Synthesis of Hantzsch 1,4-dihydropyridines under solvent-free condition using Zn[(L)proline]2 as Lewis acid catalyst

Article abstract of DOI:10.1002/jhet.5570420534

The present short communication describes a Lewis acid (Zn[(L)proline] ₂) catalysed one pot synthesis of Hantzsch 1,4-dihydropyridine (DHP) derivatives under solvent-free condition by conventional heating and microwave irradiation. The Lewis acid catalyst Zn[(L)proline]₂ used in this reaction afford moderate to good yield. The catalyst is reusable upto five cycles without appreciable loss of its catalytic activity.

Full text of DOI:10.1002/jhet.5570420534

Jul-Aug 2005
Synthesis of Hantzsch 1,4-Dihydropyridines under Solvent-free
969
Condition using Zn[(L)proline] as Lewis Acid Catalyst
2
V. Sivamurugan,* R. Suresh kumar, M. Palanichamy and V. Murugesan
Department of Chemistry, Anna University, Chennai 600025, India
Received October 18, 2004
The present short communication describes a Lewis acid (Zn[(L)proline] ) catalysed one pot synthesis of
2
Hantzsch 1,4-dihydropyridine (DHP) derivatives under solvent-free condition by conventional heating and
microwave irradiation. The Lewis acid catalyst Zn[(L)proline] used in this reaction afford moderate to good
2
yield. The catalyst is reusable upto five cycles without appreciable loss of its catalytic activity.
J. Heterocyclic Chem., 42, 969 (2005).
Introduction.
reactions, unsatisfactory yields, high temperatures and
longer reaction times [10-27]. Hence the development of
an efficient and versatile method for the preparation of
Hantzsch 1,4-DHPs is an important approach. Some of the
earlier studies reported on the synthesis of Hantzsch pyri-
dine derivatives assisted with microwave (MW) irradiation
but these methods are seriously affected by requirement of
high MW power, catalyst recyclability, separation of cata-
lyst, occurrence of side reactions and low yield [18,24,28-
Organic synthesis under solvent free conditions is of
great relevance because of emerging environmental issues
[
1]. The solvent free technique not only eliminates the use
of toxic solvents but also provides simplicity in process
and easy separation of the products [2]. Microwave accel-
erated organic synthesis (MAOS) is an effective and non-
conventional alternative route proposed during the last
decade due to drastic reduction in the reaction time and to
minimize cumbersome work-up [3,4].
Dihydropyridine (DHP) derivatives are an important
class of organic compounds in view of its application in
pharmaceuticals and hence their synthesis under solvent-
free condition is an interesting approach. 1,4-DHPs are
widely known as Ca channel blockers and they are
emerged as one of the most substantial classes of drugs for
the treatment of cardiovascular diseases [5]. The 1,4-DHP
heterocyclic ring is an essential nucleus in various bioac-
tive compounds such as vasodilator, bronchodilator, anti-
tumor, geroprotective, hepatoprotective and anti-diabetic
agents [6a,b].
Conventionally 1,4-DHPs were prepared by one-pot
three component condensation of an aryl/alkyl aldehyde, a
β-dicarbonyl compound and ammonia in the presence of
an acid catalyst under reflux conditions [7]. However the
yield of 1,4-DHPs was generally low. The classical
Hantzsch 1,4-DHPs synthesis and other modified methods
developed until recently were reviewed [8,9]. Although
numerous methods under improved conditions have been
reported many of them are suffering from serious draw-
backs such as lower catalyst life cycle, occurrence of side
3
3]. Our research group has recently reported the synthesis
of novel heterocyclics, 1,5-benzodiazepine derivatives
using Zn[(L)proline] as new catalyst under solvent-free
2
MW irradiation [34]. We report herein a mild and efficient
synthesis of Hantzsch 1,4-dihydropyridine derivatives by
adopting Hantzsch procedure using Zn[(L)proline] as an
2
2
+
inexpensive and recyclable Lewis acid catalyst under sol-
vent-free conditions.
Results and Discussion.
