The Journal of Organic Chemistry
Article
tetraethylammonium iodide (2.39 g, 9.3 mmol) and 4-chloro-2,6-
di(tridec-1-en-1-yl)pyridine 6 (4.00 g, 8.44 mmol) were added to the
mixture. The mixture was stirred under argon at 80 °C (oil bath) for
18 h. After cooling to rt, water (100 mL) and dichloromethane (100
mL) were added. The black solid was removed by filtration through a
small pad of Celite. The aqueous layer was extracted twice with
dichloromethane, and the combined organic phases were washed with
water. The organic phase was dried over sodium sulfate, filtered, and
concentrated. The resulting oil was filtered over a column of SiO2
(CH2Cl2/cyclohexane, 1/1) to give 7 (3.19 g, 3.64 mmol) as a
mixture of diastereoisomers. This mixture was dissolved in a mixture
of cyclohexane/ethanol (120 mL/80 mL). Degassed palladium on
carbon (10 wt %, 0.72 g, 0.68 mmol) was added to the solution. The
mixture was stirred under hydrogen (in a balloon) at rt for 3 days.
The palladium was removed by filtration through a small pad of
Celite. The mixture was concentrated, and the beige solid was
recrystallized from diethyl ether to afford compound 8 as a white solid
(2.11 g, 2.38 mmol, 66%). mp 62 °C; 1H NMR (CDCl3, 500 MHz) δ
7.15 (s, 4H), 2.82 (t, J = 8.0 Hz, 8H), 1.74 (q, J = 8.0 Hz, 8H), 1.25−
1.37 (m, 80H), 0.87 (t, J = 7.0 Hz, 12H); 13C{1H} NMR (CDCl3,
126 MHz) δ 163.0, 147.1, 117.8, 38.9, 32.1, 30.5, 29.85, 29.83, 29.82,
29.81, 29.8, 29.7, 29.69, 29.5, 22.8, 14.3; MS (ESI) m/z calcd for
C62H113N2: 885.89 [M + H]+; found, 885.89; Anal. Calcd for
C62H112N2: C, 84.06; H, 12.75; N, 3.16. Found: C, 84.08; H, 12.44;
N, 3.16.
Compound 9. A mixture of 4 (42 mg, 0.20 mmol), compound 1440
(540 mg, 0.44 mmol), and KOH (34 mg, 0.6 mmol) in EtOH (40
mL) was refluxed under argon overnight. Then, the solvent was
evaporated. The residue was purified by column chromatography
(SiO2, CH2Cl2) to afford the alkene as a yellow solid (355 mg, 0.165
mmol, 84%). The product was used without further purification for
the next step. A mixture of the alkene (200 mg, 0.101 mmol) and
palladium on carbon (10 wt %, 11 mg, 0.01 mmol) in cyclohexane/
EtOH (1/1 v/v, 20 mL) was stirred under hydrogen (in a balloon) at
rt for 3 days. The palladium was removed by filtration over a small
pad of Celite. The mixture was concentrated, and the residue was
purified by column chromatography (SiO2, CH2Cl2) to afford
compound 9 as a beige solid (185 mg, 0.090 mmol, 90%). mp 55
°C; 1H NMR (CDCl3, 500 MHz) δ 8.63 (d, J = 5.2 Hz, 2H), 7.34 (s,
2H), 7.27 (s, 2H), 6.38 (s, 4H), 3.95−3.81 (m, 12H), 3.18−2.95 (m,
8H), 1.74 (quint, J = 6.6 Hz, 8H), 1.67 (quint, J = 6.6 Hz, 4H), 1.47−
1.39 (m, 12H), 1.34−1.26 (m, 168H), 0.87 (t, J = 6.9 Hz, 18H);
13C{1H} NMR (CDCl3, 126 MHz) δ 161.3, 152.0, 149.1, 145.2,
135.5, 119.9, 118.0, 105.9, 72.8, 68.1, 39.7, 35.5, 30.9, 29.4, 28.8,
28.74, 28.69, 28.5, 28.4, 25.1, 21.7, 13.1; HRMS (ESI) m/z calcd for
C134H241N2O6: 1974.8609 [M + H]+; found, 1974.8583.
