blocks to an extensive number of
pharmacologically active agents. This pharmacophore is most remarkably established in
many CNS [5], antiallergic [6] and cardiovascular agents [7].
Hydrazones are important compounds for drug design and also for the preparation of
heterocyclic rings. They are a significant class of chemical intermediates, which can act as
electrophiles and as nucleophiles in Mannich-type reactions. These scaffolds display various
biological properties, such as antimicrobial [8], anti-inflammatory [9] analgesic [10] and
antipyretic [11]. Some of the hydrazine carboxylate moieties are extensively used in synthesis
of peptide and azapeptide [12].
In continuation of our work, we wish to report a new series of 2,6-diarylpiperidin-4-
ylidene hydrazinecarboxylates and their characterization by IR, NMR (1H, 13C, HSQC and
HMBC) spectra and single crystal X-ray diffraction techniques.
2. Experimental
All chemicals were obtained from commercial suppliers and used without further
purification. Melting points were determined on open capillary tubes and are uncorrected. IR
spectra were recorded on Thermo Nicolet FT-IR spectrophotometer (range 4000–400 cm-1) as
a KBr pellet. Proton NMR spectra were recorded at room temperature (298 K) on Bruker
AMX-400 spectrometer operating at 400.23 MHz using TMS as internal reference. 13C NMR
spectra were recorded in proton decoupled mode on Bruker AMX-400 spectrometer
operating at 100.63 MHz.

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2.1. General procedure
Synthesis of 1-methyl-3-alkyl-2,6-diarylpiperidin-4-ylidene)hydrazinecarboxylate (7-14)
The parent 2,6-diarylpiperidin-4-ones (1-6) were synthesized through Mannich
reaction by adopting literature method.[13,14] 3-alkyl-2,6-diarylpiperidin-4-one (1 mmol)
and acetic acid were stirred in absolute ethanol for 15min in ice cold condition. Then,
corresponding alkyl carbazate (1.5 mmol) was added and stirred for an additional 45 min.
After completion of the reaction, the reaction mixture was poured into ice cold water (50
mL). The resulting precipitate was collected by filtration and washed with a large portion of
cold water and the precipitate was collected. The crude product was recrystallized from
ethanol (Scheme 1). Characterization data for compounds (7-14) as follow.
2.1.1. methyl 2-(3-methyl-2,6-diphenylpiperidin-4-ylidene)hydrazinecarboxylate (7) White
solid, mp: 142–144 °C; yield: 89%; IR (KBr, cm-1): 3309, 3252 (NH), 1701 (C=O), 1605
1
(C=N); H NMR (400 MHz, CDCl3, ppm)δ: 7.49-7.28 (m, 10H, Ar), 7.81 (s,1H, NH), 2.85-
2.82 (d, 1H, H2, J=12Hz), 3.59-3.57 (d, 1H, H5e, J=8Hz), 2.61-2.57 (m, 1H, H3), 2.57-2.19
(q, 1H, H5a), 3.91-3.88 (dd, 1H, H6, J=11.6Hz), 0.99 (d, 3H, 3CH3, J=5.2Hz), 3.80 (s, 3H,
H10); 13C NMR (δ): 143.1, 142.6, 141.9, 128.6, 128.6, 128.5, 128.4, 128.0, 127.9, 127.8,
127.8, 127.7, 126.6, 126.5, 69.2, 61.0, 52.8, 45.1, 35.6, 12.1.
2.1.2. ethyl 2-(3-methyl-2,6-diphenylpiperidin-4-ylidene)hydrazinecarboxylate (8) White
solid, mp: 146–148 °C; yield: 86%; IR (KBr, cm-1): 3309, 3252 (NH), 1700 (C=O), Around
1
1600 (C=N); H NMR (400 MHz, CDCl3, ppm)δ: 7.44-7.25 (m, 10H, Ar), 8.05 (s,1H, NH),
3.69-3.67 (d, 1H, H2, J=8Hz), 2.86 (d, 1H, H5e, J=8Hz), 2.46-2.41 (m, 1H, H3), 2.14-2.12
(q, 1H, H5a), 3.88-3.84 (dd, 1H, H6, J=12Hz), 0.85-0.81 (t, 3H, J=5.2Hz), 1.74-1.67 (m, 1H,
13
H7b), 1.32-1.26 (m, 1H, H7a), 3.74 (s, 3H, H10); C NMR (δ): 143.2, 142.7, 128.6, 128.4,
128.0, 127.8, 127.8, 126.6, 67.5, 60.7, 52.8, 51.8, 35.9, 19.4, 12.0.

