Synthesis, structure and conformational analysis of 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one thiosemicarbazones and semicarbazones

Article abstract of DOI:10.1016/j.molstruc.2010.02.005

A series of thiosemicarbazones and semicarbazones have been synthesized and characterized by one and two dimensional NMR spectroscopy. The possible ring conformations of both the hydrazones are discussed. The chemical shifts and coupling constants suggest that the reported hydrazones adopt twin-chair conformations with equatorial orientation of the aryl substituents. Besides, the proposed conformations are further confirmed by single crystal X-ray diffraction analysis and molecular optimization geometry method. Crown Copyright

Full text of DOI:10.1016/j.molstruc.2010.02.005

Journal of Molecular Structure 970 (2010) 42–50
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis, structure and conformational analysis of 2,4-diaryl-3-
azabicyclo[3.3.1]nonan-9-one thiosemicarbazones and semicarbazones
*
R. Ramachandran, M. Rani, S. Kabilan
Department of Chemistry, Annamalai University, Annamalainagar 608002, Tamil Nadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of thiosemicarbazones and semicarbazones have been synthesized and characterized by one and
two dimensional NMR spectroscopy. The possible ring conformations of both the hydrazones are
discussed. The chemical shifts and coupling constants suggest that the reported hydrazones adopt
twin-chair conformations with equatorial orientation of the aryl substituents. Besides, the proposed con-
formations are further confirmed by single crystal X-ray diffraction analysis and molecular optimization
geometry method.
Received 12 November 2009
Received in revised form 31 January 2010
Accepted 1 February 2010
Available online 6 February 2010
Keywords:
Crown Copyright Ó 2010 Published by Elsevier B.V. All rights reserved.
2,4-Diaryl-3-azabicyclo[3.3.1]nonan-9-one
1H–1H COSY
NOESY
Conformational study
Crystal structure
1. Introduction
IR spectrophotometer (Thermo Nicolet). For compounds S9, S11–
S23, 1H and 13C NMR spectra have been recorded at 400 and
Hydrazones are of considerable pharmacological interest since a
number of derivatives have shown whole panoply of chemothera-
peutic properties [1]. Antimalarial activities of thiosemicarbazones
and semicarbazones have been previously reported [2]. Indeed,
many hydrazones exhibit promising anti-protozoan activity
through the inhibition of cysteine proteases and other targets [3–
6]. The hydrazones are also a member of class of metal-chelators
that are Schiff bases. For example iron (Fe) is essential for the bio-
logical activity of a number of plasmodial proteins, including the
rate-limiting enzyme of DNA synthesis, ribonucleotide reductase,
withholding it inhibits the growth of the malaria parasite [7,8].
On the other hand, the bicyclic compounds occupy a special place
in the structural elucidation, conformation and stereochemistry. In
connection with our earlier work on spectral [9] studies of vari-
ously substituted mono and bicyclic compounds, herein we report
the characterization of bicyclic thiosemicarbazones and semicar-
bazones using spectral and single crystal X-ray analysis.
100 MHz, respectively on a BRUKER AMX 400 MHz spectrometer
using CDCl3 as solvent and TMS as internal standard. For com-
pound S10, 1H, 13C and 2D NMR (HOMOCOSY and NOESY) spectra
have been recorded on a BRUKER AMX 500 MHz spectrometer
using CDCl3 as solvent and TMS as internal reference, for which
the operating frequency of 1H is 500 MHz and 13C is 125 MHz. All
the spectra of compounds S10–S23 were measured at a tempera-
ture of 300 K (chemical shift in d ppm).
2.2. Synthesis of 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one
thiosemicarbazones (S10–S17)
To a boiling solution of 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-
one (0.01 mol) in ethanolic chloroform (45 ml), the ethanolic chlo-
roform solution of thiosemicarbazide hydrochloride (0.01 mol)
was added drop wise with constant stirring. The reaction mixture
was refluxed for 3 h on a water bath. After cooling the solid prod-
uct was filtered off and purified by column chromatography.
