Multicomponent one pot synthesis and characterization of novel 4-furyl-1,4-dihydropyridines

Article abstract of DOI:10.14233/ajchem.2017.20199

A series of dihydropyridines were prepared from the multi-component reaction of 5-arylfuran-2-carbaldehydes, ethylacetoacetate and ammonium acetate. These compounds were characterized through elemental analysis and various spectroscopic techniques (FTIR, ¹H NMR, ¹³C NMR and mass).

Full text of DOI:10.14233/ajchem.2017.20199

Asian Journal of Chemistry; Vol. 29, No. 4 (2017), 735-741
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2017.20199
Multicomponent One Pot Synthesis and Characterization of Novel 4-Furyl-1,4-dihydropyridines
1,2
3
ANSA MADEEHA ZAFAR , SAMINA ASLAM1,3,*, SAMIA KHAKWANI ,
4
5
1,6
MUHAMMAD NAEEM KHAN , MUNAWAR ALI MUNAWAR and MISBAHUL AIN KHAN
1Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
2Department of Chemistry, Government Sadiq College Women University, Bahawalpur, Pakistan
3Department of Chemistry, The Women University Multan, Multan, Pakistan
4Applied Chemistry Centre, PCSIR Laboratory Complex, Ferozeur Road, Lahore, Pakistan
5Institute of Chemistry, University of the Punjab, Quaid-e-Aza Campus, Lahore, Pakistan
6Research and Development Labs, Shafi Reso, Ferozepur Road, Lahore, Pakistan
*Corresponding author: E-mail: drsamina.chem@wum.edu.pk
Received: 20 July 2016;
Accepted: 13 January 2017;
Published online: 31 January 2017;
AJC-18235
A series of dihydropyridines were prepared from the multi-component reaction of 5-arylfuran-2-carbaldehydes, ethylacetoacetate and
1
ammonium acetate. These compounds were characterized through elemental analysis and various spectroscopic techniques (FTIR, H
NMR, 13C NMR and mass).
Keywords: Dihydropyridines, 5-Arylfuran-2-carbaldehydes, Multicomponent reaction, Meerwein Arylation reaction.
INTRODUCTION
EXPERIMENTAL
Dihydropyridines are important class of compounds
showing interesting pharmacological properties. Most impor-
tant of these are their actions as calcium channel blockers.
Acaricidal, insecticidal, bactericidal, herbicidal, antiaggre-
gatory, cerebral antiischemic and properties such as chemo
sensitizers have also been reported [1]. Some of these
amlopidine, nifedipine and nicardipine are calcium channel
blockers and are in common clinical use for the prevention of
hypertension [1,2]. There are others which are acetylchlonestrase
inhibitors and neuroprotectants [2-8].
Most of these are available through Hantzsch dihydro-
pyridine synthesis in a multicomponent (MCR) strategy of
cyclocondensation between an aldehyde and active methylene
compound and ammonium acetate in an alcohol solvent [2,9-
13]. In continuation of our work on multicomponent reactions
for the synthesis of heterocyclic compounds of potential
biological interest, we have prepared a number of novel 1,4-
dihydropyridines by employing arylfurfurals as the aldehydic
component of the reaction. This we would like to report in the
present communication. Although various aryl aldehydes have
been employed for this synthesis and some 1,4-dihydropyridines
containing a 4-furyl substituent are reported but hitherto
arylfurfurals have not been used for such syntheses.
The reagents and chemicals used were commercially
available from Merck or Fluka and were used as such. However
when needed, were purified using normal techniques. The
solvents used were distilled and dried. Melting points were
taken on a GallenKamp melting point apparatus and are un-
corrected. FTIR spectra were recorded on a Bruker Tensor 27.
1H NMR and 13C NMR spectra were taken on Bruker DPX
instrument at 300 and 400 MHz. High resolution mass spectra
were recorded on a Fisons VG Platform II spectrometer.
Synthesis of 5-arylfuran-2-carbaldehydes (1-9): The
compounds 5-arylfuran-2-carbaldehydes (1-9) were synthe-
sized and characterized according to the reported method
[3,13].
5-(2'-Nitrophenyl)furan-2-carbaldehyde (1): Yield: 67
%; m.p.: 80-81 °C (lit. m.p. 90-92 °C) [1].
