Synthesis of green light emitting fused pyrazolinopiperidines - Photophysical and electrochemical studies

Article abstract of DOI:10.1039/c2ra22259k

We have synthesized the new, green light emitting pyrazolinopiperidines (PyP) derivatives with extended π-conjugation pathway by simple, two step reactions and are characterized using spectral and single crystal X-ray analysis. The electronic properties of PyP were studied using steady state, and time resolved spectral techniques, theoretical and electrochemical methods. PyP derivatives exhibit intense green fluorescence both in the solid and solution state with the quantum yield of 0.29 in acetonitrile. Importantly, PyP shows non-overlapping absorption and emission spectrum with the large Stokes shift value of ～8000 cm^-1. Solvent polarity dependent photophysical properties and theoretical HOMO-LUMO calculation reveal that the singlet excited state possesses significant charge transfer character. The substitution of electron donating/withdrawing substituents show negligible or little influence on the photophysical properties except the trifluoromethyl and 2,4-dichloro phenyl substituent. The electrochemical first oxidation potentials were not influenced by the substituent; however the first reduction potential becomes sensitive towards nature and position of the aryl substituent. Further, photophysical properties of PyP become sensitive to the nature of substituent (ortho/para) positions. The enhanced non-radiative decay for the 2,4-dichlorophenyl substituted PyP as compared to 2- and 4-chlorophenyl substituents (by a factor of two and seven times, respectively) emphasize the necessity for multiple electron withdrawing aryl substituents to induce the measurable charge transfer interactions. The enhanced non-radiative rate constant of trifluoromethyl substituent by eight times than methyl substituent is due to the strong intramolecular charge transfer from pyrazoline to styryl moiety. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c2ra22259k

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Synthesis of green light emitting fused
pyrazolinopiperidines - photophysical and
Cite this: RSC Advances, 2013, 3,
1243
electrochemical studies3
Shanmugam Easwaramoorthi,*a Balijapalli Umamahesh,b
Pugalendhi Cheranmadevi,b Ravindranath S. Rathorec and Kulathu Iyer
Sathiyanarayanan*b
We have synthesized the new, green light emitting pyrazolinopiperidines (PyP) derivatives with extended
p-conjugation pathway by simple, two step reactions and are characterized using spectral and single
crystal X-ray analysis. The electronic properties of PyP were studied using steady state, and time resolved
spectral techniques, theoretical and electrochemical methods. PyP derivatives exhibit intense green
fluorescence both in the solid and solution state with the quantum yield of 0.29 in acetonitrile.
Importantly, PyP shows non-overlapping absorption and emission spectrum with the large Stokes shift
value of y8000 cm21. Solvent polarity dependent photophysical properties and theoretical HOMO–LUMO
calculation reveal that the singlet excited state possesses significant charge transfer character. The
substitution of electron donating/withdrawing substituents show negligible or little influence on the
photophysical properties except the trifluoromethyl and 2,4-dichloro phenyl substituent. The electro-
chemical first oxidation potentials were not influenced by the substituent; however the first reduction
potential becomes sensitive towards nature and position of the aryl substituent. Further, photophysical
properties of PyP become sensitive to the nature of substituent (ortho/para) positions. The enhanced non-
radiative decay for the 2,4-dichlorophenyl substituted PyP as compared to 2- and 4-chlorophenyl
substituents (by a factor of two and seven times, respectively) emphasize the necessity for multiple
electron withdrawing aryl substituents to induce the measurable charge transfer interactions. The
enhanced non-radiative rate constant of trifluoromethyl substituent by eight times than methyl
substituent is due to the strong intramolecular charge transfer from pyrazoline to styryl moiety.
Received 24th September 2012,
Accepted 30th October 2012
DOI: 10.1039/c2ra22259k
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ease in modulation of emission intensity by the judicious
choice of substituents,11,12 high sensitivity towards surround-
Introduction
ing environment and specific detection of analytes.13–15 The
operating mechanism involved here has been the photo
induced electron transfer (PET) process. Several classes of
chromophores with donor-p-acceptor configuration have been
developed and among them pyrazoline based donor–acceptor
systems deserve much attention owing towards its versatility in
structure and function. The structure of 1,3-diphenyl-2-
pyrazolines (Pz) shown in Chart 1 has a five membered
heterocycle ring with two adjacent nitrogen atoms which
absorb between 200–350 nm depending upon the substituents
and exhibits intense photoluminescence both in solution and
solid state.16 Importantly, Pz exhibits unusually larger Stokes
shifts of about y4000 cm21 and show non-overlapping
absorption and emission spectra,16 a preferred parameter for
the fluorophore to be used in several fluorescence based-
applications. Exceptionally large Stokes shift that originates
from larger structural deviations between the ground and
excited state of Pz renders its use as optical brighteners,
Fluorescent probes have found widespread application that
includes probing the intracellular dynamics in biological
systems,1–3 non-invasive detection of biologically relevant
species,4–8 sensing the polarity of the micro environments in
protein,9 DNA,10 etc. As a consequence, molecules with donor-
p-acceptor configuration have been identified as one of the
preferred configurations for fluorescent probes owing to the
aChemical Laboratory, CSIR-Central Leather Research Institute, Adyar, Chennai –
600 020, India. E-mail: moorthi@clri.res.in; Fax: +91-44-24411630;
Tel: +91-44-24411630
bSchool of Advanced Sciences, Vellore Institute of Technology University, Vellore,
India. E-mail: sathiya_kuna@hotmail.com; Fax: +91 416 224 3092;
Tel: +91 0416 2244520
cBioinformatics Infrastructure Facility, Department of Biotechnology, School of Life
Science, University of Hyderabad, Hyderabad 500 046, India
Electronic Supplementary Information (ESI) available: 1H NMR, 13C NMR
3
spectra of all the compounds and absorption and fluorescence spectra of
selected compounds, crystallographic data, MO diagrams, Cartesian coordinates
of optimized geometries See DOI: 10.1039/c2ra22259k
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Chart 2
Chart 1
due to their interesting electronic properties, but also due to
their androgenic, anti-cancer, anti-depressant, anti-nocicep-
tive, anti-inflammatory, and anti-oxidant activities.34,41,42
Therefore the development of simple, non-toxic and effective
synthetic strategy becomes the significant need for the
synthesis of pyrazolines. Thus, herein we report effective
synthesis of pyrazolinopiperidines shown in Chart 2 using
isopropanol as a synthetic media. The photophysical proper-
ties of substituted SPz have been studied by means of steady
state and time resolved fluorescence spectroscopies to under-
stand the electronic properties. Systematic photophysical
studies suggest the intramolecular charge transfer interactions
between the phenyl and pyrazoline moieties. The ICT effect is
more pronounced when the phenyl group is substituted with
strong electron withdrawing trifluoromethyl group.