2. Experimental
2.3. Synthesis of 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one
2.1. Physical measurements
semicarbazones (S18–S23)
The melting points were recorded in an open capillary tube and
are uncorrected. IR spectra have been recorded in AVATAR-330 FT-
To a boiling solution of bicyclic ketone (0.01 mol) in ethanolic
chloroform (1:1), semicarbazide hydrochloride (0.012 mol) and so-
dium acetate trihydrate (0.03 mol) were added and refluxed for
about 6 h. After the usual workup, the solid was separated and
purified by column chromatography.
* Corresponding author. Tel.: +91 9443924629.
E-mail address: chemkabilan@rediffmail.com (S. Kabilan).
0022-2860/$ - see front matter Crown Copyright Ó 2010 Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2010.02.005

R. Ramachandran et al. / Journal of Molecular Structure 970 (2010) 42–50
43
Table 1
2.4. Single crystal X-ray diffraction and computational detail
Analytical data for compounds (S10–S23).
Single crystal X-ray data were collected using a Bruker Kappa
CCD diffractometer with Mo K (k = 0.71073 Å) at room tempera-
Compound
R
R1
R2
Yield (%)
M.p. (°C)
M+
a
S10
S11
S12
S13
S14
S15
S16
S17
S18
S19
S20
S21
S22
S23
H
H
H
H
Cl
H
H
H
H
H
H
H
Cl
H
H
H
F
H
H
H
H
OMe
H
H
F
Cl
H
H
H
F
H
Cl
H
Me
OMe
H
H
F
65
60
65
67
69
71
85
75
92
84
81
75
77
73
160
196
172
202
210
150
133
141
205
210
136
146
226
134
–
ture. Semi empirical absorption corrections were applied using
SADABS program. The structure was solved using direct method
and refined by full matrix least-squares method on F2 with aniso-
tropic thermal parameters for all non hydrogen atoms SHELXL-97
[10]. Hydrogen atoms bonded to the carbon atoms were placed
in chemically acceptable position. The structures were drawn by
ORTEP-3 [11] and Mercury [12] programs.
The molecular structure of compound S10 in the ground state
(in vacuum) is optimized by HF with 6-311++G(d,p) higher basis
set. The calculation is performed using Gaussian 03 program [13]
package on personal computer.
399.89
–
–
–
–
–
–
347.58
–
–
–
–
–
H
H
H
Me
3. Results and discussion
trum of compound S11 and Figs. 5 and 6 show the selected HOMO
and NOE correlations of compound S11 whereas Table 2 represents
the correlated chemical shift values of 1H–1H COSY and NOESY
spectra. In 1H NMR, there are two signals appeared at 4.34 and
4.23 ppm (J = 2.60 and 1.88 Hz, respectively) corresponds to each
one proton integral. Also, these two signals have HOMO correlation
with signals at 2.45 and 2.83 ppm, respectively. Moreover, these
two signals have strong NOE with multiplet at 7.52 ppm and sin-
glet at 2.45 and 2.83 ppm. Therefore without ambiguity, these
two signals are attributed to benzylic protons H-2 and H-4. How-
ever, signals at 2.45 and 2.83 ppm have weak HOMO correlation
with benzylic protons (H-2 and H-4) and strong correlation with
multiplet centered at 1.48 ppm. Hence, signals at 2.45 and
2.83 ppm should be due to bridgehead protons H-1 and H-5,
respectively. Of these two signals, one is highly deshielded due
to spatial interaction between the nitrogen of hydrazone analogue
and one of the bridgehead proton (Fig. 7). Owing to this interaction,
partial charges created between them. Consequently, the bridge-
3.1. Analytical data and IR spectral analysis
The reported new hydrazones (S10–S23) were synthesized as
shown in Scheme 1 and their analytical data (Table 1) are agreed
well with their proposed molecular formulae. The representative
IR spectrum (compound S11) is given in Fig. 1. In IR spectra, the
presence of C@N stretching frequency around 1640 and
1680 cmꢀ1 confirm the hydrazone formation. In semicarbazones,
the expected C@O absorption band should be merged with the
band due to C@N stretching. A collection of bands observed in
the region of 3196–3512 cmꢀ1 are due to N–H stretching frequency
of piperidine ring and hydrazone analogues while the absorption
band in the region 3070–2800 cmꢀ1 are ascribed to aromatic and
aliphatic C–H stretching frequencies.