5-(4'-Nitrophenyl)furan-2-carbaldehyde (2): Yield: 64
%; m.p.: 196 °C (lit. m.p. 192 °C) [3].
5-(2',3'-Dichlorophenyl)furan-2-carbaldehyde (3):
Yield: 59 %; m.p.: 90-92 °C [4].
5-(2',4'-Dichlorophenyl)furan-2-carbaldehyde (4):
Yield: 53 %; m.p.: 63 °C.
5-(5'-Chloro-2'-nitrophenyl)furan-2-carbaldehyde (5):
Yield: 52 %; m.p.: 76 °C.

736 Zafar et al.
Asian J. Chem.
5-(3',4'-Dichlorophenyl)furan-2-carbaldehyde (6):
Yield: 61 %; m.p.: 105 °C.
5-(3'-Nitrophenyl)furan-2-carbaldehyde (7): Yield: 61
%; m.p.: 148 °C (lit. m.p 150 °C) [2].
5-(4'-Chlorophenyl)furan-2-carbaldehyde (8): Yield:
62 %; m.p.: 118 °C [4].
(M) 49.6 %, 444.9 (M-2CH3) 54.4 %, 401.0 (M-COOC2H5)
100 %, 371.0 (M-COOC2H5-2CH3) 6.55 %, 328.0 (M-
2COOC2H5) 6.9 %, 252.1 (M-C10H5ClNO3) 14.4 %, 223.0 (M-
C13H18NO4) 5.3 %, 183.9 (M-C10H5ClNO3-COOC2H5) 10.2 %,
1
150.0 (M-C10H5ClNO3-COOC2H5-2CH3) 7.3 %. H NMR
(CDCl3), δ: 2.374 (s, 6H, 2CH3), 1.302 (t, 6H, 2CH3CH2, J =
10.62 Hz), 4.184 (q, 4H, 2CH3CH2, J = 10.41 Hz), 5.303 (s,
1H, CH), 7.28 (d, 4H, H-6", J = 6.00 Hz), 8.275 (s, 1H, H-
3"); 13C NMR (CDCl3), δ: 14.40 (CH3CH2), 60.02 (CH3CH2),
167.13 (C=O), 100.33 (CC), 145.42 (CCNH), 19.62 (CH3CNH),
33.81 (CH-furan), 145.42, 100.33, 107.92, 146.61 (furan ring),
145.27, 129.19, 116.01, 135.42, 126.24, 134.90 (phenyl ring).
Diethyl 2,6-dimethyl-4-[5'-(2"-nitrophenyl)furan-2-
yl]-1,4-dihydropyridine-3-carboxylate (13): Yield: 50 %;
m.p.: 120-122 °C; IR (KBr, νmax, cm-1): 3732.1 (N-H stretching),
3347.7 (Ar-H), 2984.9 (C-H stretching of CH3), 1648.2 (C=O
ester), 1478.8, 1336.2 (NO2). Mass: 440.2 (M) 27.4 %, 423.1
(M-CH3) 22.3 %, 395.1 (M-NO2) 15.8 %, 367.1 (M-COOC2H5)
100 %, 337.1 (M-COOC2H5-2CH3) 5.3 %, 293.1 (M-
2COOC2H5) 5.0 %, 252.1 (M-C10H6No3)18.5 %, 224.1 (M-
C10H6No3-2CH3) 6.3 %, 150.0 (M-C10H6No3-2CH3-COOC2H5)
7.8 %, 77.0 (M-C17H20NO5-NO2) 3.4 %.1H NMR (CDCl3), δ:
2.361 (s, 6H, 2CH3), 1.288 (t, 6H, 2CH3CH2, J = 10.62 Hz),
4.181 (q, 4H, 2CH3CH2, J = 10.04 Hz), 5.138 (s, 1H, CH),
6.120, 6.127 (2H of furan ring, H-3', H-4'), 6.593 (d, 1H, H-
6", J = 3.57 Hz), 7.958 and 7.82 (H-2" and H-3" respectively).
13C NMR (CDCl3), δ: 14.36 (CH3CH2), 59.82 (CH3CH2),
167.21 (C=O), 99.82 (2C), 146.129 (2C), 19.567 (2CH3),
33.378 (CH), 99.699 (CH-furan), 146.494 (C-furan), 106.453
(CH-furan), 147.037 (C-furan), 127.561 (C-aromatic), 127.228
(CH-aromatic), 127.561 (C-NO2-aromatic).
