Rapid and efficient synthesis of 1,4-dihydropyridines using a sulfonic acid-functionalized ionic liquid

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Rapid and Efficient Synthesis of 1,4-
Dihydropyridines using a Sulfonic Acid-
functionalized Ionic Liquid
Roghayeh Hossein Niaa, Manouchehr Mamaghania, Farhad Shirinia,
Khalil Tabatabaeiana & Marzieh Heidarya
a Department of Chemistry, Faculty of Sciences, University of
Guilan, P.ꢀO. Box 41335-1914, Rasht, Iran
Published online: 26 Mar 2014.
To cite this article: Roghayeh Hossein Nia, Manouchehr Mamaghani, Farhad Shirini, Khalil
Tabatabaeian & Marzieh Heidary (2014) Rapid and Efficient Synthesis of 1,4-Dihydropyridines using a
Sulfonic Acid-functionalized Ionic Liquid, Organic Preparations and Procedures International: The New
Journal for Organic Synthesis, 46:2, 152-163, DOI: 10.1080/00304948.2014.884372
To link to this article: http://dx.doi.org/10.1080/00304948.2014.884372
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Organic Preparations and Procedures International, 46:152–163, 2014
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2014.884372
Rapid and Efficient Synthesis
of 1,4-Dihydropyridines using a Sulfonic
Acid-functionalized Ionic Liquid
Roghayeh Hossein Nia, Manouchehr Mamaghani, Farhad Shirini,
Khalil Tabatabaeian, and Marzieh Heidary
Department of Chemistry, Faculty of Sciences, University of Guilan, P. O. Box
41335-1914, Rasht, Iran
4-Aryl-l,4-dihydropyridines (1,4-DHPs) constitute a major class of drugs used in the
management of cardiovascular diseases.1,2 They are analogues of NADH co-enzymes and an
important class of drugs.3 Current literature reveals that they possess a variety of biological
activities such as anti-cancer,4 broncho-dilating,5 anti-diabetic,6 neurotropic7 anti-anginal8
and other pharmacological properties.9 In particular, indenopyridines initially developed
as anti-histamines,10 are one of the most important privileged medicinal scaffolds. They
exhibit fungicidal, cytotoxic, phosphodiesterase inhibitory, coronary dilating and calcium
modulating activities, and are useful inhibitors of spermatogenesis in animals.11,12 The
preparation of 1,4-dihydropyridines by the classical Hantzsch synthesis, involve a three-
component condensation of an aldehyde with ethyl acetoacetate, and ammonia in acetic
acid or in refluxing ethanol.13–18
These methods suffer from drawbacks such as long reaction times, lower yields,
use of large volumes of organic solvents and harsh refluxing conditions. Several more
efficient methods have recently been developed for the synthesis of fused derivatives
of dihydropyridines, and include the use of microwaves,19,20 ionic liquids,21–23 metal
triflates,24,25 iodine,26 l-proline,27 ceric ammonium nitrate (CAN),28 BINOL-phosphoric
acid derivatives,29 iron (III) trifluoroacetate,30 K7[PW11CoO40],31 also grinding/solvent-
free conditions.32 Although most of these processes offer distinct advantages, but some
of them still have their own limitations in terms of yields, longer reaction times, difficult
work-up. In some cases, the catalysts used are harmful to environment and cannot be reused.
Therefore, an efficient method for the preparation of 1,4-DHP derivatives is still desirable.
Ionic liquids have attracted extensive interest as excellent alternatives to organic solvents,
due to their favorable properties. They have been found to be the solvents of choice for a
large array of organic reactions and as catalyst at the same time.33–38 Many of these ionic
Received July 12, 2013; in final form December 3, 2013.
Address correspondence to M. Mamaghani, Department of Chemistry, Faculty of Sciences,
University of Guilan, P. O. Box 41335-1914, Rasht, Iran. E-mail: m-chem41@guilan.ac.ir;
mchem41@gmail.com
152

Rapid and Efficient Synthesis of 1,4-Dihydropyridines
153
liquids, unlike many conventional solvents, are non-flammable and exert no detectable
vapor pressure. The use of ionic liquids as reaction media may offer a convenient solution
to both the solvent emission and catalytic recycling problems.
