One-pot, solvent free synthesis of hantzsch 1, 4-dihydropyridines using β-cyclodextrin as a supramolecular catalyst

Article abstract of DOI:10.2174/157017811796504891

A novel, solvent free and efficient one pot synthesis of 1, 4-dihydropyridine derivatives was achieved in good yields via three component reaction of aldehydes, ethyl acetoacetate and ammonium acetate using inexpensive β- cyclodextrin as a supramolecular catalyst. The catalyst can be recovered and reused without loss of activity.

Full text of DOI:10.2174/157017811796504891

Letters in Organic Chemistry, 2011, 8, 477-483
477
One-Pot, Solvent Free Synthesis of Hantzsch 1, 4-Dihydropyridines Using
ꢀ-Cyclodextrin as a Supramolecular Catalyst
Dipak R. Patil and Dipak S. Dalal*
Department of Organic Chemistry, North Maharashtra University, Jalgaon - 425 001(M. S.), India
Received January 15, 2011: Revised April 25, 2011: Accepted April 25, 2011
Abstract: A novel, solvent free and efficient one pot synthesis of 1, 4-dihydropyridine derivatives was achieved in good
yields via three component reaction of aldehydes, ethyl acetoacetate and ammonium acetate using inexpensive ꢀ-
cyclodextrin as a supramolecular catalyst. The catalyst can be recovered and reused without loss of activity.
Keywords: 1, 4-dihydropyridine (1, 4-DHPs), hantzsch reaction, one pot condensation, ꢀ- Cyclodextrin (ꢀ-CD).
INTRODUCTION
infrared irradiation [25], sulfated zirconia [26],
SiO2/NaIISO4 [27], TMSCl-NaI [28], SiO2/HClO4 [29], and
organocatalyst [30]. However, most of the methods involve
the use of strong acidic conditions, expensive reagents, ex-
tended reaction time, harsh condition and tedious workup
leading to the generation of large amount of toxic waste.
Most of the research have been focused on the modification
and optimization of Hantzsch reaction to maximize reaction
conversion, minimize reaction time and offer high purity of
1, 4-DHPs.
There is always something new on the old topic of
Hantzsch reaction. This is mainly due to the fact that it offers
an efficient way to prepare 1, 4-dihydropyridines (1, 4-
DHPs) which exhibit significant biological activities [1] in
the treatment of cardiovascular diseases (as calcium channel
blockers). They have been used as anticonvulsant, antide-
pressive, antionaxeity, analgesic, antitumoral, hypnotic, vas-
codialtor, bronchodilator, and anti-inflammatory agents [2].
Some clinically important drugs such as Amlodipine,
Nifedipine, Felodipine, Isradipine and Nicardipine contain-
ing the 1, 4-dihydropyridine parent nucleus have been manu-
factured and used worldwide [3]. In addition, the dihydro-
pyridine unit has been widely employed as hydride source
for reductive amination [4]. They are also useful as cognition
enhancer, neuroportectance and platelet anti-aggrigatory
agent [5]. Some of 1, 4-DHPs act as NADH mimics for the
reduction carbonyl compounds and their derivatives [6].
Some Hantzsch esters serve as biomimetic reducing agents
(NADPH model [7]). 1, 4-dihydropyridines are also good
precursors of the corresponding substituted pyridine deriva-
tives [8]. Some 1,4-DHP moieties are also reported as drug-
resistance modifiers [9] antioxidants and a drug for the treat-
ment of urinary urge incontinence [10]. The author Hantzsch
first reported the synthesis of 1,4-dihydropyridines via the
condensation of aldehyde, ethyl aceto acetate with ammonia
in refluxing alcohol or acetic acid [11] which requires longer
reaction time and low to moderate yield of product. Up till
now, numerous literature citations exist relating to various
attempts to improve the Hantzsch reaction using alternative
catalyst and greener methods [12]. In recent years, several
new efficient methods have been developed including the
use of Mg3N2 as ammonia source [13], Ph3P [14], Sc(OTf)3
[15], PhB(OH)2 [16], ionic liquids [17], the use
heteropolyacid [18], ultrasound irradiation [19], molecular
iodine [20], by fermenting baker yeast [21], solid phase
synthesis [22], tetrabutyl ammonium hydrogen sulfate [23],
PEG-400-Na2CO3 [24], water based biphasic medium using
Beta cyclodextrin (ꢀ-CD) is a cyclic oligomer of D-
glucose having heptamar glucose unit [31] possessing
toroidal cyclic structure with secondary hydroxyl groups at
C-2 and C-3 on their more open face and the primary C-6
hydroxyl group on the opposite secondary face [32]. ꢀ-CD
has the ability to bind with organic molecule in hydrophobic
central cavity by supramolecular interactions like van der
waals interaction, hydrophobic interactions, hydrogen bond-
ing and electrostatic interactions between charged part of
guest molecule and beta cyclodextrin [33]. A series of or-
ganic reactions catalyzed by ꢀ-CD has been reported that
activates the substrate by supramolecular interactions [34].