Diethyl-2,6-dimethyl 4-[5'-(2",4"-dichlorophenyl)furan-
2-yl]-1,4-dihydropyridine-3-carboxylate (14): Yield: 83 %;
m.p.: 180 °C; IR (KBr, νmax, cm-1): 3941.6 (N-H stretching),
3319.5 (Ar-H), 2986.0 (C-H stretching of CH3), 1652.7 (C=O
ester); Mass: 465.0 (M+2) 43.0 %, 463.0 (M) 76.0 %, 434.1
(M-2CH3) 70.3 %, 390.1 (M-COOC2H5) 100 %, 362.0 (M-
COOC2H5-2CH3) 15.9 %, 344.0 (M-COOC2H5-2CH3–Cl) 11.4
%, 317.0 (M-2COOC2H5) 7.9 %, 252.1 (M-C10H5Cl2O) 16.1
%, 212.0 (M-C13H18NO4) 6.0 %, 196.1 (M-C10H5Cl2O-2CH3-
C2H5) 14.9 %, 150.1 (M-C10H5Cl2O-COOC2H5-2CH3) 9.2 %.
1H NMR (CDCl3), δ: 2.283 (s, 6H, 2CH3), 1.207 (t, 6H,
2CH3CH2, J = 10.62 Hz), 4.122 (q, 4H, 2CH3CH2, J = 12.09
Hz), 5.112 (s, 1H, CH), 6.034 (d, 1H, H-3', J = 2.55 Hz),
7.622, 7.522, 7.412 (H-6", H-5", H-3" respectively), 9.052 (s,
1H, NH of dihydropyridine); 13C NMR (CDCl3), δ: 14.40
(CH3CH2), 59.95 (CH3CH2), 167.35 (C=O), 106.89 (CC),
147.43 (CNH), 19.58 (CH3CNH), 33.53 (CH-furan), 145.32,
100.51, 106.89, 112.19, 158.88 (furan ring), 132.06, 130.28,
129.91, 128.17, 127.97, 127.05 (phenyl ring).
5-(2'-Chloro-4'-nitrophenyl)furan-2-carbaldehyde (9):
Yield: 61 %; m.p.: 114 °C.
Synthesis of dihydropyridines (10-20):An arylfuran-2-
carbaldehyde (1 mmol), ethyl acetoacetate (2 mmol) and
ammonium acetate (1mmol) was refluxed in ethanol for 3 h
(reaction monitored through TLC). After cooling the reaction
mixture was poured into ice cold water. Precipitates were filtered,
washed with water and cold ethanol, dried and recrystallized
from ethanol to give dihydropyridines (10-20).
Diethyl 2,6-dimethyl-4-[5'-(4"-nitro phenyl)furan-2'-
yl]-1,4-dihydropyridine-3,5-dicarboxylate (10): Yield: 95 %;
m.p.: 145-150 °C; IR (KBr, νmax, cm-1): 3834.9 (N-H stretching),
3107.0 (Ar-H), 2984.0 (C-H stretching of CH3), 1714.3 (C=O
ester), 1512.3, 1330.4 (NO2); 1H NMR (CDCl3), δ: 2.379 (s,
6H, 2CH3), 1.319 (t, 6H, 2CH3CH2, J = 10.68 Hz), 4.234 (q,
4H, 2CH3CH2, J = 12.63 Hz), 7.74 (H-2", 6"), 8.25 (H-3",
5"); 13C NMR (CDCl3), δ: 14.08 (CH3), 61.70 (CH3-CH2),
167.20 (C=O), 107.70 (C=C), 149.98 (C-NH), 14.39 (CH3),
33.83 (CH-C), 150.21 (CH=C-O), 100.37 (CH-CH), 107.70
(CH-CH), 154.79 (CH-aromatic ring), 136.91, 130.83, 123.2,
124.80, 125.59, 149.81 (aromatic carbons); Mass: m/z: 440.2
(M) 96.7 %, 411.2 (M-2CH3) 100 %, 395.2 (M-NO2) 30.1 %,
383.1 (M-2C2H5) 23.3 %, 367.2 (M-COOC2H5) 100 %, 337.2
(M-COOC2H5-2CH3) 26.7 %, 321.1 (M-COOC2H5-C2H5O)
30.4 %, 293.1 (M-2COOC2H5) 11.7 %, 252.1 (M-C10H6NO3)
14.9 %, 196.1 (M-C10H6NO3-2C2H5) 13.8 %, 179.1 (M-
C10H6NO3-2C2H5-CH3) 10.7 %, 150.1 (M-C10H6NO3-C2H5O-
CH3) 15.4 %, 120.1 (M-C17H20NO5) 13.0 %, 55.1 (C4H5) 6.5
%, 43.0 (C2H4O) 9.9 %.