3.2. 1H NMR analysis
head
proton gets slight positive charge as shown in Fig. 7. From this,
the deshielded signal can be unambiguously assigned to syn
a-carbon acquires slight negative charge and the attached
In order to investigate the spectral assignments of reported
hydrazones (S10–S23), we have chosen S11 as the representative
compound. Figs. 2–4 show 1H NMR, 1H–1H COSY and NOESY spec-
a
Scheme 1. Schematic diagram showing the synthesis of compounds S10–S23.

44
R. Ramachandran et al. / Journal of Molecular Structure 970 (2010) 42–50
Fig. 1. IR spectrum of compound S11.
Fig. 2. 1H NMR spectrum of compound S11.
(H-5) bridgehead proton whereas shielded signal is assigned to
anti (H-1) proton.
ton is also be merged with H-6a/H-8a protons signal which
substantiated by the integral values whereas the H-7a proton sig-
nal appeared at 2.77 ppm. Among the H-7a and H-7e protons sig-
nal, H-7a proton is deshielded due to deshielding effect exerted
by the nitrogen lone pair and it creates vander Waals interaction.
Due to this, C–H(7a) bond becomes polarized and as a conse-
quence, carbon and the attached proton acquires negative and po-
sitive charges, respectively. Therefore, H-7a proton signal is highly
deshielded than H-7e proton.
a
Three and two protons signal observed, respectively at 1.48 and
1.83 ppm which have strong HOMO correlation with bridgehead
protons (H-1 and H-5) signal and the signal at 2.77 ppm. This indi-
cates that these two signals should be due to methylene protons
(C-6 and C-8). Among the said two signals (1.48 and 1.83 ppm)
deshielded signal is assigned to H-6e and H-8e protons and the
shielded one is assigned to H-6a and H-8a protons. The equatorial
proton is highly deshielded than axial proton is due to the anisot-
ropy of the C–C single bonds. Furthermore, the signal for H-7e pro-
The benzylic protons (H-2 and H-4) have also shown a cross
peak with multiplet at 7.51 ppm which suggests that the signal

R. Ramachandran et al. / Journal of Molecular Structure 970 (2010) 42–50
45
Fig. 3. 1H–1H COSY spectrum of compound S11.
Fig. 4. NOESY spectrum of compound S11.
at 7.51 ppm with four protons integral is due to ortho protons
(H-200 and H-400) of the phenyl groups. However, the ortho protons
signal at 7.51 ppm has strong HOMO correlation with quartet cen-
tered at 7.10 ppm. Hence, the signal at 7.10 ppm is due to meta
protons (H-2000 and H-4000) of the phenyl groups.
In thiosemicarbazone (S10–S17), the –NHCS and –CSNH2 pro-
tons signal appeared around 8.8 and 6 ppm, respectively whereas
in semicarbazones (S18–S23), the NHCO protons appeared around
8.8 ppm. But, the –CONH2 protons are not appeared as singlet at
6 ppm with two protons integral as that CSNH2 protons. Instead,

46
R. Ramachandran et al. / Journal of Molecular Structure 970 (2010) 42–50
there are two broad singlets appeared in the region of 4–6 ppm.
