Structural studies of PCU-hydrazones: NMR spectroscopy, X-ray diffractions, and DFT calculations

Article abstract of DOI:10.1016/j.molstruc.2011.04.030

In this article we present a detailed structural investigation for the configurational isomers of PCU-hydrazones. The structural characterization of these hydrazones was performed using NMR spectroscopy, X-ray diffraction analysis and theoretical calculat

Full text of DOI:10.1016/j.molstruc.2011.04.030

Journal of Molecular Structure 997 (2011) 46–52
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Structural studies of PCU-hydrazones: NMR spectroscopy, X-ray diffractions, and
DFT calculations
a
a
b
c
c,
⇑
´
ˇ
Jelena Veljkovic , Marina Šekutor , Krešimir Molcanov , Rabindranath Lo , Bishwajit Ganguly
,
a,
⇑
´
Kata Mlinaric-Majerski
a
-
ˇ
´
ˇ
Department of Organic Chemistry and Biochemistry, Ruder Boškovic Institute, Bijenicka cesta 54, P.O. Box 180, 10 002 Zagreb, Croatia
b
-
Department of Physical Chemistry, Ruder Boškovi´c Institute, Bijenicka cesta 54, P.O. Box 180, 10 002 Zagreb, Croatia
c Analytical Science Division, Central Salt and Marine Chemicals Research Institute (Council of Scientific and Industrial Research), Bhavnagar, Gujarat 364 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
In this article we present a detailed structural investigation for the configurational isomers of PCU-hydra-
zones. The structural characterization of these hydrazones was performed using NMR spectroscopy, X-
ray diffraction analysis and theoretical calculations. The single crystal X-ray structures of PCU-hydra-
zones 6B and 6C have been solved and used to conclusively confirm the characterization obtained via
NMR spectra of a particular isomer. Nuclear magnetic shielding values calculated for 6A–C using DFT cal-
culations were correlated with the experimentally determined chemical shifts. The computed results
were found to be in good agreement with the observed 13C NMR values. The computed NMR results
helped to ascertain the isomers of PCU-hydrazones 4A–C.
Received 7 February 2011
Received in revised form 18 April 2011
Accepted 18 April 2011
Available online 27 April 2011
Keywords:
PCU-hydrazones
NMR spectroscopy
X-ray structural characterization
Density functional calculations
Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction
arises due to the pronounced similarity of their physical and
chemical properties. In the present work, the structural charac-
Polycarbocyclic cage compounds have attracted attention of or-
ganic chemists for years, mostly because of their unique properties,
e.g. high density, moderate strain energy and great stability, which
are the result of their fascinating structural carbocyclic frame-
works [1]. In particular, pentacycloundecane derivatives have pre-
sented a fairly attractive goal and various synthetic strategies have
been developed for their acquirement [2]. In addition, some PCU
derivatives have shown a number of interesting pharmacological
properties, including antiviral and anti-Parkinsonian activities [3].
Since the preparation of the superbase, 1,8-bis(dimethyl-
amino)naphthalene, known as ‘‘proton sponge’’ [4], many families
of proton sponges have been prepared and a growing number of
their application found [5–8]. Recently, new organic superbases
with the pentacyclo[5.4.0.02,6.03,10.05,9]undecane (PCU) framework
anchored with amines and imines have been reported [9,10]. Our
current interest in different PCU proton sponges led us to the prep-
aration of PCU-hydrazones.
terization of new PCU-hydrazones was performed with NMR
spectroscopy, X-ray diffraction analysis and theoretical calcula-
tions. These combined techniques helped us determine the vari-
ous configurational isomers of the synthesized PCU-hydrazones.
The NMR chemical shift calculations performed with DFT method
have been found to correlate well with experimentally observed
chemical shifts. In some of the cases, X-ray structure analysis
determined the conformational geometries of these synthesized
PCU-hydrazones.
2. Experimental
2.1. Synthesis and NMR spectroscopy
1H and 13C NMR spectra were recorded on a Bruker AV-300 or 600
spectrometer at 300 or 600 MHz, respectively. All NMR spectra were
measured in CDCl3 using tetramethylsilane as a reference. The
assignment of the signals is based on two-dimensional homonuclear
correlated spectroscopy (COSY) and heteronuclear multiple quan-
tum coherence (HMQC). IR spectra were recorded on a FT-IR ABB Bo-
mem MB 102 spectrophotometer. MALDI-TOF MS spectra in
reflectron mode were obtained on an Applied Biosystems Voyager
DE STR instrument (Foster City, CA). Melting points were obtained
using an Original Kofler Mikroheitztisch apparatus (Reichert, Wien)
and are uncorrected. Silica gel (Merck 0.05–0.2 mm) was used for
Herein, we report the synthesis and structural characterization
of new PCU-hydrazones. The structural elucidations of cage com-
pounds have been reported to be difficult and this difficulty
⇑
Corresponding authors. Fax: +385 1 4680 195 (K. Mlinaric´-Majerski), fax: +91
278 2567562 (B. Ganguly).