Zn[(L)proline] complex was synthesised by stirring 10
2
mmol of (L)proline and 5 mmol of zinc nitrate solution at
room temperature according to our reported procedure
[34]. In the present investigation nitro, chloro, methoxy
and hydroxy substituted aryl aldehydes and heterocyclic
aldehydes such as 2-furfuraldehyde and indole-3-car-
boxyaldehyde were used for the study. In all the reactions
5 mmol of aldehyde, 11 mmol of active methylene com-
pound and 10 mmol of ammonium acetate were condensed
in the presence of 0.2 mmol of catalyst under solvent-free
condition (Scheme 1). In order to ascertain the catalytic
activity of the catalyst the reactions were carried out by
conventional heating and microwave irradiation. The
Scheme 1

9
70
V. Sivamurugan, R. Suresh kumar, M. Palanichamy and V. Murugesan
Vol. 42
microwave irradiated reactions afforded more yield than
the conventional heating. The results are listed in Table I.
All the reactions (Table I) employing MW irradiation
with microwave power supply of 200 W were completed
within 2-4 min. This is one of the major advantages and the
catalyst exhibits its ability to work with low MW power
supply and utilized very low MW power compare other
earlier reports [18,24,28-30]. It is noticed that the presence
of very low amount (0.2 mmol) of Zn-proline complex
effectively catalyses the reaction assisted with low MW
power to obtain good yield of the expected product
studies reveal that the catalyst is reusable upto five cycles
without appreciable loss of its catalytic activity and no
marginal difference in the yield of the product. The reduc-
tion of yield in the sixth cycle is due to removal of Zn-pro-
line complex on washing and decomposition of complex
due to heating. The decomposition of catalyst and leaching
out from the supported material was confirmed by atomic
absorption spectroscopy (AAS) analysis. The amount of
metal-complex present in the supported catalyst is mea-
sured by AAS from each recycling step. The results
2
+
revealed that from 1 to 5 cycles the amount of Zn ion
was marginally decreased and drastically decrease in the
[
24,29,30]. The crude products were obtained with accept-
th
2+
able purity after separation from the catalyst and reduces
cumbersome workup compare other earlier reports.
6 cycle. Table II shows the amount of Zn ion present in
the catalyst obtained from AAS analysis.
In order to evaluate the activity of catalyst, recycling
studies have been carried out with 5 mmol of 2-furfuralde-
hyde, 11 mmol of acetylacetone and 10 mmol of ammo-
nium acetate in the presence of 0.2 mmol of catalyst as a
model reaction. The results are shown in Table II. The
In order to evaluate the efficiency of our present investi-
gation a comparative study was carried out with earlier
reports. The reaction of nitrobenzaldehyde, ethyl acetoac-
etate and ammonium acetate have been taken as model
reaction. The results are listed Table III. It is observed that
Table I
Synthesis of 1,4-Dihydropyridine Derivatives
Entry
R1
R2
Conventional
Heating
Time [a]
Microwave
Irradiation
Yield
Time [a]
(min)
Yield
[b,c]
(%)
(
h)
[b,c]
(
%)
1
2
3
4
5
6
7
8
9
C6H5
OC H
1
1
2
2.5
1.5
2
1.5
1.5
1
1.5
2
2
2.5
3
2.5
2
1.5
1
80
80
75
70
81
83
85
85
88
85
83
80
78
75
80
80
85
83
85
88
83
80
78
75
80
75
84
83
85
85
2
2
3
3
2
2
2
2
2.5
3
3
3
4
4
2
2
2
2
2.5
3
3
3
4
4
3
4
3
88
90
83
80
90
90
92
96
93
95
90
87
83
80
87
90
90
93
95
93
90
93
85
85
85
90
95
95
93
90
2
5
5
5
5
5
5
5
5
5
5
4-NO -C H
OC H
2
6
4
4
4
2
3-NO -C H
OC H
2
6
2
2-NO -C H
OC H
2
6
2
3-Cl-C H4
OC H
6
2
3-OH-C H4
OC H
6
2
4-OH 3-CH O C H
OC H
3
6
3
2
3,4-(CH O) C H
OC H
3
2
6
3
2
2-Furyl
3-Indolyl
C6H5
OC H
2
1
1
0
1
OC H
2
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4-NO -C H
2
6
4
4
4
3-NO -C H
2
6
2-NO -C H
2
6
3-Cl-C H4
6
3-OH-C H4
6
4-OH 3-CH O C H
3
6 3
3,4-(CH O) C H
3
2 6 3
2-Furyl
3-Indolyl
C6H5
1
1.5
2.5
2
3
3.5
3
4
2
1.5
1
1.5
4-NO -C H
2
6
4
4
4
3-NO -C H
2
6
2-NO -C H
2
6
3-Cl-C H4
6
3-OH-C H4
6
4-OH 3-CH O-C H
3
6 3
3,4-(CH O) C H
2.5
3
4
3
2 6 3
2-Furyl
3-Indolyl
[
a] Reaction progress monitored by TLC; [b] Isolated yield after column chromatography; [c] All the products were confirmed by FTIR,
MS and elemental analysis with reported literature.