By looking towards the development of biomimetic ap-
proaches through supramolecular catalysis involving cyclo-
dextrin; herein we have attempted the Hantzsch reaction in-
volving the synthesis of 1, 4-dihydropyridine using ꢀ-CD as
catalyst under solvent free condition. Beta cyclodextrin was
used as catalyst, since it is non toxic to environment, easily
accessible and inexpensive amongst various cyclodextrin.
RESULT AND DISCUSSION
For initial studies para-nitro benzaldehyde 2, ethyl ace-
toacetate 1, ammonium acetate 3 (1: 2:1.5) as representative
reactants and 1 mmol of ꢀ-CD catalyst were selected
(Scheme 1) for optimization of reaction. We found that at the
given ratio, the ethyl acetoacetate was not totally consumed
(monitor by TLC) affording low yield of 1, 4-DHP, so we
use excess of ammonium acetate (1: 2: 3) showing total con-
sumption of ethyl acetoacetate with better yield of product
this may due to the increase in concentration of liberating
ammonia. The effects of temperature on the reaction were
*Address correspondence to this author at the Department of Organic
Chemistry, North Maharashtra University, Jalgaon - 425 001(M. S.), India;
Tel: +91- 2572257433; Fax: +91- 2572258403;
E-mail: dsdalal2007@gmail.com
1570-1786/11 $58.00+.00
© 2011 Bentham Science Publishers

478 Letters in Organic Chemistry, 2011, Vol. 8, No. 7
Patil and Dalal
NO2
CHO
O
O
+
+
O
O
Me
OEt
O2N
Beta-CD,
EtO
OEt
1
2
Me
N
H
Me
AcONH4
3
4e
Scheme 1.
Table 1. To Study Effect of Temperature Using 1 mmol of Catalyst under Solvent Free Condition
Entry
p-NO2 Benzaldehyde (mmol)
Temp. (0C)
Time
Yield (%)
1
2
3
4
5
6
7
10
10
10
10
10
10
10
0-5
30
Not proceed
4.5 hr
-
50
52
60
87
72
73
40
4 hr
60
2 hr
80
20 min
30 min
25 min
100
120
examined under solvent free condition. The yield of the
product 4e was strongly dependent on the temperature. The
formation of the product at low temperature does not fever
even after exposure to long reaction time. We found that the
reaction time decreases and yield of product get increases
with increase in temperature. This might be because of the
increase in temperature that fevers the liberation of ammonia
from ammonium acetate and promoting the condensation.
The results were summarized in Table 1 and graphically
shown in Fig. (1).
(20mmol), ammonium acetate (30mmol) and ꢀ-CD ranging
from 0.1mmol to 10mmol at 800C with vigorous stirring
(Scheme 2). We found that the better result (87%) was ob-
tained at 1mmol of catalyst for 10mmol of substrate. When
the amount of catalyst was greater than 1mmol little decrease
in the yield of product (4e) occurs. Higher amount of ꢀ-CD
did not improve the result to the great extent. The results
were summarized in Table 2.
Furthermore, the effect of various solvents from non-
polar to polar on catalytic activity was examined by using
0.1mmol of catalyst for 1mmol of substrate under various
reaction condition. The various solvent afforded the desired
product in the lower to moderate yield (46-75 %). Better
yield obtained in ethanol (75 %). We also perform the reac-
tion in pure water at 800C but it requires long reaction time
(8hr) with moderate yield of 4e (68 %). Whereas, the neat
condition furnished the DHP 4e in 87%. The results are
summarized in Table 3.