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2.1.3. methyl 2-(1,3-dimethyl-2,6-diphenylpiperidin-4-ylidene)hydrazinecarboxylate (9)
White solid, mp: 140–142 °C; yield: 80%; IR (KBr, cm-1): 3238, 3142 (NH), 1692 (C=O),
1
1601 (C=N); H NMR (400 MHz, CDCl3, ppm)δ: 7.46-7.28 (m, 10H, Ar), 7.80 (s,1H, NH),
2.79 (d, 1H, H2), 2.94-2.92 (d, 1H, H5e, J=8Hz), 2.73-2.67 (m, 1H, H3), 2.38-2.31 (q, 1H,
H5a), 3.19-3.23 (dd, 1H, H6, J= J=11.6Hz Hz), 0.90 (d, 3H, 3CH3, J=6.4Hz), 1.73 (s, 3H, N-
CH3) 3.79 (s, 3H, H10); 13C NMR (δ): 143.7, 142.8, 128.8, 128.4, 128.1, 127.6, 127.4, 127.1,
69.2, 61.7, 52.8, 45.1, 41.5, 36.1, 12.9.
2.1.4. methyl 2-(1,3-dimethyl-2,6-diphenylpiperidin-4-ylidene)hydrazinecarboxylate (10)
White solid, mp: 148–150 °C; yield: 84%; IR (KBr, cm-1): 3224, 3139 (NH), 1693 (C=O),
1
Around 1600 (C=N); H NMR (400 MHz, CDCl3, ppm)δ: 7.45-7.26 (m, 10H, Ar), 7.81
(s,1H, NH), 2.85-2.82 (d, 1H, H2, J=12Hz), 3.08-3.06 (d, 1H, H5e, J=8Hz), 2.53 (m, 1H,
H3), 2.35-2.32 (q, 1H, H5a), 3.26-3.23 (dd, 1H, H6, J=11.6Hz), 0.81 (d, 3H, 3CH3), 1.71 (s,
13
3H, N-CH3), 1.29-1.26 (t, 3H, CH3), 4.20-4.19 (d, 2H, OCH2); C NMR (δ): 143.8, 142.8,
128.8, 128.4, 128.1, 127.6, 127.4, 127.1, 69.1, 61.7, 52.9, 45.1, 41.5, 36.1, 14.5, 12.9.
2.1.5. methyl 2-(3-ethyl-1-methyl-2,6-diphenylpiperidin-4-ylidene)hydrazinecarboxylate (11)
White solid, mp: 144-146 °C; yield: 80%; IR (KBr, cm-1): 3298, 3238, 3142 (NH), 1695
(C=O), 1602 (C=N); 1H NMR (400 MHz, CDCl3, ppm)δ: 7.43-7.26 (m, 10H, Ar), 7.79 (s,1H,
NH), 2.76-2.73 (d, 1H, H2, J=12Hz), 3.08-3.06 (d, 1H, H5e, J=8Hz), 2.58-2.54 (m, 1H, H3),
2.35-2.29 (q, 1H, H5a), 3.26-3.22 (dd, 1H, H6, J=11.6Hz), 0.89 (t, 3H, J=8Hz) 1.25-1.17 (m,
1H, 3CH2), 1.75 (m, 1H, 3CH2), 1.71 (s, 3H, N-CH3), 3.77 (s, 3H, OCH3); 13C NMR (δ):
144.5, 144.0, 128.8, 128.4, 127.7, 127.4, 127.1, 71.6, 65.3, 56.3, 42.0, 36.0, 30.7, 29.7, 21.5,
19.4.
2.1.6. ethyl 2-(3-ethyl-1-methyl-2,6-diphenylpiperidin-4-ylidene)hydrazinecarboxylate (12)
White solid, mp: 144-146 °C; yield: 80%; IR (KBr, cm-1): 3252, 3142 (NH), 1690 (C=O),