organic scintillators,16 and UV-stabilizers.17 It has been known
that pyrazolines absorption, fluorescent properties and con-
sequent changes in Stokes shift values can be tailored by
means of electron donating/withdrawing substituents on the
phenyl ring.18,19 Nonetheless, it is noteworthy that larger
number of electron withdrawing groups are sometimes
necessary to induce the PET processes in Pz. For instance,
substitution up to three fluorine atom in the phenyl ring of Pz
has not been sufficient enough to induce PET as identified
from the unaltered fluorescence quantum yield (WF) with
respect to unsubstituted compound. Nonetheless, the PET
process becomes operative by the addition of one more
fluorine atom to the phenyl (tetra fluorophenyl) as evident
from reduction in WF value by the factor of sixteen.20,21 Indeed,
the PET process operated in donor–acceptor substituted Pz has
been used to probe intracellular pH,22 to sense copper(I),23,24
and cation complexation through additional tetrathia and
tetraoxa-monoaza-15-crown-5 substitution.18 Shen et al. have
demonstrated that 1,3,5-triphenyl-2-pyrazoline also undergoes
intermolecular PET process in presence of suitable acceptor
like 1,4-dicyanonaphthalene.25 Despite significant attempts in
tuning the electronic properties of pyrazolines through
substitution the absorption and emission spectra lies only in
the blue region of the UV-visible spectrum. Longer wavelength
absorbing and emitting pyrazolines have not been paid much
attention so far except the one reported by Feng et al.26 They
have reported the one- and two-photon absorption studies of
styrylpyrazoline (SPz, Chart 1), but systematic photophysical
studies are yet to be done. It should be noted that, elongation
of p-conjugation has also been employed to extend the
absorption and emission spectrum beyond 500 nm. For
instance, the presence of double bonds between the pyrazoline
and phenyl ring has red-shifted the absorption maximum by
y40 nm.26 Thus, inspired by the interesting electronic
properties of pyrazolines we have attempted to synthesize
pyrazolinopiperidines that show green fluorescence.
Results and discussion
The synthesis of the pyrazolinopiperidines given in Chart 2
was accomplished by a two step process as outlined in
Scheme 1. 1-Benzyl-3,5-dibenzylidinepiperidine-4-one deriva-
tives (4) were synthesized according to the reported proce-
dure.43 Conversion of 6 into 4 was successfully achieved by
using 1 mole of N-benzyl-4-piperidone, 2 moles of substituted
aryl aldehyde in 15 ml of methanol under stirring conditions,
followed by dropwise addition of 5 mole % NaOH. Reaction
between phenyl hydrazine and bisbenzylidine derivatives
afforded pyrazolinopiperidines in excellent yields.44,45 The
synthetic details, reaction time, yields for all the derivatives are
summarized in Table 1.
A survey of nonpolar, polar, protic and aprotic solvents
revealed that the isopropanol would be the best synthetic
media, and works even without any catalyst. Initially the
reaction was carried out in ethanol and the products were
A variety of methods including domino reaction,27 carboa-
mination,28 1,3-dipolar cycloaddition,29 diazoalkane,30
Mannich,31 tandem,32 and hydro-hydrazination,33,34 have been
developed for the synthesis of pyrazolines. Synthesis of these
compounds has also been achieved by employing catalysts like
zirconium,35 palladium,36 zinc,33 selenium,37 Yb(OTf)3,38
sodium benzene sulfonate39 and DABCO.40 The availability
of these diverse synthetic methods for pyrazolines are not only
Scheme 1 Synthesis of 5-benzyl-7-benzylidene-3,3a,4,5,6,7-hexahydro-2,3-
diphenyl-2H-pyrazolo[4,3-c]pyridines.
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Table 1 Synthesis of pyrazolinopiperidines using Isopropanol (1a–f, 2a–i)a
Product
R
% Yieldb, (Weight in g)c Time (h) Mp (uC)
1
H
86 (0.980)
88 (1.066)
89 (1.1500
93 (1.291)
90 (1.140)
87 (1.182)
14
166–168
158–160
183–185
157–159
167–169
151–153
203–205
194–196
166–168
173–174
195–196
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2-CH3
2-OCH3
2-F
2-Cl
2-CF3
16.5
14.5
12
12.5
13
18.5
12.5
15.5
11.5
13
2,4-di Cl 62 (0.921)
4-CH3
4-OCH3
4-F
92 (1.111)
86 (1.110)
94 (1.159)
91 (1.190)
4-Cl
a
All the reactions were carried out by employing 0.0025 mol of
dibenzylidine derivatives (4a–4p), 0.0025 mol of phenyl hydrazine in
b
c
25 ml of isopropanol. Isolated yields. Isolated weights (g).
isolated in moderate yields after refluxing the reaction mixture
for 48 h. Though n-butanol, N,N-dimethylformamide, and
dimethyl sulfoxide offered good yields, the product isolation
became tedious task when compared to isopropanol. Attempt
has been made to synthesize these compounds in acetic acid,
ethanol, methanol, THF, acetone, chloroform, dichloro-
methane, and diethyl ether and details are summarized in
the supporting information (Table S1, ESI ). Relatively higher
3
yields were noted when the phenyl ring is substituted with
electron withdrawing than the electron donating groups.
Specifically, 94, 93, 87, 91 and 90% yields were noted
respectively for 4-F, 2-F, 2-CF3, 4-Cl and 2-Cl substituents.
Similarly, electron donating groups viz. 4-Me, 2-Me, 4-MeO and
2-MeO substituted phenyl ring gave 92, 88, 86 and 89% yields.
When reactions were carried out with disubstituted aldehyde
viz. 2,4-dichlorophenyl, only lower yield was noted due to steric
hindrance (Table 1).
All the synthesized compounds were characterized by FTIR,
1H NMR, 13C NMR and HRMS analyses. Single crystal structures
of some of the representative compounds were determined to
examine the conformations of these compounds and are shown
in Fig. 1 a–c. The five membered dihydropyrazole ring (N1/N2/
C3/C3A C217A) adopts an envelope conformation with atom C3
at the flap of the envelope and an adjacent 6-membered
piperidine ring (C3A C214/N5/C6/C7/C7A) assumes a chair
conformation, but substantially distorted from ideal geometry.
…
…
Short intramolecular C–H halogen and C–H O contacts were
observed in 1b, 1c and 1f leading to modulation of their
photophysical properties (vide infra) (detailed single crystal
X-ray crystallographic discussion are given in SI).
The electronic properties of pyrazolinopiperidines have
been studied by absorption and fluorescence spectroscopy.
UV-visible absorption spectra of all the samples were recorded
in acetonitrile solvent and the data are summarized in Table 2.
