LETTER
Synthesis of 1,4-Dihydropyridines
511
(4) (a) Xia, J. J.; Wang, G. W. Synthesis 2005, 2379.
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and references therein.
Hz, 4 H), 5.01 (s, 1 H), 5.97 (s, 1 H), 7.11–7.32 (m, 5 H). 13
NMR (62.9 MHz, CDCl3): d = 14.1, 19.5, 39.4, 59.3, 104.1,
127.5, 128.8, 135.7, 144.1, 145.9, 167.8. FT-IR (KBr): 3334,
1690, 1654, 1494, 1243, 1127, 721 cm–1.
Diethyl 4-(3-Methylphenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (4b)
C
(5) Itoh, T.; Nagata, K.; Miyazaki, M.; Ishikawa, H.; Kurihara,
A.; Ohsawa, A. Tetrahedron 2004, 60, 6649.
Mp 122–124 °C. 1H NMR (250 MHz, CDCl3): d = 1.28 (t,
J = 7.1 Hz, 6 H), 2.31 (s, 3 H), 2.34 (s, 6 H), 4.10 (q, J = 7.1
Hz, 4 H), 4.98 (s, 1 H), 5.96 (s, 1 H), 6.94–6.99 (m, 1 H),
7.09–7.15 (m, 3 H). 13C NMR (62.9 MHz, CDCl3): d = 14.2,
19.5, 21.6, 39.5, 59.8, 104.0, 125.1, 127.7, 127.8, 128.0,
128.8, 144.1, 147.7, 167.6. FT-IR (KBr): 3344, 1692, 1648,
1490, 1212, 1130, 723 cm–1.
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Chem. 2006, 261, 88.
Diethyl 4-(4-Methylphenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (4c)
Mp 135–137 °C. 1H NMR (250 MHz, CDCl3): d = 1.28 (t,
J = 7.1 Hz, 6 H), 2.30 (s, 3 H), 2.32 (s, 6 H), 4.14 (q, J = 7.1
Hz, 4 H), 4.98 (s, 1 H), 6.09 (s, 1 H), 7.04 (d, J = 7.8 Hz, 2
H), 7.23 (d, J = 7.8 Hz, 2 H). 13C NMR (62.9 MHz, CDCl3):
d = 14.3, 19.4, 21.2, 39.1, 59.7, 103.9, 127.8, 128.9, 135.2,
144.3, 145.0, 168.0. FT-IR (KBr): 3343, 1690, 1651, 1491,
1213, 1122, 772 cm–1.
Diethyl 4-(3-Chlorophenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (4d)
Mp 130–132 °C. 1H NMR (250 MHz, CDCl3): d = 1.25 (t,
J = 7.1 Hz, 6 H), 2.33 (s, 6 H), 4.12 (q, J = 7.1 Hz, 4 H), 4.98
(s, 1 H), 6.03 (s, 1 H), 7.12–7.29 (m, 4 H). 13C NMR (62.9
MHz, CDCl3): d = 14.2, 19.5, 39.6, 59.9, 103.4, 126.2,
127.8, 128.2, 133.5, 143.4, 144.6, 149.8, 167.6. FT-IR
(KBr): 3323, 1703, 1649, 1491, 1215, 1124, 802 cm–1.
Diethyl 4-(4-Chlorophenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (4e)
(12) Chari, M. A.; Syamasundar, K. Catal. Commun. 2005, 6,
624.
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Kornienko, A. Org. Lett. 2006, 8, 899.
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Mp 144–146 °C. 1H NMR (250 MHz, CDCl3): d = 1.24 (t,
J = 7.2 Hz, 6 H), 2.33 (s, 6 H), 4.11 (q, J = 7.2 Hz, 4 H), 4.97
(s, 1 H), 5.88 (s, 1 H), 7.23–7.19 (m, 4 H). 13C NMR (62.9
MHz, CDCl3): d = 14.3, 19.6, 39.2, 59.9, 103.8, 127.9,
129.4, 131.7, 144.1, 146.3, 167.5. FT-IR (KBr): 3360, 1695,
1651, 1487, 1212, 1122, 789 cm–1.