In view of these results, we then selected the optimized
reaction condition to determine the scope of ꢀ-CD catalyzed
reaction under solvent free condition. A range of structurally
diverse aldehyde (1mmole), ethyl acetoacetate (2mmole),
ammonium acetate (3mmole), and catalytic amount of ꢀ-CD
(0.1mmole) were subjected for stirring under solvent free
condition at 800C (Scheme 3) to produce corresponding 1, 4-
DHPs in short time. The results were presented in Table 4. In
all cases, the crude product was obtained by extracting reac-
tion mixture in ethyl acetate and purified by recrystallization
in ethanol and column chromatography wherever needed.
Aliphatic, aromatic and heterocyclic aldehyde has been stud-
ied and gives the corresponding products in good to excel-
lent yield. It has been found that the aliphatic aldehyde re-
quires shorter reaction time than aromatic ones. The electron
Fig. (1). Effect of temperature for 1mmol of catalyst in synthesis of
1, 4 - DHP (4e) under solvent free condition.
After the preliminary investigation, our effects were di-
rected towards the evaluation of catalytic activity by using
para - nitro benzaldehyde (10mmol), ethyl acetoacetate

One-Pot, Solvent Free Synthesis of Hantzsch
Letters in Organic Chemistry, 2011, Vol. 8, No. 7
479
NO2
CHO
O
O
+
+
O
O
Me
OEt
O2N
Beta-CD,
80 0C
EtO
OEt
1
2
Me
N
H
Me
AcONH4
3
4e
Scheme 2.
Table 2. To Study Effect of Catalyst at 800C under Different Catalytic Condition
Entry
p-NO2 Benzaldehyde (mmol)
Time
Catalyst (mmol)
Yield (%)
1
2
10a
10a
10a
10a
10a
10a
10a
10b
10b
10b
10b
10b
10b
10b
3.5 hr
2.05 hr
50 min
42 min
20 min
2.0 hr
Nil
0.125
0.25
0.5
1
80
68
77
83
87
66
73
61
56
58
67
65
66
63
3
4
5
6
1.5
2
7
3.0 hr
8
3.5 hr
2.5
3
9
4.5 hr
10
11
12
13
14
4.15 hr
4.5 hr
3.5
4
4.45 hr
4.55 hr
7.0 hr
4.5
5
10
aunder solvent free condition.
bin10 ml of ethanol.
Table 3. To Study Effect of Various Solvent for Catalytic Activitya
Entry
Solvent
Temperature (0C)
Time (hr)
Yield (%)b
1
2
Hexane
CCl4
reflux
reflux
reflux
80
8
6.15
4.5
1.5
7
46
45
48
61
51
57
68
46
75
38
68
70
3
Chloroform
Acetic acid
THF
4
5
reflux
reflux
reflux
80
6
DCM
8.5
3
7
Methanol
Acetonitrile
Ethanol
8
4.15
3.15
1
9
80
10
11
12
DMSO c
80
Water
80
8
Ethanol: Water (50:50)
80
7.5
aReaction was carried out with p-NO2 Benzaldehyde (1 mmol), ethyl aceto acetate (2mmol), ammonium acetate (3mmol) and catalytic amount of ꢀ-CD (0.1mmol).
bIsolated yield.
cCatalyst not recovered.

480 Letters in Organic Chemistry, 2011, Vol. 8, No. 7
Patil and Dalal
O
O
O
R
O
R
+
OHC
Beta-CD,
80 0C
Me
OEt
EtO
OEt
Me
N
H
Me
1
+
2
AcONH4
4
3
Scheme 3.
Table 4. Beta Cyclodextrin-Catalyzed Hantzsch Synthesis of 1, 4-Dihydropyridine Under Solvent Free Condition at 800C a
Entry
R
Time
Product
Yield b
(%)
Melting point (0C)
Measured [Reported]
1
2
3
4
5
6
7
H
10 min
20 min
60 min
35 min
20 min
1.5 hr
4a
4b
4c
4d
4e
4f
95
86
90
92
87
90
88
176 [178-180]35
122 [118-120]35
158-160[156-158]16
166 [164-166]16
130 [130-132]16
146-148
CH3
C6H5
m-NO2C6H4
p- NO2C6H4
p- FC6H4
p- ClC6H4
30 min
4g
143 [144-146]16
8
3,4- (OCH3)2 C6H3
3,4,5- (OCH3)3 C6H2
2- Furyl
2.15 hr
2.5 hr
4h
4i
89
91
93
88
137 [138-140]15
142 [140-142]35
163 [160-162]14
196-198
9
10
11
10 min
30 min
4j
2- Pyridil
4k
aAll the reactions were performed using 0.1 mmol of catalyst.
