Synthesis of 1,4-dihydropyridines under solvent free conditions and investigation of their photo physical properties

Article abstract of DOI:10.1016/j.saa.2011.09.062

Synthesis of five 4-aryl substituted 1,4-dihydropyridines was developed following condensation of multi component reaction strategy using yttrium triflate as a catalyst. The absorption and fluorescence properties of structurally related 4-aryl 1,4-dihydropyridines in different solvents of varied polarities was investigated. The absorption maxima of these compounds follow no order of solvent polarity and nature of substitution. The spectral characteristics are solvent and compound specific. Fluorophores with electron withdrawing group have larger fluorescence quantum yields and greater solvatochromism than the compounds with electron donating groups. Protic solvents yielded higher fluorescence quantum efficiency. The chemical shift of the proton attached to C-4 and the carbonyl stretching frequency of bis acetyl groups at 3 and 5-positions exhibited a linear relationship with Hammett's para substituent constants while no such relationship exists between the latter and electronic absorption maxima, fluorescence emission maxima, fluorescence quantum efficiency and Stokes shift.

Full text of DOI:10.1016/j.saa.2011.09.062

Spectrochimica Acta Part A 85 (2012) 210–216
Contents lists available at SciVerse ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Synthesis of 1,4-dihydropyridines under solvent free conditions and
investigation of their photo physical properties
∗
J. Ramchander, Gajula Raju, N. Rameshwar, T. Sheshashena Reddy, A. Ram Reddy
Department of Chemistry, University college of Science, Osmania University Campus, Hyderabad, Andhra Pradesh 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 August 2011
Accepted 29 September 2011
Synthesis of five 4-aryl substituted 1,4-dihydropyridines was developed following condensation of multi
component reaction strategy using yttrium triflate as a catalyst. The absorption and fluorescence prop-
erties of structurally related 4-aryl 1,4-dihydropyridines in different solvents of varied polarities was
investigated. The absorption maxima of these compounds follow no order of solvent polarity and nature
of substitution. The spectral characteristics are solvent and compound specific. Fluorophores with elec-
tron withdrawing group have larger fluorescence quantum yields and greater solvatochromism than
the compounds with electron donating groups. Protic solvents yielded higher fluorescence quantum effi-
ciency. The chemical shift of the proton attached to C-4 and the carbonyl stretching frequency of bis acetyl
groups at 3 and 5-positions exhibited a linear relationship with Hammett’s para substituent constants
while no such relationship exists between the latter and electronic absorption maxima, fluorescence
emission maxima, fluorescence quantum efficiency and Stokes shift.
Keywords:
Dihydropyridine
Solvatochromism
Stokes shift
Fluorophore
©
2011 Elsevier B.V. All rights reserved.
1
. Introduction
acetoacetate, a ␤-ketoester is another variation in the preparation
of 3,5-disubstituted 1,4-dihydropyridines [15]. Suneet Shukla et al.
have observed that the 1,4-dihydropyridines inhibited the photo
labeling of both wild-type and mutant ABCG2 due to their absorp-
tion and emission characteristics in the UV–vis region facilitating
the investigations in the direction of multi drug therapy [16]. In
spite of profound significance, the synthesis of DHPs in the envi-
ronment friendly conditions is not much explored and their photo
physical behavior, the emission characteristics of these potential
drugs is not explored. Therefore, in this paper, we report a facile
method of synthesis of five 4-aryl-1,4-dihydropyridines employ-
ing Y(OTf)3 as a new catalyst under organic solvent free conditions
and a detailed study of the absorption and steady state fluorescence
properties of the structurally related 1,4-dihydropyridines.
Synthesis of pyridine involving dihydropyridines (DHPs) as
intermediates is Hantzsch discovery [1]. However, when the four
component Hantzsch reaction keeping aromatic aldehyde as one
of the components was conducted the resulting 4-aryl dihyropy-
ridines led to a new thrust in the area of DHPs chemistry as they
have become valuable drugs for heart disease with useful effects
on angina, hypertension and in biological systems, particularly
in NADH triggered biological redox reactions [2]. DHPs, such as
nifedipine, nitrendipine, and nimodipine have found commercial
utility as calcium blockers [3,4]. A number of DHP calcium antag-
onists have been introduced as potential drugs for the treatment
of congestive heart failure [5,6]. Among DHPs with other types of
bioactivity, cerebrocrast [7] has been introduced as a neuroprotec-
tant and cognition enhancer. In addition, a number of DHPs with
anti platelet aggregator activity [8], as chemical agents in the treat-
ment of Alzheimer’s disease [9] and as a chemo sensitizer in tumor
therapy [10] have also been discovered. A recent computational
analysis of the comprehensive medical chemistry data base found
that the DHP frame work to be among the most prolific chemo
types found. Thus the synthesis of this heterocyclic nucleus is of
continuing interest [11–14]. Use of 1,3-diketones instead of ethyl
2. Experimental
2.1. Materials
Aromatic aldehydes, acetyl acetone, ammonium acetate and
yttrium triflate were purchased from Aldrich and used without fur-
ther purification. Silica gel G (ACME) and silica gel finer than 60-120
mesh (ACME), was used for thin layer and column chromatography
respectively. All the solvents employed were of spectroscopic grade
and used without further purification.