These observations led us to attempt the synthesis of some 1,4-DHPs scaffolds in
the presence of SO3H-functional Brønsted-acidic halogen-free ionic liquid [DMBSI]HSO4
which bears a butanesulfonic acid group in 1,2-dimethylimidazolium cation as catalyst
(Scheme 1).
Scheme 1
In continuation of our recent interest in the development of efficient and environmen-
tally friendly procedures for the synthesis of biologically important heterocycles,39–42 it
was thought worthwhile to devise an efficient and eco-friendly method for the synthesis
of 4-aryl-l,4-dihydropyridine derivatives to provide privileged scaffolds for the generation
of target compounds for drug discovery. In this protocol 4-aryl-l,4-dihydropyridines were
synthesized by a rapid and efficient one-pot four-component approach, using 1,2-dimethyl-
3-butanesulfonyl imidazolium bisulfate ([DMBSI]HSO4) ionic liquid under solvent-free
conditions in high to excellent yields (Scheme 2).
Scheme 2
In the initial experiments, different solvents and temperatures in the presence of
ionic liquid [DMBSI]HSO4 were screened for the synthesis of 4-aryl-l,4-dihydropyridines
4c. As a model experiment to determine the ideal conditions, equimolar amounts of 4-
chlorobenzaldehyde, dimedone, ethyl acetoacetate and ammonium acetate were condensed

154
Mamaghani et al.
in the presence of [DMBSI]HSO4 in various solvents. The results showed that the use
of [DMBSI]HSO4 under solvent-free conditions at 60◦C for 3 min is the most efficient
condition. To optimize the reaction conditions, we also verified the amount of catalyst
needed for the preparation of 4c, and the best result was obtained using 0.06 g (0.18 mmol)
[DMBSI]HSO4/1 mmol substrate.
The ionic liquid is easily separated from the reaction medium by washing with water.
To demonstrate its reusability the washed ionic liquid is distilled under vacuum for reuse
in subsequent reactions. After four successive runs, catalytic activity of the catalyst was
retained without significant loss of activities. The advantages of present method in com-
parisons with other reported methods for the synthesis of the 4-aryl-l,4-dihydropyridines,
are summarized in Table 1.
Table 1
Comparison of Synthesis of 4a in the Presence of Different Catalystsa
Entry
Catalyst
Condition
Time
Yield (%)lit.
1
2
3
4
5
6
7
8
9
HClO4-SiO2
K7[PW12CoO40]
l-proline
Solvent-free/90◦C
CH3CN/reflux
C2H5OH/Reflux
C2H5OH/rt
Solvent-free/70◦C
Solvent-free/rt
Solvent-free/90◦C
Solvent-free/80◦C
Solvent-free/60◦C
8 min
35 min
6 h
9543
8044
9245
9046
9047
9548
9549
75
Yb(OTf)3
5 h
Nanocrystalline TiO2
Ni0-nanoparticle
[HMIM]BF4
[MBSI]HSO4
[DMBSI]HSO4
35 min
15 min
10 min
10 min
3 min
b
94c
(a) Reaction conditions: benzaldehyde, dimedone, ethyl acetoacetate and ammonium acetate.
(b) 1-Methyl-3-butanesulfonylimidazolium bisulfate. (c) The present work.
To demonstrate the efficiency and applicability of the present method, various arylalde-
hydes were used for the synthesis of a variety of 4-aryl-l,4-dihydropyridine derivatives.
As shown in Table 2, aryl aldehydes (1) bearing either electron-withdrawing or electron-
donating groups, reacted well to give the corresponding products 4 in high yields (80–95%).