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1
1600 (C=N); H NMR (400 MHz, CDCl3, ppm)δ: 7.45-7.26 (m, 10H, Ar), 7.80 (s,1H, NH),
2.78-2.75 (d, 1H, H2, J=12Hz), 3.11-3.08 (d, 1H, H5e, J=8Hz), 2.57 (s, 1H, H3), 2.35 (s, 1H,
H5a), 3.29-3.25 (dd, 1H, H6, J=11.6Hz), 0.81 (d, 3H, J=6.4Hz), 1.33-1.29 (t, 3CH3), 1.75 (s,
3H, N-CH3), 4.27-4.23 (q, 2H, OCH2); 13C NMR (δ): 143.9, 143.0, 128.7, 128.4, 128.2,
127.6, 127.4, 17.1, 75.7, 68.9, 61.6, 51.9, 41.5, 36.3, 20.2, 14.5, 11.9.
2.1.7..methyl
2-(2,6-bis(4-methoxyphenyl)-1,3-dimethylpiperidin-4-
ylidene)hydrazinecarboxylate (13) White solid, mp: 140-142 °C; yield: 82%; IR (KBr, cm-1):
1
3234, 3128 (NH), 1691 (C=O), 1603 (C=N); H NMR (400 MHz, CDCl3, ppm)δ: 7.34-6.87
(m, 8H, Ar), 7.73 (s,1H, NH), 2.73-2.70 (d, 1H, H2, J=14Hz), 2.85-2.82 (d, 1H, H5e,
J=12Hz), 2.64-2.60 (m, 1H, H3), 2.33-2.26 (q, 1H, H5a), 3.13 (dd, 1H, H6, J=11.6Hz), 0.88
(d, 3H, J=2.4Hz), 3.79 (t, 3CH3), 1.69 (s, 3H, N-CH3), 4.27-4.23 (q, 2H, OCH2), 3.79 (s, 6H,
OCH3); 13C NMR (δ): 159.0, 158.8, 135.9, 135.0, 129.0, 128.1, 114.1, 113.7, 68.5, 55.3, 55.2,
52.8, 45.2, 41.2, 36.2, 12.9.
2.1.8.
ethyl
2-(2,6-bis(4-methoxyphenyl)-1,3-dimethylpiperidin-4-
ylidene)hydrazinecarboxylate (14) White solid, mp: 142-144 °C; yield: 86%; IR (KBr, cm-1):
1
3240, 3131 (NH), 1693 (C=O), Around 1600 (C=N); H NMR (400 MHz, CDCl3, ppm)δ:
7.27-6.79 (m, 8H, Ar), 7.70 (s,1H, NH), 2.67-2.64 (d, 1H, H2, J=12Hz), 2.77-2.75 (d, 1H,
H5e, J=12Hz), 2.57-2.50 (m, 1H, H3), 2.24-2.18 (q, 1H, H5a), 3.06-3.02 (dd, 1H, H6,
J=11.6Hz), 0.88 (d, 3H, J=6.4Hz), 1.22-1.19 (t, 3H, CH3), 4.14-4.13 (q, 2H, OCH2), 1.61 (s,
3H, N-CH3), 3.73 (s, 6H, OCH3); 13C NMR (δ): 159.0, 158.8, 136.0, 135.1, 129.0, 128.1,
114.0, 113.7, 68.5, 61.6, 55.3, 55.2, 45.2, 41.3, 36.2, 14.5, 12.9.
2.2. X-ray crystallography
Crystal was grown by slow evaporation technique using ethanol as solvent.
Diffraction data were collected on a Oxford Diffraction diffractometer using Cu–Kα radiation