The relative fluorescence quantum yields of DHPs were mea-
sured using 9,10-diphenylanthracene as reference.
∗ Corresponding author. Tel.: +91 9849684195; fax: +91 4027090020.
E-mail address: a ramreddy@yahoo.com (A.R. Reddy).
1
386-1425/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2011.09.062

J. Ramchander et al. / Spectrochimica Acta Part A 85 (2012) 210–216
211
R
5.30
5.25
5.20
-NO2
CHO
O
O
O
O
Y(OTf)3
0 ºC
+
+
NH4OAc
3
8
2
N
H
4
R
1
R=H, NO
2
, Cl, OCH
3
and CH
3
5.15
-H
-Cl
Scheme 1. Synthesis of 4-aryl-1,4-dihydropyridines under solvent-free conditions.
5
.10
.05
2.2. Materials characterization
-
CH
3
-OCH
5
3
The melting points reported were uncorrected and determined
in Polmon instrument (model No. MP-96). The IR spectra were
recorded on Bruker Infrared model Tensor-27. The H NMR spectra
-
0.4
-0.2
0.0
0.2
0.4
0.6
0.8
1
Hammett substitution constant
were recorded on 400 MHz of Bruker Ultrashield (Avance-III) Nano
Bay spectrometers using TMS as internal standard. The EI mass
spectra were recorded on a VG micro mass 7070-H. UV–vis spectra
were recorded on Elico SL 159 UV–vis spectrophotometer. Steady
state fluorescence was investigated on Shimadzu RF-5301PC spec-
trofluorophotometer, with 5 nm excitation and emission slit widths
Fig. 1. Dependence of C-4 1H chemical shift on the Hammett substitution constant
in the aryl ring of dihydropyridines.
−
(
KBr): cm 1, 3321(␯N-H), 1671(␯C O). 1H NMR (CDCl ): (ppm),
2.3 (t, 6H), 2.3 (s, 3H), 2.3 (s, 6H), 5.1 (s, 1H), 6.2 (s, 1H), 7.1 (d, 2H),
.1 (d, 2H). C18H21NO2 (283): Observed (Calc): (%) C, 75.93 (76.29),
H, 7.20 (7.47), N, 4.68 (4.94).
3
◦
3
at 18 C employing 1 cm quartz cell. Elemental composition was
determined by elemental analyzer, Elementar, Vario EL model.
8
2.3. Synthesis of DHPs
3. Results and discussion
1
,4-Dihydro pyridines (4) were synthesized from a combina-
Preparation of the compounds 4 (a–e) was developed following
tion of aldehyde (1) acetyl acetone (2) and ammonium acetate (3)
under mild and solvent-free condition as shown in Scheme 1. The
reaction was completed between 1.40 and 3.50 h at 80 C and the
crude product was isolated by precipitation upon the addition of
cold water to the reaction mixture and later decanting the aque-
ous layer. The residue was extracted with a suitable solvent. The
solvent was removed under vacuum and the impurities by column
chromatography of silica gel 60–120 mesh. The yield and mp of the
dihydropyridines prepared are shown in Table 1.
the four component cyclocondensation reaction by mixing aro-
matic aldehyde (1 mmol) and ammonium acetate (1 mmol) with
acetylacetone (2 mmol) in presence of yttrium triflate as a cata-
◦
◦
lyst under solvent free conditions at 80 C. This method was not
only afforded the products in excellent yields but also avoids the
problems associated with handling, safety, and pollution. This cata-
lyst is eco-friendly, non-volatile, non-explosive and easy to handle.
Thus, the 1,4-dihydropyridines prepared by employing five differ-
ent aldehydes are shown in Table 1.