Interestingly, this one-pot multi-component approach also afforded an efficient protocol for
the synthesis of bis-4-aryl-l,4-dihydropyridines (6, 8, Table 2, Schemes 3 and 4) in excellent
yields (85–92%).
Encouraged by these results, we extended the scope of this protocol to the synthesis
of fused tricyclic 4-aryl-l,4-dihydropyridines by the reaction of equimolar amounts of
arylaldehyde (1), 1,3-indanedione (9), ethyl acetoacetate (3) and NH4OAc in the presence of
[DMBSI]HSO4 under the aforementioned optimized solvent-free conditions and obtained
indenopyridines (Scheme 5) in excellent yields (88–95%) and short reaction times (2–5 min)
(Table 2).

Rapid and Efficient Synthesis of 1,4-Dihydropyridines
155
Scheme 3
Scheme 4
Scheme 5

156
Mamaghani et al.
Table 2
Synthesis of 4-Aryl-l,4-dihydropyridine 4a–4u, 6a, 6b, 8, 10a–10f
Compound
Yielda (%)
Time (min.)
mp. (◦C)
Lit. mp.lit. (◦C)
4a
4b
4c
4d
4e
94
95
94
90
90
95
80
90
87
85
95
94
80
80
85
80
85
78
80
95
80
90
92
85
90
92
95
93
95
88
3
3
3
5
6
2
12
5
6
3
3
6
6
7
3
12
2
10
6
3
206–208
188–191
240–242
258–259
233–235
193–194
247–249
220–222
202–204
70–73
241–243
227–230
203–205
243–244
236–238
238–240
244–246
200–203
225–227
270–271
>300
257–258
143–145
138–140
249–251
216–218
224–226
200–203
208–210
259–260
202–20446
184–18646
245–24650
260–26146
232–23446
188–19051
245–24752
220–22253
202–20452
66–6746
241–24446
223–22552
198–20054
240–24155
234–23554
241–24254
243–24454
193–19540
220–22240
—
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
4t
4u
6a
6b
8
10a
10b
10c
10d
10e
10f
6
5
5
6
3
2
2
3
—
—
—
—
—
—
—
—
2
4
—
—
The reaction profile of the present protocol is very clean and no side-products are
formed. The structures of all the newly synthesized products were confirmed by spectro-
scopic (IR, 1H-NMR, 13C-NMR) and elemental analyses and for the known derivatives, by
comparison of their spectroscopic data and melting points with those of literature reports.
Attempts to extend these conditions to aliphatic aldehydes such as propionaldehyde or
butyraldehyde with dimedone, ethyl acetoacetate and ammonium acetate, gave a complex
mixture due to aldol condensations.

Rapid and Efficient Synthesis of 1,4-Dihydropyridines
157
In summary, we have successfully demonstrated remarkable catalytic activity of
[DMBSI]HSO4 as an emerging green catalyst and developed a reliable, clean and eco-
friendly, benign protocol for the synthesis of versatile 1,4-dihydropyridine derivatives. The
operational simplicity, easy work-up of the products, use of [DMBSI]HSO4 as a green
catalyst, mild reaction conditions, short reaction times, high to excellent yields, solvent-
free conditions and reusability of the catalyst, are the advantages of this protocol. The
method is amenable for the iterative generation of combinatorial libraries.
Experimental Section
Mps were recorded on a Bu¨chi B-545 apparatus in open capillary tubes. IR spectra (KBr)
were determined on a Shimadzu IR-470 spectrometer. NMR spectra were recorded on a
Bruker DRX (500 and 400 MHz) (1H) and Bruker DRX (125 and 100 MHz) (13C) in DMSO-
d6 and CDCl3 as solvent with TMS as an internal standard; δ was quoted in ppm and J in
Hz. Elemental analyses were performed on a Carlo-Erba EA1110CNNO-S analyzer and
agreed (within 0.30) with the calculated values. Chemicals were purchased from Merck
and Fluka. All solvents used were dried and distilled according to standard procedures.