Jul-Aug 2005
Synthesis of Hantzsch 1,4-Dihydropyridines
971
Table II
The Catalyst Recycling Studies [a]
EXPERIMENTAL
The FTIR spectra of the products were recorded on a Nicolet
60 FTIR using KBr pellet technique. The elemental analyses
Catalyst
recycle
Conventional
Time [b] Yield [c]
Microwave irradiation
3
Time [b]
(min)
Yield [c]
(%)
were carried out in a Heraeus CHNO-rapid analyser. The mass
spectra were recorded on a Finnigan Mat 8230MS spectrometer.
(
h)
(%)
2
+
The amount of Zn ions was measured by GBC 932 plus atomic
absorption spectrometer.
I
II
III
IV
V
1
1
1
1
1
1
80
80
78
75
75
60
3
3
3
3
3
3
90 (0.056)*
85(0.053)
80(0.050)
80(0.048)
80(0.048)
68(0.035)
a) Synthesis of Bis[(L)proline]Zn Complex.
(L)proline (20 mmol) was dissolved in absolute ethanol (50
mL) containing potassium hydroxide (20 mmol) and stirred well
for 15 min. In order to maintain the metal to ligand ratio of 1:2,
VI
[
a] Model reaction: 5 mmol of 2-furfuraldehyde, 11 mmol of acetyl ace-
1
0 mmol of Zn(NO ) .6H O was dissolved in a small quantity of
3 2 2
tone and 10 mmol of ammonium acetate in the presence of 0.2 mmol of
catalyst; [b] Reaction progress monitored by TLC analysis; cIsolated
yield; *Values in the paranthesis indicates amount of Zn2 ions measured
by AAS (in mmoles).
double distilled water and this solution was added in drops to the
L)proline solution. The contents were vigorously stirred at room
(
+
temperature for 6 h. Zn[(L)proline] complex was obtained as a
2
white solid. It was collected by filtration and dried at 70 °C in
-1
vacuum for 6 h. Yield: 94%. FT IR (ν cm ): 3206, 2995, 1605,
Table III
1
516, 1403, 1239, 825 and 533.
A Comparative Study of Present Methodology with Other Reports
Anal. Calcd for C H N O Zn. C, 40.91; H, 5.49; N, 9.54.
1
0 16 2 4
Found: C, 40.74; H, 5.60; N, 9.30.
b) Synthesis of 1,4-Dihydropyridines.
Conventional Method.
Catalyst
MW power
W)
Time
(min)
Yield
(%)
Reference
(
Zn[(L)proline]2
-
200
700a
2
4
90
32
Present work
28
4-Nitrobenzaldehyde (5 mmol), ethyl acetoacetate (11 mmol)
and ammonium acetate (10 mmol) were thoroughly mixed with
5
0% aqueous
solution of
NaBGMS*
AcOH
Bentonite/HNO3
-
-
700
5
65
29
0
.2 mmol of catalyst and adsorbed on neutral alumina. The alu-
mina supported mixture was taken in a 15 ml clean stainless steel
autoclave and thermostated at 70 °C up to the time indicated in
Table I. After completion of reaction, the mixture was diluted
with dichloromethane and the product was seperated by simple
filtration. The alumina supported catalyst was regenerated for
reuse in the next reaction. The excess solvent in the product was
removed by evaporation and purified by column chromatography
400
600
600 [a]
600 [a]
4
5
4
4
60
85
90
88
30
24
18
32
*
Sodium butylmonoglycolsulphate; [a] Reactions carried out in ethanol
medium
(
silicagel 100-200 mesh, n-hexane to ethyl acetate ratio = 80:20,
v/v). The product was obtained as a yellow crystalline solid. The
same procedure was adopted for other reactions. The reaction
time and yield for all the reactions are presented in Table I.
earlier reports utilized high MW power with low yield of
1
,4-DHPs. Some of the reported methodology required a
high catalyst amount, longer reaction time and low recy-
cling ability. The present methodology exhibits great
advantages and eliminates the problems associated with
earlier reports.