2
.3.1. Characterization of DHPs: spectral data
As the reaction was carried out under solvent-free conditions,
clean products were obtained. However, traces of impurities asso-
ciated with the catalytic modification were removed by either
recrystallization from ethyl acetate and pet.ether mixture (1:2) or
by column chromatography over silica gel (Merck 60–120 mesh)
using ethyl acetate and pet.ether (2.5:7.5) as the mobile phase. The
yields presented in Table 1 are the best results obtained with a
1:1:2:0.01 ratio of aromatic aldehyde: ammonium acetate: acety-
lacetone: yttrium triflate. It was noticed that the aromatic aldehyde
with electron donating group readily yielded the DHP while the
electron withdrawing groups responded slowly
1
-(5-acetyl-2,6-dimethyl-4-phenyl-1,4-dihydro-3-pyridinyl)-
◦
−1
1
-ethanone, (4a), Yield: 91%, mp: 180–181 C. IR (KBr): cm , 3263
1
(
␯N-H), 1698 (␯C O). H NMR (CDCl ): (ppm), 1.3 (t, 6H), 2.3 (s,
3
6
H), 5.1 (s, 1H), 5.7 (s, 1H), 7.3 (m, 5H). C17H19NO (269): Observed
2
(
Calc): (%): C, 75.68 (75.81) H, 7.06 (7.11), N, 5.02 (5.20)
1
-(5-acetyl-4-[4-chloro phenyl]-2,6-dimethyl-1,4-dihydro-3-
◦
pyridinyl)-1-ethanone, (4b), Yield: 89%, mp: 190–192 C. IR (KBr):
cm , 3423 (␯N-H), 1700 (␯C O). H NMR (CDCl ): (ppm), 2.3 (t,
6
−
1
1
3
H), 2.3 (s, 6H), 5.1 (s, 1H), 5.8 (s, 1H), 7.3 (m, 4H). C17H18NO Cl
2
(
4
303.5): Observed (Calc): (%) C, 66.93 (67.21), H, 5.86 (5.97), N,
.42 (4.61).
-(5-acetyl-2,6-dimethyl-4-(4-nitro
1
phenyl)-1,4-dihydro-3-
3.1. IR and 1H NMR studies
◦
pyridinyl)-1-ethanone, (4c), Yield: 86%, mp: 189–191 C. IR (KBr):
cm , 3328(␯N-H), 1701(␯C O). H NMR (CDCl ): (ppm), 2.2 (t,
6
−
1
1
The synthesized compounds were characterized by IR, 1H NMR,
and mass spectral analysis and they are in good agreement with
reported data [15]. It is interesting to note that the Hammett’s para
3
H), 2.4 (s, 6H), 5.3 (s, 1H), 6.0 (s, 1H), 7.4 (d, 2H), 8.2 (d, 2H).
C17H18N O (314): Observed (Calc): (%) C, 64.62 (64.96), H, 5.48
2
4
(
5.77), N, 8.74 (8.91).
substituent constants and the carbonyl stretching frequency (ꢀCO)
1
-(5-acetyl-4-[4-methoxyphenyl]-2,6-dimethyl-1,4-dihydro-
of the acetyl substituent at C-3 and C-5 and the proton chemi-
cal shift values of C-4 attached proton bears a linear relationship.
Fig. 1 shows the relationship between the proton chemical shift val-
ues of the proton attached to C-4 and the Hammett’s substituent
constants while Fig. 2 gives the relationship between the carbonyl
stretching frequency of the acetyl substituent at C-3 and C-5 and
the Hammett’s substituent constants. The carbonyl stretching fre-
quency in IR is a fundamental mode of vibrations that depends on
◦
3
-pyridinyl) ethanone, (4d), Yield: 92%, mp: 171–173 C. IR (KBr):
−
1
1
cm , 3287(␯N-H), 1697(␯C O). H NMR (CDCl ): (ppm), 2.3 (t,
3
6
(
7
H), 2.3 (s, 6H), 3.8 (s, 3H), 5.1 (s, 1H), 5.9 (s, 1H), 6.8 (d, 2H), 7.2
d, 2H). C18H21NO3 (299): Observed (Calc): (%) C, 72.08 (72.22), H,
.07 (7.07), N, 4.50 (4.68).
1
-(5-acetyl-2,6-dimethyl1-4-(4-methyl phenyl)-1,4-dihydro-
◦
3
-pyridinyl)-1 ethanone, (4e), Yield: 90%, mp: 175–176 C. IR

2
12
J. Ramchander et al. / Spectrochimica Acta Part A 85 (2012) 210–216
Table 1
◦
1
,4-dihydropyridines prepared under solvent-free conditions at 80 C.
mp ( C) (Observed) (Literature)a
◦
S. No
R
Time (h)
Yield (%)
4
4
4
4
4
a
b
c
d
e
H
Cl
NO2
OCH3
CH3
1.50
2.15
3.50
1.40
2.00
91
89
86
92
90
180–181
190–192
189–191
171–173
175–176
183–185
NA
197–203
172–173
172–173
a
Ref. [15].
inductive effect, mesomeric effect and field effects. Therefore, in
the absence of any secondary bonding forces like the hydrogen
bonding, the linear relationship between the carbonyl stretching
frequency and the Hammett’s substituent constants reveal the con-
jugation of the phenyl ring at C-4 with the acetyl substituent at
C-3 in the DHPs. Unlike in IR, the proton chemical shift values in
proton NMR depend on various factors and it is expected that a lin-
ear relationship between the proton chemical shift values of C-4
attached proton and the Hammett’s substituent constants may not
exist. Interestingly Fig. 1 shows a good linear relationship between
the proton chemical shift values of C-4 attached proton and their
respective Hammett’s substituent constants. This shows that the
two rings, i.e., the phenyl ring and the dihydropyridine ring in 4-
aryl-1,4-dihydropyridines, are in one plane. Based on the above two
qualitative correlations it can be predicted that the C-4 carbon may
have substantial Sp2 character which renders extensive delocal-
ization of electrons from dihydropyridine ring to phenyl ring and
acetyl substituent at C-3 and C-5 to phenyl ring. Similar structure
activity relationship was observed by Zamponi et al. in the case of
arylsubstituted-4-isoxazolyl-1,4-dihydropyridines [17].
the electronic absorption studies are tabulated in Tables 2–6.