Diethyl 4-(4-Hydroxyphenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (4f)
Mp 230–232 °C. 1H NMR (250 MHz, CDCl3): d = 1.25 (t,
J = 7.1 Hz, 6 H), 2.34 (s, 6 H), 4.12 (q, J = 7.1 Hz, 4 H), 5.32
(s, 1 H), 5.77 (s, 1 H), 7.24–7.41 (m, 4 H). 13C NMR (62.9
MHz, CDCl3): d = 14.1, 19.3, 39.4, 59.8, 103.9, 127.9,
130.9, 130.4, 142.3, 148.5, 167.8. FT-IR (KBr): 3331, 1689,
1656, 1490, 1244, 1126, 720 cm–1.
Diethyl 4-(3-Nitrophenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (4g)
(24) General Procedure for the Synthesis of 1,4-Dihydro-
pyridines 4
Mp 164–166 °C. 1H NMR (250 MHz, CDCl3): d = 1.33 (t,
J = 7.1 Hz, 6 H), 2.36 (s, 6 H), 4.12 (q, J = 7.1 Hz, 4 H), 5.10
(s, 1 H), 6.20 (s, 1 H), 7.31 (t, J = 7.9 Hz, 1 H), 7.66 (d,
A mixture of aldehyde 1 (5 mmol), ethyl acetoacetate 2 (10
mmol), NH4OAc (3, 10 mmol), and PhB(OH)2 (10 mol%)
was refluxed in EtOH (10 mL) for 4–5 h. The reaction
mixture was poured into cold H2O and extracted with
EtOAc. The organic layer was washed with brine, dried over
Na2SO4, and concentrated. The crude product was purified
by recrystallization from EtOH to afford 1,4-dihydropyr-
idines 4 in 75–95% yields. The aqueous layer containing the
catalyst could be evaporated under reduced pressure to give
a white solid, which could be reused.
J = 7.8 Hz, 1 H), 8.03 (d, J = 7.9 Hz, 1 H), 8.15 (s, 1 H). 13
C
NMR (62.9 MHz, CDCl3): d = 14.2, 19.5, 39.9, 60.0, 103.0,
121.3, 123.1, 128.6, 134.6, 145.1, 148.1, 150.0, 167.3. FT-
IR (KBr): 3344, 1705, 1645, 1527, 1487, 1215, 1123, 704
cm–1.
Diethyl 4-(4-Nitrophenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (4h)
Mp 130–132 °C. 1H NMR (250 MHz, CDCl3): d = 1.23 (t,
J = 7.1 Hz, 6 H), 2.35 (s, 6 H), 4.13 (q, J = 7.1 Hz, 4 H), 5.10
(s, 1 H), 6.16 (s, 1 H), 7.50 (d, J = 8.6 Hz, 2 H), 8.14 (d,
J = 8.6 Hz, 2 H). 13C NMR (62.9 MHz, CDCl3): d = 14.2,
19.5, 40.1, 60.3, 103.0, 123.6, 128.9, 145.0, 146.2, 155.2,
167.2. FT-IR (KBr): 3317, 1705, 1647, 1521, 1348, 1215,
1122, 707 cm–1.
All compounds were fully characterized by mp, IR, 1H NMR
and 13C NMR spectroscopy. These data are in full agreement
with those previously reported in the literature.26
Diethyl 4-(Phenyl)-2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarboxylate (4a)
Mp 156–158 °C. 1H NMR (250 MHz, CDCl3): d = 1.25 (t,
J = 7.1 Hz, 6 H), 2.33 (s, 3 H), 2.32 (s, 6 H), 4.11 (q, J = 7.1
Diethyl 4-(4-Methoxyphenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (4i)
Synlett 2008, No. 4, 509–512 © Thieme Stuttgart · New York