The SO3H-functionalized ionic liquid [DMBSI]HSO4 was synthesized according to the
literature.56,57
Synthesis of 1,2-Dimethylimidazolium-3-butanesulfonate (DMIBS)
To a solution of 1,2-dimethylimidazole (9.61 g, 0.10 mol) in ethanol (25 ml) 1,4-
butanesultone (13.60 g, 0.10 mol) was added in portions over 30 min, and the mixture
was then stirred for 48 h at room temperature. The white precipitate thus formed was
collected and washed with petroleum ether (2 × 10 ml). The product was recrystallized
from EtOH, to give DMIBS as white solid, mp. 268–270◦C, in 95% yield.
Synthesis of 1,2-Dimethyl-3-butanesulfonylimidazolium Bisulfate
Equimolar amounts of 1,2-dimethylimidazoliumbutanesulfonate (DMIBS) andsulfuricacid
solutions (96%) were mixed and stirred for 6 h at 80◦C. The reaction mixture was subjected
to drying under vacuum (10 mm Hg) at 70◦ for 2 h to remove any volatile. The residue was
washed by stirring with ether (2 × 10 ml) to remove unreached material and dried under
vacuum again (10 mm Hg) for 30 min. The IL was obtained quantitatively in high purity
as a colorless viscous oil.57
1H-NMR (400 MHz, D2O): δ 1.45 (m, 2H, –CH2–), 1.68 (m, 2H, –CH2–), 2.32 (s, 3H,
CH3), 2.66 (t, J = 7.6, -CH2-S), 3.49 (s, 3H, CH3), 3.88 (t, J = 7.2, 2H, -CH2-N), 7.05 (d,
J = 2.0, 1H, CH ), 7.10 (d, J = 2.0, 1H, CH); 13C-NMR (100 MHz, D2O): δ 8.6, 20.9,
27.6, 34.4, 47.3, 50.0, 120.7, 122.0, 144.1.
Anal. Cald. for C9H18N2O7S2 (330.38): C, 32.72; H, 5.49; N, 8.48. Found: C, 32.56;
H, 5.41; N, 8.35.
General Procedure for the Preparation of 4a–4u, 6a, 6b, 8, 10a–10f
A mixture of 1 mmol each of ethyl acetoacetate, NH4OAc, 1,3-diketone and aldehyde
in a flask containing a magnetic stirring bar and [DMBSI]HSO4 (0.18 mmol, 0.06 g)

158
Mamaghani et al.
was heated at 60◦C in an oil bath. Stirring at 60◦C was continued until disappearance of
the starting materials (monitored by TLC, SiO2, ethyl acetate/petroleum ether: 1/3). The
reaction mixture was cooled to RT and stirred with water. The resultant solid product was
collected and the aqueous filtrate containing the ionic liquid was saved for recycling (see
below). The solid obtained was stirred with ethyl acetate and collected again to furnish the
desired pure product (when 1,3-indandione was used as the 1,3-diketone, the product was
washed with petroleum ether).
The aqueous filtrate was evaporated to recover the ionic liquid. The crude recovered
liquid was washed with diethyl ether (2 × 5 ml) and dried under vacuum to be reused in
subsequent reactions.
Spectroscopic data for selected products:
Ethyl 1,4,5,6,7,8-Hexahydro-4-(p-anisyl)-2,7,7-trimethyl-5-oxoquinoline-3-
carboxylate (4g)
1
White powder, IR (KBr. cm−1): 3290, 3070, 2950, 1688, 1600; H-NMR (400 MHz,
CDCl3): δ 0.96 (s, 3H, CH3), 1.08 (s, 3H), 1.23 (t, J = 7.2, 3H, CH3), 2.17, 2.25 (d, J =
16.0, diastereotopic CH2-CNH), 2.21, 2.32 (d, J = 16.8, diastereotopic CH2-CO), 2.38 (s,
3H, CH3), 3.75 (s, 3H, OCH3), 4.10 (q, J = 7.2, 2H, OCH2-CH3), 5.02 (s, 1H, CH), 6.35
(br s, 1H, NH), 6.76 (d, J = 8.8, 2H, Ar-H), 7.24 (d, J = 8.8, 2H, Ar-H).
