Synthesis of N3,N5,4-triaryl-2,6-dimethyl-1,4- dihydropyridine-3,5-dicarboxamides

Full text of DOI:10.1134/S107042801107027X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 7, pp. 1123–1124. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.L. Gein, M.I. Kazantseva, A.A. Kurbatova, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 7,
pp. 1103–1104.
SHORT
COMMUNICATIONS
Synthesis of N3,N5,4-Triaryl-2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarboxamides
V. L. Gein, M. I. Kazantseva, and A. A. Kurbatova
Perm State Pharmaceutical Academy, ul. Polevaya 2, Perm, 614990 Russia
e-mail: geinvl48@mail.ru
Received April 21, 2010
DOI: 10.1134/S107042801107027X
The known Hantzsch dihydropyridine synthesis is
convenient for the preparation of 1,4-dihydropyridine
derivatives having similar substituents in positions 2/6
and 3/5. It is based on the reaction of β-keto ester with
aldehyde and ammonia [1]. Modifications of this reac-
tion were reported, where β-diketones, malonic acid
esters, β-keto acids, β-aminocrotononitrile, ethyl cy-
anoacetate, and cyanoacetamide were used instead of
β-keto esters [2]. While continuing studies in this field,
we were the first to perform reactions of N-arylaceto-
acetamides with aromatic aldehydes and ammonia with
a view to obtain new 1,4-dihydropyridine derivatives.
The reactions were carried out by heating the reactants
in boiling alcohol over a period of 3 h, and the prod-
ucts were the corresponding N3,N5,4-triaryl-2,6-di-
methyl-1,4-dihydropyridine-3,5-dicarboxamides Ia–If.
NH group in the pyridine ring (3348–3408 cm–1).
Compounds Ia–If displayed in the H NMR spectra
1
signals from protons in the aromatic rings and substit-
uents therein, a six-proton singlet from two methyl
groups (δ 2.24–2.45 ppm) a singlet from the 4-H
proton in the pyridine ring (δ 4.84–5.05 ppm), a signal
from the N1H proton (δ 7.95–8.50 ppm), and a two-
proton signal from amide NH groups (δ 9.21–
9.25 ppm). In the mass spectrum of Id we observed the
molecular ion peak and peaks of fragment ions which
were consistent with the assumed structure.
2,6-Dimethyl-N3,N5,4-triphenyl-1,4-dihydropyri-
dine-3,5-dicarboxamide (Ia). A mixture of 39 g
(0.22 mol) of acetoacetanilide, 10.16 ml (0.1 mol) of
benzaldehyde, 8 ml (0.11 mol) of concentrated aque-
ous ammonia, and 60 ml of ethanol was heated for 3 h
under reflux, 40 ml of warm water was added, the
mixture was cooled and treated with 60% aqueous
ethanol, and the precipitate was filtered off and recrys-
tallized from ethanol. Yield 6.5 g (15%), mp >300°C.
IR spectrum, ν, cm–1: 3408, 3272 (NH); 1680 (C=O);
Compounds Ia–If were isolated as light yellow
crystalline substances which were soluble in DMF,
DMSO, and hot ethanol and insoluble in water. The IR
spectra of Ia–If contained absorption bands due to
stretching vibrations of the amide carbonyl group
(1656–1688 cm–1), double C=C bonds (1600–
1632 cm–1), amide NH groups (3264–3312 cm–1), and
1
1652 (C=C). H NMR spectrum, δ, ppm: 2.02 s (6H,
CH3), 4.89 s (1H, 4-H), 7.03 m (15H, Harom), 8.00 s
R2
R1
R1
CHO
O
O
O
O
NH3
2
+
N
N
N
Me
H
H
R1
R2
H
Me
N
H
Me
Ia–If
R1 = R2 = H (a); R1 = 2-MeO, R2 = H (b); R1 = H, R2 = 4-Cl (c); R1 = H, R2 = 3-O2N (d);
R1 = H, R2 = 4-O2N (e); R1 = H, R2 = 2-Cl (f).
1123

GEIN et al.
1124
(1H, NH), 9.23 s (2H, NH). Found, %: C 76.37, 76.68;
H 5.84, 5.99; N 9.65, 9.98. C27H25N3O2. Calculated, %:
C 76.57; H 5.95; N 9.92.
69.36; H 5.04, 5.11; N 11.85, 11.92. C27H24N4O4. Cal-
culated, %: C 69.22; H 5.16; N 11.96.