The observed broad singlet is due to restricted rotation about the
NCO bond in NMR time scale. In addition, the presence of NCO
bond in semicarbazone analogue may lead to existence of different
amide conformers. In order to study the amide conformation in
S18–S23, NH2 protons are designated as Ha and Hb as shown in
Fig. 8. Fig. 8a–8d provides the appropriate amide conformation of
semicarbazone compounds. Of the Fig. 8a–8d, the cis form
(Fig. 8c and 8d) is more stable due to their intramolecular hydro-
gen bonding between N(1) and N(a) or N(1) and N(b). Table 3 contains
the proton chemical shifts of compounds S10–S23.
3.3. 13C NMR analysis
The representative 13C NMR spectrum (compound S11) is de-
picted in Fig. 9 and the chemical shifts of compounds S10–S23
are given in Table 4. Assignment of both piperidine and cyclohex-
ane ring carbon signals were assigned by comparing the parent ke-
tones. However, in compounds S11, S12, S19 and S20, two signals
observed around 163 and 161 ppm are due to fluorine attached
ipso carbons. The observed two signals are due to C–F coupling be-
tween carbon and attached fluorine atom. Similarly another pair of
signal observed for all hydrazones in the region 133–140 ppm are
assigned to C-20 and C-40 ipso carbons.
Fig. 5. 1H–1H COSY correlation of compound S11.
For thiosemicarbazones (S10–S17), the C@S and C@N carbons
signal appeared around 175 and 159 ppm, respectively whereas
in semicarbazone compounds (S18–S23), the C@O/C@N carbon sig-
nals show around 158 ppm. For both the hydrazones, the ring car-
bon signals observed identically. However, there are two signals
around 64 and 63 ppm are conveniently assigned to C-2 and C-4
carbons, respectively. Whereas, the bridgehead carbons C-1 and
C-5 appeared around 46 and 39 ppm, respectively except com-
pounds S14 and S22. Interestingly, C-5 carbon signal shielded by
7 ppm due to spatial interaction between C-5 proton and lone pair
nitrogen in hydrazone analogue. This interaction induces a polarity
on the syn
a C–H(e) bond so that the syn a-equatorial proton (H-
5e) gets slight positive charge and the C-5 carbon gets slight neg-
ative charge as shown in Fig. 7. Consequently, the proton is
deshielded and carbon is shielded. Therefore, the deshielded signal
is assigned to C-1 carbon and shielded signal is assigned to C-5 car-
Fig. 6. NOESY correlation of compound S11.
Table 2
Selected 1H–1HCOSY and NOESY correlation chemical shifts of compound S11.
Signal
Correlations in
HOMOCOSY
Correlations in
NOESY
4.34 (d, 1H, H-2a)
4.23 (d, 1H, H-4a)
2.83 (s, 1H, H-5e)
2.45 (s, 1H, H-1e)
2.77 (m, 1H, H-7a)
7.51
1.83, 2.45, 7.51
1.83, 7.51
1.51, 1.83, 4.23
1.51, 1.83, 4.34
1.39, 1.83,
1.51, 1.83, 2.45
1.51, 1.83, 2.83
1.51, 1.83
4.34, 7.51
1.51, 1.83
7.10
1.51, 1.83, 2.45, 2.83, 4.23, 4.34
Fig. 7. CH(5e)–NH bond interaction.
Fig. 8. The possible hydrazone analogue conformations.

R. Ramachandran et al. / Journal of Molecular Structure 970 (2010) 42–50
47
Table 3
1H NMR Chemical shifts of compounds S10–S23 [
D
d (ppm)].