From the above tables it can be observed that though compounds
studied here are 1,4-dihydropyridines, they have exhibited all
the three absorption maxima characteristic of cross-conjugated
1,2- or 1,6-dihydropyridines. This may be due to the presence
of two acetyl groups in the 3 and 5 positions that would have
created a cross conjugated system leading to a new transition
at 250–300 nm. The unsubstituted 4-phenyl-1,4-dihydropyridine
(4a) exhibited absorption in the longer wavelength region than
the remaining 1,4-dihydropyridines. The presence of two acetyl
groups at 3 and 5 positions created a cross conjugated system
and with substantial p character of the C-4 make two rings in 4-
phenyl-1,4-dihydropyridine and their respective substituent lie in
one plane. The above observation can be further supported from the
1
Figs. 1 and 2 of H NMR and IR investigations. However, unlike in IR
1
and H NMR, the electronic absorption studies displayed no such
relationship between electronic transition energies and para Ham-
mett substituent constant. This is further demonstrated in Fig. 4
wherein a plot between electronic absorption maxima and para
Hammett substituent constant is shown. This can be due to the
cross conjugation imparted by two acetyl groups at C-3 and C-
5
positions of 1,4-dihydropyridine. The scattered points in Fig. 4
3.2. UV–vis studies
indicates that no linear relationship exist between the absorption
maxima and the para substituent. Thus the electronic absorption
spectral technique is the unique technique that can detect cross
conjugation while NMR and IR spectra fail to recognize such cross
conjugation in a molecule. From Tables 2–6 it can be observed
that there is no relationship exists between the energies of elec-
tronic transitions and the solvent polarity. When compared among
the ten solvents investigated, a broad generalization can be given
that the protic solvents and DMF could cause a bathochromic shift
while cyclohexane solvent led a hypsochromic shift of longer wave-
length absorption band. However a less polar chloroform (∈ = 4.81)
medium has given the absorption maximum at longer wavelength
Dihydropyridines are conjugated structures and as a result
they absorb the UV–vis light starting from 210 nm in the elec-
tronic absorption spectrum. 1,4-dihydropyridines usually have two
absorption maxima, band I in the region of 200–240 nm and band
III at 300–400 nm. A third band, band II at 250–300 nm is fre-
quently present in cross-conjugated 1,2- or 1,6-dihydropyridines
and has been used to distinguish these from their 1,4 isomers
which normally display a two-banded spectrum [18]. The elec-
tronic absorption spectra of all the compounds prepared are
shown in Fig. 3 in methanol. Similar spectra were obtained in
the remaining solvents. The spectral characteristics obtained in
1701
1700
1699
1698
1697
-
NO
2
-
Cl
-H
-
OCH
3
-0.4
-0.2
0.0
0.2
0.4
0.6
0.8
Hammett substitution constant
Fig. 2. Dependence of carbonyl stretching frequency on the Hammett substitution
constant in the aryl ring of dihydropyridines.
Fig. 3. The electronic absorption spectra of dihydropyridines [6.2 × 10−5] in
methanol.

J. Ramchander et al. / Spectrochimica Acta Part A 85 (2012) 210–216
213
Table 2
Spectral characteristics of 1-(5-acetyl-2,6-dimethyl-4-phenyl-1,4-dihydro-3-pyridinyl)-1-ethanone (4a).
2
−1
)
S. No
Solvent
Solvent polarity
ꢁabs.max (nm) (∈, dm mol
ꢁflu.max (nm)
Stoke shift
Ф
f
−
1
(
dielectric constant)
(cm
)
3
3
3
−7
1
2
3
4
5
6
7
8
9
Cyclohexane
Benzene
Chloroform
1,2-Dichloroethane
2-Propanol
Ethanol
Methanol
Acetonitrile
Dimethylformamide
Ethanol + HCl
2.02
2.28
4.81
10.42
20.80
25.3
33.00
36.64
38.25
211(1.8 × 10 ), 253.5(44 × 10 ), 354(0.7 × 10 )
454
474
499
460
456
457
464
429
462
494
6222
6003
6841
4386
4737
4573
5044
3863
3865
6212
9 × 10
2 × 10
3
3
−7
−6
276(37.8 × 10 ), 369(0.11 × 10 )
3
3
271(37.9 × 10 ), 372(0.37 × 10 )
1.4 × 10
3
3
3
−6
243.5(33 × 10 ), 280.4(20 × 10 ), 380(1.37 × 10 )
2 × 10
3
3
3
−6
−6
223.5(1.9 × 10 ), 268.5(53 × 10 ), 375(1.3 × 10 )
4.3 × 10
3
3
3
238.5(30 × 10 ), 278.5(24 × 10 ), 378(0.52 × 10 )
1 × 10
3
3
3
−6
−7
221(31 × 10 ), 283.5(26 × 10 ), 376(26 × 10 )
3.7 × 10
3
368(0.19 × 10 )
1 × 10
3
−6
392(1.5 × 10 )
5 × 10
3
3
3
−5
1
0
238.5(30 × 10 ), 278.5(24 × 10 ), 378(0.52 × 10 )
1.2 × 10
Table 3
Spectral characteristics of 1-(5-acetyl-4-[4-chloro phenyl]-2,6-dimethyl-1,4-dihydro-3-pyridinyl)-1-ethanone (4b).