Representative absorption spectra of compound 1 given in
Fig. 2 shows two intense, well resolved peaks with maximum at
256 and 353 nm. The peak at 353 nm has been attributed to
the transition from singlet ground state (S0) to the first singlet
excited state (S1) and the peak at 256 nm is due to the S0 A S2
Fig. 1 Crystal structures of (a) 1b, (b) 1c, and (c) 1f with non-H atoms shown as
probability ellipsoids at 30% levels. The radii of hydrogens are on an arbitrary
scale.
transition. However, the structurally similar compound,
1-phenyl-3-((dimethylamino)
styryl)-5-(dimethylamino)phe-
nyl)-2-pyrazoline [p-dimethyl amine substituted SPz, SI,
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Table 2 Photophysical data of selected compounds measured in acetonitrile solvent
Compound Substituent labs nm (e 104
M
21cm21
)
lfl nmb Stokes shift (cm21
)
Wfl
tfl nsd Kr [108 s21
]
Knr[108 s21
]
c
1
H
221 (1.95), 256 (3.23), 353 (2.38)
255 (1.12), 350 (1.12)
503
509
8448
8763
8649
9002
9024
9135
8672
8168
8209
8688
8992
0.29 3.27
0.22 2.59
0.31 2.66
0.24 2.35
0.15 1.08
0.02 0.41
0.04 0.67
0.28 3.08
0.18 2.00
0.32 3.26
0.29 2.87
0.88
0.85
1.17
1.10
1.42
0.49
0.60
0.92
0.91
0.98
1.01
2.17
3.01
2.59
3.22
7.84
23.90
14.33
2.33
4.09
2.09
2.47
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2-CH3
2-OCH3
2-F
224 (3.38), 255 (3.05), 302a (1.60), 351 (2.77) 504
222 (2.35), 253 (4.22), 350 (2.98)
223 (2.76), 254 (3.11), 353 (2.32)
222 (1.60), 251 (1.85), 353 (1.40)
224 (3.25), 256 (1.75), 356 (1.20)
223 (2.38), 259 (3.00), 354 (2.47)
511
518
521
515
498
2-Cl
2-CF3
2,4-DiCl
4-CH3
4-OCH3
4-F
225 (3.10), 264(2.47), 286a (2.12), 354 (2.69) 499
255 (2.74), 351 (2.1)
259 (1.13), 352(0.91)
505
515
4-Cl
a
b
c
Shoulder. Molecules are excited at respective absorption maximum. Fluorescence quantum yields are measured with reference to
d
proflavin in water (pH = 7). The decay profiles were monitored at respective fluorescence maximum.
Scheme S1 ] shows absorption peaks at 259, 314, and 378 nm.
498 nm in the solid state and the corresponding fluorescence
spectrum is given in Fig. 3. Solid and solution state
fluorescence spectra of 1 are closely overlapped; however, the
FWHM of the former is slightly smaller (ca. 535 cm21) than
that of the solution state.
Considering the interesting electronic properties of pyr-
azolines, we have synthesized pyrazolinopiperidines with
various electron withdrawing (F, Cl, CF3) and donating (CH3,
OCH3) substituents on the 2nd and 4th positions of the phenyl
ring to see the substituent effect on the electronic properties.
The detailed UV-visible absorption and fluorescence spectral
data of substituted pyrazolinopiperidines summarized in
Table 2 suggests that the absorption maximum has not been
significantly altered except the changes in the molar extinction
coefficients of high energy peaks with the nature and position
3
This has been attributed to the transitions originated
respectively from the phenyl ring, n A p*, and p A p* levels.46
The S0 A S1 absorption of 1 is blue shifted by about 25 nm
with respect to reported compound, despite the same
chromophoric unit. This feature is due to the steric constraint
imposed by the six-membered piperidine ring on the C(4) and
C(5) of pyrazoline ring which in turn reduces the efficient
p-conjugation between the two moieties. The steady-state
fluorescence spectrum of 1 was observed at 503 nm with
mirror image relationship to the lowest energy absorption
band. Due to the larger Stokes shift (ca. 8400 cm21) that
originated from the sizable structural distortions at the excited
state, the overlap between the absorption and emission bands
becomes negligible (Fig. 2), which is a desired factor for the
dyes to be used in many fluorescence-based applications. The
fluorescence quantum yields of all the compounds in various
solvents were measured with reference to proflavin (0.34) in
water (pH = 7).47 The pyrazoline 1 is strongly fluorescent and
the WF in acetonitrile is determined to be 0.29. Compound 1
also shows strong, bright green emission with a maximum at
of the substituents (Fig. S3, ESI ). This result is quite
3
surprising when compared to the chemistry of pyrazolines
where the minute substituent variations or conformational
biases alter the spectral properties significantly.22 Possibly, the
intervening double bond between the pyrazolines and the
Fig. 3 Solid state fluorescence spectra of selected compounds measured at 45u,
Fig. 2 UV-visible absorption (black) and fluorescence (blue) spectra of 1 in
front surface configuration. Excitation wavelength = 350 nm.
acetonitrile solvent. Excitation wavelength = 353 nm.
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phenyl moieties attenuate the conformational strain caused by
the substituents. Thus the electronic properties of styryl
pyrazolines remain insensitive to the substituent. Indeed,
our hypothesis has been supported by the single crystal X-ray
structures and geometries optimized using Gaussian 03
programme48 at B3LYP/6-31G level, which show the relatively
unperturbed structural changes on substitution. Nonetheless,
both solid and solution state fluorescence emission show
notable changes with respect to the electron withdrawing/
donating nature as well as the position of the substituents. It is
likely that the substituent probably modulates the electron
density of styryl moieties in such a way that it can either act as
an electron-acceptor or donor and induces charge transfer
interactions between the pyrazoline and styryl group upon
excitation which thereby alters the fluorescence properties.
Consequently, the Stokes shift value increases by 100 to 600
cm21 depending upon the substituent except 4-methyl group
where it decreases by 200 cm21. It will be interesting to
compare the effect of substituent position, because this
information is vital in determining the substituent effect on
the degree of structural changes that occurs between the
ground and the excited states. As expected, the bulkier
substituent methyl and methoxy group at 2-position show
larger Stokes shift by y500 cm21 than their respective
4-position analogues. This behaviour suggests that 2-substi-
tuents being closer to the pyrazoline moiety possess strong
steric constraint and cause larger structural changes between
the ground and excited state upon excitation. On the other
hand, the steric constraint becomes minimal in 4-substituted
compounds. Stokes shift values even smaller than the parent
compound 1 are observed for some cases. Further, as can be
seen from Table 2, the fluorescence quantum yield of the
parent compound undergoes moderate to drastic changes with
respect to the nature and position of the substituent. A
common trend has not been derived for the fluorescence
quantum yields with respect to electron withdrawing/donating
nature of the substituent as well as to the substitution
position. However, the substitution of chlorine at 2-position
suppresses the fluorescence quantum yield by the factor of two
when compared to 1 due to the steric effect. Interestingly, the
fluorescence quantum yield of 2-CF3 substituted compound 1c
is measured as 0.02, a value approximately fourteen times
smaller than the parent compound. This feature is probably
due to the charge transfer from pyrazoline to styryl moiety
(vide infra). Further information about the excited state
processes can be gained from the fluorescence lifetime of
pyrazolinopiperidines which is measured by the time corre-
lated single photon counting method by exciting the sample at
375 nm, 150 ps pulse using Nanoleds. The decay profiles of
pyrazoline derivatives dissolved in acetonitrile are given in
Fig. 4. The decay profiles can be fitted with single exponential
function and the lifetime data are summarized in Table 2. The
fluorescence lifetime of 1, 1a, 1b, 1c, 1e, 2a, 2b, 2d, and 2e are
measured, respectively to be 3.27, 2.59, 2.66, 2.35, 1.08, 3.08,
2.00, 3.26, 2.87 ns. Generally, the fluorescence lifetimes of
2-substituted compounds have relatively been smaller than
Fig. 4 Fluorescence lifetime decay profiles of pyrazolinopiperidines dissolved in
acetonitrile. The samples are excited at 375 nm and the decay profiles were
monitored at respective emission maximum
that of the unsubstituted compound, 1. Specifically, when the
bulky CH3 group is substituted at 2-position, the steric
hindrance exerted at the pyrazoline and styryl junction reduces
lifetime by y0.7 ns. This interpretation is further supported
by the nearly similar fluorescence lifetime of 1 and 2a (with
CH3 group at 4-position). Smaller lifetime for methoxy
substituent (2.66 ns for 1b and 2.00 ns for 2b) is not clear in
this study and however, suggests the role of other effects like
inductive effect. The mesomeric effect of the methoxy group is
dominating its inductive effect.