bIsolated yield.
donor and electron withdrawer group also effect on the reac-
tion time (as shown in Table 4). The role of catalyst has been
confirmed when the similar reaction carried without addition
of catalyst under similar condition, it requires long reaction
time and lower yield of desire product. The recovered ꢀ-CD
was recrystallized twice from deionized water and then dried
FT-IR spectra of pure ꢀ-CD and recovered ꢀ-CD after suc-
cessive reactions. It shows that all FT-IR spectra are quite
similar. No new peaks appear in the recycled ꢀ-CD which
indicates that no chemical reaction occurred with ꢀ-CD.
From a mechanistic point of view ꢀ-CD may favors the
knoevenogel condensation through activation of carbonyl
0
at temperature of 110 C and recycled. Fig. (2) shows the
(a)
(b)
Fig. (2). (a) FT-IR spectrum of pure ꢀ-CD.
(b) Where a, b and c are FT-IR of first, second and third recycled ꢀ-CD.

One-Pot, Solvent Free Synthesis of Hantzsch
Letters in Organic Chemistry, 2011, Vol. 8, No. 7
481
Table 5. Study on the Reuse of ꢀ-CD
Recycle
1
2
3
4e Yield (%)
86
85
85
H
O
O
O
O
H
O
keto
enol
O
O
R
O
:NH3
H
O
O
O
O
O
Knoevenagal
condensation
O
-H2O
H2N
6
R
R
O
O
+ 6
O
C2H5O
OC2H5
CH3
O
Michael add.
H3C
O
HN
O
7
5
-H2O
Cyclisation
R
O
O
C2H5O
H3C
OC2H5
CH3
N
H
Scheme 4. Proposed mechanism for synthesis of 1, 4-dihydropyridine.
group of aldehyde via hydrogen bonding (supramolecular
interaction) [34] by providing microenvironment inside the
cavity of ꢀ-CD with one equivalent of ethyl acetoacetate OR
ꢀ-CD may favors the condensation of second equivalent of
beta ketoester with ammonia affording 6. Condensation of
these two fragments (Michael type addition) gives interme-
diate 7, which subsequently cyclizes followed by dehydra-
tion to corresponding 1, 4-dihydropyridine (Scheme 4).
General Procedure for the Preparation of Hantzsch 1, 4-
dihydropyridines
A mixture of aldehyde (1mmol), ethyl acetoacetate
(2mmol), ammonium acetate (3mmol), and catalytic amount
of beta cyclodextrin (0.1mmol) was heated with stirring at
800C under solvent free condition for appropriate time
(Table 4, monitored by TLC).The reaction mixture after
being cool to room temperature was poured into water
extracted three times with ethyl acetate. The organic layer
washed with 10% NaHCO3 solution, dried over anhydrous
Na2SO4, filtered and concentrate in rota evaporator to leave
crude product which was purified by recrystalization in
ethanol and column chromatography over silica gel using
hexane: ethyl acetate (10%) as eluent wherever needed. The
aqueous layer was lyophilized at lower temperature to
recovered precipitated cyclodextrin by filtration, allows dry-
ing and reused.
EXPERIMENTAL SECTION
Chemicals required for the synthesis were obtained from
Aldrich and Spectrochem. Melting points were uncorrected
and IR spectra were recorded Schimadzu FT-IR model IR-
1
Affinity-1 using KBr. HNMR spectra were recorded at 300
MHz in CDCl3 using TMS as an internal standard. Mass
spectra were under ESI mode, on Thermo Finnigan (Model-
LCQ Advantage MAX) mass spectrometer.

482 Letters in Organic Chemistry, 2011, Vol. 8, No. 7
Patil and Dalal
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CONCLUSION
In summary, we have described a simple and highly effi-
cient method for one pot three component synthesis of 1,4-
dihydropyridins in good to excellent yields from various
aliphatic, aromatic and heterocyclic aldehydes, ethyl ace-
toacetate, ammonium acetate in the presence of ꢀ-CD as a
supramolecular catalyst under solvent free condition. The
catalyst has been quantitatively recovered and reused. The
experimental protocol is simple, mild affording high yields
and represents an attractive alternative to existing methods.