Microwave Irradiation Method.
2
-Furfuraldehyde (5 mmol), acetylacetone (11 mmol) and
ammonium acetate (10 mmol) were thoroughly mixed with 0.2
mmol of catalyst and adsorbed on 5 g of neutral alumina. The alu-
mina supported mixture was taken in an open Erlenmeyer flask
and irradiated using a household microwave oven (model: IFB
Conclusions.
1
7PM 1S) with a power range of 200w and a pulse of 15 seconds.
The present investigation concludes that Zn[(L)proline]2
complex is found to be a novel catalyst for the preparation
of Hantzsch 1,4-dihydropyridine derivatives under sol-
vent-free condition with excellent yields. This catalyst can
be used to synthesis 1,4-DHPs employing a wide range of
aldehydes including heterocyclic aldehydes and β-dicar-
bonyl compounds. Microwave-irradiated reactions in the
presence of this catalyst afford moderate to good yield in
short reaction periods. The catalyst exhibits good catalytic
activity even in low MW power (≈ 200 w) when compare
with earlier studies and eliminates the problems associated
with previous reports. The catalyst is reusable up to five
cycles without appreciable loss of its catalytic activity.
The progress of the reaction was monitered by TLC (silica gel
precoated plate, eluent: n-hexane to ethyl acetate ratio = 80 : 20,
v/v). After completion of the reaction, the mixture was diluted
with dichloromethane and the product was seperated by simple
filtration. The excess solvent was removed by distillation and the
crude product was purified by column chromatography (n-hexane
to ethyl acetate ratio = 80:20). The above mentioned procedure
was followed for all the reactions. The reaction time and yield for
all the reactions are as in Table I.
Recycling Studies.
2
-Furfuraldehyde (5 mmol), acetylacetone (11 mmol) and
ammonium acetate (10 mmol) were thoroughly mixed with cata-
lyst (0.2 mmol) and adsorbed on neutral alumina (5 g) was taken

972
V. Sivamurugan, R. Suresh kumar, M. Palanichamy and V. Murugesan
Vol. 42
as model reaction. The progress of reaction was monitored by
TLC analysis. The alumina supported catalyst recovered after
completion of the reaction was thoroughly washed with
dichloromethane until complete removal of the organic compo-
nents. Further, the catalyst was washed with small portions of
methanol and dried in vaccum at 70 °C for 6 h. The dried catalyst
was used for next cycle and the same procedure was adopted for
all the recycling studies. The reaction time and yield for different
cycles are presented in Table II.
Anal. Calcd. for C H NO (319.14): C, 63.94; H, 6.63; N,
17 21 5
4.39; O, 25.05. Found: C, 63.85; H, 6.50; N, 4.45; O, 25.15.
Diethyl 4-(3–Indolyl) 2,6-dimethyl-1,4-Dihydropyridine 3,5-
Dicarboxylate (10).
This compound has FTIR (KBr): 3360 (N-H str), 3083 (Ar C-
H str), 2980 (Ali. C-H str), 1702 (C=O str). MS (EI) m/z: 368
(100.0%), 369 (10.1%).
Anal. Cacld. for C21H24N2O4 (368.17): C, 68.46; H, 6.57; N,
.60; O, 17.37. Found: C, 68.50; H, 6.65; N, 7.54; O, 17.30.
7
Diethyl 4-Phenyl 2,6-dimethyl-1,4-dihydropyridine 3,5-
Dicarboxylate (1).
3,5-Diacyl-4-phenyl-2,6-dimethyl-1,4-dihydropyridine (11).
This compound has FTIR (KBr): 3313(N-H str), 3035 (Ar C-
H str), 2985 (Ali C-H str), 1675 (C=O str). MS(EI): m/z: 329 (M,
This compound has FTIR (KBr): 3365 (N-H str), 3075 (Ar C-
H str), 2976 (Ali. C-H str), 1725 (C=O str). MS (EI) m/z: 269 (M,
100 %).
8
5 %).
Anal. Calcd. for C H NO (329.16): C, 69.28; H, 7.04; N,
Anal. Calcd. for C H NO (269.14): C, 75.81; H, 7.11; N,
1
9
23
4
17 19
2
4
.25; O, 19.43. Found: C, 69.15; H, 7.10; N, 4.15; O, 19.40.