Ethyl 1,4,5,6,7,8-Hexahydro-4-(3-hydroxyphenyl)-2-methyl-5-oxoquinoline-3-
carboxylate (4t)
1
White powder, IR (KBr. cm−1): 3400, 3290, 1670, 1605; H-NMR (500 MHz, CDCl3):
δ 1.14 (t, J = 7.1, 3H, OCH2-CH3), 1.89 (m, 2H, CH2-CH2-CH2), 2.32 (s, 3H, CH3),
2.29–2.52 (m, 4H, CH2-CH2-CH2), 4.00 (q, J = 7.1, 2H, OCH2-CH3), 4.95 (s, 1H, CH),
5.1 (br s, 1H, NH), 6.54 (d, J = 8.3, 1H, Ar-H), 6.70 (m, 2H, Ar-H), 6.94 (t, J = 8.0, 1H,
Ar-H), 8.58 (br s, 1H, OH).
Anal. Cald. for C19H21NO4 (327.37): C, 69.71; H, 6.47; N, 4.28. Found: C, 69.92; H,
6.40; N, 4.21.
Ethyl 4-(4-Formylphenyl)-1,4,5,6,7,8-hexahydro-2-methyl-5-oxoquinoline-3-
carboxylate (4u)
White powder, IR (KBr. cm−1): 3280, 3200, 2904, 3080, 2840, 2750, 1690, 1600; 1H-NMR
(400 MHz, DMSO-d6): δ 1.13 (t, J = 7.0, 3H, OCH2-CH3), 1.88–2.14 (m, 6H, CH2),
2.20 (s, 3H, CH3), 4.00 (q, J = 7.0, 2H, OCH2-CH3), 4.84 (s, 1H, CH), 6.82 (br s, 1H,
NH), 6.95–7.01 (m, 4H, Ar-H), 6.70–6.72 (m, 2H, Ar-H), 9.10 (s, 1H, CHO); 13C-NMR
(100 MHz, DMSO-d6): δ 14.6, 18.8, 21.2, 26.6, 35.2, 37.2, 59.5, 104.2, 111.3, 127.2, 127.3,
127.4, 145.2, 145.4, 152.1, 167.5, 195.2, 205.5.
Anal. Cald. for C20H21NO4 (339.39): C, 70.78; H, 6.24; N, 4.13. Found: C, 70.61; H,
6.08; N, 4.26.

Rapid and Efficient Synthesis of 1,4-Dihydropyridines
159
bis-Ethyl 4,5,6,7,8-Hexahydro-4-(4-ethoxyphenyl)-2,7,7-trimethyl-5-oxoquinoline-3-
carboxylate (6a)
White powder, IR (KBr. cm−1): 3300, 3200, 3080, 2950, 1700, 1600; 1H-NMR (400 MHz,
CDCl3): δ 0.94 (s, 3H, CH3), 0.96 (s, 3H, CH3), 1.08 (s, 6H, CH3), 1.23 (t, J = 7.0, 6H,
CH2-CH3), 1.90 (br s, 4H), 2.14–2.32 (m, 8H, CH2), 2.39 (s, 3H, CH3), 2.40 (s, 3H, CH3),
3.95 (br s, 4H, OCH2-CH2), 4.09 (q, J = 7.0, 4H, OCH2CH3), 5.01 (s, 2H, CH), 6.45 (br s,
2H, NH), 6.74 (d, J = 8.6, 4H, Ar-H), 7.21 (d, J = 8.6, 4H, Ar-H); 13C-NMR (100 MHz,
CDCl3): δ 13.8, 14.3, 19.4, 19.5, 26.0, 26.1, 27.2, 28.2, 29.5, 32.6, 32.7, 35.6, 35.7, 41.1,
41.2, 48.3, 50.7, 53.7, 59.8, 61.9, 67.3, 67.5, 106.4, 112.4, 112.5, 113.8, 113.9, 114.0,
128.9, 129.0, 139.5, 143.1, 143.2, 143.3, 147.8, 148.1, 157.2, 167.6, 195.5, 195.6.