[4,4′-Bipyridine]-3,3′-dicarbonitrile (17). A mixture of 3,3′-
dibromo-4,4′-bipyridine28 15 (436 mg, 1.39 mmol) and CuCN
(310 mg, 3.47 mmol) in NMP (5 mL) was heated at 200 °C
overnight. After cooling to rt, a saturated aqueous solution of EDTA
in 20% ammonia was added (150 mL). The resulting green solution
was filtered, and the residue was washed abundantly with water (800
mL). The filtrate was concentrated to 200 mL and extracted with
ethyl acetate (3 × 50 mL). The organic phases were combined, dried
over Na2SO4, and evaporated. The remaining NMP was removed
under vacuum at 75 °C for 2 h. The residue was purified by column
chromatography (SiO2, CH2Cl2/AcOEt 3:1) to afford compound 17
2,2′-Dimethyl-[4,4′-bipyridine] 1,1′-Dioxide (11). A mixture of
2,2′-dimethyl-4,4′-bipyridine37 10 (570 mg, 3.09 mmol), acetic acid
(20 mL, 0.35 mol), and hydrogen peroxide (30% in water, 10 mL, 0.1
mol) was stirred at 80 °C for 2 days. After cooling to rt, the solvents
were evaporated. The residue was dissolved in CHCl3 (50 mL), and
then, a saturated solution of NaCl was added (50 mL). The aqueous
layer was extracted twice with CHCl3, and the combined organic
phases were washed with water. The organic phase was dried over
sodium sulfate, filtered, and concentrated. The residue was purified by
column chromatography (SiO2, CH2Cl2/MeOH, 10/1) to afford
compound 11 as a white-beige solid (401 mg, 1.85 mmol, 60%). mp
1
(149 mg, 0.72 mmol, 52%) as a white solid. mp 180 °C; H NMR
(CDCl3, 500 MHz) δ 9.10 (s, 2H), 9.00 (d, J = 5.2 Hz, 2H), 7.57 (d, J
= 5.2 Hz, 2H); 13C{1H} NMR (CDCl3, 126 MHz) δ 154.1, 153.7,
146.0, 123.7, 115.0, 109.0; HRMS (ESI) m/z calcd for C12H7N4:
207.0665 [M + H]+; found, 207.0662.
1
dec > 180 °C; H NMR (CDCl3, 400 MHz) δ 8.29 (d, J = 6.7 Hz,
9-(Tricos-12-yn-11-ylidene)-9H-cyclopenta[1,2-c:4,3-c′]-
dipyridine (18). To a mixture of 3,3′-dibromo-4,4′-bipyridine28 15
(462 mg, 1.47 mmol), PdCl2(PPh3)2 (103 mg, 0.15 mmol), copper(I)
iodide (28 mg, 0.15 mmol), and 1-dodecyne (733 mg, 4.41 mmol)
was added freshly distilled triethylamine (15 mL) under argon. The
solution was stirred at 70 °C overnight. After evaporation of the
solvents, the solid was taken in ethyl acetate and washed with water.
The aqueous phase was extracted with ethyl acetate (3 × 10 mL). The
combined organic phases were dried over Na2SO4, filtered, and
concentrated to dryness. The crude product was purified by column
chromatography (SiO2, cyclohexane/AcOEt, 2:1) to afford com-
pound 18 (457 mg, 0.94 mmol, 64%) as a brown powder that
contained traces of starting material 15 that were difficult to fully
eliminate. 1H NMR (CDCl3, 500 MHz) δ 10.02 (s, 1H), 9.17 (s, 1H),
8.66 (m, 2H), 7.73 (dd, J = 18.9, 5.0 Hz, 2H), 2.98 (t, J = 7.9 Hz,
2H), 2.65 (t, J = 7.2 Hz, 2H), 1.84 (quint, J = 7.9 Hz, 2H), 1.74
(quint, J = 7.3 Hz, 2H), 1.55−1.47 (m, 4H), 1.43−1.37 (m, 4H),
1.36−1.27 (m, 20H), 0.89−0.85 (m, 6H); 13C{1H} NMR (CDCl3,
126 MHz) δ 148.4, 148.1, 146.9, 146.6, 144.3, 143.4, 134.3, 133.9,
133.6, 131.8, 115.7, 115.0, 107.0, 83.6, 37.4, 32.0, 29.8, 29.8, 29.7,
29.7, 29.5, 29.5, 29.3, 28.9, 28.6, 22.8, 20.5, 14.3; MS (ESI) m/z calcd
for C34H49N2: 485.39 [M + H]+; found, 485.39. HRMS (ESI) m/z
calcd for C34H49N2: 485.3890 [M + H]+; found, 485.3889.