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(λ = 1.54184 Å) at 293 K with a crystal size of 0.20 x 0.18 x 0.16 mm. The structure was
solved by direct methods and successive Fourier difference syntheses (SHELXS–97) [15] and
refined by full matrix least square procedure on F2 with anisotropic thermal parameters. All
non-hydrogen atoms were refined (SHELXL–97) [16] and placed at chemically acceptable
positions. A total of 736 parameters were refined with 6525 unique reflections which covered
the residuals to R1 = 0.0699. Crystallographic data have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publications number CCDC 1000037 for 7.
Copies
of
the
data
can
be
obtained
free
of
charge
via
http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033: or e-mail:
deposit@ccdc.cam.ac.uk.
3. Results and discussion
3.1. IR spectral analysis of compounds (7-14)
IR spectra of the synthesized compounds (7-14) showed the presence of new νC=O
band in the region of 1692–1721 cm-1 and the target compounds were confirmed by the
presence of hydrazone N–H stretching frequency around 3422–3128 cm-1. The absorption
band for
C=N group appeared around 1600–1605 cm-1 The absorption bands observed in the
.
ν
region 3060–2873 cm-1 are ascribed due to the aromatic and aliphatic C–H vibrations.
3.2. NMR spectra
3.2.1. 1H NMR spectral analysis of compound 8
1H NMR spectrum of compound 8 is taken as a representative (Fig. 1). The
numbering of carbons is shown in Scheme 2 and the protons are numbered accordingly. The
1
signals in the H NMR spectrum were assigned based on their positions, multiplicities and
integration. The coupling constants of H5 and H6 bonds could not be extracted due to slight

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broadening of the signal in most of the cases. The broadening is probably due to the amido-
imidol tatutomerism present in the hydrazones. A broad singlet appeared at 8.05 ppm might
be due to the amide proton. The signals in the 7.44-7.25 ppm range are due to aromatic
protons. The signals at H7a and H7b proton appeared around 1.74-1.67 and 1.32-1.26 ppm.
The equatorial proton peak of H5e observed at 2.86 ppm is appeared as a broad singlet
instead of doublet of doublets and the axial proton peak of H5a is observed at 2.19-2.12 ppm
as a triplet. The H6 proton appeared at 3.88-3.84 ppm as a doublet of doublets with coupling
constant value of 12.0 Hz. One proton peak of H2 appears at 3.69-3.67 ppm as a doublet with
coupling constant value of 8.0 Hz due to the presence of one proton (H3). The signal of H3
proton is observed at 2.46-2.41 ppm as a multiplet. The methoxy proton of H10 appeared at
3.74 ppm as a singlet. Piperidine NH proton appeared as a broad singlet at 1.90 ppm.
3.2.2. 13C NMR spectral analysis of compound 8
13C NMR compound 8 is taken as a representative (Fig. 2). The aromatic carbons
absorbed in the range of 128.6-126.6 ppm and ipso carbons of the two phenyl groups
absorbed at 143.2 and 142.7 ppm respectively. The methyl group at carbon C8 is observed at
12.0 ppm. The piperidine ring carbons of compound 8, the C2 and C6 carbons are observed
in the downfield region at 67.5 and 60.7 ppm respectively. The C3 and C5 carbons are
observed in the upfield region at 51.8 and 35.9 ppm respectively. The C7methylene carbon is
13
observed at 19.4 ppm. The methyl group of C10 carbazate appeared at 52.8. The C NMR
signals for all the carbon atoms appeared as expected. However, the signals due to C=O and
C=N carbon signals are very weak and difficult to be detected. Similar observation was
experienced for some hyrazone derivatives earlier [17]. It is also observed that, 13C NMR
spectrum of alkyl cabazates dose not show any carbonyl (C=O) carbon signals [18-20].
3.2.3. 2D NMR spectral analysis of compound 8
HSQC