Diethyl-2,6-dimethyl 4-[5'-(2",3"-dichlorophenyl)furan-
2'-yl]-1,4-dihydropyridine-3-carboxylate (11): Yield :43 %;
m.p.: 110-112 °C; IR (KBr, νmax, cm-1): 3902.4 (N-H stretching),
3327.9 (Ar-H), 2982.2 (C-H stretching of CH3), 1651.7 (C=O
ester); Mass: 465.1 (M+2) 13.9 %, 463.1 (M) 24.1 %, 434.1
(M-2CH3) 21.2 %, 390.1 (M-COOC2H5) 47.4 %, 364.0 (M-
COOC2H5-2CH3), 344.0 (M-COOC2H5-C2H5O), 252.1 (M-
C10H5Cl2O) 8.9 %, 196.1 (M-C10H5Cl2O-2CH3-C2H5) 5.1 %,
173.0 (M-2COOC2H5-C6H3Cl2) 7.1 %, 149.0 (M-C10H5Cl2O-
2C2H5O-CH3) 7.9 %. 1H NMR (CDCl3), δ: 2.358 (s, 6H, 2CH3),
1.261 (t, 6H, 2CH3-CH2, J = 10.71 Hz), 4.197 (q, 4H, 2CH3-
CH2, J = 10.86 Hz), 5.265 (s, 1H, CH), 7.027 (d, 1H, H-4", J
= 2.55), 7.179 (t, 1H, H-5"), 7.265 (d, 1H, H-6"); 13C NMR
(CDCl3), δ: 14.40 (CH3CH2), 59.93 (CH3CH2), 167.29 (C=O),
100.62 (CC), 145.20 (CC), 19.62 (CH3C), 33.60 (CH-furan
part), 100.62 (CH-furan), 145.20 (C-furan), 106.84 (CH-furan),
125.69, 127.04, 128.04, 131.76, 134.07, 145.20 (aromatic
ring). Anal. calcd. (%): (C23H23Cl2NO5): C, 59.64; H, 4.96; N,
3.02; Found (%): C, 59.71; H, 4.88, N, 2.84 %
Diethyl-2,6-dimethyl-4-[5'-(5"-chloro-2"-nitrophenyl)-
furan-2-yl]-1,4-dihydropyridine-3-carboxylate (15): Yield:
59 % m.p.: 135 °C; IR (KBr, νmax, cm-1): 3745.5 (N-H stretching),
3353.1 (Ar-H), 2985.4 (C-H stretching of CH3), 1651.4 (C=O
ester), 1476.3, 1363.8 (NO2). Mass: 476.1 (M+2) 16.9 %, 474.1
(M) 57.5 %, 457.1 (M-CH3) 48.0 %, 444.1 (M-2CH3) 8.2 %,
429.1 (M-NO2) 26.6 %, 401.1 (M-COOC2H5) 100 %, 373.1
(M-COOC2H5-2CH3) 11.2 %, 355.1 (M-COOC2H5-NO2) 26.1
%, 327.1 (M-2COOC2H5) 9.7 %, 283.1 (M-2COOC2H5-NO2)
Diethyl-2,6-dimethyl-4-[5'-(2"-chloro-4"-nitrophenyl)-
furan-2'-yl]1,4-dihydropyridine-3-carboxylate (12): Yield:
59 %, m.p.: 220 °C, IR (KBr, νmax, cm-1): 3311.9 (N-H stretching),
3087.5 (Ar-H), 2983.5 (C-H stretching of CH3), 1652.7 (C=O
ester), 1487.3, 1332.7 (NO2).Mass: 476.0 (M+2)14.4 %, 473.9

Vol. 29, No. 4 (2017)
Multicomponent One Pot Synthesis and Characterization of Novel 4-Furyl-1,4-dihydropyridines 737
16.2 %, 252.1 (M-C10H5ClNO3) 48.9 %, 224.1 (M-C13H18NO4)
12.0 %, 150.1 (M-C10H5ClNO3-COOC2H5-2CH3) 19.0 %. 1H
NMR (CDCl3), δ: 2.355 (s, 6H, 2CH3), 1.267 (t, 6H, 2CH3CH2,
J = 10.68 Hz), 4.179 (q, 4H, 2CH3CH2, J = 9.66 Hz), 5.140
(s,1H,CH), 6.127 (d, 1H, H-3', J = 2.45 Hz), 6.576 (s, 1H, H-
4'), 7.502 (s, 1H, H-6"); 13C NMR (CDCl3), δ: 14.34 (CH3CH2),
59.83 (CH3CH2), 167.216 (2C=O), 99.672 (2C), 146.958 (2C),
19.611 (2CH3), 33.499 (2CH), 99.672 (CH-furan), 145.481
(C-furan), 106.675 (CH-furan), 132.567 (C-aromatic), 131.537
(CH-aromatic), 128.529 (CH-aromatic), 123.779 (CH-
aromatic), 146.107 (C-NO2-aromatic).