Compound H-2a
(d)
H-4a
(d)
H-1e
(s)
H-5e
(s)
H-7a
(m)
H-6e, H-8e and NH H-6a and
H-7e
CH3/
OCH3
NHCS
(s)
CSNH2/
CONH2 (s)
Aromatic
protons
(dd)
H-8a
S10
4.36
4.26
(s)
2.5
2.97
2.83
1.84
1.40–1.58 (m)
–
8.92
6.5
7.26–7.57 (m)
S11
S12
S13
4.34
4.36
4.34
4.24
4.26
4.23
2.46
2.51
2.47
2.85
2.9
2.88
2.77
2.75
2.75
1.83 (m)
1.82
1.8
1.41–1.58 (m)
1.54 (m)
1.53 (m)
–
–
–
8.75
8.87
8.85
6.32
6.39
6.38
7.11–7.50
6.99–7.42 (m)
7.50, (q); 7.39
(t)
7.99 (t); 7.25–
7.44
7.22 (q); 7.44
(q)
6.94 (q); 7.47
(q)
1.43 (m)
1.43
(quintet)
1.42
(quintet)
1.38
(quintet)
S14
S15
S16
S17
S18
S19
S20
S21
S22
S23
4.76
4.31
4.32
4.29
4.38
4.35
4.38
4.35
4.66
4.2
2.81
(m)
2.45
3.22
(d)
2.88
(m)
2.91
2.81
2.8
1.76
1.50–1.60
(m)
1.50 (m)
–
8.71
8.88
6.28
6.44
6.34
6.33
1.84
2.37 (s)
4.26
2.5
2.81
2.8
1.86
1.38–1.58 (m)
1.47 (m)
1.47
3.85 (d) 8.84
3.83 (d) 8.74
4.18
(s)
4.25
2.43
2.85
3
2.82
2.49
2.45
2.51
2.49
1.87
6.83–7.36 (m)
2.85
2.74
2.71
2.68
1.81 (m)
1.73 (m)
1.76–1.85 (m)
1.74 (m)
1.71–1.75 (dd)
–
7.94
8.8
4.8
7.31–7.44 (m)
7.07–7.62 (m)
7.00–7078 (m)
7.28–7.79 (m)
7.23–8.00 (m)
6.25
5.00
6.30
4.90
6.20
4.99
6.25
4.90
6.15
4.90
6.20
4.26
4.3
1.48 (m)
1.43 (m)
1.71 (q)
–
3.04
3.23
3.12
2.8
1.41
(quintet)
1.41
(quintet)
1.40
(quintet)
–
8.87
9.54
7.65
7.88
4.29
1.46–1.59
(m)
1.50–1.64
(m)
ꢀ
4.77
(d)
4.33
4.65
(d)
4.21
2.80 (m)
2.46
–
2.80 (s) 1.82 (dd)
1.44 (m)
2.37
7.21 (q);
7.47(q)
Fig. 9. 13C NMR spectrum of compound S11.
bon. For compounds S14 and S22, the benzylic and bridgehead car-
bons signal appeared around 61/60 and 41/34 ppm, respectively.
This is due to van der Waals interaction between chlorine and ben-
zylic/bridgehead protons (Fig. 10).
The ring methylene carbon signals C-6, C-7 and C-8 of cyclo-
hexane are observed around 26, 21 and 28 ppm, respectively.
Among the three carbon signals, C-7 carbon is shielded by about
7 ppm than C-6 and C-8. As stated earlier, this is due to van der
Waals interaction between axial proton of C-7 carbon and lone
pair nitrogen in piperidine ring. Owing to this interaction, C-
7(H-a) bond becomes polarized. As a result, the proton acquires
slight positive charge and carbon acquires slight negative charge.
Therefore, the C-5 carbon is shielded and the proton is
deshielded.
Fig. 10. Interaction between the Cl at ortho position and benzylic/bridge-head
protons.

48
R. Ramachandran et al. / Journal of Molecular Structure 970 (2010) 42–50
Table 4
13C NMR Chemical shifts of compounds S10–S23 [
D
d (ppm)].