5.20; O, 11.88. Found: C, 75.74; H, 7.05; N, 5.10; O, 11.75.
Diethyl 4 (4-Nitro phenyl) 2,6-dimethyl-1,4-dihydropyridine 3,5-
3,5-Diacyl-4-(4-nitro phenyl)-2,6-dimethyl-1,4-dihydropyridine
Dicarboxylate (2).
(12).
This compound has FTIR (KBr): 3329 (N-H str), 3088 (Ar C-
H str), 2975 (Ali. C-H str), 1690 (C=O str). MS (EI) m/z: 374 (M,
This compound has FTIR (KBr): 3370 (N-H str), 3070 (Ar C-
H str), 2983 (Ali. C-H str), 1723 (C=O str). MS (EI) m/z: 314 (M,
100 %), 315 (8 %).
9
0 %), 375 (10 %).
Anal. Calcd. for C H N O (374.15): C, 60.95; H, 5.92; N,
Anal. Calcd. for C H N O (314.13): C, 64.96; H, 5.77; N,
1
9
22
2
6
17 18 2 4
7
.48; O, 25.64. Found: C, 60.90; H, 5.85; N, 7.40; O, 25.60.
8.91; O, 20.36. Found: C, 64.80; H, 5.65; N, 8.83; O, 20.30.
Diethyl 4 (3-Chloro phenyl)-2,6-dimethyl-1,4-dihydropyridine
3,5-Diacyl 4 (3-chloro phenyl) 2,6-dimethyl 1,4-dihydropyridine
3
,5-Dicarboxylate (5).
(15).
This compound has FTIR (KBr): 3339 (N-H str), 3075 (Ar C-
H str), 2970 (Ali. C-H str), 1684 (C=O str). MS (EI) m/z: 363 (M,
This compound has FTIR (KBr): 3363 (N-H str), 3080 (Ar C-
H str), 2985 (Ali. C-H str), 1720 (C=O str). MS (EI) m/z: 303 (M,
95 %).
8
5 %), 365 (15.0%).
Anal. Calcd. for C H ClNO (363.12): C, 62.72; H, 6.09; N,
Anal. Calcd. for C H ClNO (303): C, 67.21; H, 5.97; N,
1
9
22
4
17 18
2
3
.85; O, 17.59. Found: C, 62.68; H, 6.03; N, 3.75; O, 17.65.
4.61; O, 10.53. Found: C, 67.26; H, 5.85; N, 4.55; O, 10.45.
Diethyl 4 (3-Hydroxy phenyl)-2,6-dimethyl-1,4-dihydropyridine
3,5-Diacyl-4-(3-hydroxyphenyl)-2,6-dimethyl-1,4-dihydropyri-
3
,5-Dicarboxylate (6).
dine (16).
This compound has FTIR (KBr): 3405 (O-H str), 3345 (N-H
str), 3080 (Ar C-H str), 2993 (Ali. C-H str), 1687 (C=O str). MS
This compound has FTIR (KBr): 3415 (O-H str), 3368 (N-H
str), 3070 (Ar C-H str), 2982 (Ali. C-H str), 1723 (C=O str). MS
(EI) m/z: 285 (M, 100 %), 286 (12 %).
(
EI) m/z: 345 (M, 90 %), 346 (13 %).
Anal. Calcd for C H NO (345.16): C, 66.07; H, 6.71; N,
Anal. Calcd. for C H NO (285.14): C, 71.56; H, 6.71; N,
1
9
23
5
17 19
3
4
.06; O, 23.16. Found: C, 66.16; H, 6.65; N, 4.13; O, 23.20.
4.91; O, 16.82. Found: C, 71.45; H, 6.60; N, 4.85; O, 16.90.
Diethyl 4-(4-Hydroxy–3-methoxyphenyl)-2,6-dimethyl-1,4-
3,5-Diacyl-4-(4-hydroxy-3-methoxyphenyl)-2,6-dimethyl-1,4-
dihydropyridine 3,5-Dicarboxylate (7).
dihydropyridine (17).