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In the HSQC spectrum of compound 8 (Fig. 3), the 13C signal at 12.0 ppm has a cross
peak with the proton resonance at 0.83 ppm. The triplet at 0.83 ppm is designated for the
methyl proton, and hence the signal at 12.0 ppm is assigned to methyl carbon conveniently.
The up field signal at 19.4 ppm has cross peak with the two methylene protons appearing as
multiplets centered at 1.28 and 1.71 ppm. So the signal appeared at 19.4 ppm is assigned to
the methylene carbon attached to C3 carbon. Another 13C signal in the aliphatic region at 67.5
ppm has a cross peak with the doublet due to benzylic proton H2 at 3.68 ppm, which
confirms that the signal at 67.5 ppm is obviously due to the benzylic carbon C2. The signal at
60.7 ppm is conveniently assigned to C6 benzylic carbon by considering its cross peak with
the doublet of doublet at 3.86 ppm. From this, it is clear that the peak at 60.7 ppm is assigned
to C6 carbon atom of the pipridine ring. The signal appeared at 35.9 ppm shows cross peak
with two protons resonating at 2.16 and 2.86 ppm. The doublet of doublet at 2.16 ppm and
multiplet at 2.86 ppm are due to the H5a and H5e protons, and hence the signal at 35.9 ppm is
assigned for C5 carbon. The multiplet at 2.43 ppm has correlation with carbon signal at 51.8
ppm. From this, it is clear that the peak at 51.8 ppm is for C3 carbon. In the higher frequency
region, the signals at 142.7 and 143.3 ppm have no correlations with proton signals and for
the unambiguous assignment of these quaternary carbon signals, HMBC spectrum is
recorded.
HMBC
The individual assignment of the quaternary carbon signals at 142.7, 143.3 and 155.2
ppm is carried out from its HMBC spectrum (Fig. 4). Among these three signals, the lower
frequency signal at 142.7 ppm has good correlation with the H2 proton and ortho protons (α-
correlation) signals. It clearly indicates that the signal at 142.7 ppm is due to benzene ring
ipso carbon attached to C2 carbon atom. The higher frequency signal at 143.3 ppm has α-
correlation with H5 (2.16 ppm) and ortho protons and β-correlation with H5 (2.16 ppm)

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proton signal and it is explicit that the signal at 143.3 ppm is due to benzene ring ipso carbon
attached to C6 carbon. The less intense signal at 155.2 ppm is due to ipso carbon C4 and also
it has α-correlation with H5 proton.
3.3. Single crystal X-ray structural analysis of (E)-methyl 2-(3-methyl-2,6-diphenylpiperidin-
4-ylidene)hydrazinecarboxylate 7
The structure and geometry of compound 7 in the solid state is established by single
crystal x-ray structural analysis. Compound 7 crystallizes in a monoclinic system with eight
molecules per unit cell. The ORTEP of compound 7 is given in Fig.5 and the corresponding
packing diagram is shown in Fig.6. Crystal data and structure refinement data are given in
Table 1. Selected bond distances, bond angles and torsion angles are given in Table 2. The
configuration about C=N bond (C(3)–N(2)) is E and the C(2)–C(3)–N(2)–N(3) dihedral angle
is -177.4(4)°. C(3)–N(2) bond distance is 1.266 (4) Å which exemplifies its double bonded
nature whereas, the C–N single bond distances associated with the heterocyclic ring are C(5)–
N(1) = 1.446(6) Å and C(1)–N(1) = 1.474(7) Å respectively [21].
Two phenyl groups are equatorially oriented as evidenced by the dihedral angles
[C(3)–C(4)–C(5)–C(15) = 179.2(4); C(15)–C(5)–N(1)–C(1) = 177.1(4) and C(9)–C(1)–C(2)–
C(3) = -177.5(4); C(9)–C(1)–N(1)–C(5) = -176.4(5)
also equatorially oriented [C(4)–C(3)–C(2)–C(6) = -178.2(5) and N(1)–C(1)–C(2)–C(6) =
177.5(5) ]. The bond parameters associated with the ester function [O(1)–C(7)–O(2)] clearly
°]. Similarly, the methyl group at C-2 is
°
evidences the partial delocalization of π electron density over it [C(7)–O(1) = 1.208(4) and
C(7)–O(2) = 1.341(5) Å] and in fact the partial delocalization extends up to C(7)–N(3) bond
as well [C(7)–N(3) = 1.334(5) Å]. From the geometrical parameters, it is observed that the
piperidine ring adopts chair conformation and the atoms N(1) and C(3) deviate from the plane
defined by C1/C2/C4/C5 to an extent of 0.654 and 0.643 Å on either side of the plane. The