2,6-Dimethyl-4-(4-nitrophenyl)-N3,N5-diphenyl-
1,4-dihydropyridine-3,5-dicarboxamide (Ie). Yield
45%, mp >300°C. IR spectrum, ν, cm–1: 3420, 3312
(NH); 1670 (C=O); 1632 (C=C). 1H NMR spectrum, δ,
ppm: 2.06 s (6H, CH3), 5.79 s (1H, 4-H), 7.07 m (14H,
Compounds Ib–If were synthesized in a similar
way.
N3,N5-Bis(2-methoxyphenyl)-2,6-dimethyl-4-
phenyl-1,4-dihydropyridine-3,5-dicarboxamide
(Ib). Yield 33%, mp 194–196°C. IR spectrum, ν, cm–1:
H
arom), 8.44 s (1H, NH), 9.25 s (2H, NH). Found, %:
1
C 69.42, 69.36; H 5.04, 5.11; N 11.85, 11.92.
C27H24N4O4. Calculated, %: C 69.22; H 5.16; N 11.96.
3352, 3304 (NH); 1685 (C=O); 1648 (C=C). H NMR
spectrum, δ, ppm: 2.02 s (6H, CH3), 3.64 s (6H,
OCH3), 4.95 s (1H, 4-H), 7.03 m (13H, Harom), 8.43 s
(1H, NH), 9.24 s (2H, NH). Found, %: C 72.14, 72.18;
H 6.44, 6.29; N 8.65, 8.70. C29H29N3O4. Calculated, %:
C 72.03; H 6.04; N 8.69.
4-(2-Chlorophenyl)-2,6-dimethyl-N3,N5-di-
phenyl-1,4-dihydropyridine-3,5-carboxamide (If).
Yield 31%, mp 215–217°C. IR spectrum, ν, cm–1:
1
3432, 3304 (NH); 1680 (C=O); 1632 (C=C). H NMR
spectrum, δ, ppm: 2.04 s (6H, CH3), 5.49 s (1H, 4-H),
7.06 m (14H, Harom), 8.44 s (1H, NH), 9.24 s (2H,
NH). Found, %: C 71.04, 70.78; H 5.34, 5.31; N 9.15,
9.19. C27H24ClN3O2. Calculated, %: C 70.81; H 5.28;
N 9.18.
4-(4-Chlorophenyl)-2,6-dimethyl-N3,N5-di-
phenyl-1,4-dihydropyridine-3,5-dicarboxamide (Ic).
Yield 33%, mp 205–207°C. IR spectrum, ν, cm–1:
1
3392, 3264 (NH); 1656 (C=O); 1648 (C=C). H NMR
spectrum, δ, ppm: 2.05 s (6H, CH3), 5.09 s (1H, 4-H),
7.08 m (14H, Harom), 8.50 s (1H, NH), 9.24 s (2H,
NH). Found, %: C 71.04, 70.78; H 5.34, 5.31; N 9.15,
9.19. C27H24ClN3O2. Calculated, %: C 70.81; H 5.28;
N 9.18.
The IR spectra were recorded in mineral oil on
1
a Specord M-80 spectrometer. The H NMR spectra
were measured relative to TMS on a Bruker DRX-500
instrument at 500.13 MHz using DMSO-d6 as solvent.
The mass spectrum of Id (electron impact, 70 eV) was
obtained on a Finnigan MAT INCOS-50 instrument.
2,6-Dimethyl-4-(3-nitrophenyl)-N3,N5-diphenyl-
1,4-dihydropyridine-3,5-dicarboxamide (Id). Yield
39%, mp 205–207°C. IR spectrum, ν, cm–1: 3440,
REFERENCES
1
3304 (NH); 1680 (C=O); 1632 (C=C). H NMR spec-
trum, δ, ppm: 2.07 s (6H, CH3), 4.79 s (1H, 4-H),
7.07 m (14H, Harom), 8.39 s (1H, NH), 9.25 s (2H,
NH). Mass spectrum, m/z: 468 [M – H]+, 451 [M –
NH3]+, 376 [M – PhNH]+, 346 [M – C6H4NO2]+, 93
[M – PhNH2]+, 77 [M – Ph]+. Found, %: C 69.42,
1. Sagitullina, G.P., Glidzinskaya, G.V., Sitnikov, G.V., and
Sagitullin, R.S., Khim. Geterotsikl. Soedin., 2002,
p. 1518.
2. Matern, A.I., Charushin, V.N., and Chupakhin, O.N., Usp.
Khim., 2007, vol. 76, p. 27.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011