Further use of this catalyst will be reported in due course.
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ACKNOWLEDGEMENT
The authors are thankful to Dr. K. B. Patil, Vice–
Chancellor, North Maharashtra University, Jalgaon, (India)
for providing necessary facilities. We are also thankful to
DST, New Delhi for the financial assistance under Fast
Track Scheme for Young Scientist.
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activating source. J. Mex. Chem. Soc. 2007, 51 (4), 181-184.
(a) Heravi, M. M.; Behbahani, F. K.; Oskooic, H. A.; Shoer, R. H.
Catalytic aromatization of Hantzsch 1, 4-dihydropyridines by ferric
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One-Pot, Solvent Free Synthesis of Hantzsch
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FT-IR (KBr, cm-1): 3341, 2925, 1687, 1650, 1123, 738; H-NMR
(CDCl3, 300 MHz, ppm): ꢄ = 1.21(t, 6H), 2.33(s, 6H), 4.08(q, 4H),
4.98(s, 1H), 5.61(s, 1H), 7.11-7.29(m, 5H); m/e = 330.3 [M+1],
352 [M+ Na].
[27]
[28]
[29]
Diethyl 4- (3-nitrophenyl)-2, 6-dimethyl-1, 4-dihydropyridine-3,
5-dicarboxylate(4d)
FT-IR (KBr, cm-1): 3323, 2923, 1698, 1672, 1459, 1376, 1117,
1
786; H NMR (CDCl3, 300 MHz, ppm): ꢄ = 1.22(t, 6H), 2.36(s,
6H), 4.08(q, 4H), 5.09(s, 1H), 5.82(s, 1H), 8.12(s, 1H), 8.02(d, 1H),
7.99(d, 1H), 7.37(t, 1H); m/e = 375.1[M+1], 397[M +Na].
Diethyl 4- (4-nitrophenyl)-2, 6-dimethyl-1, 4-dihydropyridine-3,
5-dicarboxylate (4e)
FT-IR (KBr, cm-1): 3318, 2924, 1701, 1648, 1459, 1348, 1120,
863; 1H-NMR (CDCl3, 300 MHz, ppm): ꢄ = 1.21(t, 6H), 2.35(s,
6H), 4.09(q, 4H), 5.09(s, 1H) 5.70(brs, 1H), 7.44(d, 2H), 8.08(d,
2H); m/e = 375.2[M+1], 397[M +Na].
[30]
Diethyl 4- (4-flurophenyl)-2, 6-dimethyl-1, 4-dihydropyridine-3,
5-dicarboxylate (4f)
[31]
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1
FT-IR (KBr, cm-1): 3341, 2924, 1686, 1650, 1123, 856; H-NMR
Cao, Y.; Xiao, X.; Lu, R.; Guo, Q. 1H NMR titration and quantum
calculation for the inclusion complexes of styrene and ꢀ-methyl
styrene with ꢀ, ꢁ and ꢂ-cyclodextrins. J. Mol. Stru. 2003, 660, 73.
Szitli, Introduction and General Overview of Cyclodextrin Chemis-
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(CDCl3, 300 MHz, ppm): ꢄ = 1.21(t, 6H), 2.32(s, 6H), 4.09(q, 4H),
4.96(s, 1H) 5.65(brs, 1H), 6.8 – 7.25(m, 4H); m/e = 348.1[M+1],
370[M+ Na].
Diethyl 4- (4-clorophenyl)-2, 6-dimethyl-1, 4-dihydropyridine-
3, 5-dicarboxylate (4g)
[33]
[34]
1
FT-IR (KBr, cm-1): 3358, 2960, 1695, 1651, 1118, 831; H-NMR
(a) Ji, H-B.; Shi, D-P.; Shao, M. li Z.; Wanf L-F Transition metal-
free and substrate-selective oxidation of alcohols using water as an
only solvent in the presence of ꢁ-cyclodextrin Tetrahedron Lett.
2005, 46, 2517 (b) Surendra, K.; Krishnaveni, N.S.; Mahesh A.;
Rao, K. R. Supramolecular catalysis of strecker reaction in water
under neutral condition in presence of beta cyclodextrin. J. Org.
