1666
R.-A. Fallahpour
SHORT PAPER
Table Pyridine Derivatives Prepared
Prod- Yield
Mp
(°C)
MS
(m/z)
1H NMR (CDCl3), , J (Hz)
13C NMR (CDCl3),
ucta
(%)
2
35
74 75 251
96 97 267
7.29 (s, 2 H), 2.32 (s, 2 H)
153.19, 141.44, 128.63, 21.19
4
79
7.47 (s, 2 H), 4.72 (s, 2 H)
5
81
80
97
265
249
9.96 (s, 1 H), 7.84 (s, 2 H)
188.00, 142.19, 125.95, 125.18
10
65
8.70 (d, 2 H, J = 7.80), 8.61 (d, 2 H, J = 7.80), 8.29
156.40, 155.24, 149.14, 149.03, 136.83,
(s, 2 H), 7.84 (ddd, 2 H, J = 8.30, 7.80, 1.95), 7.32 (ddd, 123.64, 121.83, 121.32, 21.34
2 H, J = 8.30, 7.80, 1.95), 2.53 (s, 3 H)
11
12
55
58
186
178
275
275
8.56 (d, 2 H, J = 7.80), 8.41 (s, 2 H), 8.27 (s, 2 H), 7.15
(dd, 2 H, J = 7.80, 1.95), 2.51 (s, 3 H), 2.49 (s, 6 H)
156.19, 155.43, 148.87, 148.05, 124.67,
123.54, 122.10, 122.03, 21.34, 21.17
8.54 (d, 2 H, J = 7.80), 8.52 (d, 2 H, J = 7.80), 8.24 (s,
2 H), 7.67 (dd, 2 H, J = 7.80, 1.95), 2.53 (s, 3 H), 2.44
(s, 6 H)
155.22, 153.90, 149.36, 137.46, 133.30,
121.26, 120.89, 21.33, 18.39
13
14
50
61
154
166
275
261
8.39 (d, 2 H, J = 7.80), 8.28 (s, 2 H), 7.72 (t, 2 H, J = 7.80), 157.73, 155.90, 155.47, 148.93, 136.96,
7.18 (d, 2 H, J = 7.80), 2.66 (s, 6 H), 2.53 (s, 3 H) 123.14, 121.65, 118.34, 24.67, 21.42
10.28 (s, 1 H), 8.88 (s, 2 H), 8.75 (d, 2 H, J = 7.80), 8.63 191.75, 157.22, 155.18, 149.40, 144.00,
(d, 2 H, J = 7.80), 7.90 (ddd, 2 H, J = 8.30, 7.80, 1.95), 137.02, 124.37, 121.33, 119.77
7.39 (ddd, 2 H, J = 8.30, 7.80, 1.95)
a Satisfactory microanalyses obtained: C 0.22, H 0.23, N 0.47.
refluxed for 3 h. EtOH was removed and H2O (20 mL) was added.
Excess NaBH4 was destroyed by the addition of 1 N HCl (5 mL) and
the solution was neutralised with Na2CO3. The aqueous phase was
extracted with CH2Cl2 (3 × 30 mL). The combined organic phases
were dried (MgSO4) and solvent was removed. Compound 4 was
then purified on silica gel using CH2Cl2/EtOAc (3:1); yield: 0.34 g
(79%) (Table).
vantage of the published methods is that the starting ma-
terials are not easily accessible or the yield is low.
In conclusion, the method presented here allows the syn-
thesis of derivatives of 2,2’:6’,2’’-terpyridine not only at
the central pyridine ring but also at the terminal pyridine
rings. The methyl groups are very reactive, e.g. they can
be oxidised and a 2,2’:6’,2’’-terpyridine-4,4’,4’’-tricarboxy-
lic acid obtained.23 In addition, the yields are reasonable
and the starting materials are either commercially avail-
able or easily accessible.
2,6-Dibromopyridine-4-carbaldehyde (5)
To a solution of oxalyl chloride (0.17 g, 1.35 mmol) in CH2Cl2 (10
mL) at 78 °C was added under N2 a solution of DMSO (0.23 g,
2.94 mmol) in CH2Cl2 (2 mL). After 10 min a solution of 4 (0.33 g,
1.23 mmol) in CH2Cl2 (5 mL) was added. The mixture was stirred
for 15 min and Et3N (0.62 g, 6.13 mmol) was added. The cooling
bath was removed and H2O (20 mL) was added at r.t. The aqueous
phase was extracted with CH2Cl2 (3 × 30 mL). The combined or-
ganic phases were dried (MgSO4) and the solvent was removed.
Compound 4 was then purified on silica gel using CH2Cl2/hexane
(1:1); yield: 0.26 g (81%) (Table).
All reagents were used as supplied. Silica gel (0.060 0.200 mm)
was obtained from Chemie Uetikon. Melting points were measured
on Büchi 535 and are not corrected. 1H and 13C NMR spectra were
recorded on Bruker AM 250 spectrometer and referenced against
TMS. Time of flight (Maldi) spectra were recorded using a PerPe-
spective Biosystems Voyagers-RP Biospectrometry Workstation.
2,6-Dihydroxy-4-methylpyridine (1) was supplied by Merck.
Stille Coupling Reaction; General Procedure
A mixture of 2,6-dibromopyridines 2 and 5 (200 mg), stannyl com-
pounds 6 9 (2 mol equiv) and (Ph3P)4Pd (0.02 mol equiv) was heat-
ed under N2 in toluene (50 mL) for 16 h. Upon cooling to r.t., sat.
NH4Cl (20 mL) was added and the organic phase separated. The
aqueous phase was extracted with toluene (3 × 20 mL). The com-
bined organic phases were dried (MgSO4) and the solvent was re-
moved. Concd HCl (20 mL) was added to the residue and extracted
with CH2Cl2 (3 × 30 mL). The aqueous phase was cautiously neutr-
alised with solid NaOH. After extraction with CH2Cl2 (3 × 30 mL)
the combined organic phases were dried (MgSO4) and the solvent
was removed. The terpyridine ligands were then purified on silica
gel with CH2Cl2/hexane (3:2). All compounds were recrystallised
from EtOH (Table).
2,6-Dibromo-4-methylpyridine (2)
A mixture of 2,6-dihydroxy-4-methylpyridine (1) (10.0 g, 0.080
mol) and PBr3 (32.5 g, 0.012 mol) was heated at 175 °C in an auto-
clave for 6 h. The autoclave was cooled down over a period of 20 h.
H2O (300 mL) was cautiously added to the black product and fil-
tered. The dark aqueous phase was extracted with CH2Cl2 (5 × 40
mL). The combined organic phases were dried (MgSO4) and the
solvent was removed. Compound 2 was then purified on silica gel
using CH2Cl2/hexane (4:1); yield: 7.0 g (35%) (Table).
2,6-Dibromo-4-hydroxymethylpyridine (4)
NaBH4 (0.30 g, 0.079 mol) was added in portions to a solution of 3
(0.50 g, 0.016 mol) in EtOH (30 mL) at 0 °C and the mixture was
Synthesis 2000, No. 12, 1665–1667 ISSN 0039-7881 © Thieme Stuttgart · New York