E-mail addresses: ganguly@csmcri.org (B. Ganguly), majerski@irb.hr (K. Mlina-
ric´-Majerski).
0022-2860/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2011.04.030

´
47
J. Veljkovic et al. / Journal of Molecular Structure 997 (2011) 46–52
chromatographic purifications. Solvents were purified by distilla-
tion. Pentacyclo[5.4.0.02,6.03,10.05,9]undecane-8,11-dione 1 was pre-
pared according to the procedure described in literature [11].
2.82–2.89 (m), 3.03–3.11 (m), 3.52–3.69 (m). 13C NMR (75 MHz,
CDCl3), d: 36.9, 37.4, 38.2, 38.3, 38.6, 39.5, 40.2, 40.6, 41.1, 42.0,
42.6, 44.3, 45.2, 45.7, 46.0, 46.1, 46.6, 48.1, 48.2, 48.6, 48.8, 50.4,
51.1, 171.1, 172.2, 172.5. HRMS (MALDI) calculated for
[C15H22N4 + H]+ 259.1917, found 259.1929.
2.1.1. Synthesis of pentacyclo[5.4.0.02,6.03,10.05,9]undecane-8,11-dione
bis(diphenylhydrazone) (6)
Diketone 1 (380 mg, 2.18 mmol) was dissolved in 15 ml of abso-
lute ethanol or methanol and then N,N-diphenylhydrazine
(802 mg, 4.36 mmol) was added to the stirred solution. The reac-
tion mixture was refluxed for 5 h and after that time the solvent
was evaporated yielding the crude product as dark brown oil quan-
titatively. The obtained oil was purified by means of column chro-
matography (silica, eluent ethyl-acetate:chloroform = 5:95) and
three isomers of compound 6 were isolated.
Isomer 6A, white solid, yield 67 mg (6%). m.p. 170–171 °C. IR
(KBr, cmÀ1): 2926 (w), 1586 (m), 1490 (m), 749 (w), 693 (w). 1H
NMR (300 MHz, CDCl3), d: 1.32 (d, 1H, J = 11.15 Hz), 1.37 (d, 1H,
J = 11.15 Hz), 2.19–2.23 (m, 2H), 2.55–2.58 (m, 2H), 2.81–2.85
(m, 2H), 3.37–3.41 (m, 2H), 6.98–7.01 (m, 4H), 7.00–7.03 (m, 8H),
7.19–7.23 (m, 8H). 13C NMR (75 MHz, CDCl3), d: 38.1, 40.4, 43.9,
45.2, 46.8, 121.4, 123.1, 129.2, 148.5, 169.4. HRMS (MALDI) calcu-
lated for [C35H30N4 + H]+ 507.2543, found 507.2529.
2.2. X-ray diffraction data
Monocrystals of compounds 6B and 6C for X-ray analysis were
obtained from a CH3OH/CH2Cl2 solvent mixture. Single crystal
measurements were performed on an Oxford Diffraction Xcalibur
Nova R diffractometer (CCD detector, microfocus Cu tube). Pro-
gram package CrysAlis PRO [12] was used for data reduction. The
structures were solved using SHELXS97 and refined with SHELXL97
[13]. The models were refined using the full-matrix least squares
refinement; all non-hydrogen atoms were refined anisotropically.
Hydrogen atoms were located from the difference Fourier map
and refined as free entities. Molecular geometry calculations were
performed by PLATON [14], and molecular graphics were prepared
using ORTEP-3 [15] and CCDC-Mercury [16]. Crystallographic data
collection and refinement data for the structures reported in this
paper are shown in Table 1.
