4,4′′-Functionalized 4′-(4-Bromophenyl)-2,2′:6′,2′′-terpyridines
1
solid: 580 mg (55%); mp 163-164 °C; H NMR δ 4.01 (s, 3H,
central pyridine rings in consecutive layers with mean interplanar
distances of 3.4 Å in the solid state (Figure 3a), which is
comparable to those of 4′-(dimethylamino)terpyridine53 (3.47
Å) and 4′-(4-anilino)terpyridine (3.5 Å). Also, they possess
adjacent planes that are parallel to each other in a head-to-tail
fashion (Figure 3b). Moreover, the central pyridine rings are
slightly slipped with respect to each other to maximize π-π
interactions between the stacked pyridine rings.52
pyrCO2CH3), 7.57 (d, 2H, 3,5-ArH, J ) 8.7 Hz), 7.58 (d, 2H, 2,6-
ArH, J ) 8.4 Hz), 7.92 (d, 1H, COCHdCH, J ) 16.2 Hz), 8.05
(dd, 1H, 5-pyrH, J1 ) 4.8 Hz, J2 ) 1.8 Hz), 8.25 (d, 1H, COCHd
CH, J ) 15.9 Hz), 8.7 (s, 1H, 3-pyrH), 8.88 (dd, 1H, 6-pyrH, J1 )
4.8 Hz, J2 ) 0.9 Hz); 13C NMR δ 53.1, 121.4, 122.4, 125.3, 126.2,
130.4, 132.4, 134.2, 139, 144, 150, 155.3, 165.3, 188.6. HRMS
(EI): [M + Na]+ calcd for C16H12BrNO3Na, 367.9898; found,
367.9899.
1-(3-Oxo-3-[2-(4-cyanopyridyl)]propen-1-yl)-4-bromoben-
zene (4b). To a stirred solution of 4-bromobenzaldehyde (2.07 g,
11.2 mmol) and 2-acetyl-4-cyanopyridine (2b; 1.72 g, 11.8 mmol)
in THF (2 mL) at 25 °C was added quickly basic Al2O3 (15 g).
The mixture was then irradiated in the microwave at 250 W for 15
min. After cooling, CHCl3 (3 × 50 mL) was added, and the mixture
was filtered. The filtrate was concentrated in vacuo to give a solid,
which was washed with MeOH (3 × 25 mL) to afford the product
Conclusion
Substituted 2′-azachalcones (4a, 4b) were conveniently
synthesized using microwave-assisted solid-state aldol conden-
sation procedures. Symmetrical and unsymmetrical mono- and
disubstituted 4′-(4-bromophenyl)terpyridines (5a-j) were con-
structed by utilizing the two-step Kro¨hnke26 methodology with
pyridinium iodide salts of substituted 2-acetylpyridines (3a-
d) and modified 4-bromo-2′-azachalcones (4a-d). X-ray crystal
structures of ester 4a, azachalcone 4b, diester 5a, dimethyl 5c,
ester 5g, and methyl 5j, as well as solid-state crystal packing
of diester terpyridine 5a, were obtained. Ongoing work utilizes
these unsymmetrically disubstituted 4′-(4-bromophenyl)-2,2′;6′,2′′-
terpyridines in the assembly of supramacromolecular oligomeric
materials.
1
4b as a light yellow solid: 1.92 g (56%); mp 184-185 °C; H
NMR δ 7.57 (s, 4H, 2,3,5,6-ArH), 7.71 (dd, 2H, 5-pyrH, J1 ) 4.8
Hz, J2 ) 1.5 Hz), 7.93 (d, 1H, COCHdCH, J ) 16.2 Hz), 8.19 (d,
1H, COCHdCH, J ) 15.9 Hz), 8.39 (s, 1H, 3-pyrH), 8.91 (dd,
1H, 6-pyrH, J1 ) 5.1 Hz, J2 ) 0.9 Hz); 13C NMR δ 116.1, 120.5,
122.1, 124.9, 125.6, 128.2, 130.5, 132.5, 133.9, 144.9, 150.1, 155.1,
187.5. HRMS (EI): [M + Na]+ calcd for C15H9BrN2ONa,
334.9796; found, 334.9812.
1-(3-Oxo-3-[2-(4-methylpyridyl)]propen-1-yl)-4-bromoben-
zene (4c). To a stirring solution of 4-bromobenzaldehyde (1.02 g,
5.53 mmol) and 2-acetyl-4-methylpyridine (2c; 760 mg, 5.57 mmol)
in MeOH (25 mL) at 25 °C was added aqueous NaOH (1 M, 5
mL). The mixture was stirred for 1 h at 25 °C and then filtered
and washed with H2O (15 mL). The precipitate was dissolved in
CH2Cl2 (150 mL) and extracted with H2O (2 × 100 mL). The
combined organic fractions were dried (MgSO4) and concentrated
in vacuo to give the product 4c as a light yellow solid: 1 g (60%);
Experimental Section
1-[2-(4-Cyano-2-pyridyl)-2-oxoethyl]pyridinium Iodide (3b).