Anal. Cald. for C46H56N2O8 (764.95): C, 72.23; H, 7.38; N, 3.66. Found: C, 72.10; H,
7.21; N, 3.52.
bis-Ethyl 4-(4-Ethoxyphenyl)-1,4,5,6,7,8-hexahydro-2-methyl-5-oxoquinoline-3-
carboxylate (6b)
White powder, IR (KBr. cm−1): 3300, 3200, 3080, 2940, 1695, 1600; 1H-NMR (400 MHz,
DMSO): δ 1.14 (t, J = 7.0, 6H, OCH2CH3), 1.80–2.30 (m, 16H, CH2, OCH2-CH2), 2.28
(s, 6H, CH3), 3.93 (br s, 4H, OCH2-CH2), 3.98 (q, J = 7.0, OCH2-CH3), 4.83 (s, 2H, CH),
6.74 (d, J = 8.6, 4H, Ar-H), 7.03 (d, J = 8.6, 4H, Ar-H), 9.08 (br s, 2H, N-H); 13C-NMR
(100 MHz, CDCl3-d6): δ 14.7, 18.7, 21.3, 26.0, 26.6, 35.1, 37.2, 59.5, 67.4, 104.3, 111.8,
114.2, 128.8, 140.5, 1450, 151.6, 157.2, 167.4, 195.2.
Anal. Cald. for C42H48N2O8 (708.84): C, 71.17; H, 6.82; N, 3.95. Found: C, 71.05; H,
6.64; N, 3.86.
bis-Ethyl 1,4,5,6,7,8-Hexahydro-4-(2-ethoxyphenyl)-2,7,7-trimethyl-5-oxoquinoline-3-
carboxylate (8)
1
White powder, IR (KBr. cm−1): 3300, 3085, 2950, 1700, 1680, 1646, 1600; H-NMR
(400 MHz, CDCl3): δ 0.99 (s, 3H, CH3), 1.00 (s, 3H, CH3), 1.03 (s, 3H, CH3), 1.04 (s, 3H,
CH3), 1.19 (t, J = 7.0, 3H, OCH2-CH3), 1.20 (t, J = 7.2, 3H, OCH2-CH3), 2.01–2.20 (m,
8H, CH2), 2.22–2.27 (m, 4H, OCH2-CH2), 2.29 (s, 3H, CH3), 2.31 (s, 3H, CH3), 4.00–4.09
(m, 8H, OCH2-CH2, OCH2-CH3), 5.37 (s, 2H, CH), 6.83 (d, J = 7.6, 2H, Ar-H), 6.84
(t, J = 7.2, 2H, Ar-H), 7.10 (td, J = 7.8, 1.5, 2H, Ar-H), 7.35 (d, J = 7.2, 2H, Ar-H);
13C-NMR (100 MHz, CDCl3): δ 14.3, 19.0, 20.4, 26.8, 27.2, 29.6, 32.5, 40.8, 50.9, 59.6,
68.3, 105.3, 111.5, 120.0, 127.3, 128.8, 131.5, 135.0, 143.7, 149.9, 156.8, 168.0, 196.1.
Anal. Cald. for C46H56N2O8 (764.95): C, 72.23; H, 7.38; N, 3.66. Found: C, 72.16; H,
7.23; N, 3.71.