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observed dihedral angles associated with the heterocyclic ring also support the chair
conformation of it [N(1)–C(1)–C(2)–C(3) = -56.3(5); C(2)–C(3)–C(4)–C(5) = -56.0(6); C(3)–
C(4)–C(5)–N(1) = 55.8(6); C(4)–C(5)–N(1)–C(1) = -60.0(6); C(4)–C(3)–C(2)–C(1) =
56.0(5); C(2)–C(1)–N(1)–C(5) = -57.8(7)°]. The phenyl rings show conventional bond
parameters.
4. Conclusions
A series of 3-alkyl-2,6-diarylpiperidin-4-ylidene)hydrazinecarboxylate have been
synthesized successfully in appreciable yields and were characterized by IR and NMR
spectra. Single crystal XRD analysis was also performed for compound 7. The Single crystal
XRD studies clearly furnish the conformations of the hydrazone along with the orientation of
–C=N–NH bond syn to C5.
Acknowledgments
We gratefully acknowledge the UGC Networking Resource Centre, University of Hyderabad
for providing the characterization facilities. First author C. Udhaya Kumar expresses his
sincere thanks to Dr. R. Chandrasekar, Associate Professor, School of Chemistry, University
of Hyderabad and his research group for providing laboratory facility.

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REFERENCE
[1] O. Faria, M. Prizza, A. Granba, G. Pifferri, Eur.J.Med.Chem.Ther., 14 (1979) 27.
[2] U. Das, H.N. Pati, H. Sakagami, K. Hashimoto, M. Kawase, J. Balzarini, E. D. Clercq,
J.R. Dimmock, J. Med. Chem., 54 (2011) 3445.
[3] A.R. Katrizky Advances in Heterocyclic Chemistry Academic press, London. 78 (1965)
135.
[4]. A. S. Kiselyov, C. Dominguez, Tetrahedron Lett., 40 (1999) 5111.
[5]. A. Ahmed, K.I. Molvi , S. Nazim, I. Baig , T. Memon, M, Rahil, J. Chem. Pharm. Res.,
4(1) (2012) 872.
[6]. L. Chaturvedi, N. Khurana, S. Patil, A. Gajbhiye, International Journal of
Pharmacology and Pharmaceutical Technology, 1 (2012) 2277.
[7]. J.S. Amato, J.Y.L. Chung, R.J. Cvetovich, R.A. Reamer, D. Zhao, G. Zhou, X. Gong,
Org. Process Res. Dev., 8 (2004) 939.
[8]. P. Kodisundaram, S. Amirthaganesan, T. Balasankar, J. Agric. Food Chem., 61 (2013)
11952.
[9]. S.M. Sondhi, M. Dinodia, A. Kumar, Bioorg. Med. Chem., 14 (2006) 4657.
[10]. A.C. Cunha, J.L.M. Tributino, A.L.P. Miranda, C.A.M. Fraga, E.J. Barreiro, J. Il
Farmaco., 57 (2002) 999.
[11]. S.K. Sridhar, A. Ramesh, Biol. Pharm. Bull., 24 (2001) 1149.
[12]. R. E. Melendez, W.D. Lubell, J. Am. Chem. Soc., 126 (2004) 6759.
[13]. M. Balasubramanian, N. Padma, Tetrahedron, 19 (1963) 2135.
[14]. C.R. Noller, V. Baliah, J. Am. Chem. Soc., 70 (1948) 3853.
[15] G.M. Sheldrick, Acta Crystallogrphy, 46 (1990) 467.
[16] G.M. Sheldrick, SHELXL-97, University of Gottingen, Gottingen, Germany,
1997.
[17] J.D. Knight, D.L. Weddle II, J. McLaughlin, A. Straumanis, C.F. Beam, Chem.
Educator.14 (2009) 1.
[18] http://www.sigmaaldrich.com/spectra/fnmr/FNMR001528.PDF
[19] http://www.sigmaaldrich.com/spectra/fnmr/FNMR010374.PDF
[20] http://www.sigmaaldrich.com/spectra/fnmr/FNMR009582.PDF
[21] Mercury; Crystallographic Software from CCDC (<http://www.ccdc.cam.ac.uk>)

