8896
S. P. Stanforth et al. / Tetrahedron 60 (2004) 8893–8897
compound was obtained as an orange oil (44%) (eluent,
petroleum ether bp 60–80 8C/ethyl acetate 4:6). nmax (KBr):
for the preparation of ethyl 2-phenylpyridine-3-carboxylate
and was obtained as a brown oil. 1H NMR: (CDCl3) d 8.67
(dd, 1H, JZ5, 2 Hz, py-H), 8.17 (dd, 1H, JZ8, 2 Hz, py-H)
7.24 (dd, 1H, JZ8, 2 Hz, py-H), 4.40 (q, 2H, JZ7 Hz, ester-
CH2–) 3.14 (t, 2H, JZ7 Hz, –CH2–), 1.76 (m, 2H, –CH2–),
1.41 (t, 3H, JZ7 Hz, ester-CH3) and 1.00 (t, 3H, JZ7 Hz,
1
1724 and 1187 cmK1. H NMR: (CDCl3) d 8.08 (s, 1H,
py-H), 4.60 (t, 2H, JZ6 Hz, ring-CH2–), 4.43 (q, 2H, JZ
7 Hz, ester-CH2–), 3.17 (overlapping triplets, 5H, ester-
CH3, ring-CH2–), 1.72 (m, 2H, –CH2–), 1.43 (t, 2H, JZ
7 Hz, –CH2–) and 0.99 (t, 3H, JZ7 Hz, –CH3) ppm, 13C
NMR: (CDCl3) d 165.9 (CO), 163.4 (CO), 162.3 (C), 143.8
(C), 138.2 (CH), 132.9 (C), 129.5 (C), 66.9 (CH3), 62.1
(CH3), 38.7 (CH2), 29.7 (CH2), 26.9 (CH2), 23.6 (CH2) and
14.2 (CH2) ppm, HRMS (CI): calcd for C14H18NO4 (MCH)
264.1236, found 264.1234. When the experiment was
repeated using methyl 2,3-dioxohexanoic acid in place of
compound 2b, the methyl ester 11 was obtained which had
the following 1H NMR spectral data (CDCl3): d 8.09 (s, 1H,
py-H), 4.60 (t, 2H, JZ7 Hz, ring-CH2–), 3.96 (s, 3H, –CH3),
3.16 (m, 4H, 2!-CH2–), 1.72 (sextet, 2H, JZ7 Hz, –CH2–)
and 0.98 (t, 3H, JZ7 Hz, –CH3) ppm.
1
–CH3) ppm. This H NMR spectral data is consistent with
that reported in the literature.19
3.1.8. 6-Phenylpyridine-2,5-dicarboxylic acid 5-ethyl
ester and ethyl 2-phenylpyridine-3-carboxylate. To a
solution of diethyl 6-phenylpyridine-2,5-dicarboxylate 6d
(0.3 g, 1.00 mmol) in ethanol (20 mL) was added a solution
of KOH (0.12 g, 1.00 mmol, in 2 mL of water) and the
mixture was stirred at room temperature for 3 h. The pH was
then adjusted to 1 and the mixture was extracted with
dichloromethane (25 mL), washed with water (2!5 mL)
and evaporated to give the 6-phenylpyridine-2,5-di-
carboxylic acid 5-ethyl ester as a brown oil (0.22 g, 81%).
1H NMR: (CDCl3) d 8.32 (d, 1H, JZ8 Hz, py-H), 8.27 (d,
1H, JZ8 Hz, py-H), 7.53–7.48 (m, 5H, Ph-H), 4.20 (q, 2H,
JZ7 Hz, ester-CH2–) and 1.08 (t, 3H, JZ7 Hz, ester-CH3)
ppm. 6-Phenylpyridine-2,5-dicarboxylic acid 5-ethyl ester
(0.22 g, 0.81 mmol) was placed in a round bottom flask and
heated gently by means of a Bunsen burner for 2 min. The
resulting distillate was collected giving ethyl 2-phenyl-
3.1.5.
Ethyl
8-oxo-2-isopropyl-5,6-dihydro-8H-
pyrano[3,4-b]pyridine-3-carboxylate 10c. The ethyl
ester was obtained as an orange oil (44%) (eluent: petroleum
ether bp 60–80 8C/ethyl acetate 4:6). nmax (KBr): 1722 and
1187 cmK1. 1H NMR: (CDCl3) d 7.94 (s, 1H, py-H), 5.85 (t,
2H, JZ6 Hz, ring-CH2–), 4.42 (q, 2H, JZ7 Hz, ester-
CH2–), 3.74 (septet, 1H, –CH–), 3.13 (t, 2H, JZ6 Hz, ring-
CH2–), 1.43 (t, 3H, JZ7 Hz, ester-CH3) and 3.39 (d, 6H,
JZ7 Hz, 2!isopropyl-CH3) ppm, 13C NMR: (CDCl3) d
167.0 (CO), 166.4 (CO), 162.2 (C), 143.8 (C), 137.4 (CH),
132.8 (C), 129.4 (C), 66.8 (–CH3), 62.1 (CH3), 32.9 (CH2),
27.0 (CH2), 22.2 (CH2), 21.1 (CH2) and 14.2 (CH2) ppm,
HRMS (CI): calcd for C14H18NO4 (MCH) 264.1236, found
264.1233.