Ethyl 4,5-Dihydro-2-methyl-5-oxo-4-p-tolyl-1H-indeno[1,2-b]pyridine-3-
carboxylate (10a)
Red powder, IR (KBr. cm−1): 3250, 3080, 1700, 1630, 1580; 1H-NMR (400 MHz, CDCl3):
δ 1.17 (t, J = 7.0, 3H, OCH2-CH3), 2.28 (s, 3H, CH3), 2.51 (s, 3H, Ar-CH3), 4.07 (q, 2H,
J = 7.0, OCH2-CH3), 5.00 (s, 1H, CH), 6.75 (br s, 1H, NH), 7.06 (d, J = 7.6, 2H, Ar-H),
7.24 (d, J = 7.6, 2H, Ar-H), 7.29–7.39 (m, 4H, Ar-H); 13C-NMR (100 MHz, CDCl3): δ

160
Mamaghani et al.
14.1, 19.9, 21.1, 36.8, 60.0, 108.3, 111.0, 116.8, 121.4, 127.8, 130.0, 131.2, 134.0, 135.9,
136.2, 142.9, 143.1, 152.6, 167.4, 192.0.
Anal. Cald. for C23H21NO3 (359.15): C, 76.86; H, 5.89; N, 3.90. Found: C, 76.82; H,
5.75; N, 3.81.
Ethyl 4-(4-Chlorophenyl)-4,5-dihydro-2-methyl-5-oxo-1H-indeno[1,2-b]pyridine-
3-carboxylate (10b)
Red powder, IR (KBr. cm−1): 3274, 1701, 1639, 1506; 1H-NMR (500 MHz, CDCl3): δ 1.16
(t, J = 7.1, 3H, OCH2-CH3), 2.51 (s, 3H, CH3), 4.07 (q, J = 7.1, 2H, OCH2-CH3), 5.02 (s,
1H, CH), 7.02 (br s, 1H, NH), 7.12 (m, 1H, Ar-H), 7.22 (d, J = 8.4, 2H, Ar-H), 7.29–7.32
(m, 4H, Ar-H), 7.38 (m, 1H, Ar-H); 13C-NMR (125 MHz, CDCl3): δ 14.4, 19.4, 37.2, 60.1,
107.0, 109.7, 119.1, 121.1, 128.1, 128.4, 129.7, 129.8, 130.1, 131.5, 131.9, 134.4, 136.9,
145.5, 145.8, 154.3, 167.7, 192.4.
Anal. Calcd. for C22H18ClNO3 (379.84): C, 69.57; H, 4.78; N, 3.69. Found: C, 69.50;
H, 4.85; N, 3.73.
Ethyl 4-(4-Fluorophenyl)-4,5-dihydro-2-methyl-5-oxo-1H-indeno[1,2-b]pyridine-
3-carboxylate (10c)
Red powder, IR (KBr. cm−1): 3350, 3095, 1690, 1650, 1620; 1H-NMR (500 MHz, CDCl3):
δ 1.16 (t, J = 7.1, 3H, OCH2-CH3), 2.48 (s, 3H, CH3), 4.08 (m, 2H, OCH2-CH3), 5.03 (s,
1H, CH), 6.96 (t, J = 8.6, 2H, Ar-H), 7.13 (m, 1H, Ar-H, Ar-H), 7.29–7.34 (m, 5H, Ar-H),
7.38 (m, 1H, Ar-H); 13C-NMR (125 MHz, CDCl3): δ 14.5, 20.1, 37.2, 60.5, 108.4, 110.8,
115.3 (d, 2JC-F = 21.24), 117.7, 121.8, 129.8 (d, 3JC-F = 8.04), 130.6, 131.8, 134.3, 136.4,
142.1, 144.0, 153.5, 161.6 (d, 1JC-F = 246.10), 167.7, 192.7.
Anal. Calcd. for C22H18FNO3 (363.38): C, 72.72; H, 4.99; N, 3.85. Found: C, 72.65;
H, 5.13; N, 3.76.