107.30, 159.60 (4C of furan ring), 122.41, 124.94, 130.07,
130.48, 131.28, 132.69 (6C of 3, 4-dichloro phenyl ring);
Mass: 467.0 (M+4) 7.4 %, 465.0 (M+2) 35.5 %, 463.0 (M)
53.2 %, 434.0 (M-2CH3) 65.7 %, 390.0 (M-COOC2H5) 100
%, 357.9 (M-COOC2H5-Cl) 27.0 %, 344.0 (M-COOC2H5-Cl-
CH3) 14.1 %, 317.0 (M-COOC2H5-COOC2H5) 8.7 %, 290.0
(M-COOC2H5-COOC2H5-2CH3) 5.5 %, 252.1 (M-C10H5Cl2O)
25.8 %, 223.0 (M-C10H5Cl2O-2CH3) 9.6 %, 179.1 (M-
C10H5Cl2O-COOC2H5) 20.8 %.Anal. calcd. (%):C23H23Cl2NO5
C, 59.64; H, 4.96; N, 3.02; Found (%): C, 60.45; H, 5.21; N,
3.03 %.
Diethyl 2,6-dimethyl-4-[5'-(2"-chloro-5"-nitro phenyl)-
furan-2'-yl]-1,4-dihydropyridine-3,5-dicarboxylate (16):
Yield: 25 %; m.p.: 160 °C; IR (KBr, νmax, cm-1): 3730.0 (N-H
stretching), 3104.6 (Ar-H), 2985.3 (C-H stretching of CH3),
1656.3 (C=O ester), 1520.5, 1383.4 (NO2).Mass: 476.1 (M+2)
18.2 %, 474.1 (M) 58.5 %, 457.1 (M-CH3) 64.5 %, 445 (M-
2CH3) 85.9 %, 401.1 (M-COOC2H5) 100 %, 373 (M-2CH3-
COOC2H5) 27.2 %, 328 (M-2COOC2H5)13.3 %, 252.1 (M-
C10H5ClNO3) 24.6 %, 224.1 (M-C10H5ClNO3-2CH3)8.9 %,
150.1 (M-C10H5ClNO3-2CH3-COOC2H5) 14.4 %, (M-
C10H5ClNO3-2CH3-COOC2H5-NH) 6.3 %. 1H NMR (CDCl3)
δ: 2.178 (s, 6H, 2CH3), 1.323 (t, 6H, 2CH3CH2, J = 10.65 Hz),
4.241 (q, 4H, 2CH3CH2, J = 8.31 Hz), 5.290 (s, 1H, CH),
7.270 (1H, H-3"), 7.542 (1H, H-4"), 8.613 (1H, H-6"); 13C
NMR (CDCl3), δ: 14.111 (2CH3), 60.026 (2CH2), 167.267
(2C=O), 100.205 (2C), 151.318 (2C-N), 14.379 (2CH3),
30.902 (CH), 149.232 (C), (furan), 100.205 (CH), 107.172
(CH), 160.092 (C), 136.787 (C-aromatic), 123.231 (CH),
146.106 (C-N), 122.920 (CH), 130.642 (CH), 135.168 (C-
Cl); Anal. calcd. (%): C23H23N2O7Cl: C, 58.26; H, 4.85: N,
5.90; Found (%): C, 58.04; H, 4.70; N, 5.46.