Compound 19. To a solution of 1-dodecyne (1.50 g, 9.0 mmol) in
dry THF (30 mL) was added n-BuLi (6.0 mL of 1.6 M in hexane, 9.6
mmol) at −78 °C under argon. The resulting solution was stirred for
30 min at this temperature, and a solution of anhydrous ZnCl2 (1.31
g, 9.6 mmol) in dry THF (7 mL) was added. After 30 min of stirring
at −78 °C, the solution was warmed to rt. This zinc derivative was
then added via a double tipped needle to a solution of 3,3′-dibromo-
4,4′-bipyridine28 15 (0.942 g, 3.0 mmol) and Pd(PPh3)4 (0.173 g,
0.15 mmol) in dry THF (15 mL) under argon. The mixture was
refluxed overnight. After cooling to rt, the solution was quenched with
2H), 7.48 (d, J = 2.9 Hz, 2H), 7.36 (dd, J = 2.9, 6.7 Hz, 2H), 2.57 (s,
6H); 13C{1H} NMR (CDCl3, 126 MHz) δ 149.7, 139.9, 133.1, 123.5,
120.7, 18.2; MS (ESI) m/z calcd for C12H13N2O2: 217.10 [M + H]+;
found, 217.10; Anal. Calcd for C12H12N2O2: C, 66.65; H, 5.59; N,
12.96. Found: C, 66.55; H, 5.67; N, 12.78.
[4,4′-Bipyridine]-2,2′-diyldimethanol (13). A mixture of com-
pound 11 (200 mg, 0.92 mmol) and acetic anhydride (20 mL, 0.21
mol) was heated under reflux under argon overnight. Then, the
solvent was evaporated. A mixture of the residue (intermediate 12: 1H
NMR (CDCl3, 500 MHz) δ 8.73 (d, J = 5.1 Hz, 2H), 7.57 (s, 2H),
7.47 (dd, J = 5.1, 1.9 Hz, 2H), 5.31 (s, 4H), 2.19 (s, 6H)), K2CO3
(500 mg, 3.6 mmol), MeOH (10 mL), and H2O (2 mL) was stirred at
rt overnight. CHCl3 (50 mL) and a NaCl saturated solution were
added (50 mL). The aqueous layer was extracted twice with CHCl3,
and the combined organic phases were washed with water. The
organic phase was dried over sodium sulfate, filtered, and
concentrated. The residue was purified by column chromatography
(SiO2, CH2Cl2/MeOH 10/1) to afford compound 13 as a white solid
(121 mg, 0.56 mmol, 62%) that was used without further purification
1
due to its limited solubility. mp > 300 °C; H NMR (CDCl3, 400
MHz) δ 8.68 (d, J = 5.4 Hz, 2H), 7.53 (s, 2H), 7.45 (d, J = 5.4 Hz,
2H), 4.86 (s, 4H); MS (ESI) m/z calcd for C12H13N2O2: 217.10 [M
+ H]+; found, 217.10; Anal. Calcd for C12H12N2O2: C, 66.65; H, 5.59;
N, 12.96. Found: C, 66.75; H, 5.70; N, 12.71.
[4,4′-Bipyridine]-2,2′-dicarbaldehyde (4). A mixture of compound
13 (105 mg, 0.54 mmol) and MnO2 (201 mg, 2.31 mmol) in CHCl3
(10 mL) was heated under refluxed under argon for 2 h. The mixture
was filtered, and the filtrate was concentrated. The residue was
purified by column chromatography (SiO2, CH2Cl2/MeOH, 10/1) to
afford compound 4 as a white-yellow solid (81 mg, 0.381 mmol,
71%). The product was characterized by comparison with literature
data.36
3362
J. Org. Chem. 2021, 86, 3356−3366