Isomer 6B, white solid, yield 546 mg (49%). m.p. 169–172 °C. IR
(KBr, cmÀ1): 2971 (w), 1588 (s), 1490 (s), 751 (m), 694 (m). 1H
NMR (600 MHz, CDCl3), d: 1.42 (d, 1H, J = 10.84 Hz), 1.64 (d, 1H,
J = 10.84 Hz), 2.33–2.36 (m, 1H), 2.49–2.53 (m, 1H), 2.55–2.62 (m,
1H), 2.68–2.73 (m, 1H), 2.75–2.78 (m, 1H), 2.78–2.81 (m, 1H),
2.86–2.90 (m, 1H), 2.90–2.94 (m, 1H), 6.98–7.02 (m, 2H), 7.02–
7.05 (m, 2H), 7.05–7.07 (m, 4H), 7.07–7.08 (m, 4H), 7.20–7.23
(m, 4H), 7.24–7.28(m, 4H). 13C NMR (150 MHz, CDCl3), d: 38.1,
38.4, 39.9, 41.1, 44.0, 44.6, 46.0, 47.3, 52.4, 121.8, 121.9, 123.1,
123.3, 129.1, 129.2, 147,7, 148.2, 162.6, 169.5. HRMS (MALDI) cal-
culated for [C35H30N4 + H]+ 507.2543, found 507.2529.
Isomer 6C, white solid, yield 139 mg (13%). m.p. 172–174 °C. IR
(KBr, cmÀ1): 2975 (w), 1587 (m), 1489 (s), 751 (m), 701 (m), 693
(m). 1H NMR (600 MHz, CDCl3), d: 1.47 (d, 1H, J = 10.89 Hz), 1.90
(d, 1H, J = 10.89 Hz), 2.40–2.46 (m, 2H), 2.55–2.59 (m, 2H), 2.60–
2.64 (m, 2H), 3.18–3.24 (m, 2H), 6.95–6.98 (m, 4H), 6.98–7.02
(m, 8H), 7.16–7.23 (m, 8H). 13C NMR (150 MHz, CDCl3), d: 38.0,
38.1, 40.4, 45.2, 52.3, 121.2, 123.0, 129.2, 148.3, 167.5. HRMS
(MALDI) calculated for [C35H30N4 + H]+ 507.2543, found 507.2529.
2.3. Computational details
All calculations were performed with the density functional
theory using Becke’s three-parameter exchange functional with
correlation functional of Lee, Yang, and Parr (B3LYP) [17,18]. All
species were fully optimized with 6-31+GÃ basis set [19], and har-
monic vibrational frequency calculations were used to confirm that
the optimized structures were minima, as characterized by posi-
tive vibrational frequencies. The optimized geometries of PCU
derivatives and the reference compound tetramethylsilane (TMS)
optimized at B3LYP/6-31+GÃ level were considered for 13C NMR
chemical shifts using the gauge-independent atomic orbital (GIAO)
methodology [20]. All quantum chemical calculations were per-
formed using Gaussian 03, Revision E.01 program [21].
3. Results and discussion
3.1. Synthesis and characterization of PCU-derivatives 2–6
2.1.2. 3,5-[bis(N,N-diphenylhydrazine)]-4-
oxahexacyclo[5.4.1.02,6.03,10.05,9.08,11]dodecane 5
The synthesis of PCU-hydrazones started from Cooksons’ dione
1, as shown in Scheme 1.
Compound 5 can be isolated if the reaction time in preparation
of hydrazone 6 is shorter. Purification of compound 5 was done by
washing the crude product with methanol in which the oxa-deriv-
ative is poorly soluble. m.p. 130–132 °C. IR (KBr, cmÀ1): 3354 (w),
2969 (m), 1588 (s), 1494 (s), 1336 (m), 1330 (m), 1267 (m), 750 (s),
695 (s). 1H NMR (300 MHz, CDCl3), d: 1.46 (d, 1H, J = 10.31 Hz),
1.79 (d, 1H, J = 10.31 Hz), 2.53 (br s, 2H), 2.66–2.73 (m, 4H), 2.75
(br s, 2H), 6.96–7.00 (m, 4H), 7.14–7.24 (m, 16H). 13C NMR
(75 MHz, CDCl3), d: 42.1, 42.9, 44.3, 45.4, 55.0, 106.9, 120.6,
122.2, 128.9, 149.5.
The treatment of diketone 1 with hydrazine hydrate, instead of
the PCU-hydrazone 2, afforded diaza-compound 3 as a sole isolated
product. However, PCU-hydrazones 4 and 6 have been successfully
prepared from diketone 1 and corresponding dimethyl- or diphen-
ylhydrazine, respectively. We used the hydrazone 4 as a starting
material for preparation of hydrazone
2 by exchange with
H2NNH2. Although similar exchange has been reported in the liter-
ature [22], again, instead of hydrazone 2 we obtained diaza-PCU-
derivative 3. It is also worth to mention that the formation of
hydrazone 6 is a two-step process which proceeds via intermediate
5. Moreover, we were able to isolate and characterize oxa-PCU
derivative 5 (see Section 2). Compound 5 is quite stable as a solid,
however, in the solution dehydration to hydrazone 6 takes place.