Diethyl 2,6-dimethyl-4-[5'-(2",5"-dichlorophenyl furan-
2'-yl]-1,4-dihydropyridine-3,5-dicarboxylate (17) : Yield,
90 %; m.p.: 150 °C; IR (KBr, νmax, cm-1): 3334.5 (Ar-H), 2982.1
(C-H stretching of CH3), 1648.3 (C=O ester); Mass: 467.0
(M+4) 7.6 %, 465.0 (M+2) 9.4 %, 463.0 (M) 64.6 %, 434.0
(M-2CH3) 65.6 %, 390.0 (M-COOC2H5) 100 %, 362.0 (M-
COOC2H5-2CH3)16.9 %, 317.0 (M-2COOC2H5) 7.6 %, 252.1
(M-C10H5Cl2O) 17.0 %, 224.1 (M-C10H5Cl2O-2CH3) 5.3 %.
1H NMR (CDCl3), δ: 2.368 (s, 6H, 2CH3), 1.305 (t, 6H,
2CH3CH2, J = 10.65 Hz), 4.231 (q, 4H, 2CH3CH2, J = 10.37
Hz), 5.273 (s, 1H, CH), 7.284 (d, 1H, H-3", J = 6.60 Hz),
7.047 (d, 1H, H-4", J = 2.52 Hz), 7.711 (1H, H-6"); 13C NMR
(CDCl3), δ: 14.442 (2CH3), 19.572 (2CH3), 60.044 (2CH2),
167.381 (2C=O), 100.400 (2C), 147.048 (2C), 33.495 (CH),
159.144 (C), 100.400 (CH-furan), 106.942 (CH), 159.144 (C),
126.878 (CH), 132.643 (C-Cl), 130.720 (CH) and 131.720
(C-Cl).
Diethyl 2,6-dimethyl-4-[5'-(3"-nitrophenyl)furan-2’-
yl]-1,4-dihydropyridine-3,5-dicarboxylate (19): Yield: 61 %;
m.p.: 178 °C; IR (KBr, νmax, cm-1): 3334.70 (Ar-H), 1684.46
(C=O ester), 1345.92, 1537.60 (NO2). Mass: 440.0 (M) 49.5
%, 411.0 (M-2CH3) 71.1 %, 367.0 (M-COOC2H5) 100 %,
339.0 (M-COOC2H5-CH3) 13.2 %, 321.0 (M-COOC2H5-NO2)
13.5 %, 294.0 (M-COOC2H5-NO2-2CH3) 10.1 %, 252.1 (M-
C13H18NO4) 15.3 %, 196.0 (M-C13H18NO4-2C2H5) 13.2 %,
179.0 (M-C13H18NO4-COOC2H5)9.1 %, 150.0 (M-C13H18NO4-
2CH3) 17.3 %; 1H NMR, (CDCl3) δ: 2.379 (s, 6H, 2CH3), 1.319
(t, 6H, 2CH3CH2, J = 10.68 Hz), 4.234 (q, 4H, 2CH3CH2, J =
12.63 Hz), 5.273 (s, 1H, CH), 7.266 (1H, H-5"), 8.41 (1H, H-
2"), 8.15 (1H, H-4"), 7.87 (1H, H-6"); 13C NMR (CDCl3), δ:
14.36 (CH3CH2), 59.82 (CH3CH2), 167.21 (C=O), 99.82 (2C),
146.129 (2C), 19.567 (2CH3), 33.378 (CH), 99.699 (CH-
furan), 146.494 (C-furan), 106.453 (CH-furan), 147.037 (C-
furan), 129.571 (C-aromatic), 135.82 (CH-aromatic), 146.961
(C-NO2-aromatic); Anal. calcd. (%): C23H24N2O7: C, 62.57;
H, 5.45; N, 6.36; Found (%): C, 63.49; H, 5.68; N, 6.48 %.