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Table 1
Crystal data and structure refinement data for 7
Empirical formula
C20 H23 N3 O2
337.42
Formula weight
Temperature
293(2) K
Wavelength
1.54184 Å
Crystal system, space group
Unit cell dimensions
Monoclinic, P 21/c
a = 13.3736(7) Å
ɑ = 90°
b = 16.5810(12) Å
β = 103.079(5)°
c = 16.9875(8) Å
γ = 90°
Volume
3669.2(4) A3
8, 1.225 Mg/m3
0.641 mm-1
Z, Calculated density
Absorption coefficient
F(000)
1448
Crystal size
0.20 x 0.18 x 0.16
3.39 to 67.06°.
Theta range for data collection
-14<=h<=15, -19<=k<=13,
-20<=l<=14
Limiting indices
Reflections collected / unique
Completeness to theta
13227 / 6525
98.3 %
Absorption correction
Semi-empirical from equivalents
0.903 and 0.880
Full-matrix least-squares on F2
6525 / 0 / 736
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
0.940
Final R, RW (obs, data)
0.0699, 0.1450

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Table 2
Selected bond lengths [Å], bond angles [ ° ] and torsion angles for 7
bond lengths
C(3)-N(2)
C(3)-C(2)
C(3)-C(4)
N(5)-N(6)
C(1)-N(1)
C(1)-C(9)
C(1)-C(2)
C(2)-C(6)
C(4)-C(5)
C(5)-N(1)
C(5)-C(15)
C(7)-O(1)
C(7)-N(3)
C(7)-O(2)
C(8)-O(2)
C(9)-C(10)
C(9)-C(14)
C(10)-C(11)
C(11)-C(12)
C(12)-C(13)
C(13)-C(14)
C(15)-C(16)
C(15)-C(20)
C(16)-C(17)
C(17)-C(18)
C(18)-C(19)
C(19)-C(20)
C(1)-C(2)
1.266(4)
1.498(5)
1.502(6)
1.391(5)
1.474(7)
1.501(5)
1.530(7)
1.528(7)
1.514(7)
1.446(6)
1.512(6)
1.208(4)
1.334(5)
1.341(5)
1.445(6)
1.365(6)
1.383(6)
1.377(6)
1.363(8)
1.378(9)
1.400(7)
1.363(6)
1.376(6)
1.381(7)
1.373(8)
1.357(7)
1.388(7)
1.401(4)
bond angles
N(2)-C(3)-C(2)
N(2)-C(3)-C(4)
C(2)-C(3)-C(4)
N(1)-C(1)-C(9)
N(1)-C(1)-C(2)
C(9)-C(1)-C(2)
C(3)-C(2)-C(6)
C(3)-C(2)-C(1)
C(6)-C(2)-C(1)
C(5)-C(4)-C(3)
N(1)-C(5)-C(4)
N(1)-C(5)-C(15)
C(4)-C(5)-C(15)
O(1)-C(7)-N(3)
O(1)-C(7)-O(2)
N(3)-C(7)-O(2)
119.6(4)
128.4(4)
112.0(4)
109.4(4)
108.8(4)
112.4(4)
113.1(4)
109.2(4)
112.4(4)
109.5(4)
109.8(5)
111.1(4)
110.4(4)
124.2(5)
122.6(5)
113.2(5)