…
In addition, there is short intra-molecular C–H O contacts
which would stabilize the structure and probably lead to
increased fluorescence lifetime in 2-MeO substitution over the
4-MeO substitution. There is no such short intra-molecular C–
…
H
O contacts in the 4-MeO substituted compound. In
contrast, suppressed lifetime by a factor of three for 1e (2-Cl)
has been attributed to the charge transfer interaction between
pyrazoline and chloro-substituted styryl moieties rather than
the steric factor. Indeed, the lowest fluorescence lifetime of 0.4
ns among the compounds studied here are observed for 1c (2-
CF3). This result is in concurrence with the fluorescence
quantum yield and Stokes shift values. To further understand
the nature of the charge transfer interaction, we have
measured the solvent polarity dependent photophysical
studies, which are discussed below in detail.
The fluorescence maximum of pyrazolinopiperidines
becomes red-shifted while going from low to high polar
solvents as shown in Fig. 5, a feature generally noted for the
charge transfer type of interactions between the donor and
acceptor group of the molecule. For the detailed study we have
selected three compounds viz.1, 1e and 1f that exhibit
relatively stronger charge transfer interactions. The magnitude
of the solvent-driven red shift is characteristic of the
substituent and the maximum of y50 nm shift is observed
for 1e while going from polar to non-polar solvents. On the
other hand, the electron donating substituents in 1 do show
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Fig. 5 Fluorescence spectrum i) 1 ii) 1e and decay profiles of iii) 1 iv) 1e in various solvents with different polarity.
the solvent polarity induced red-shifted fluorescence. Further
understanding in this regard has been gleaned from the
solvent polarity dependent fluorescence quantum yields and
lifetime measurements. The fluorescence quantum yields of 1,
is measured to 0.35, 0.4, 0.35, 0.35, and 0.29 respectively in
toluene, tetrahydrofuran, dichloromethane, dimethyl sulfox-
ide and acetonitrile solvent. Similarly, the fluorescence life-
time of 1 extracted from the decay profile shown in Fig. 5
corresponds to 3.5 ¡ 0.2 ns for all the solvents studied here.
Thus the overall result indicates that the observed fluores-
cence is from the singlet state with considerable amount of the
charge transfer character and not from the completely charge
separated state. In contrast, the fluorescence quantum yields
for 1e and 1f in nonpolar solvent, toluene is measured to be
0.07 and 0.18 whereas that of in polar solvent, acetonitrile
corresponds to 0.02, and 0.04 respectively; here the quantum
yield has been suppressed at least by a factor of three while
going from non-polar to polar solvent. Further, the fluores-
cence lifetime of 0.9 and 1.60 ns respectively for 1e, and 1f in
toluene has been reduced to 0.4 and 0 .67 ns in acetonitrile. To
obtain the quantitative relationship, we calculated the
radiative (Kr = 1/t0, t0 = WF/tF) and non-radiative (Knr = (1 2
WF)/tF) rate constant49 and the latter is plotted against the
solvent polarity parameter ET(30).50 While the non-radiative
rate constant of 1 is insensitive to ET(30) parameter (Fig. S4,
ESI ), 1e and 1f show approximately three times accelerated
3
non-radiative rate in acetonitrile when compared to the
nonpolar solvent, toluene. This observation is attributed to
the strong charge transfer from pyrazoline to substituted
phenyl moiety upon excitation. Thus, based on the above
results it can be concluded that the charge transfer interac-
tions in pyrazolines can be tuned by the judicious choice of
strong electron withdrawing substitution on the phenyl ring.
To understand the spectral and electrochemical properties
of these molecules, we have calculated frontier molecular
orbitals using the Gaussian 03 programme at B3LYP/6-31G
level. The geometry optimized structure (Fig. S5, ESI ) at the
3
same level of theory is used as inputs for the molecular orbital
(MO) calculations. The input for the geometry optimization is
derived from the single crystal X-ray structure of 1. Though the
light absorbing moiety maintains near planarity, the phenyl
ring slightly deviates from planarity by a factor of 46u with
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respect to ethylene bridge. In addition, the bond length of C–C
single bond that connects the olefinic bond and the phenyl
ring is calculated to be 1.47 Å, a value smaller than the typical
C–C bond length, 1.54 Å. Such findings are consistent with the
experimental result that a small, but significant electronic
interaction exists between the pyrazoline and phenyl groups
through intervening olefinic bond. The molecular orbital
diagram of 1, 1e, and 1f are given in Fig. 6. The highest
occupied molecular orbital (HOMO) and lowest unoccupied
molecular orbital (LUMO) energy levels of the pyrazoline
studied here are perturbed to the maximum extent of only
¡0.15 eV with the substitution, however, the higher energy
levels HOMO-1, HOMO-2, LUMO + 1, and LUMO + 2 undergo
notable changes characteristic of the substituent. For the
parent compound 1, the orbital coefficients in HOMO are
localized on the pyrazoline, N-phenyl and olefinic moiety. On
the other hand, the orbital coefficients have been shifted to
styryl group in LUMO. This result suggests that the singlet
excited states possess a considerable amount of charge
transfer character. In line with the MO energy level changes
upon substitution, the orbital coefficients of all the MO’s have
not been perturbed with the substitution except the ones with
2-CF3 and 2,4-dichloro groups, particularly the LUMO’s as
shown in Fig. 6. Indeed, a significant amount of orbital
coefficient is found to be localized on substituents like CF3
and chlorine on styryl group that induces more charge transfer
interaction between the pyrazoline and styryl moiety. This
observation is in line with the photophysical studies that only
CF3 and dichloro substituents exhibit more pronounced
charge transfer interactions than the remaining substituents.