Chem. 2006, 71, 2532-2534. (c) Pavan Kumar, V.; Prash Reddy,
V.; Shridhar,R.; Srinivas, B.; Narendra, M.; Rao, K. R. Su-
pramolecular synthesis of 3-indolyl-3-hydroxy oxindoles under
neutral condition in water. J. Org. Chem. 2008, 73, 1646-1648. (d)
Krishnaveni, N. S.; Surendra, K.; and K. R. Rao, Study of Michael
addition of beta cyclodextrin – thiol complexes to conjugated
alkene in water. Chem. Comm. 2005, 669-671.
(CDCl3, 300 MHz, ppm): ꢄ = 1.21(t, 6H), 2.32(s, 6H), 4.09(q, 4H),
4.95(s, 1H) 5.58(brs, 1H), 7.23 – 7.15(m, 4H); m/e = 362.1[M-1],
364.1[M+1].
Diethyl 4- (3, 4-dimethoxyphenyl)-2, 6-dimethyl-1, 4-
dihydropyridine-3, 5-dicarboxylate (4h)
FT-IR (KBr, cm-1): 3344, 3093, 2981, 1687, 1651, 1209, 1120; 1H-
NMR (CDCl3, 300 MHz, ppm): ꢄ = 1.23(t, 6H), 2.33(s, 6H), 3.81(s,
3H), 3.83(s, 3H), 4.10(q, 4H), 4.94(s, 1H) 5.52(s, 1H), 6.70 –
6.87(m, 3H); m/e = 389.1, 388.1[M-1].
Diethyl 4- (3, 4, 5-trimethoxyphenyl)-2, 6-dimethyl-1, 4-
dihydropyridine-3, 5-dicarboxylate (4i)
FT-IR (KBr, cm-1): 3356, 2980, 1695, 1647, 1205, 1130; 1H-NMR
(CDCl3, 300 MHz, ppm): ꢄ = 1.25(t, 6H), 2.34(s, 6H), 3.79(s, 9H),
4.12(q, 4H), 4.97(s, 1H), 5.54(s, 1H), 6.51(s, 2H); m/e = 418.2 [M-
1], 420.1[M+1], 419.1
[35]
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Nayak, A. S.; Achaiah, G.; Malla Reddy, V. Rapid microwave
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Diethyl 4- (furan-2-yl)-2, 6-dimethyl-1, 4-dihydropyridine-3, 5-
dicarboxylate (4j)
Spectral data for some selected compounds.
Diethyl-2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate
(4a)
FT-IR (KBr, cm-1): 3345, 2980, 1707, 1149; 1H-NMR (CDCl3, 300
MHz, ppm): ꢄ = 1.25(t, 6H), 2.32(s, 6H), 4.15(q, 4H), 5.2(s, 1H),
5.77(s, 1H), 5.93 – 7.21(m, 3H).
FT-IR (KBr, cm-1): ꢃ = 3350, 2987, 1693, 1654, 1116; 1H-NMR
(CDCl3, 300 MHz, ppm): ꢄ = 1.30(t, 6H), 2.19(s, 6H), 3.26(s, 2H),
4.17(q, 4H), 5.15(s, 1H).
Diethyl 4- (pyridin-2-yl)-2, 6-dimethyl-1, 4-dihydropyridine-3,
5- dicarboxylate (4k)
Diethyl-2,
4,
6-trimethyl-1,
4-dihydropyridine-3,
5-
FT-IR (KBr, cm-1): 3273, 3172, 2929, 1689, 1643, 1116; 1H-NMR
(CDCl3, 300 MHz, ppm): ꢄ = 1.2(t, 6H), 2.25(s, 6H), 4.08(q, 4H),
5.17(s, 1H), 7.12(t, 1H), 7.46(d, 1H), 7.57(t, 1H), 8.37(brs, 1H),
8.48(d, 1H); m/e = 331
dicarboxylate (4b)
1
FT-IR (KBr, cm-1): 3344, 2983, 1697, 1645, 1136; H-NMR (CD-
Cl3, 300 MHz, ppm): ꢄ = 0.96(d, 3H),1.31(t, 6H), 2.26(s, 6H),
3.82(q, 1H), 4.2(q, 4H), 5.51(s, 1H).
Diethyl 4-(phenyl)-2, 6-dimethyl-1, 4-dihydropyridine-3, 5-
dicarboxylate (4c)