Compound C-1
C-2
C-4
C-5
C-6 C-7
C-8
C-9
C@S/
C@O
C-20
C-40
Other aryl carbons
S10
S11
46.40 65.38 63.79 39.14 27.39 21.46 28.64 161.89 179.13 141.89 141.32 126.86, 127.10, 127.50, 127.82, 128.52, 128.65
46.29 64.72 63.10 39.06 27.25 21.38 28.46 161.29 179.12 137.37 136.83 163.50, 160.91, 136.83, 115.08, 115.48, 115.28
128.61,128.35
S12
46.28 64.84 63.16 39.05 27.40 21.38 28.59 160.95 179.59 144.43 143.85 164.40, 161.96 130.15, 122.72, 122.39, 114.85, 114.60,
114.35, 114.20, 113.93, 113.69
S13
S14
S15
S16
S17
46.29 64.90 63.22 39.03 27.29 21.39 28.49 160.92 179.37 140.20 139.65 133.750, 133.431, 128.90, 128.81, 128.44, 128.166
42.17 62.32 60.60 34.94 27.18 21.00 28.48 160.12 179.38 138.77 138.14 132.85, 130.08, 128.93, 128.65, 126.91
46.55 65.30 63.62 39.34 27.37 21.43 28.59 162.35 179.38 139.00 138.44 137.32, 137.01, 129.22, 129.14, 126.95, 126.72
46.34 65.10 63.48 39.12 27.50 21.34 28.70 161.99 178.98 143.58 143.01 158.87, 159.07, 128.88, 127.88, 113.92, 113.80
46.51 64.90 63.30 39.26 27.33 21.48 28.56 162.26 179.03 134.03 133.44 129.56, 129.45, 119.41, 119.16, 113.08, 112.92, 112.65,
112.23
S18
S19
S20
46.33 65.07 63.57 38.52 26.90 21.49 28.24 158.35
46.40 65.11 63.04 38.55 26.81 21.47 28.13 158.53
46.08 65.00 62.77 38.21 26.83 21.34 28.11 158.24
142.44 142.07 126.32, 126.87, 127.13, 127.26, 127.42, 128.41
138.05 137.72 164.28, 163.43, 137.72, 115.41, 115.20
145.07 144.82 163.52, 161.82 129.97, 129.88, 129.82, 129.74, 128.30,
122.44, 114.50, 114.26, 114.05, 113.89, 113.67
S21
S22
46.17 65.27 62.93 38.24 26.85 21.41 28.08 157.98
41.99 61.97 60.20 34.19 26.97 21.08 28.38 156.84
144.52 144.28 129.67, 127.55, 127.06, 125.04
139.04 138.46 129.99, 129.92, 128.72, 128.67, 128.46, 128.31, 126.94,
126.81
S23
46.37 65.33 63.42 38.61 26.90 21.52 28.25 158.18
137.05 136.84 139.45, 139.04 126.77, 126.99, 128.31, 129.06, 129.11
3.4. Stereochemistry and conformational analysis
Besides, the NOE between NH proton in hydrazone analogue and
H-5 bridgehead proton clearly reveals that the H-5 proton is syn
to the hydrazone analogue. From the chemical shifts, coupling con-
stants and NOE analysis, the compounds (S10–S23) may adopt
twin-chair conformations. This is further confirmed by the single
crystal X-ray analysis.
In order to understand the conformational analysis of piperi-
dine and cyclohexane rings, vicinal coupling constants are more
important parameter. However, the present set of hydrazones, cou-
pling constants values could not be resolved well because all the
signals appeared as singlet and multiplet except benzylic protons.
Therefore, conformation of two six membered rings were success-
fully achieved with the help of chemical shift parameters, single
crystal X-ray analysis and semi empirical calculation. However,
the obtained vicinal couplings constants of J2a1e and J4a5e values
around 2 Hz suggest that axial–equatorial couplings. Therefore,
benzylic and bridgehead protons occupy axial and equatorial ori-
entations, respectively. Besides, the strong NOEs between H-1
and H-2 and also between H-1 and H-4 clearly confirm that the
benzylic and bridgehead protons are occupying axial and equato-
rial dispositions, respectively. Similarly, the H-7a proton has strong
NOE with H-7e proton and its adjacent equatorial protons. This
NOE states that the signal at 1.83 ppm is due to equatorial protons.