Products 4 and 6 were obtained as mixtures of three possible
configurational isomers A, B and C (Fig. 1) in a ratio of 1:9:2 and
1:8:2, respectively. The A and C are meso compounds and that fact
simplifies the NMR spectra since all the atoms except the methy-
lene group at C-4 exist as pairs. In the 13C NMR spectrum of the
mixture, based on the symmetry elements of the assumed isomers,
there should be, besides the 16 aromatic signals and 4 signals cor-
responding to four different carbons of C@N groups, 5 signals
2.1.3. Synthesis of pentacyclo[5.4.0.02,6.03,10.05,9]undecane-8,11-dione
bis(dimethylhydrazone) (4)
Compound 4 was synthesized in the same manner as compound
6 using diketone 1 and N,N-dimethylhydrazine, the only difference
being that the isomers of compound 4 could not be successfully
isolated from the mixture despite of the use of various separation
techniques. No intermediate formation was noticed in this reaction
and the obtained mixture was isolated quantitatively as dark
brown oil. IR (KBr, cmÀ1): 3434 (w), 2954 (s), 2863 (m), 1748 (s),
1665 (s), 1466 (s), 963 (m). 1H NMR (300 MHz, CDCl3), d: 1.51–
1.64 (m), 1.83–1.91 (m), 2.37 (s), 2.41 (s), 2.47 (s), 2.56–2.66 (m),

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J. Veljkovic et al. / Journal of Molecular Structure 997 (2011) 46–52
48
Table 1
Crystallographic, data collection and structure refinement details for hydrazones 6B and 6C.
Compound
6B
6C
Empirical formula
C
35H30N4
C35H30N4
506.63
Formula (wt./g molÀ1
)
506.63
Crystal dimensions (mm)
Space group
0.27 Â 0.23 Â 0.15
P 1
0.37 Â 0.30 Â 0.23
P 21/c
a (Å)
b (Å)
c (Å)
10.1957(5)
11.2141(6)
12.9827(7)
10.7051(1)
16.5369(1)
15.1857(1)
a
(°)
110.889(5)
90
b (°)
102.558(4)
97.928(1)
c
(°)
92.416(4)
90
Z
2
4
V (Å3)
1341.93(12)
1.254
0.575
2662.62(3)
1.264
0.580
Dcalc (g cmÀ3
l
)
(mmÀ1
)
H
range (°)
2.67–76.07
3.97–76.25
T (K)
293 (2)
293 (2)
Diffractometer type
Range of h, k, l
Reflections collected
Independent reflections
Observed reflections (I ꢀ 2
Absorption correction
Rint
Xcalibur Nova
Xcalibur Nova
À10 < h < 12; À13 < k < 14; À16 < l < 16
À13 < h < 13; À20 < k < 16; À18 < l < 19
12,091
5532
4496
25,869
5532
4992
r)
Multi-scan
0.0315
0.0620
0.1858
1.090
Free
472
0.391; À0.260
Multi-scan
0.0198
0.0386
0.1087
1.075
Free
473
0.189; À0.163
R (F)
Rw (F2)
Goodness of fit
H atom treatment
No. of parameters
D
qmax
,
D
qmin (eÅ–3
)
N
N
3
2
3
N
N
/THF
H2NNMe2
1M NH2NH2
H2NNH2 H2O
aps. EtOH
aps. EtOH
O
reflux 18h
NNMe2
NNMe2
1
4
O
NNH2
NNH2
NNH2
2
NH2NPh2
NNH2
aps. EtOH or MeOH
reflux, 5h
Δ
NHNPh2
NNPh2
NNPh2
O
5
6
NHNPh2
Scheme 1.
corresponding to configurational isomer A, 5 signals for configura-
tional isomer C, and 9 signals corresponding to configurational iso-
mer B in the aliphatic region. Some signals overlap in the actual
spectrum. Based on the molecular symmetry of the configurational
isomers and the observed 13C NMR signals, it appears that B is the
major isomer in this case (Table 2).
We could successfully isolate all three isomers of the phenyl
PCU-derivative 6A, 6B and 6C by means of column chromatogra-
phy and we were able to determine their exact structures by eluci-
dation of their corresponding 1H and 13C NMR spectra, Table 2. The
isomer 6B is obtained as a major product, whereas the isomers 6A
and 6C are yielded in a much smaller quantity, especially isomer

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49
J. Veljkovic et al. / Journal of Molecular Structure 997 (2011) 46–52
A
B
C
Fig. 1. The possible configurational isomers of PCU-hydrazones 4 and 6.