Ethyl 4-(3-Chlorophenyl)-4,5-dihydro-2-methyl-5-oxo-1H-indeno[1,2-b]pyridine-
3-carboxylate (10d)
Red powder, IR (KBr. cm−1): 3260, 1700, 1635, 1580; 1H-NMR (400 MHz, CDCl3): δ 1.17
(t, J = 7.2, 3H, OCH2-CH3), 2.55 (s, 3H, CH3), 4.09 (m, 2H, OCH2-CH3), 5.02 (s, 1H,
CH), 6.66 (br s, 1H, NH), 7.09–7.13 (m, 2H, Ar-H), 7.14 (t, J = 1.6, 1H, Ar-H), 7.20 (t, J =
7.8, 1H, Ar-H), 7.27–7.43 (m, 4H, Ar-H); 13C-NMR (100 MHz, CDCl3): δ 14.0, 20.1, 37.2,
60.2, 107.5, 110.3, 116.7, 121.7, 126.4, 126.6, 128.0, 129.4, 130.3, 131.3, 133.7, 134.1,
135.9, 143.7, 147.8, 152.5, 167.0, 191.8.
Anal. Cald. for C22H18ClNO3 (379.84): C, 69.57; H, 4.78; N, 3.69. Found: C, 69.51;
H, 4.61; N, 3.85.
Ethyl 4-(2,4-Dichlorophenyl)-4,5-dihydro-2-methyl-5-oxo-1H-indeno[1,2-b]pyridine-
3-carboxylate (10e)
1
Red powder, IR (KBr. cm−1): 3269, 1699, 1637; H-NMR (500 MHz, CDCl3): δ 1.17 (t,
J = 7.1, 3H, OCH2CH3), 2.48 (s, 3H, CH3), 4.06–4.09 (m, 2H, OCH2-CH3), 5.40 (s, 1H,

Rapid and Efficient Synthesis of 1,4-Dihydropyridines
161
CH), 7.12 (m, 1H, Ar-H), 7.16 (dd, J = 8.7, 2.0, 1H, Ar-H), 7.29–7.32 (m, 5H, Ar-H), 7.37
(m, 1H, Ar-H); 13C-NMR (125 MHz, CDCl3): δ 14.4, 20.2, 35.4, 60.6, 107.6, 109.8, 117.8,
121.8, 127.6, 129.6, 130.8, 131.8, 132.2, 133.0, 134.3, 134.3, 136.2, 142.3, 144.9, 153.7,
167.4, 192.2.
Anal. Calcd. for C22H17Cl2NO3 (414.28): C, 63.78; H, 4.14; N, 3.38. Found: C, 63.71;
H, 4.07; N, 3.30.
Ethyl 4,5-Dihydro-4-(4-isopropylphenyl)-2-methyl-5-oxo-1H-indeno[1,2-b]pyridine-
3-carboxylate (10f)
1
Red powder, IR (KBr. cm−1): 3280, 3090, 2950, 1700, 1638, 1600; H-NMR (500 MHz,
CDCl3): δ 1.17 (t, J = 7.1, 3H, OCH2-CH3), 1.22 (d, J = 6.90, 6H, CH-(CH3)2), 2.55 (s,
3H, CH3), 2.84 (sept., J = 6.9, 1H, CH-(CH3), 4.07–4.12 (m, 2H, OCH2-CH3), 5.02 (s, 1H,
CH), 6.50 (br s, 1H, NH), 7.07 (d, J = 6.6, 1H, Ar-H), 7.12 (d, J = 8.1, 2H, Ar-H), 7.27
(d, J = 8.1, 2H, Ar-H), 7.34–7.39 (m, 2H, Ar-H), 7.40 (d, J = 7.1, 1H, Ar-H); 13C-NMR
(125 MHz, CDCl3): δ 14.4, 19.6, 24.4, 34.0, 37.2, 60.2, 108.0, 110.7, 118.5, 121.3, 126.5,
128.1, 130.0, 131.4, 134.7, 144.1, 144.1, 146.8, 154.1, 168.1, 192.7.
Anal. Calcd. for C25H25NO3 (387.47): C,77.49; H, 6.50; N, 3.61. Found: C, 77.42; H,
6.41; N, 3.69.
Acknowledgment
The authors are grateful to the Research Council of University of Guilan for the financial
support of this research work.
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