2
−1
S. No
Solvent
Solvent polarity
ꢁabs.max (nm) (∈, dm mol
)
ꢁflu.max(nm)
Stoke
shift(nm)
Ф
f
(
dielectric constant)
3
3
−5
−5
−5
1
2
3
4
5
Cyclohexane
Benzene
Chloroform
1,2-Dichloroethane
2-Propanol
2.02
2.28
4.81
10.42
20.80
251(22 × 10 ), 347(8 × 10 )
454
473
489
465
458
107
114
119.5
100
78.5
1.5 × 10
1.2 × 10
3.1 × 10
3
3
280(9.2 × 10 ), 359(7.6 × 10 )
3
3
254.5(19.3 × 10 ),369.5(7.6 × 10 )
3
3
−5
249.5(25.4 × 10 ), 365(8.4 × 10 )
1 × 10
3
3
3
−5
218(4.3 × 10 ), 246.5(3.6 × 10 ), 270(26.4 × 10 ),
7.2 × 10
3
3
79.5(10.5 × 10 )
3
3
3
−5
6
7
8
9
Ethanol
Methanol
Acetonitrile
Dimethylformamide
Ethanol + HCl
25.3
210(1.9 ×10 ), 248.5(20.7 × 10 ), 379(9.7 × 10 )
457
455
429
435
478
78
75.5
60
60
99
4.2 × 10
3
3
−5
−6
−5
33.00
36.64
38.25
223.5(2.72 × 10 ), 379.5(10 × 10 )
3 × 10
6 × 10
1 × 10
3
3
250.5(27.5 × 10 ), 369(8.6 × 10 )
3
375(5.4 × 10 )
3
3
3
−6
1
0
210(1.9 × 10 ), 248.5(20.7 × 10 ),379(9.7 × 10 )
4.9 × 10
Table 4
Spectral characteristics of 1-(5-acetyl-2,6-dimethyl-4-(4-nitro phenyl)-1,4-dihydro-3-pyridinyl)-1-ethanone (4c).
2
−1
)
S. No
Solvent
Solvent polarity
ꢁabs.max (nm) (∈, dm mol
ꢁflu.max(nm)
Stoke shift
(nm)
Ф
f
(
dielectric constant)
3
3
3
−5
−5
−4
−5
−5
−5
−5
1
2
3
4
5
6
7
Cyclohexane
Benzene
Chloroform
1,2-Dichloroethane
2-Propanol
Ethanol
2.02
2.28
4.81
10.42
20.80
25.3
211(0.81 × 10 ), 283.5(59.7 × 10 ), 352(16.3 × 10 )
454
475
430
439
459
432
446
102
112
58
75
98
8.3 × 10
2.7 × 10
1.7 × 10
1.1 × 10
3.9 × 10
2.3 × 10
1.9 × 10
3
363(9.6 × 10 )
3
3
293.5(55.88 × 10 ), 372(12.66 × 10 )
3 3
211(3.69 × 10 ), 364(10.2 × 10 )
3
3
3
211(3.69 × 10 ), 286(60 × 10 ), 361(14.4 × 10 )
3
3
3
236(33.4 × 10 ), 298.5(49.75 × 10 ), 363(16 × 10 )
69
84
3
3
3
Methanol
33.00
218.5(30 × 10 ), 256(0.75 × 10 ), 296(53.3 × 10 ),
3
3
62(15.5 × 10 )
3
3
−4
−5
−5
8
9
0
Acetonitrile
Dimethylformamide
Ethanol + HCl
36.64
38.25
293.5(57.7 × 10 ), 364(14 × 10 )
444
451
504
80
88
141
1.2 × 10
7.6 × 10
4.6 × 10
3
3
293.5(50.6 × 10 ), 363(10.8 × 10 )
3
3
3
1
236(33.4 × 10 ), 298.5(49.75 × 10 ), 363(16 × 10 )
than the relatively more polar 1,2-dichloroethane (∈ = 10.42) sol-
biochemical reactions. In earlier days fluorescence character-
istics were employed as tool to distinguish 1,2-(1,6-) from
vent.