3.5. Crystal structure and theoretical analysis
Table 5 gives crystal data, data collection, and refinement
parameters of compound S18 whereas Table 6 shows the selected
bond lengths and angles of non hydrogen atoms. Fig. 11 shows the
ORTEP diagram of the compound S18 with 30% probability level.
The asymmetric unit contains two crystallographically indepen-
dent molecules (A and B). The bond distances between C21–O1
and C21–N4 are less than that of the standard values. This may
be due to the partial double bond character between C21 and O1
and C21 and N4.
Table 5
Crystal data and structure refinement parameters for S18.
Table 6
Geometric parameters of compound S18.
Empirical formula
Formula weight
Wavelength (Å)
C21H24N4O
348.44
Atoms
Length
Atoms
Length
0.71073
Triclinic, P1
ꢀ
C(1)–C(5)
C(1)–C(6)
C(1)–C(2)
C(1)–H(1)
C(2)–N(1)
C(2)–C(9)
C(3)–N(1)
C(3)–C(15)
N(2)–N(3)
1.496(2)
1.541(2)
1.543(2)
0.9800(1)
1.465(2)
1.516(2)
1.459(2)
1.518(2)
1.3875(19)
C(3)–C(4)
C(4)–C(5)
C(4)–C(8)
C(6)–C(7)
C(7)–C(8)
C(21)–O(1)
C(21)–N(4)
C(21)–N(3)
1.542(2)
1.504(2)
1.542(3)
1.529(2)
1.518(3)
1.229(2)
1.347(2)
1.351(2)
Crystal system, space group
Cell dimensions
a (Å)
b (Å)
10.2564(2)
12.1453(3)
15.4442(4)
90
92
101
4
c (Å)
a
(°)
b (°)
c
(°)
Z
Dcalc (g/cm3)
1.227
1886.50(8)
Atoms
Angle
Atoms
Angle
Volume (Å3)
C(5)–C(1)–C(6)
C(5)–C(1)–C(2)
C(6)–C(1)–C(2)
N(1)–C(2)–C(9)
N(1)–C(2)–C(1)
C(9)–C(2)–C(1)
N(1)–C(3)–C(15)
N(1)–C(3)–C(4)
C(15)–C(3)–C(4)
C(5)–C(4)–C(8)
C(5)–C(4)–C(3)
C(8)–C(4)–C(3)
107.19(14)
108.95(14)
115.10(14)
110.49(13)
109.99(13)
112.43(14)
111.69(13)
110.79(13)
110.29(13)
107.10(14)
107.96(13)
115.20(13)
N(2)–C(5)–C(1)
N(2)–C(5)–C(4)
C(1)–C(5)–C(4)
C(7)–C(6)–C(1)
C(8)–C(7)–C(6)
C(7)–C(8)–C(4)
C(10)–C(9)–C(14)
C(10)–C(9)–C(2)
C(14)–C(9)–C(2)
O(1)–C(21)–N(4)
O(1)–C(21)–N(3)
N(4)–C(21)–N(3)
119.10(14)
129.22(15)
111.53(13)
113.66(14)
112.71(16)
114.00(14)
117.70(16)
120.33(14)
121.96(15)
123.25(16)
120.61(16)
116.10(17)
h Range for data collection (°)
F(0 0 0)
Index range
Number of parameters
Absorption correction
Goodness-of-fit
1.32–28.31
744
ꢀ13 6 h 6 10, ꢀ16 6 k 6 16, ꢀ20 6 l 6 20
501
None
0.997
0.180 and ꢀ0.143
Largest diff. peak and hole
(e Åꢀ3
)
Data/restraints/parameters
Refinement method
8630/0/501
Full-matrix least-squares on F2 (SHELXL-
97)

R. Ramachandran et al. / Journal of Molecular Structure 970 (2010) 42–50
49
Table 7
Optimized geometrical parameters of compound S10.