Table 2
1H and 13C NMR chemical shifts for PCU derivatives 6A, 6B and 6C and computed 13C NMR chemical shifts at the B3LYP/6-31+GÃ level given in parenthesis.
15*
4a
4s
4a
4s
H
4a
4s
H
6
H
H
14*
13*
H
6
H
15*
5
14*
13*
5
5
9
9
6
12*
9
10
10
3
3
10
2
3
N
2
12*
8
8
2
7
7
8
7
N
N(Ph)
N
2
N
N
1
11
1
11
1
11
N
N
N
N
N(Ph)
12
2
6A
13
13
N
12
14
15
14
15
6C
1H (ppm)
6B
1H (ppm)
1H (ppm)
13C (ppm)
13C (ppm)
13C (ppm)
1
2
3
3.37–3.41 (2H, m)
2.81–2.85 (2H, m)
2.19–2.23 (2H, m)
43.9 (49.1)
40.4
45.2
2.75–2.78 (1H, m)
2.55–2.62 (1H, m)
2.49–2.53 (1H, m)
38.4 (40.6)
41.1
44.6
2.40–2.46 (2H, m)
2.60–2.64 (2H, m)
2.55–2.59 (2H, m)
40.4 (41.7)
38.1
45.2
4a
4s
5
6
7
1.32 (1H, d, J = 11.15 Hz)
1.37 (1H, d, J = 11.15 Hz)
2.19–2.23 (2H, m)
2.81–2.85 (2H, m)
3.37–3.41 (2H, m)
–
38.1
1.42 (1H, d, J = 10.84 Hz)
1.64 (1H, d, J = 10.84 Hz)
2.33–2.36 (1H, m)
2.68–2.73 (1H, m)
2.86–2.90 (1H, m)
–
38.1
1.47 (1H, d, J = 10.89 Hz)
1.90 (1H, d, J = 10.89 Hz)
2.55–2.59 (2H, m)
2.60–2.64 (2H, m)
2.40–2.46 (2H, m)
–
38.0
45.2
40.4
43.9 (51.4)
169.4
46.0
39.9
44.0 (49.1)
169.5
45.2
38.1
40.4 (45.4)
167.5
8
9
2.55–2.58 (2H, m)
2.55–2.58 (2H, m)
–
46.8 (49.6)
46.8 (52.1)
169.4
2.90–2.94 (1H, m)
2.78–2.81 (1H, m)
–
47.3 (51.3)
52.4 (59.4)
162.6
3.18–3.24 (2H, m)
3.18–3.24 (2H, m)
–
52.3 (55.1)
52.3 (59.9)
167.5
10
11
12
–
–
–
147.7
–
148.3
148.2
12Ã
13
148.5
–
121.4
–
129.2
–
123.1
–
–
7.07–7.08 (4H, m)
7.05–7.07 (4H, m)
7.20–7.23 (4H, m)
7.24–7.28 (4H, m)
6.98–7.02 (2H, m)
7.02–7.05 (2H, m)
121.8
121.9
129.1
129.2
123.1
123.3
6.98–7.02 (8H, m)
–
121.2
–
13Ã
14
7.00–7.03 (8H, m)
–
7.19–7.23 (8H, m)
–
6.98–7.01 (4H, m)
7.16–7.23 (8H, m)
–
129.2
–
14Ã
15
6.95–6.98 (4H, m)
–
123.0
–
15Ã
6A which we isolated in an amount sufficient only for the record-
ing of various spectra. During the isolation we have noticed that
isomer 6A rearranges to isomer 6B in the solution. Similar rear-
rangement was observed for the isomer 6C, but with a slower rate
(Fig. S6). Obviously, the 6A, 6B and 6C are configurational isomers
stable in the solid state but rearrange to the most stable configura-
tional isomer 6B in the solution.
protons and resonance at d 2.55–2.59 ppm which was attributed
to H-3/H-5. Protons H-3/H-5 showed COSY correlation to the reso-
nance at d 3.18–3.24 ppm which is the interaction with H-9/H-10.
The remaining methine resonances at d 2.60–2.64 ppm and d 2.40–
2.46 ppm showed correlation with each other and were assigned as
the H-2/H-6 and H-1/H-7, respectively. The assignment of the pro-
tons H-2/H-6 at the resonance d 2.60–2.64 ppm was proved by the
correlation with the protons H-9/H-10. Since the proton resonance
at d 6.98–7.02 ppm (J = 8.1 Hz) showed correlation with the pro-
tons at d 7.16–7.23 ppm (J = 8.1 Hz), they were assigned as the phe-
nyl protons H-13 and H-14, respectively. The remaining resonance
The 1H NMR spectrum of isomer 6C showed geminal bridge
methylene protons resonance at d 1.47 and d 1.90 ppm (d,
J = 10.89 Hz), which were assigned to H-4a and H-4s, respectively.