We have also compared the frontier orbitals of ortho vs. para
phenylene substitution. Evidently, the HOMO, LUMO energy
undergoes slight or negligible changes, which is in concur-
rence with the nearly unchanged UV-visible absorption
maximum irrespective of ortho or para phenylene substitution
(Fig. S6–S8, ESI ). Nonetheless, the electron density on the
3
5-aryl substituents in LUMO + 1 orbital (Fig. 6) suggests that, it
would be possible to induce intramolecular electron transfer
between the electronically decoupled, 5-aryl and pyrazoline
moieties by the judicious choice of 5-aryl substituent.
To check the validity of molecular orbitals, the electro-
chemical properties of pyrazolines were measured by cyclic
voltammetry (CV) in acetonitrile using 0.1 M tetrabutyl
ammonium perchlorate as a supporting electrolyte and the
Fig. 6 Molecular orbital diagram of pyrazolinopiperidines calculated using
Gaussian 03 programme at B3LYP/6-31G level of theory. Hydrogen atoms are
omitted for clarity.
Fig. 7 Cyclic voltammograms of compounds measured at the scan rate of 50
mV s21 in acetonitrile using glassy carbon as working electrode and 0.1 M TBAP
as supporting electrolyte.
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representative CV is given in Fig. 7. The first oxidation and
first reduction potential of all the compounds are summarized
in Table 3. As can be seen from the Fig. 7, all the compounds
are oxidized irreversibly between the potential range of 0.54–
0.69 V versus Ferrocenium/Ferrocene redox couple. The first
oxidation process of pyrazolines would be attributed to the
irreversible oxidation of N-aryl group of pyrazole ring. Since,
the electron withdrawing/donating groups are substituted on
the styryl moiety and not on the N-aryl moiety, effect of
substituents on the oxidation potential has been smaller and
in fact, negligible in few cases. This observation is in
concurrence with the calculated data that the preferential
location of HOMO is more localized on pyrazoline ring, which
has not been affected by substitution to a significant extent. In
contrast, the first reduction process is spread over a larger
potential range 22.3 to 21.94 V and is characteristic of the
substituents X and Y. A greater reduction potential of 22.3 V is
observed for the parent compound 1. Apparently, the electron
withdrawing fluorine and chlorine group sufficiently lowers
the reduction potential at least by 0.3 V except 1d, which shows
only 0.15 V lowering in the reduction potential. The first
reduction step involves the addition of an electron to the
pyrazoline moiety to form the radical anion. Further, from the
first oxidation and reduction potential, the HOMO and the
LUMO energy levels can be calculated using the relationship
and high yielding two step reactions. The introduction of double
bond between the pyrazoline and phenyl moiety red-shifted the
absorption and fluorescence spectral maximum due to the
extension of p-conjugation pathway. Consequently, green emit-
ting pyrazolines have been developed. The non-overlapping
absorption and fluorescence spectrum of these compounds and
consequent larger Stokes shift values ca. 8000 cm21 underscores
their importance in fluorescence based applications. The
theoretical calculations and solvent polarity dependent fluores-
cence properties suggest that the singlet excited state of the
pyrazoline possess significant charge transfer interaction between
the pyrazoline and styryl moiety. Indeed, these charge transfer
interactions were influenced by the electron donating/ with-
drawing substituents to a lesser extent except 2-trifluoro methyl
and 2,4-dichloro groups. The present study also demonstrates the
distinct photophysical behaviour with respect to aryl substitution
position (ortho or para) owing to their difference in ortho and para
phenylene positions. This is line with the well-known fact that
ortho substituent exerts higher steric effect than para substitu-
ents. As a consequence ortho isomers have comparatively lesser
electronic interaction with phenyl ring than the para isomer.
Further, to induce the intramolecular charge transfer process,
strong electron withdrawing groups such as CF3 and multiple
halogen substituents become necessary. The electrochemical
reduction potential of the pyrazolinopiperidines has been
significantly influenced by the nature as well as position of the
substituents. We believe that the present study provide firm basic
understanding of the photophysical properties of pyrazolinopi-
peridines and will guide to design novel pyrazolines that show
strong intramolecular charge transfer interactions and also
absorb in different regions of the UV-visible spectrum.
E
HOMO = Eox + 4.4 and Ered + 4.4 respectively.51–53 Evidently, the
redox and theoretical data (compiled in Table 3) reveals that
the HOMO energy calculated from the oxidation potential
approximately matches with that of theoretical value. In fact,
as shown in Table 3, the energy gap calculated from the point
of intersection of normalized absorption and emission spectra
is in good agreement with electrochemical HOMO–LUMO gap.
Experimental section
Conclusions
General information
Pyrazolinopiperidines with different electron donating/electron
withdrawing substituents were synthesized by simple, greener
All the chemicals were purchased from commercial sources
and were used without further purification unless otherwise
Table 3 Electrochemical, theoretical HOMO–LUMO, and free energy changes for electron transfer process of pyrazolinopiperidines
Cmpd.
aEox (V)
aEred (V)
bEHOMO (eV)
bELUMO (eV)
cEg(eV)
dHOMO (eV)
dLUMO (eV)
eEg(eV)
fEg(eV)
1
0.60
0.61
0.56
0.69
0.71
0.65
0.63
0.61
0.54
0.65
0.67
22.31
22.13
22.20
21.98
22.17
22.14
22.03
22.03
22.10
21.99
21.94
25.00
25.01
24.96
25.09
25.11
25.05
25.03
25.01
24.94
25.05
25.07
22.09
22.27
22.20
22.42
22.23
22.26
22.37
22.37
22.30
22.41
22.46
2.91
2.74
2.76
2.67
2.88
2.79
2.66
2.64
2.64
2.64
2.61
24.79
24.79
24.57
24.90
24.95
25.01
25.09
24.73
24.68
24.98
25.06
21.31
21.22
21.06
21.47
21.50
21.69
21.63
21.22
21.17
21.50
21.63
3.48
3.56
3.51
3.43
3.46
3.32
3.46
3.51
3.51
3.48
3.43
2.86
2.90
2.83
2.86
2.82
2.82
2.81
2.86
2.88
2.89
2.84
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
a
The redox potential of compounds obtained from cyclic voltammetry using glassy carbon as working electrode with reference to Fc/Fc+
b
couple. 0.1 M Tetrabutylmmonium perchlorate was used as a supporting electrolyte. EHOMO/LUMO HOMO and LUMO energy levels calculated
from the redox potentials. Eg = electrochemical HOMO–LUMO energy gap. HOMO, LUMO energy calculated using Gaussian 03 programme
at B3LYP/6-31G level. Computed HOMO–LUMO energy gap. Optical HOMO–LUMO energy gap (Zero–Zero transition energy estimated from
the point of intersection of normalized absorption and emission spectra in acetonitrile).
c
d
e
f
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specified. Melting points were determined using micropro-
cessor digital melting point apparatus and are uncorrected.1H
NMR spectra were taken at 400 MHz and 300 MHz and 13C
NMR spectra were taken at 100 and 75 MHz using CDCl3 as the
solvent with TMS as an internal standard. HRMS analysis was
recorded using double focusing electron impact method.