To a stirred warmed (60 °C) solution of I2 (4.68 g, 18.5 mmol) in
pyridine (27 mL) under N2 was added 2-acetyl-4-cyanopyridine
(2b; 2.7 g, 18.5 mmol), which was stirred at 100 °C for 1 h. The
crystals that formed upon cooling were filtered and washed with
CHCl3 (2 × 25 mL) and Et2O (2 × 25 mL) to give the product 3b
as green crystals: 5.5 g (85%); mp 226-227 °C; 1H NMR (DMSO-
d6) δ 6.58 (s, 2H, COCH2), 8.32 (m, 3H, 5-pyrH, 3,5-ArH), 8.45
(s, 1H, 3-pyrH), 8.78 (t, 1H, 4-ArH, J ) 7.8 Hz), 9.07 (d, 2H,
2,6-ArH, J ) 6.6 Hz), 9.12 (d, 1H, 6-pyrH, J ) 4.8 Hz); 13C NMR
(DMSO-d6) δ 66.4, 116.9, 121.1, 123.7, 127.7, 130.4, 146.1, 146.4,
150.6, 151.2, 190. HRMS (EI): [M - I]+ calcd for C13H10N3O,
224.0824; found, 224.0836.
1
mp 123-125 °C; H NMR δ 2.47 (s, 3H, pyrCH3), 7.32 (d, 1H,
5-pyrH, J ) 4.2 Hz) 7.56 (d, 2H, 3,5-ArH, J ) 9 Hz), 7.59 (d, 2H,
2,6-ArH, J ) 8.4 Hz), 7.88 (d, 1H, COCHdCH, J ) 16.2 Hz),
8.03 (s, 1H, 3-pyrH), 8.27 (d, 1H, COCHdCH, J ) 16.2 Hz), 8.6
(d, 1H, 6-pyrH, J ) 4.8 Hz); 13C NMR δ 21.3, 121.9, 124, 125,
128.1, 130.3, 132.3, 134.3, 143.3, 148.6, 148.9, 154.1, 189.7. HRMS
(EI): [M + Na]+ calcd for C15H12BrNONa: 324.0000; found,
323.9992.
General Procedures for the Preparation of 4′-(4-Bromophen-
yl)-2,2′;6′,2′′-terpyridines. Route A. To a stirred solution of the
pyridinium iodide salt of the substituted 2-acetylpyridines 3 and
the modified 2′-azachalcones 4 in MeOH or EtOH was added excess
NH4OAc, and the mixture was refluxed overnight. The precipitate,
which was formed upon cooling, was filtered and washed with
MeOH. The precipitate collected from the filtration was column
chromatographed (basic Al2O3), eluting with CHCl3, to give the
product.
Route B. To a stirred solution of the pyridinium iodide salt of
the substituted 2-acetylpyridines 3 and the modified 2′-azachalcones
4 in AcOH was added excess NH4OAc, and the mixture was
refluxed overnight. The solution was concentrated in vacuo to give
a paste, which was neutralized with Na2CO3 (1 M) and extracted
with CHCl3. Organic layers were combined and dried (MgSO4),
and then the solvent was evaporated in vacuo to give a residue
that was column chromatographed (basic Al2O3), eluting with an
EtOAc/hexane mixture (1:1), to give the product.
4′-(4-Bromophenyl)-4,4′′-dimethoxycarbonyl-2,2′;6′,2′′-terpyr-
idine (5a). To a stirred solution of 3a (1.1 g, 3.2 mmol) and 4a
(1.22 g, 3.2 mmol) in MeOH (30 mL) was added excess NH4OAc
(8 g, 104 mmol). Then, via route A, the product, 5a, was isolated
as a light yellow solid: 820 mg (51%); mp 280-281 °C; 1H NMR
δ 4.06 (s, 6H, pyrCO2CH3), 7.67 (d, 2H, 3,5-ArH, J ) 8.4 Hz),
7.76 (d, 2H, 2,6-ArH, J ) 8.7 Hz), 7.93 (dd, 2H, 5,5′′-pyrH, J1 )
4.8 Hz, J2 ) 1.5 Hz), 8.73 (s, 2H, 3,3′′-pyrH), 8.87 (d, 2H, 6,6′′-
pyrH, J ) 4.8 Hz), 9.18 (s, 2H, 3′,5′-pyrH); 13C NMR δ 53, 119.5,
1-(3-Oxo-3-[2-(4-methoxycarbonylpyridyl)]propen-1-yl)-4-
bromobenzene (4a). A neat, stirred mixture of 2-acetyl-4-(meth-
oxycarbonyl)pyridine (2a; 550 mg, 3.07 mmol) and 4-bromoben-
zaldehyde (570 mg, 3.08 mmol) was heated to 60 °C, and then
acidic Al2O3 (9.94 g) was added. The mixture was then irradiated
in the microwave at 250 W for 15 min. After cooling, CHCl3 (3 ×
50 mL) was added and the mixture was filtered. The filtrate was
concentrated in vacuo to give a solid, which was washed with
MeOH (3 × 25 mL) to afford the product 4a as a light yellow
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