The COSY spectrum shows correlations between these methylene

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J. Veljkovic et al. / Journal of Molecular Structure 997 (2011) 46–52
6B
6C
Fig. 2. ORTEP-3 [15] drawing of 6B and 6C. Atomic displacement ellipsoids are drawn for the probability of 50% and hydrogen atoms are depicted as spheres of arbitrary radii.
at d 6.95–6.98 ppm was assigned to H-15. The positions of the cor-
responding carbon signals were obtained from the HMQC
spectrum.
The same methodology was used to solve the NMR spectra of
isomer 6A, and the data of all NMR assignments are given in
Table 2.
sion 5.31, November 2009 and updates 2010 [23]. They are
especially common in sterically strained compounds. NAN bonds
longer than 1.42 Å are present in 13 out of 23 crystal structures
comprising a diphenlyhydrazone moiety which have been depos-
ited in the CSD. Due to steric strain, C@NAN angles vary widely be-
tween 100 and 130°, as was the case in 6B and 6C (data provided in
the deposited cif files). Similar steric strain can be observed in
analogous diphenylmethylenes: 19% of the fragments (1613 out
of 8463 structures) display elongated bonds (more than the sum
of covalent radii), with bond angles 100–125°.
However, the attempts to separate the PCU-methyl derivatives
4 have failed. The structural determination of 6A–6C using 13C
NMR studies can help to establish the conformational geometries
of 4A–4C. To ascertain this, we have performed the geometry opti-
mizations using B3LYP/6-31+GÃ level for 6A–6C and 4A–4C, respec-
tively. Furthermore, we have calculated the 13C NMR chemical
shifts for 6A–6C and 4A–4C configurational isomers at the same le-
vel of theory. The observed 13C NMR chemical shifts of 6A–6C were
compared with the calculated 13C NMR chemical shifts to examine
the reliability and its efficacy to establish the conformational
geometries of 4A–4C. First, we have performed the DFT B3LYP/6-
31+GÃ calculations for 6A–6C to determine the relative stabilities
of these configurational isomers. The calculated geometries were
further taken for 13C NMR spectral studies. The phenyl groups of
the optimized 6A–6C configurational isomers were modeled with
vinyl groups to minimize the computational time. The positions
of the atoms in 6A–6C retained the same locations, except for
hydrogens which were placed to the deleted carbon centers
(Fig. S7).
The calculated results suggest that 6B is energetically more sta-
ble than the corresponding isomers 6A and 6C, which corroborates
the experimental observation (Fig. 3). The orientations of phenyl
groups are similar to the X-ray structure obtained for 6B (Fig. 2
and Fig. 3). The 13C NMR of 6A, 6B and 6C showed an interesting
trend in their observed chemical shifts (Table 2). The aliphatic cage
carbons show that their chemical shifts depend on the orientation
of imine nitrogen lone-pairs. The imine nitrogen lone-pair closer to
the carbon centers leads to deshielding of the carbon nuclei com-
pared to the case where such lone-pairs are away from these cen-
ters. The imine nitrogen lone-pairs are orientated in the opposite
direction in the case of 6B (Figs. 2 and 3) and it can be seen that
The major isomer 6B is an unsymmetrical molecule and its NMR
spectra are more complex. The geminal methylene protons H-4a
(1.42 ppm, d, J = 10.84 Hz) and H-4s (1.64 ppm, d, J = 10.84 Hz)
which exhibit COSY interactions with H-3 (d 2.49–2.53 ppm) and
H-5 (d 2.33–2.36 ppm) again were the starting point to solve the
NMR spectra of isomer 6B. The H-5 interactions with the resonance
at d 2.68–2.73 ppm and d 2.90–2.94 ppm were assigned as the
interactions with H-6 and H-9 where only H-6 can interact with
H-7 (d 2.89–2.90 ppm). Also, H-3 interactions with the resonance
at d 2.55–2.62 ppm and d 2.78–2.81 ppm were assigned as the
interactions with H-2 and H-10 where only H-2 can interact with
H-1 (d 2.75–2.78 ppm). Regarding the phenyl groups, there are
two sets of signals which are assigned according to the coupling
constants and the positions in the symmetrical isomers 6A and
6C (Table 2). The assignments of the carbon resonances were ob-
tained by APT and HMQC spectra. The structures of isomers 6B
and 6C were also determined by single X-ray crystallography,
Fig. 2.