This compound has FTIR (KBr): 3415 (O-H str), 3340 (N-H
str), 3073 (Ar C-H str), 2980 (Ali. C-H str). 1701 (C=O str). MS
This compound has FTIR (KBr): 3420 (O-H str), 3368 (N-H
str), 2990 (Ali. C-H str), 1730 (C=O str). MS (EI) m/z: 315 (M,
100 %).
(
EI) m/z: 375 (M, 84 %), 376 (10 %).
Anal. Calcd. for C H NO (375.17): C, 63.99; H, 6.71; N,
Anal. Calcd. for C H NO (315.15): C, 68.55; H, 6.71; N,
2
0
25
6
18 21
4
3
.73; O, 25.57. Found: C, 63.80; H, 6.65; N, 3.78; O, 25.60.
4.44; O, 20.29. Found: C, 68.40; H, 6.60; N, 4.35; O, 20.20.
Diethyl 4-(3,4-Dimethoxyphenyl)-2,6-dimethyl-1,4-dihydropyri-
3,5-Diacyl-4-(3,4-dimethoxyphenyl)-2,6-dimethyl-1,4-dihy-
dine 3,5-Dicarboxylate (8).
dropyridine (18).
This compound has FTIR (KBr): 3355 (N-H str), 3075 (Ar C-
H str), 2994 (Ali. C-H str), 1696 (C=O str). MS (EI) m/z: 389 (M,
This compound has FTIR (KBr): 3370 (N-H str), 3075 (Ar C-
H str), 2976 (Ali. C-H str), 1727 (C=O str). MS (EI) m/z: 329 (M,
85 %), 330 (15 %).
1
00 %), 390 (15 %).
Anal. Calcd. for C H NO (389.18): C, 64.77; H, 6.99; N,
Anal. Calcd. for C H NO (329.16): C, 69.28; H, 7.04; N,
2
1
27
6
19 23
4
3
.60; O, 24.65. Found: C, 64.69; H, 6.91; N, 3.54; O, 24.70.
4.25; O, 19.43. Found: C, 69.20; H, 6.95; N, 4.10; O, 19.35.
Diethyl 4(2-Furyl)-2,6-dimethyl-1,4-dihydropyridine 3,5-
3,5-Diacyl-4-(2-furyl)-2,6-dimethyl-1,4-dihydropyridine (19).
Dicarboxylate (9).
This compound has FTIR (KBr): 3360 (N-H str), 3076 (Ar C-
H str), 2984 (Ali. C-H str), 1724 (C=O str). MS (EI) m/z: 259 (M,
100 %), 260 (7 %).
This compound has FTIR (KBr): 3360 (N-H str), 3010 (C-H
str), 1705 (C=O str). MS (EI) m/z: 319 (M, 90 %), 320 (10 %).

Jul-Aug 2005
Synthesis of Hantzsch 1,4-Dihydropyridines
973
Anal. Calcd. for C H NO (259.12): C, 69.48; H, 6.61; N,
This compound has FTIR (KBr): 3355 (N-H str), 3080 (Ar C-
H str), 2990 (Ali. C-H str), 1996 (C=O str). MS (EI) m/z: 291 (M,
1
5
17
3
5
3
.40; O, 18.51. Found: C, 69.40; H, 6.51; N, 5.35; O, 18.39.
,5-Diacyl-4-(3–indolyl)-2,6-dimethyl-1,4-dihydropyridine (20).
This compound has FTIR (KBr): 3363 (N-H str), 3073 (Ar C-
9
0 %), 292 (10 %).
Anal. Calcd. for C H NO (291.11): C, 61.85; H, 5.88; N,
1
5
17
5
4.81; O, 27.46. Found: C, 61.74; H, 5.75; N, 4.70; O, 27.35.
H str), 2984 (Ali. C-H str), 1728 (C=O str). MS (EI) m/z: 308 (M,
Dimethyl 4 (3-Indolyl)-2,6-dimethyl-1,4-dihydropyridine 3,5-
Dicarboxylate (30).
8
9
7 %), 309 (13 %).
Anal. Calcd. for C H N O (308.15): C, 74.00; H, 6.54; N,
.08; O, 10.38. Found: C, 74.10; H, 6.60; N, 9.15; O, 10.30.
1
9 20 2 2
This compound has FTIR (KBr): 3350 (N-H str), 3095 (Ar C-
H str), 2980 (Ali. C-H str), 1702 (C=O str). MS (EI) m/z: 340 (M,
Dimethyl-4-phenyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicar-
boxylate (21).