Interatomic distances (Å)
C1–C4
C1–N48
C1–C29
C2–C3
C2–C18
C2–N48
C3–C12
C3–C50
1.460
1.494
1.539
1.609
1.541
1.584
1.603
1.349
C4–C50
1.302
1.613
1.705
1.470
1.469
1.566
1.293
1.400
C10–C15
C12–C15
C40–C42
C40–N44
C40–O47
N41–C50
N41–N42
Bond angle (°)
C1–C4–C50
C2–C3–C50
C2–C3–N48
C3–C2–N48
C3–C50–C4
C4–C1–N48
C4–C1–C29
C10–C15–C12
105.02
83.07
C10–C4–C50
C12–C3–C50
N42–N41–C50
N42–C40–N44
N42–C40–O47
C44–C40–O47
N48–C2–C18
N48–C1–C29
91.88
109.58
120.46
120.10
119.92
119.97
106.27
114.90
112.62
112.62
130.06
100.31
113.31
113.96
Torsion angle (°)
C1–N48–C2–C3
C2–N48–C1–C4
C3–C2–C18–C19
C3–C12–C15–C10
C4–C10–C15–C12
58.17
C15–C10–C4–C50
C30–C29–C1–N48
N48–C2–C3–C50
N48–C1–C4–C50
–41.70
–92.25
–51.90
52.26
–50.80
–88.82
–56.51
48.43
Fig. 11. ORTEP diagram of compound S18.
In the conformational analysis of compound S18, six membered
heterocyclic piperidine ring adopts normal chair conformation
with the puckering parameters [14] being q2 and q3 are 0.045 Å
and 0.5773 Å, respectively. The total puckering amplitude,
QT = 0.5791 Å; h = 4.46°. Similarly, cyclohexane ring also adopts
normal chair conformation with puckering parameters being q2
and q3 are 0.136 Å and 0.559 Å, respectively. QT = 0.575 (2) Å,
h = 13.73°. In both the molecules, phenyl rings occupy equatorial
orientations. The packing of the molecule in the crystal lattice is gi-
ven in Fig. 12 which shows that compound S18 is stabilized by
strong intermolecular N–HꢁꢁꢁꢁO hydrogen bonding of 2.89 (2) Å.
The optimized structural parameters (bond lengths, bond an-
gles and dihedral angles) for thermodynamically preferred geome-
try of compound S10 determined by HF level with 6-311G(d,p)
basis set are listed in Table 7, with the atom numbering scheme
of the molecule is shown in Fig. 13. As given in Table 7, most of
the optimized bond lengths and bond angles are slightly overesti-
mated as well as underestimated, because the molecular states are
Fig. 13. Optimized structure of compound S10.
Fig. 12. Packing diagram of compound S18.

50
R. Ramachandran et al. / Journal of Molecular Structure 970 (2010) 42–50
different during experimental and theoretical process. One isolated
molecule is considered in gas phase during theoretical calculation,
while many packing molecules are treated in condensed phase
during the experimental measurement. However, the ring part of
optimized parameters of the molecule shows good agreement with
X-ray data [15]. Piperidine and cyclohexane ring moieties are
essentially adopt chair conformation as evident from the torsional
of Technology, Madras, for recording single crystal X-ray data
collection.
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and
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ꢀ41.70°]. In the molecular optimized structure, the hydrazone ana-
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4. Conclusion
All the synthesized 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one
hydrazones (S10–S23) were characterized by analytical and spec-
tral (1H NMR, 13C NMR, HOMOCOSY and NOESY) methods. Besides,
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pound (S18) whereas the molecular optimization geometry was
carried out for compound S10. From the chemical shifts, coupling
constants and single crystal X-ray analysis, the title hydrazones
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NMR and IR data for other investigated compounds can be ob-
tained on personal demand from authors. Crystallographic data
for the structural analysis have been deposited with the Cambridge
Crystallographic Data Centre, CCDC-698833. Copy of this informa-
tion may be obtained free of charge from The Director, CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (Fax: +44 1223 336033; e-
mail: deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
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Authors are thankful to NMR Research Centre, IISc, Bangalore
for recording NMR and Department of Chemistry, Indian Institute