Significant deviations of NAN bonds can be observed (Table 3),
which are result of strain due to sterically bulky NNPh2 substitu-
ents. Particularly notable are extremely elongated N1AN2 bond
of isomer 6C and N3AN4 bond of 6B, which are significantly longer
than the sum of covalent radii of nitrogen atoms (1.42 Å).
Elongated NAN bonds are relatively rare, but not uncommon.
About 900 such bonds (length 1.42–1.52 Å; a few examples of even
longer bonds are outliers and probably results of unresolved er-
rors) are found in the Cambridge Structural Database (CSD), ver-
Table 3
NAN bond lengths (Å) for PCU derivatives 6B and 6C.
Compound
N1AN2
N3AN4
6B
6C
1.385(2)
1.446(1)
1.460(2)
1.407(1)

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51
J. Veljkovic et al. / Journal of Molecular Structure 997 (2011) 46–52
6B
6A
6C
Fig. 3. B3LYP/6-31+GÃ optimized geometries of three isomers of compound 6 and their relative energies (kJ/mol).
4
4
4
3
5
5
3
5
3
10
9
9
10
2
1
6
7
6
7
2
6
2
9
10
7
1
1
8
8
11
11
8
11
4B
4C
4A
Fig. 4. B3LYP/6-31+GÃ optimized geometries of three isomers of compound 4 and their relative energies (kJ/mol).
C7 carbon is more deshielded compared to C1 (Table 2). A similar
situation is observed for the aliphatic carbon centers C9 and C10
Table 4
Computed 13C NMR chemical shifts (in ppm) for compounds 4A, 4B and 4C at the
B3LYP/6-31+GÃ level. Experimental 13C NMR chemical shifts assigned for 4A–4C are
given in parenthesis.
,
respectively. In the case of 6A and 6C, the imine lone-pairs are
either oriented towards C1 and C7 carbons or C9 and C10 carbons
and the lone-pair effect on the chemical shift values of these car-
bon centers should be observed. The 13C chemical shifts showed
the variation in these aliphatic carbon centers for 6A and 6C (Ta-
Atoms
13C (ppm)
4A
4B
4C
1
7
9
47.4 (42.6)
47.4 (42.6)
47.5 (45.6)
47.5 (45.6)
39.5 (37.4)
47.0 (42.1)
47.2 (46.1)
54.9 (50.5)
39.3 (36.9)
39.3 (36.9)
55.3 (51.1)
55.3 (51.1)
ble 2). It has been reported that the 13C NMR of
a-position to imine
center is significantly influenced due to steric compression effect
[24]. The 13C NMR chemical shift calculations using GIAO method
[20] with B3LYP/6-31+GÃ level of theory predicted the observed
trend for 6A–6C, respectively (Table 2). The variation in the chem-
ical shift values of C1, C7 and C9, C10 compared to the experimen-
tally observed values presumably arises due to the modeling of
phenyl groups with the vinyl units. Nevertheless, the effect of
imine lone-pairs on the 13C chemical shift values for these carbon
centers was observed. Interestingly, the isomer 6C was found to be
more stable than 6A by 1.9 kJ/mol which corroborates the experi-
mental ratios obtained for these isomers. These results indicate
that the NMR chemical shift can ascertain the conformation geom-
etries in similar systems.
10
assignments of 13C NMR chemical shifts for the configurational iso-
mers 4A–4C were based on the relative comparisons of the com-
puted and observed chemical shift values (Table 4). The relative
trend of chemical shifts assigned from the observed 13C NMR spec-
trum for 4B was found to be in good agreement with the calculated
chemical shifts for C1, C7 and C9, C10 carbon atoms (Table 4).
4. Conclusions
The DFT B3LYP/6-31+GÃ calculations were extended with 4A–
4C. The calculated results suggest that 4B is the most stable isomer
compared to 4A and 4C, respectively (Fig. 4). The calculated prod-
uct ratios using the energies obtained for the three isomers were
1:7.1:1.7 in reasonable agreement with the observed results.
Further, the 13C NMR chemical shifts have been calculated for
the optimized geometries of 4A–4C. The calculated chemical shifts
are given in Table 4. The variation in the observed chemical shifts
of the aliphatic carbons C1, C7 and C9, C10 (4A–4C) were found to be
similar to the values obtained for 6A–6C (Tables 2 and 4). The
In the present work, novel PCU-hydrazones have been synthe-
sized. The structural elucidations of PCU-hydrazones configura-
tional isomers were carried out with NMR, single crystal X-ray
analysis and DFT calculations. The complete resonance assignments
of the 1H and 13C NMR signals for the PCU-hydrazones 6A–C are
given by using 1D and 2D NMR techniques. Nuclear shielding
obtained by using DFT calculations for the optimized molecular
geometries of 6A–C are applied for the identification of similar
configurational isomers of PCU-hydrazones 4A–C.