1
pyridine-3-carboxylate as a brown oil (0.08 g, 42%). H
NMR: (CDCl3) d 8.76 (dd, 1H, JZ5, 2 Hz, py-H), 8.10 (dd,
1H, JZ8, 2 Hz, py-H), 7.50–7.54 (m, 2H, Ph-H), 7.40–7.44
(m, 3H, Ph-H), 7.34 (dd, 1H, JZ8, 5 Hz, py-H), 4.14 (q, 2H,
JZ7 Hz, ester-CH2–) and 1.04 (t, 3H, JZ7 Hz, ester-CH3)
1
ppm. This H NMR spectral data is consistent with that
reported in the literature.20
3.2. Synthesis of bipyridine derivatives 6e–g. General
method
3.1.6. Ethyl 8-oxo-2-phenyl-5,6-dihydro-8H-pyrano[3,4-
b]pyridine-3-carboxylate 10d. This compound was
obtained as a an orange oil which crystallised from ethanol
giving a white crystalline solid (39%), mp 162 8C. nmax
To a stirred solution of amidrazone 1b17 (0.5 g, 3.68 mmol)
in ethanol (15 mL) was added appropriate a,b-diketoester
218 (3.38 mmol) and 2,5-norbornadiene 5 (3.46 g,
36.8 mmol). This solution was heated at reflux under an
atmosphere of nitrogen for 20 h, allowed to cool to room
temperature, and evaporated under reduced pressure giving
the crude product which was purified by column chroma-
tography over silica gel.
(KBr): 1736, 1701, 1182 and 1139 cmK1 1H NMR:
.
(CDCl3) d 8.01 (s, 1H, py-H), 7.60 (m, 1H, Ph-H), 7.40
(m, 4H, Ph-H), 4.65 (t, 2H, JZ5 Hz, ring-CH2–), 4.19 (q,
2H, JZ7 Hz, ester-CH2–), 3.22 (t, 2H, JZ5 Hz, ring-CH2–)
and 1.03 (t, 3H, JZ7 Hz, ester-CH3) ppm, 13C NMR:
(CDCl3) d 167.4 (CO), 161.9 (CO), 158.8 (CH), 143.5 (C),
138.8 (C), 137.6 (CH), 133.8 (C), 131.0 (C), 129.2 (C),
128.8 (C), 128.3 (C), 66.8 (CH3), 62.1 (CH2), 27.1 (CH2)
and 13.6 (CH2) ppm, Anal. for C17H15NO4: calcd C, 68.68;
H, 5.09; N, 4.71, found C, 68.54; H, 4.84; N, 4.60.
3.2.1. Ethyl 6-propyl-2,20-bipyridine-5-carboxylate 6e.
This compound was obtained as an orange oil (81%)
(eluent: ethyl acetate/petroleum ether bp 60–80 8C 1:1).
nmax (KBr): 1718, 1252 and 1093 cmK1. 1H NMR: (CDCl3)
d 8.70 (dd, 1H, JZ5, 2 Hz, py-H), 8.52 (d, 1H, JZ8 Hz,
py-H), 8.28 (s, 2H, py-H), 7.84 (dt, 1H, JZ8, 2 Hz, py-H),
7.33 (m, 1H, py-H), 4.40 (q, 2H, JZ7 Hz, ester-CH2–), 3.22
(m, 2H, –CH2–), 1.83 (sextet, 2H, JZ7 Hz, –CH2–), 1.43 (t,
3H, JZ7 Hz, ester-CH3) and 1.04 (t, 3H, JZ7 Hz, –CH3)
ppm, HRMS (CI): calcd for C16H19N2O2 (MCH) 271.1446,
found 271.1443.
3.1.7. 6-Propylpyridine-2,5-dicarboxylic acid 5-ethyl
ester and ethyl 2-propylpyridine-3-carboxylate.
6-Propylpyridine-2,5-dicarboxylic acid 5-ethyl ester
(0.15 g, 56%) was synthesised from diethyl 6-propyl-
pyridine-2,5-dicarboxylate 6b following the procedure
described below for the preparation of 6-phenylpyridine-
2,5-dicarboxylic acid 5-ethyl ester and was obtained as a
brown oil. 1H NMR: (CDCl3) d 8.40 (d, 1H, JZ8 Hz, py-H),
8.12 (d, 1H, JZ8 Hz, py-H), 4.44 (q, 2H, JZ7 Hz, ester-
CH2–), 3.18 (t, 2H, JZ7 Hz, –CH2–), 1.08 (m, 2H, –CH2–)
1.43 (t, 3H, JZ7 Hz, ester-CH3) and 1.02 (t, 3H, JZ7 Hz,
–CH3). Ethyl 2-propylpyridine-3-carboxylate (0.17 g, 70%)
was synthesised from 6-propylpyridine-2,5-dicarboxylic
acid 5-ethyl ester following the procedure described below
3.2.2. Ethyl 6-isopropyl-2,20-bipyridinyl-5-carboxylate
6f. This compound was obtained as an orange waxy solid
(80%), mp 66–70 8C, (eluent: ethyl acetate/petroleum
1
ether bp 60–80 8C 1:1). H NMR: (CDCl3) d 8.69 (d, 1H,
JZ5 Hz, py-H), 8.59 (d, 1H, JZ8 Hz, py-H), 8.28 (d, 1H,