Fluorescence quantum yields were obtained by using pro-
flavine in water (pH = 7) as a standard (0.34).The solid state
fluorescence spectra were measured using standard front face
configuration at 45u. Fluorescence lifetime of pyrazolines was
measured by the time correlated single photon counting
method. The fluorescence decay curves are measured by
exciting the molecules at 375 nm, ,200 ps light using Nano
LED. The cyclic voltammetry experiments were performed
using glassy carbon as working electrode, platinum wire as
counter electrode and Ag/AgCl as reference electrode. 0.1 M
tetrabutylammonium perchlorate was used as a supporting
electrolyte.
128.0, 128.3, 128.3, 128.7, 128.9, 129.2, 129.5, 136.1, 137.5,
141.7, 146.7, 151.6; HRMS for C32H29N3 Calculated [M+] m/z
455.2361, Found 455.2344.
7-(2-Methylbenzylidene)-5-benzyl-3,3a,4,5,6,7-hexahydro-3-(2-
methylphenyl)-2-phenyl-2H-pyrazolo[4,3-c]pyridine (1a)
Fluorescence green solid; mp: 158–160 uC; IR (KBr, cm21):
3026, 2942, 2805, 2794, 1938, 1596, 1494, 1379, 1253, 1122,
1
1043, 979, 892, 768, 679; H NMR (CDCl3, 400 MHz): d (ppm)
2.37 (s, 6H), 2.51–2.45 (t, J = 12.0 Hz, 1H), 3.10–3.06 (dd, J =
16.0, 4.0 Hz, 1H), 3.37–3.27 (m, 2H), 3.62–3.51 (dd, J = 34.0,
12.0 Hz, 2H), 3.76–3.65 (m, 1H), 3.89–3.85 (d, J = 16.0 Hz, 1H),
4.96 (s, 1H), 6.81–6.78 (t, J = 6.0 Hz, 1H), 6.97–6.95 (d, J = 8.0
Hz, 2H), 7.03–7.01 (d, J = 8.0 Hz, 2H), 7.25–7.07 (m, 14H), 7.33
(s, 1H); 13C NMR (CDCl3, 100 MHz): d (ppm) 19.6, 20.2, 25.6,
54.6, 55.9, 61.9, 67.7, 68.0, 114.6, 120.1, 125.2, 125.4, 125.5,
126.5, 127.3, 127.7, 128.2, 128.3, 128.8, 129.0, 129.2, 130.1,
130.3, 130.7, 134.9, 137.4, 137.5, 146.7; HRMS for
C
34H33N3Calculated [M+] m/z 483.2674, Found 483.2671.
Synthesis of 1-benzyl-3,5-dibenzylidinepiperidine-4-one
derivatives (4a–4p).
7-(2-Methoxybenzylidene)-5-benzyl-3,3a,4,5,6,7-hexahydro-3-(2-
methoxyphenyl)-2-phenyl-2H-pyrazolo[4,3-c]pyridine (1b)
A mixture of N-benzyl-4-piperidone (0.01 mol) and correspond-
ing aromatic aldehyde (0.02 mol) in 15 ml of MeOH was stirred
for 15 min followed by dropwise addition of 5 mol % NaOH.
The completion of reaction was monitored by TLC. After the
completion of reaction, the solid obtained was filtered and
washed with water. The crude product was recrystallized using
ethanol and THF in 1 : 1 ratio. The pure compound so
obtained was used as starting material for the synthesis of 1,
1a–1f and 2a–2i.
Yellow solid; mp: 183–185 uC; IR (KBr, cm21): 3027, 2936, 2833,
2772, 1596, 1497, 1455, 1437, 1382, 1314, 1293, 1247, 1127,
1085, 1050, 1025, 1002, 914, 872, 782, 692; 1H NMR (CDCl3,
400 MHz): d (ppm) 2.48–2.42 (t, J = 12.0 Hz, 1H), 3.26–3.17 (m,
2H), 3.39–3.34 (m, 1H), 3.49–3.46 (d, J = 12.0 Hz, 1H), 3.65 (s,
3H), 3.73–3.70 (d, J = 12.0 Hz, 1H), 3.86 (s, 3H), 3.98–3.94 (d, J =
16.0 Hz, 1H), 5.06–5.03 (d, J = 12.0 Hz, 1H), 6.79 (t, J = 7.8 Hz,
1H), 6.90–6.84 (m, 4H), 7.01–6.99 (d, J = 8.0 Hz, 2H), 7.24–7.12
(m, 10H), 7.39–7.36 (m, 2H); 13C NMR (CDCl3, 100 MHz): d
(ppm) 54.9, 55.0, 55.3, 55.5, 56.0, 61.7, 64.7, 110.4, 110.4,
114.7, 119.7, 119.9, 121.2, 121.6, 125.1, 127.1, 127.1, 128.2,
128.2, 128.3, 128.7, 129.0, 129.1, 129.6, 130.3, 138.1, 146.7,
152.2, 156.2, 157.8; HRMS for C34H33N3O2 Calculated [M+] m/z
515.2573, Found 515.2579.
Synthesis of 5-benzyl-7-(benzylidine)-3-(phenyl)-2-phenyl-
3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridines (1, 1a–1f
and 2a–2i).
A mixture of 4 (0.0025 mol) and phenyl hydrazine (0.0025 mol)
were taken in 25 ml of isopropanol and was allowed to
refluxing for an appropriate time (Table 1). The completion of
reaction was monitored by TLC using ethylacetate and hexane
mixture (1 : 9) as eluant. After the completion of reaction, the
reaction mixture was brought to room temperature and
poured into the crushed ice with constant stirring. The yellow
solid obtained was filtered and washed with water. The crude
product was allowed to dry and subjected to column
chromatography using ethyl acetate and hexane as an eluent.
The isolated final product was recrystalized using ethanol and
THF in 1 : 1 ratio.
7-(2-(Trifluoromethyl)benzylidene)-5-benzyl-3-(2-
(trifluoromethyl)phenyl)-3,3a,4,5,6,7-hexahydro-2-phenyl-
2H-pyrazolo[4,3-c]pyridine (1c)
Yellow solid; mp: 151–153 uC; IR (KBr, cm21): 3033, 2918, 2761,
1946, 1597, 1495, 1379, 1317, 1286, 1160, 1121, 1037, 897, 771,
686; 1H NMR (CDCl3, 300 MHz) : d (ppm) 2.57–2.50 (t, J = 10.5
Hz, 1H), 3.07–3.03 (d, J = 12.0 Hz, 1H), 3.46–3.31 (m, 2H), 3.60
(s, 2H), 3.74–3.70 (d, J = 12.0 Hz, 1H), 5.20–5.16 (d, J = 12.0 Hz,
1H), 6.86–6.84 (t, J = 6.0 Hz, 1H), 7.02–6.99 (d, J = 9.0 Hz, 2H),
7.21–7.14 (m, 8H), 7.45–7.43 (m, 4H), 7.61–7.56 (t, J = 7.5 Hz,
1H), 7.74–7.72 (t, J = 6.0 Hz, 2H), 7.92–7.89 (d, J = 9.0 Hz, 1H);
13C NMR (CDCl3, 75 MHz): d (ppm) 53.8, 56.3, 61.3, 66.6, 114.4,
120.3, 122.6, 126.2, 127.2, 127.4, 127.8, 128.2, 128.6, 128.8,
130.9, 131.3, 133.3, 137.4, 149.6; HRMS for C34H27F6N3
Calculated [M+] m/z 591.2109, Found 591.2112.