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J. Veljkovic et al. / Journal of Molecular Structure 997 (2011) 46–52
[5] A.F. Pozharskii, Russ. Chem. Rev. 67 (1998) 1.
[6] H.A. Staab, T. Saupe, Angew. Chem. 100 (1988) 895;
Acknowledgements
Angew. Chem. Int. Ed. Engl. 27 (1988) 865.
[7] R.W. Alder, Chem. Rev. 89 (1989) 1215.
[8] A.L. Llamas-Saiz, C. Foces-Foces, J. Elguero, J. Mol. Struct. 328 (1994) 297.
[9] A. Singh, B. Ganguly, Eur. J. Org. Chem. 23 (2007) 420.
[10] A. Singh, B. Ganguly, New J. Chem. 33 (2009) 583.
[11] A.P. Marchand, R.W. Allen, J. Org. Chem. 39 (1974) 1596.
[12] CrysAlis PRO, Oxford Diffraction Ltd., UK, 2007.
[13] G.M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr. A64 (2008) 112.
[14] A.L. Spek, J. Appl. Crystallogr. 36 (2003) 7.
The authors gratefully acknowledge to the Ministry of Science,
Education, and Sports of the Republic of Croatia. (Grant Nos. 098-
0982933-2911 and 098-1191344-2943) and the Department of
Science and Technology, (DST) New Delhi, India, (Grant No. DST/
INT/CROATIA/P8/05). One of the authors RL is thankful to UGC,
New Delhi, India for Junior research fellowship.
[15] L.J. Farrugia, J. Appl. Crystallogr. 30 (1997) 565.
[16] C.F. Macrae, P.R. Edgington, P. McCabe, E. Pidcock, G.P. Shields, R. Taylor, M.
Towler, J. ven de Streek, J. Appl. Crystallogr. 39 (2006) 453.
Appendix A. Supplementary material
[17] A.D. Becke, J. Chem. Phys. 98 (1993) 5648.
[18] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37 (1988) 785.
[19] W.J. Hehre, L. Radom, P.v.R. Schleyer, J.A. Pople, Ab Initio Molecular Orbital
Theory, Wiley, New York, 1988.
CCDC 807889 and 807890 contain the supplementary crystallo-
graphic data for this paper. These 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 336033). Supplementary
data associated with this article can be found, in the online version,
at doi:10.1016/j.molstruc.2011.04.030.
[20] K. Wolinski, J.F. Hinton, P. Pulay, J. Am. Chem. Soc. 112 (1990) 8251.
[21] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar,
J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A.
Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa,
M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox,
H.P. Hratchian, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E.
Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y.
Ayala, K. Morokuma, G.A. Voth, P. Salvador, J. J. Dannenberg, V.G. Zakrzewski,
S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K.
Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J.
Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L.
Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M.
Challacombe, P.M.W. Gill, B. Johnson, W. Chen. M.W. Wong, C. Gonzalez, J.A.
Pople, Gaussian 03, Revision E.01, Gaussian, Inc., Wallingford CT, 2004.
[22] G.R. Newkome, D.L. Fishel, J. Org. Chem. 31 (1966) 677.
[23] F.H. Allen, Acta Crystallogr., Sect. B: Struct. Sci. B58 (2002) 380.
[24] (a) C.A. Bunnell, P.L. Fuchs, J. Org. Chem. 42 (1977) 2614;
(b) N.K. Wilson, J.B. Stothers, Top. Stereochem. 8 (1974) 1.
References
[1] (a) G.W. Griffin, A.P. Marchand, Chem. Rev. 89 (1989) 997;
(b) A.P. Marchand, Chem. Rev. 89 (1989) 1011;
(c) A.P. Marchand, Advances in Theoretically Interesting Molecules, vol. 1, JAI
Press, USA, 1989.
[2] (a) A.P. Marchand, Aldrichim. Acta 28 (1995) 95;
(b) A.P. Marchand, Synlett 2 (1991) 73.
[3] W.J. Geldenhuys, S.F. Malan, J.R. Bloomquist, A.P. Marchand, C.J. Van der Schyf,
Med. Res. Rev. 25 (2005) 21.
[4] R.W. Alder, P.S. Bowman, W.R. Steele, D.R. Winterman, Chem. Commun. 13
(1968) 723.