1
,4-dihydropyridines. The latter, usually fluoresce in the solid state
3
.3. Steady state fluorescence studies
as well as in solution on exposure to ultraviolet light. The emission
maxima for 1,2-(1,6-)-dihydropyridines display either a weak yel-
low or blue-green fluorescence (443–505 nm) or no fluorescence
at all and 1,4-dihydropyridines display the fluorescence maximum
Fluorescence of dihydropyridines was used for their detec-
tion on thin-layer chromatograms or for following certain
Table 5
Spectral characteristics of 1-(5-acetyl-4-[4-methoxyphenyl]-2,6-dimethyl-1,4-dihydro-3-pyridinyl)-1-ethanone (4d).
2
−1
)
S. No
Solvent
Solvent polarity
ꢁabs.max (nm) (∈, dm mol
ꢁflu.max (nm)
Stoke shift
(nm)
Ф
f
(
dielectric constant)
3
3
3
−5
1
2
3
4
5
Cyclohexane
Benzene
Chloroform
1,2-Dichloroethane
2-Propanol
2.02
2.28
4.81
10.42
20.80
216(0.7 × 10 ), 270.5(17.5 × 10 ), 347(5.88 × 10 )
429
470
501
478
455
82
104
133
111.5
75.5
3.4 × 10
−6
3
3
281(16.2 × 10 ), 366(4.6 × 10 )
7 × 10
3
3
3
−5
−6
240.5(2.7 × 10 ), 274.5(17 × 10 ), 368(4.99 × 10 )
1.9 × 10
3
3
272.5(18.2 × 10 ), 366.5(5 × 10 )
6 × 10
3
3
3
−6
218.5(4.2 × 10 ), 256.5(3.8 × 10 ), 270.5(19.7 × 10 ),
7 × 10
3
3
79.5(4.9 × 10 )
3
3
3
−6
−6
−6
−6
6
7
8
9
Ethanol
Methanol
Acetonitrile
Dimethylformamide
Ethanol + HCl
25.3
215(0.07 × 10 ), 244.5(17.6 × 10 ), 378(5 × 10 )
432
457
451
435
479
54
79
85
69
101
6 × 10
3
3
3
33.00
36.64
38.25
225(27 × 10 ), 296(11.13 × 10 ), 378(4.95 × 10 )
8 × 10
3
3
3
221.5(50.9 × 10 ),271.5(19.4 × 10 ), 366(4.97 × 10 )
2 × 10
3
366(3.25 × 10 )
3 × 10
3
3
3
−6
1
0
215(0.07 × 10 ), 244.5(17.6 × 10 ), 378(5 × 10 )
8 × 10

2
14
J. Ramchander et al. / Spectrochimica Acta Part A 85 (2012) 210–216
Table 6
Spectral characteristics of 1-(5-acetyl-2,6-dimethyl1-4-(4-methyl phenyl)-1,4-dihydro-3-pyridinyl)-1-ethanone (4e).
ꢀ
ꢁ
2
ε−1
Á
−1
2
−1
S. No
Solvent
ꢂf =
−
ꢁabs.max (nm) (∈, dm mol
)
ꢁflu.max (nm)
Stoke shift
nm)
Ф
f
2
ε−1
2Á2+1
(
3
3
3
−6
−5
−5
−5
−5
−5
−5
−5
−5
1
2
3
4
5
6
7
8
9
Cyclohexane
Benzene
Chloroform
1,2-Dichloroethane
2-Propanol
Ethanol
Methanol
Acetonitrile
Dimethylformamide
Ethanol + HCl
2.02
2.28
4.81
10.42
20.80
25.3
33.00
36.64
38.25
215(1.8 × 10 ), 251(18 × 10 ), 351.5(8.5 × 10 )
454
471
493
443
461
459
454
428
435
495
103
107
126
79
82
80
75
61
62
116
9 × 10
3
364(8 × 10 )
1.3 × 10
3.6 × 10
3
3
3
238(0.88 × 10 ), 263(16.97 × 10 ), 367(9.5 × 10 )
3
364(8.99 × 10 )
1 × 10
8 × 10
5 × 10
4 × 10
3
3
3
218(3.7 × 10 ), 269.5(19.5 × 10 ), 379(11.1 × 10 )
3
3
3
230.5(2.9 × 10 ), 248.5(18 × 10 ), 379(10.8 × 10 )
3
3
224.5(23 × 10 ), 379.5(10.6 × 10 )
3
3
250(22.7 × 10 ), 367(9.4 × 10 )
1.2 × 10
3
373.5(6.5 × 10 )
1 × 10
3
3
3
−5
1
0
230.5(2.9 × 10 ), 248.5(18 × 10 ), 379(10.8 × 10 )
4.6 × 10
2
2
2
2
2
2
2
2
8900
8800
8700
8600
8500
8400
8300
8200
spectra it can be inferred that the fluorescence spectrum is a mir-
ror image of the absorption spectrum and exhibits all the three
bands, i.e., transitions I, III and II, irrespective of the excitation
wavelength. The mirror image relationship between the fluores-
cence and absorbance spectra supports a rigid planar structure for
the 4-phenyl-1,4-dihydropyridine system. Tables 2–6 summarizes
-
CH3
-Cl
the spectral characteristics, i.e., absorption maxima (ꢁ ), fluores-
A
cence maxima (ꢁF), extinction coefficient (∈), stokes shift ((ꢁF−ꢁ )
A
and fluorescence quantum yield (ФF) of 4-aryl-dihydropyridines
in ten organic solvents. Akin to the absorption spectra, the fluo-
rescence emission maxima of these 4-phenyl-1,4-dihydropyridines
do not vary significantly with the substituent in the phenyl ring
of dihydropyridines and follow no linear relationship between the
fluorescence emission maxima and para Hammett substituent con-
stant as is demonstrated in fig 7. From Fig. 7 it is observed that
the emission maxima almost remained constant in a particular
solvent. The effects of solvent polarity on the absorption and fluo-
rescence are one origin of Stokes’ shift. The interactions between
the solvent and solute affect in the energy difference between the
ground and excited states. This energy difference is described by
the Lippert–Mataga equation, Eq. (1) [18].