Diethyl 2,5-dimethyl-4-[5'-(4"-chlorophenyl)furan-2'-
yl]-1,4-dihydropyridine-3,5-dicarboxylate (20):Yield: 24 %;
m.p.: 150-152 °C; Mass: 431 (M+2)15.8 %, 429.1 (M) 48.9
%, 400.0 (M-2CH3) 55.4 %, 356.0 (M-COOC2H5) 100 %,
328.0 (M-COOC2H5-2CH3) 10.7 %, 283.0 (M-COOC2H5) 7.4
%, 252.1 (M-C13H18NO4) 9.9 %, 178.0 (M-C13H18NO4-
COOC2H5) 13.9 %. 1H NMR (CDCl3), δ: 2.355 (s, 6H, 2CH3),
1.295 (t, 6H, 2CH3CH2, J = 10.62 Hz), 4.207 (q, 4H, 2CH3CH2,
J = 12.21 Hz), 5.232 (s, 1H, CH), 6.484 (d, 1H, H-4', J = 2.49
Hz), 7.288 (d, 2H, H-3", H-5", J = 6.54 Hz), 7.469 (d, 2H, H-
2", H-6", J = 6.48 Hz); 13C NMR (CDCl3), δ: 14.40 (2CH3),
59.92 (2CH2), 167.43 (2C=O), 100.595 (2C), 30.985 (CH),
145.305 (2C), 19.581 (2CH3), 158.98 (C), 106.260 (CH),
106.763 (CH), 150.946 (C), 128.680 (2CH), 129.837 (2CH),
132.120 (C) and 124.466 (CH).
RESULTS AND DISCUSSION
Although furyl containing 1,4-dihydropyridines have been
reported but there does not seem to be mention of 4-aryl-
furfuryl-1,4-dihydropyridines which are reported in this
communication. 5-Arylfuran-2-carbaldehydes (1-9) used for
this synthesis were obtained from Meerwein arylation of furan-
2-carbaldehyde [3] (Scheme-I).
Diethyl 2,6-dimethyl-4-[5'-(3",4"-dichlorophenyl)-
furan-2'-yl]-1,4-dihydropyridine-3,5-dicarboxylate (18):
Yield: 83 %; m.p.: 145 °C; IR (KBr, νmax, cm-1): 3654.0 (N-H
stretching), 3330.0 (Ar-H), 2981.2 (C-H stretching of CH3),
1650.9 (C=O ester); 1H NMR (CDCl3), δ: 2.368 (s, 6H, 2CH3),
1.305 (t, 6H, 2CH3CH2, J = 10.65 Hz), 4.231 (q, 4H, 2CH3CH2,
J = 10.37 Hz), 7.43, 7.27, 7.30 (H-2", 5", 6"); 13C NMR (CDCl3),
δ: 19.58 (2CH3), 14.39 (2CH3CH2), 59.92 (2CH3CH2), 167.29
(2C=O), 100.64 (2C), 149.69 (2C, C-2), 33.66 (CH), 106.96,
NH2
50% H2O+HCl, CuCl2
CHO
O
+
R
-5 °C
CHO
O
R
(1-9)
Scheme-I

738 Zafar et al.
Asian J. Chem.
When 5-arylfuran-2-carbaldehydes (1-9) were reacted
hydes and final products along with reaction time are given in
Table-1.
All 5-arylfuran-2-carbaldehydes smoothly underwent this
multicomponent Hanztsch condensation with ethyl acetoacetate
with ethyl acetoacetate and ammonium acetate in refluxing
ethanol, the desired arylated products (10-20) were obtained
in good yields (Scheme-II). The structure of different alde-
R
O
O
O
O
R
+
ethanol,
reflux
NH4 CH3
-O
O
+
CH3
H3C
O
H3C
O
O
CH3
CHO
+
H3C
CH3
N
H
(10-20)
Scheme-II
TABLE-1
DIETHYL 4-(5'-ARYLFURAN-2'-YL)-2,6-DIMETHYL-1,4-DIHYDROPYRIDINES
Compound No.
Aldehyde
Time (h)
Final product
TLC
NO2
EtOAc:n-Hexane
O
6.0
10
NO2
1:4
OHC
O
C2H5OOC
H3C
COOC2H5
CH3
N
H
Cl
Cl
O
EtOAc:n-Hexane
O
OHC
6.0
11
1:4
C2H5OOC
H3C
COOC2H5
CH3
Cl
Cl
N
H
NO2
Cl
EtOAc:n-Hexane
O
O
O
NO2
6.0
12
OHC
O
1:4
Cl
C2H5OOC
H3C
COOC2H5
CH3
N
H
NO2
EtOAc:n-Hexane
6.0
13
14
OHC
O
1:4
C2H5OOC
H3C
COOC2H5
CH3
O2N
N
H
Cl
Cl
EtOAc:n-Hexane
Cl
6.5
OHC
O
1:4
C2H5OOC
H3C
COOC2H5
CH3
Cl
N
H

Vol. 29, No. 4 (2017)
Compound No.