5-Benzyl-7-benzylidene-3,3a,4,5,6,7-hexahydro-2,3-diphenyl-
2H-pyrazolo[4,3-c]pyridine (1)
Fluorescence green solid; mp: 166–168 uC; IR (KBr, cm21):
3027, 2916, 2841, 2750, 1597, 1568, 1496, 1450, 1381, 1284,
1
1117, 1083, 918, 894, 749, 695; H NMR (CDCl3, 400 MHz): d
(ppm) 2.53–2.47 (t, J = 12.0 Hz, 1H), 3.19–3.15 (dd, J = 16.0, 4.0
Hz, 1H), 3.37–3.22 (m, 2H), 3.69–3.59 (dd, J = 22.0, 12.0 Hz,
2H), 4.06–4.03 (d, J = 12.0 Hz, 1H), 4.61–4.58 (d, J = 12.0 Hz,
1H), 6.84–6.80 (t, J = 8.0 Hz, 1H), 7.05–7.03 (d, J = 8.0 Hz, 2H),
7.17–7.12 (m, 2H), 7.25–7.19 (m, 8H), 7.27–7.32 (m, 4H), 7.37–
7.35 (m, 4H); 13C NMR (CDCl3, 100 MHz): d (ppm) 54.4, 55.3,
55.6, 61.9, 71.8, 115.1, 120.3, 126.2, 126.4, 127.3, 127.4, 127.7,
7-(2-Fluorobenzylidene)-5-benzyl-3-(2-fluorophenyl)-
3,3a,4,5,6,7-hexahydro-2-phenyl-2H-pyrazolo[4,3-c]pyridine
(1d)
Fluorescence green solid; mp: 157–159 uC; IR (KBr, cm21):
3021, 2916, 2869, 2755, 1632, 1596, 1493, 1455, 1385, 1309,
1278, 1230, 1123, 1029, 976, 889, 749, 692; 1H NMR (CDCl3,
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400 MHz): d (ppm) 2.59–2.53 (t, J = 12.0 Hz, 1H), 3.15–3.11 (dd,
J = 12.0, 4.0 Hz, 1H), 3.41–3.34 (m, 2H), 3.68–3.59 (dd, J = 22.0,
16.0 Hz, 2H), 3.88–3.84 (d, J = 16.0 Hz, 1H), 5.03–5.00 (d, J =
12.0 Hz, 1H), 6.86–6.83 (t, J = 6.0 Hz, 1H), 7.13–7.01 (m, 7H),
137.3, 137.3, 137.6, 138.7, 146.9, 151.8; HRMS for
C
34H33N3Calculated [M+] m/z 483.2674, Found 483.2688.
7-(4-Methoxybenzylidene)-5-benzyl-3,3a,4,5,6,7-hexahydro-3-(4-
methoxyphenyl)-2-phenyl-2H-pyrazolo[4,3-c]pyridine (2b)
Yellowish white solid; mp: 166–168 uC; IR (KBr, cm21): 3025,
7.22–7.15 (m, 9H), 7.29 (s, 1H), 7.51–7.47 (t, J = 8.0 Hz, 1H); 13
C
NMR (CDCl3, 100 MHz): d (ppm) 54.4, 54.9, 55.6, 61.7, 64.1,
114.9, 115.4, 115.7, 118.9, 119.0, 120.5, 123.6, 123.7, 125.1,
125.1, 127.3, 128.0, 128.0, 128.3, 128.8, 128.9, 129.0, 129.1,
129.3, 129.4, 129.9, 130.6, 130.6, 137.4, 146.2, 151.2, 158.7,
159.3, 161.1, 161.8; HRMS for C32H27F2N3 Calculated [M+] m/z
491.2173, Found 491.2159.
2933, 2798, 1601, 1509, 1459, 1382, 1295, 1247, 1176, 1030,
1
882, 830, 754, 699; H NMR (CDCl3, 400 MHz) : d (ppm) 2.48–
2.43 (t, J = 10.0 Hz, 1H), 3.18–3.14 (dd, J = 12.0, 4.0 Hz, 1H),
3.33–3.21 (m, 2H), 3.70–3.59 (dd, J = 32.0, 12.0 Hz, 2H), 3.79 (s,
3H), 3.81 (s, 3H), 4.05–4.02 (d, J = 12.0 Hz, 1H), 4.54–4.51 (d, J =
12.0 Hz, 1H), 6.83–6.79 (t, J = 8.0 Hz, 1H), 6.89–6.84 (m, 4H),
7.05–7.03 (d, J = 8.0 Hz, 2H), 7.19–7.12 (m, 4H), 7.30–7.21 (m,
8H); 13C NMR (CDCl3, 100 MHz) : d (ppm) 55.2, 55.3, 55.5, 71.4,
113.7, 114.6, 115.2, 120.2, 126.2, 127.3, 128.3, 128.7, 128.8,
128.9, 130.9, 133.6, 137.6, 146.9, 151.9, 158.9, 159.1; HRMS for
C34H33N3O2 Calculated [M+] m/z 515.2573, Found 515.2586.
7-(2-Chlorobenzylidene)-5-benzyl-3-(2-chlorophenyl)-
3,3a,4,5,6,7-hexahydro-2-phenyl-2H-pyrazolo[4,3-c]pyridine
(1e)
Fluorescence green solid; mp: 167–169 uC; IR (KBr, cm21):
3025, 2918, 2805, 2750, 1594, 1494, 1441, 1383, 1305, 1284,
1200, 1118, 1030, 978, 885, 747, 695; 1H NMR (CDCl3, 400
MHz): d (ppm) 2.66–2.60 (t, J = 12.0 Hz, 1H), 3.12–3.08 (dd, J =
16.0, 4.0 Hz, 1H), 3.40–3.33 (m, 1H), 3.51–3.47 (m, 1H), 3.65–
3.58 (dd, J = 16.0, 12.0 Hz, 2H), 3.83–3.79 (d, J = 16.0 Hz, 1H),
5.26–5.23 (d, J = 12.0 Hz, 1H), 6.85–6.81 (t, J = 8.0 Hz, 1H), 6.98–
6.95 (d, J = 12.0 Hz, 2H),7.09–7.06 (dd, J = 8.0, 4.0 Hz, 1H),
7.26–7.11 (m, 11H), 7.40–7.35 (t, J = 6.0 Hz, 3H), 7.61–7.58 (dd,
J = 8.0, 4.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz): d (ppm) 53.9,
55.5, 56.1, 61.5, 67.2, 114.7, 120.4, 123.3, 126.2, 127.2, 128.0,
128.2, 128.7, 128.8, 128.9, 129.6, 129.7, 130.5, 132.0, 134.1,
134.5, 137.4, 138.9, 145.9, 150.6; HRMS for C32H27Cl2N3
Calculated [M+] m/z 523.1582, Found 523.1582.