9
0 %), 341 (8 %).
Anal. Calcd. for C H N O (340.14): C, 67.05; H, 5.92; N,
1
9 20 2 4
8
.23; O, 18.80. Found: C, 67.10; H, 5.85; N, 8.14; O, 18.65.
This compound has FTIR (KBr): 3370 (N-H str), 3075 (Ar C-
H str), 2980 (Ali. C-H str), 1708 (C=O str). MS (EI) m/z: 301 (M,
Acknowledgement.
9
3 %), 302 (10 %).
Anal. Calcd. for C H NO (301.13): C, 67.76; H, 6.36; N,
The authors are grateful to the University Grants Commission
for the financial support in the form of major sponsored project.
One of the authors (V. Sivamurugan) thanks the Council of
Scientific and Industrial Research (CSIR) for the award of Senior
Research Fellow.
1
7
19
4
4
.65; O, 21.24. Found: C, 67.80; H, 6.30; N, 4.63; O, 21.15.
Dimethyl 4-(4-Nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine
3
,5-Dicarboxylate (22).
This compound has FTIR (KBr): 3367 (N-H str), 3095 (Ar C-
H str), 2980 (Ali. C-H str), 1697 (C=O str). MS (EI) m/z: 346 (M,
REFERENCES AND NOTES
9
5 %), 347 (8 %).
Anal. Calcd. for C H N O (346.12): C, 58.96; H, 5.24; N,
1
7 18 2 6
*
To whom correspondence should be addressed: E-mail: siva-
muruganv@rediffmail.com, Tele Fax: +91-44-22200660.
8
.09; O, 27.72. Found: C, 58.80; H, 5.10; N, 8.15; O, 27.65.
[
[
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,5-Dicarboxylate (25).
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This compound has FTIR (KBr): 3363 (N-H str), 3065 (Ar C-
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3
37 (20 %).
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[
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7
18
4
1
1
0.56; N, 4.17; O, 19.06. Found: C, 60.79; H, 5.35; N, 4.10; O,
9.10.
[
and I. –J. Chen, Bioorg. & Med. Chem., 10, 719 (2002); [b] W. –D. Busse,
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[
7] A. Hantzsch, Justus Liebigs Ann. Chem., 215, 1 (1882).
This compound has FTIR (KBr): 3435 (O-H str), 3348 (N-H
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EI) m/z: 317 (M, 90 %), 318 (14 %).
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[
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4311 (2000).
1
7
19
5
6
4
.41; O, 25.21. Found: C, 64.30; H, 6.10; N, 4.35; O, 25.17.
[
Dimethyl 4-(4-Hydroxy-3-methoxyphenyl)-2,6-dimethyl-1,4-
dihydropyridine 3,5-Dicarboxylate (27).
[
[
12] L. Ohberg and J. Westman, Synlett., 1296 (2001).
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This compound has FTIR (KBr): 3430 (O-H str), 3357 (N-H
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8
0, 992 (1958).
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(
EI) m/z: 347 (M, 100 %), 348 (10 %).
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.03; O, 27.64. Found: C, 62.15; H, 6.02; N, 3.93; O, 27.60.
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1
8
21
6
[
4
Dimethyl 4 (3,4-Dimethoxyphenyl)-2,6-dimethyl-1,4-dihy-
dropyridine 3,5-Dicarboxylate (28).
[
18] M. Anniyappan, D. Muralidharan and P. T. Perumal, Synth.
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This compound has FTIR (KBr): 3363 (N-H str), 3065 (Ar C-
H str), 2973 (Ali. C-H str), 1704 (C=O str). MS (EI) m/z: 361 (M,
[
1
00 %).
Anal. Calcd. for C H NO (361.15): C, 63.15; H, 6.41; N,
1
9
23
6
3
.88; O, 26.56. Found: C, 63.04; H, 6.35; N, 3.80; O, 26.50.
[
Dimethyl 4 (2-Furyl)-2,6-dimethyl-1,4-dihydropyridine 3,5-
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[22] R. Lavilla, J. Chem. Soc., Perkin Trans. 1, (9), 1141 (2002).

974
V. Sivamurugan, R. Suresh kumar, M. Palanichamy and V. Murugesan
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[
1
[
(
[
[
[
27] W. H. Correa and J. L. Scott, Green Chemistry, 3, 296 (2001).
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