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C(10)-C(9)-C(14)
C(10)-C(9)-C(1)
C(14)-C(9)-C(1)
C(9)-C(10)-C(11)
C(12)-C(11)-C(10)
C(11)-C(12)-C(13)
C(12)-C(13)-C(14)
C(9)-C(14)-C(13)
C(20)-C(15)-C(16)
C(20)-C(15)-C(5)
C(16)-C(15)-C(5)
C(15)-C(16)-C(17)
C(18)-C(17)-C(16)
C(19)-C(18)-C(17)
C(18)-C(19)-C(20)
C(15)-C(20)-C(19)
C(5)-N(1)-C(1)
117.5(5)
122.2(5)
120.3(5)
123.2(6)
119.4(7)
119.7(6)
120.4(6)
119.8(6)
119.1(5)
121.8(5)
119.0(5)
120.2(5)
120.4(5)
120.3(6)
119.9(6)
120.1(5)
112.9(4)
117.4(3)
121.5(4)
115.9(4)
C(3)-N(2)-N(3)
C(7)-N(3)-N(2)
C(7)-O(2)-C(8)
Torsion angle
C(3)-C(4)-C(5)-C(15) 179.2(4)
C(15)-C(5)-N(1)-C(1) 177.1(4)
C(9)-C(1)-C(2)-C(3) -177.5(4)
C(9)-C(1)-N(1)-C(5) -176.4(5)
C(4)-C(3)-C(2)-C(6) -178.2(5)
N(1)-C(1)-C(2)-C(6)
N(1)-C(1)-C(2)-C(3)
C(2)-C(3)-C(4)-C(5)
177.5(5)
-56.3(5)
-56.0(6)
C(2)-C(3)-N(2)-N(3) -177.4(4)
C(3)-C(4)-C(5)-N(1)
C(4)-C(5)-N(1)-C(1)
C(4)-C(3)-C(2)-C(1)
C(2)-C(1)-N(1)-C(5)
55.8(6)
-60.0(6)
56.0(5)
-57.8(7)

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Figures
CH3
10
O
O
9
HN
Ha
7
8
N
4
CH3
Hb
3
5
1
N
6
2
H
Fig.1. 1H NMR spectrum of compound 8.

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CH3
10
O
O
9
HN
Ha
8
CH3
N
7
4
Hb
3
5
1
N
6
2
H
Fig.2. 13C NMR spectrum of compound 8.

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CH3
10
O
O
9
HN
Ha
8
CH3
N
7
4
Hb
3
5
1
N
6
2
H
Fig.3. HSQC spectrum of compound 8.

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CH3
10
O
O
9
HN
Ha
8
CH3
N
7
4
Hb
3
5
1
N
6
2
H
Fig.4. HMBC spectrum of compound 8.

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Fig.5. ORTEP view of compound 7.

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Fig.6. Packing diagram of compound 7.

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Scheme 1
CH3
10
O
O
9
HN
Ha
7
8
N
4
CH3
Hb
3
5
1
N
6
2
H
Scheme 2

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Highlights
ꢀ Synthesis of 3-alkyl-2,6-diarylpiperidin-4-ylidene)hydrazinecarboxylate.
ꢀ Spectral characterization by IR, 1D and 2D NMR.
ꢀ Single crystal XRD analysis of methyl 2-(3-methyl-2,6-diphenylpiperidin-4-
ylidene)hydrazinecarboxylate.