Multicomponent One Pot Synthesis and Characterization of Novel 4-Furyl-1,4-dihydropyridines 739
Aldehyde
Time (h)
Final product
TLC
Cl
Cl
NO2
EtOAc:n-Hexane
O
6.0
15
OHC
O
1:4
C2H5OOC
H3C
COOC2H5
CH3
O2N
N
H
O2N
NO2
Cl
EtOAc:n-Hexane
O
6.0
16
OHC
O
1:4
Cl
C2H5OOC
H3C
COOC2H5
CH3
N
H
Cl
Cl
Cl
EtOAc:n-Hexane
O
6.0
6.0
6.0
17
18
19
OHC
O
1:4
C2H5OOC
H3C
COOC2H5
CH3
Cl
N
H
Cl
Cl
EtOAc:n-Hexane
O
Cl
O
OHC
1:4
C2H5OOC
H3C
COOC2H5
CH3
Cl
N
H
NO2
O
EtOAc:n-Hexane
O
OHC
1:4
C2H5OOC
H3C
COOC2H5
CH3
NO2
N
H
Cl
EtOAc:n-Hexane
O
6.0
20
1:4
Cl
OHC
O
C2H5OOC
H3C
COOC2H5
CH3
N
H
and relatively less toxic ammonium acetate. The analytical
data of the compounds is given in experimental part. The brief
discussion however follows:
The IR spectra of compounds 10-20 show the absorbtion
peaks due to C=O of ester group at 1648-1714 cm-1; the
aromatic ring at 3080-3350 cm-1 and the N-H stretching at
3310-3945 cm-1. The 1H NMR spectra of these dihydropyridines
show the signals of six protons of two methyl groups at C-2
and C-6 in the range of δ 2.17 to 2.37, six protons of the ester
at C-3, C-5 in the range of δ 1.203-1.323 and the J values
show a narrow range of 10.62-10.70 Hz. The methylene signal
of the ester is shown in the range of δ 4.075-4.241 and the J-
values are in a wide range of 8.31-12.63 Hz, the protons of
aromatic rings are in the expected positions.
The 13C NMR spectra displayed the signals for the carbons
of esters in the range of δ 14.08-14.44, 59.82-60.70 and

740 Zafar et al.
Asian J. Chem.
167.07-167.43 (CH3, CH2 and C=O respectively), the signals
for the carbons of the furan ring are in the range of δ 145.26-
146.49, 99.69-101.89, 106.84-112-19 and 147.03-149.23 (C-
2', C-3', C-4' and C-5' respectively) and the carbons of the
phenyl group are found in the corresponding ranges with some
variations due to their different substituents.
observed at M+-73 (100 %) which denotes a M+ minus an ester
group. The general pattern observed for the mass fragmentation
is observed as follows (Scheme-III).
ACKNOWLEDGEMENTS
As far as the mass spectra are concerned, there are M+
peaks corresponding to the expected masses as well as M++2
and M++4 peaks for the expected halogen compounds. As in
compound 1 (m/z 301.2) and as well as in others, a peak is
A.M. Zafar and S. Aslam like to thank Higher Education
Commission, Government of Pakistan for Indigenous
scholarships. M.A. Khan is grateful to HEC for their analytical
support program.
COOC2H5
C2H5OOC
H3C
CH3
N
H
m/z:251.66
O
O
C2H5OOC
H3C
COOC2H5
CH3
O
-2CH3
-30
N
H
C2H5OOC
COOC2H5
-
C
m/z:395.71
O
N
O
C
H
2 H
m/z:365.71
5
O
O
O
-2CH3
H3C
O
C2H5OOC
-30
H3C
N
H
CH3
m/z:352.71
N
H
m/z:392.71
O
O
O
HO
H3C
N
CH3
H3C
N
CH3
H
H
m/z:277.71
m/z:259.71
Expected mass fragmentation pattern
Scheme-III

Vol. 29, No. 4 (2017)
Multicomponent One Pot Synthesis and Characterization of Novel 4-Furyl-1,4-dihydropyridines 741
7. A. Debache, W. Ghalem, R. Boulcina, A. Belfaitah, S. Rhouati and B.
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