-
OCH3
-
NO2
-
H
-
0.4
-0.2
0.0
0.2
0.4
0.6
0.8
Hammett substituent constant
Fig. 4. Dependence of absorption maxima on the Hammett substitution constant in
the aryl ring of dihydropyridines.
ꢂ
ꢃ
2
2
2
ε − 1
Á − 1
(ꢃE − ꢃG)
VA − VF =
−
+ Const
(1)
at 395–480 nm. Although the characteristic fluorescence of numer-
ous dihydropyridines has been known for a long time only a few
fluorescence spectra have been measured. The effect of solvent
polarity on the photo physical properties of 1,4-dihydropyridines
was investigated in ten different organic solvents of different polar-
ity. Fig. 5 shows the fluorescence spectra of compound 4e in
different solvents and Fig. 6 demonstrates the fluorescence spec-
tra of 4b, 4d and 4e in cyclohexane respectively. From the above
2
3
hc 2ε − 1
2Á + 1
a
ꢂ
ꢃ
2
ε − 1
Á − 1
ꢂf =
−
2
2ε − 1
2Á + 1
Fig. 6. Fluorescence spectra of 1-(5-acetyl-4-[4-chloro phenyl]-2,6-dimethyl-1,
−
5
4
-dihydro-3-pyridinyl)-1-ethanone (4b) [5.49 × 10 ], 1-(5-acetyl-4-[4-methoxy-
−5
phenyl]-2,6-dimethyl-1,4-dihydro-3-pyridinyl)-1-ethanone (4d) [5.57 × 10
]
Fig. 5. Fluorescence spectra of 1-(5-acetyl-2,6-dimethyl1-4-(4-methyl phenyl)-1,4-
dihydro-3-pyridinyl)-1-ethanone (4e) [5.88 × 10− ] in different solvents.
and 1-(5-acetyl-2,6-dimethyl1-4-(4-methyl phenyl)-1,4-dihydro-3-pyridinyl)-1-
5
−5
ethanone (4e) [5.88 × 10 ] in cyclohexane.

J. Ramchander et al. / Spectrochimica Acta Part A 85 (2012) 210–216
215
emission maxima of these 1,4-dihydropyridines in chloroform sol-
vent is always noticed at longer wavelength and have larger Stokes
shift values (except 4c) among all the solvents investigated. The
order of stokes shift is 4c > 4d > 4a > 4e > 4b.It is interesting to note
that more polar aprotic solvent like acetonitrile and DMF, more
polar protic solvents like methanol, isopropanol and ethanol causes
the fluorescence emission maximum blue shifted as in the case of
non polar aprotic solvent cyclohexane. However, in less polar chlo-
rine containing aprotic solvents and in benzene, the fluorescence
emission maximum is red shifted.
2
2
2
2
2
2
2
2
3400
3200
3000
2800
2600
2400
2200
2000
-Cl
The relative fluorescence quantum efficiency, Фf, of
1
,4-dihydropyridines have been determined employing 9,10-
diphenylanthracene as standard and the values obtained are shown
−
7
−4
-
OCH3
-NO2
in Tables 2–6. They vary in between 1 × 10 and 3.93 × 10 and
these values do not follow the order of Stokes shift. However,
examination of the above tables reveal that though the compounds
investigated were 1,4-dihydropyridines, they are dim fluorescent
like their 1,2-(1,6-) counterparts. This can be attributed to cross
conjugation present in 1,4-dihydropyridines. The fluorescence
quantum efficiency of compound 4c which has a NO2 group, a
strong electron withdrawing group, still has the larger quantum
yield followed by compound 4b which is again attached to a
ring deactivating chloro group. The quantum yield of compound
-
CH3
-H
0.0
-
0.4
-0.2
0.2
0.4
0.6
0.8
Hammett substitution constant
Fig. 7. Dependence of fluorescence emission maxima on the Hammett substitution
constant in the phenyl ring of dihydropyridines.