7-(4-Fluorobenzylidene)-5-benzyl-3-(4-fluorophenyl)-
3,3a,4,5,6,7-hexahydro-2-phenyl-2H-pyrazolo[4,3-c]pyridine
(2c)
Yellow solid; mp: 173–174 uC; IR (KBr, cm21): 3030, 2939, 2816,
2756, 1999, 1596, 1506, 1372, 1280, 1224, 1156, 1029, 975, 826,
1
751, 680; H NMR (CDCl3, 400 MHz): d (ppm) 2.51–2.48 (t, J =
10.0 Hz, 1H), 3.15–3.10 (dd, J = 12.0, 4.0 Hz, 1H), 3.32–3.21 (m,
2H), 3.69–3.60 (dd, J = 16.0, 12.0 Hz, 2H), 3.99–3.96 (d, J = 12.0
Hz, 1H), 4.59–4.56 (d, J = 12.0 Hz, 1H), 6.86–6.82 (t, J = 8.0 Hz,
1H), 7.07–6.97 (m, 6H), 7.30–7.13 (m, 10H), 7.35–7.32 (m, 2H);
13C NMR (CDCl3, 100 MHz): d (ppm) 54.2, 55.2, 55.6, 61.9, 71.1,
115.1, 115.2, 115.4, 116.1, 116.3, 120.6, 125.3, 127.4, 127.7,
127.8, 128.3, 128.8, 128.8, 131.0, 131.1, 132.1, 146.5, 151.4,
163.5; HRMS for C32H27F2N3 Calculated [M+] m/z 491.2173,
Found 491.2172.
7-(2,4-Dichlorobenzylidene)-5-benzyl-3-(2,4-dichlorophenyl)-
3,3a,4,5,6,7-hexahydro-2-phenyl-2H-pyrazolo[4,3-c]pyridine (1f)
Fluorescence green solid; mp: 203–205 uC; IR (KBr, cm21):
3028, 2806, 2747, 1591, 1494, 1383, 1308, 1104, 1028, 820, 754,
696; H NMR (CDCl3, 400 MHz): d (ppm) 2.63–2.57 (t, J = 12.0
7-(4-Chlorobenzylidene)-5-benzyl-3-(4-chlorophenyl)-
3,3a,4,5,6,7-hexahydro-2-phenyl-2H-pyrazolo[4,3-c]pyridine
(2d)
Yellow solid; mp: 195–196 uC; IR (KBr, cm21): 3024, 2956, 2882,
1
Hz, 1H), 3.09–3.05 (dd, J = 16.0, 4.0 Hz, 1H), 3.32 (m, 1H), 3.48–
3.44 (m, 1H), 3.66–3.58 (dd, J = 20.0, 12.0 Hz, 2H), 3.78–3.75 (d,
J = 12.0 Hz, 1H), 5.20–5.17 (d, J = 12.0 Hz, 1H), 6.88–6.84 (t, J =
8.0 Hz, 1H), 6.94–6.92 (d, J = 8.0 Hz, 2H), 7.00–6.98 (d, J = 8.0
Hz, 1H), 7.28–7.12 (m, 10H), 7.42 (s, 2H), 7.54–7.52 (d, J = 8.0
Hz, 1H); 13C NMR (CDCl3, 100 MHz): d (ppm) 53.9, 55.4, 55.9,
61.6, 114.7, 120.8, 122.3, 126.6, 127.4, 128.3, 128.948, 129.2,
129.5, 130.0, 132.6, 133.9, 134.0, 135.2, 137.3, 137.4, 145.6,
150.4; HRMS for C32H25Cl4N3 Calculated [M+] m/z 591.0803,
Found 591.0801.
2794, 1903, 1596, 1488, 1375, 1291, 1131, 1091, 1010, 898, 825,
1
751, 690; H NMR (CDCl3, 400 MHz): d (ppm) 2.50–2.47 (t, J =
12.0 Hz, 1H), 3.14–3.10 (dd, J = 12.0, 4.0 Hz, 1H), 3.26–3.14 (m,
2H), 3.68–3.59 (dd, J = 24.0, 12.0 Hz, 2H), 3.98–3.95 (d, J = 12.0
Hz, 1H), 4.59–4.56 (d, J = 12.0 Hz, 1H), 6.86–6.83 (t, J = 6.0 Hz,
1H), 7.01–6.99 (d, J = 8.0 Hz, 2H), 7.18–7.12 (m, 4H), 7.23–7.20
(m, 4H), 7.29–7.25 (m, 4H), 7.34–7.30 (m, 4H); 13C NMR
(CDCl3, 100 MHz): d (ppm) 54.2, 55.1, 55.5, 61.9, 71.2, 115.1,
120.7, 125.1, 127.4, 127.5, 128.4, 128.5, 128.5, 128.8, 128.8,
129.5, 130.7, 131.5, 133.3, 133.5, 134.5, 135.3, 137.3, 140.1,
146.3, 151.3; HRMS for C32H27Cl2N3 Calculated [M+] m/z
523.1582, Found 523.1577.
7-(4-Methylbenzylidene)-5-benzyl-3,3a,4,5,6,7-hexahydro-3-(4-
methylphenyl)-2-phenyl-2H-pyrazolo[4,3-c]pyridine (2a)
Fluorescence green solid; mp: 194–196 uC; IR (KBr, cm21):
3026, 2922, 2793, 1597, 1494, 1301, 1291, 1131, 1032, 898, 815,
751, 695; 1H NMR (CDCl3, 400 MHz): d (ppm) 2.34 (s, 6H),
2.49–2.44 (t, J = 10.0 Hz, 1H), 3.19–3.15 (dd, J = 16.0, 4.0 Hz,
1H), 3.32–3.20 (m, 2H), 3.69–3.58 (dd, J = 32.0, 16.0 Hz, 2H),
4.06–4.03 (d, J = 12.0 Hz, 1H), 4.57–4.54 (d, J = 12.0 Hz, 1H),
6.83–6.81 (t, J = 8.0 Hz, 1H), 7.05–7.03 (d, J = 8.0 Hz, 2H), 7.16–
7.12 (m, 8H), 7.27–7.20 (m, 8H); 13C NMR (CDCl3, 100 MHz): d
(ppm) 21.1, 21.3, 54.5, 55.3, 55.6, 61.9, 71.7, 115.1, 120.2,
126.1, 127.2, 128.3, 128.7, 128.9, 129.0, 129.5, 129.9, 133.3,
Acknowledgements
B. U. expresses his thanks to VIT management for providing
financial support through research associateship. We thank
Prof. A. B. Mandal, Director, CSIR-CLRI for his encourage-
ment. The authors thank Prof. P. Ramamurthy, and Dr C.
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