In the above equation, h is Planck’s constant, c is the speed of
light, and a is the radius of the cavity in which the fluorophore
resides. ꢀA and ꢀF are the wave numbers (cm ) of the absorp-
tion and emission, Á refractive index and ε is dielectric constant
respectively. The first parentheses in Eq. (1), is difference of two
terms ((ε − 1)/(2ε + 1) and (Á − 1)/(2Á + 1)), the difference of these
terms accounts for the spectral shifts due to reorientation of the
solvent molecules and hence called the orientation polarizability
4
4
c is about 100–1000 times larger than the quantum yield of
a. It is interesting to observe that the compound 4c which has
−
1
electron withdrawing NO2 group in the 4-phenyl ring has more
fluorescence quantum yield than compound 4e, which has elec-
tron donating group –OCH3 at the respective position. Mild polar
aprotic solvents such as chloroform, dichloroethane, benzene
caused a red shift in fluorescence emission maximum and have
decreased the quantum yield when compared with polar protic
solvents. For example, compound 4a shows the fluorescence
emission maximum intensity at 499 nm in chloroform, at 456 nm
in 2-propanol and at 464 nm in methanol while the fluorescence
2
2
(
ꢂf). The plot between ꢂf of nine different solvents and the Stokes
shift of compound 4a is given in Fig. 8. revealed that there is no lin-
ear relationship exist between ꢂf and Stokes shift indicating that
the solvent play a solvent specific role and no significant solva-
tochromism.
From Tables 2–6 it can be observed that the Stokes shift, a
parameter, which indicates the difference in the properties and
structure of the fluorophore between the ground state S , and the
first excited state S vary in between 6841 cm
and 3863 cm in acetonitrile for compound 4a. Similarly, for com-
pound 4b, the Stokes shift values vary in between 6792 cm in
−
6
−6
and
quantum yields in these solvents are 1.4 × 10 , 4.3 × 10
−
6
3
.7 × 10 respectively. The fluorescence quantum yield is always
higher in the hydroxylic solvents than in the other non hydroxylic
solvents. Similar results were reported by Wenska and co workers
in case of bioactive 9-oxo-imidazo [1,2-a] purine derivatives [19]
and Takara et al. in the fluorescence of ortho-aminobenzoic acid
derivatives [20].
0
−
1
in chloroform
1
,
−
1
−
1
−1
cyclohexane and 3678 cm in dimethylformamide. For compound
d the Stokes shift values vary in between 6496 cm in benzene
and 3625 cm in chloroform. The fluorescence emission spectrum
of 1,4-dihydropyridines is highly sensitive to solvent. Fluorescence
−
1
4
4. Conclusion
−
1
The experimental procedure for the synthesis of 1,4-
dihydropyridines is an important supplement to the existing
methods for the synthesis of 1,4-dihydropyridines under solvent-
free conditions with improved yields. This method has also been
found to have the ability to tolerate a wide variety of substituents.
The electronic absorption spectra of 1,4-dihydropyridines have not
displayed significant solvatochromism and the absorption maxima
follow neither the order of solvent polarity nor substitution depen-
dency. Compounds with electron withdrawing groups have larger
fluorescence quantum yields than the compounds with electron
donating groups. Among all the solvents investigated, acetonitrile
medium causes the emission maxima blue shifted in all the com-
pounds. Compound 4c with a strong electron withdrawing group
showed greater solvatochromism than the remaining compounds.
Spectral characteristics are solvent and compound specific. In
protic solvents the fluorescence quantum yields are larger. The C-4
attached proton chemical shift values and the carbonyl stretching
frequency of bis acetyl groups at 3,5-positions showed a linear
relationship with that of Hammett’s para substituent constants
while there is no such relationship exist between the latter and
electronic absorption maxima, fluorescence emission maxima,
7
6
6
5
5
4
4
3
000
500
000
500
000
500
000
3
1
2
1
. Cyclohexane
2. Benzene
3
4
5
6
7
8
. Chloroform
. 1,2-Dichloroethane
. 2-propanol
. Dimethylformamide
. Ethanol
9
5
4
7
. Acetonitrile
9. Methanol
6
8
500
-
0.05
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
Fig. 8. The Lippert-Mataga plot for compound 4a.

2
16
J. Ramchander et al. / Spectrochimica Acta Part A 85 (2012) 210–216
fluorescence quantum yields, Stokes shift and solvatochromism
due to cross conjugation.
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Acknowledgements
[
(
One of the authors J. Ramchander (JR) would like to thank the
Registrar, Osmania University for providing financial support under
Faculty Development Program and Head, department of chemistry,
Osmania University.
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