Synthesis and single-crystal X-ray characterization of 4,4″- functionalized 4′-(4-bromophenyl)-2,2′:6′,2″- terpyridines

Article abstract of DOI:10.1021/jo052036l

To expand the utility of bis(terpyridine) metal connectivity, the selective symmetrical and unsymmetrical 4,4″-functionalization (-CN, -Me, -CO ₂Me) of 4′-(4-bromophenyl)-2,2′:6′,2″- terpyridines was achieved using the Kroehnke synthesis. The f

Full text of DOI:10.1021/jo052036l

Synthesis and Single-Crystal X-ray Characterization of
4,4′′-Functionalized 4′-(4-Bromophenyl)-2,2′:6′,2′′-terpyridines
Ibrahim Eryazici,† Charles N. Moorefield,‡ Semih Durmus,§ and George R. Newkome*,†,§
Departments of Polymer Science and Chemistry and the Maurice Morton Institute of Polymer Science,
The UniVersity of Akron, Akron, Ohio 44325-4717
newkome@uakron.edu
ReceiVed September 28, 2005
To expand the utility of bis(terpyridine) metal connectivity, the selective symmetrical and unsymmetrical
4,4′′-functionalization (-CN, -Me, -CO2Me) of 4′-(4-bromophenyl)-2,2′:6′,2′′-terpyridines was achieved
using the Kro¨hnke synthesis. The final substituted 2,2′:6′,2′′-terpyridines along with their corresponding
1
intermediates, 4a-c, were recrystallized and characterized by H NMR and 13C NMR as well as X-ray
crystallography; COSY correlations were also conducted to permit definitive proton assignment.
Introduction
synthesized solar cells,16-21 could be expanded if new poly-
functional motifs were available.
Over the past decade, the coordination and supramolecular
chemistry associated with 2,2′:6′,2′′-terpyridines has been
studied intensively. However, limited accessibility to unsym-
metrically functionalized terpyridines has restricted their po-
tential use in the construction of more complex infrastructures.
Because their metal complexes have been shown to possess
interesting novel luminescent properties,1-5 their potential
applications as chemosensors6,7 and fluorescent immunoassay
agents,8-11 as well as their use in catalysis12-15 and dye-
Substituted 2,2′:6′,2′′-terpyridines have been synthesized via
their N-oxide8,22,23 and 1,2,4-triazine analogues24 (the Sauer25
method), the Kro¨hnke,26 Potts,27 and Jameson28 methods, and
(9) Galaup, C.; Couchet, J.-M.; Bedel, S.; Tisne`s, P.; Picard, C. J. Org.
Chem. 2005, 70, 2274-2284.
(10) Mukkala, V.-M.; Takalo, H.; Liitti, P.; Hemmila¨, I. J. Alloys Compd.
1995, 225, 507-510.
(11) Wong, K. M. C.; Tang, W.-S.; Chu, B. W. K.; Zhu, N.; Yam, V.
W. W. Organometallics 2004, 23, 3459-3465.
(12) Sato, Y.; Nakayama, Y.; Yasuda, H. J. Organomet. Chem. 2004,
689, 744-750.
(13) Cui, Y.; He, C. Angew. Chem., Int. Ed. 2004, 43, 4210-4212.
(14) Cui, Y.; He, C. J. Am. Chem. Soc. 2003, 125, 16202-16203.
(15) Nakayama, Y.; Baba, Y.; Yasuda, H.; Kawakita, K.; Ueyama, N.
Macromolecules 2003, 36, 7953-7958.
* To whom correspondence should be addressed. Phone: (330) 972-5468.
† Department of Polymer Science.
‡ Maurice Morton Institute of Polymer Science.
§ Department of Chemistry.
(1) Yam, V. W. W.; Wong, K. M. C.; Zhu, N. Angew. Chem., Int. Ed.
2003, 42, 1400-1403.
(2) Ulrich, G.; Ziessel, R. J. Org. Chem. 2004, 69, 2070-2083.
(3) Coppo, P.; Duati, M.; Kozhevnikov, V. N.; Hofstraat, J. W.; De Cola,
L. Angew. Chem., Int. Ed. 2005, 44, 1806-1810.
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1999, 38, 4262-4267.
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Ikeda, N.; Han, L. Chem. Lett. 2005, 34, 344-345.
(17) Nazeeruddin, M. K.; Pe´chy, P.; Renouard, T.; Zakeeruddin, S. M.;
Humphry-Baker, R.; Comte, P.; Liska, P.; Cevey, L.; Costa, E.; Shklover,
V.; Spiccia, L.; Deacon, G. B.; Bignozzi, C. A.; Gra¨tzel, M. J. Am. Chem.
Soc. 2001, 123, 1613-1624.
(18) Sapp, S. A.; Elliot, C. M.; Contado, C.; Caramori, S.; Bignozzi, C.
A. J. Am. Chem. Soc. 2002, 124, 11215-11222.
(19) Wang, Z.-S.; Yamaguchi, T.; Sugihara, H.; Arakawa, H. Langmuir
2005, 21, 4272-4276.
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Soc. 2005, 127, 12351-12356.
(20) Aiga, F.; Tada, T. Sol. Energy Mater. Sol. Cells 2005, 85, 437-
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(21) Hwang, S.-H.; Moorefield, C. N.; Godinez, L. A.; Nanriquez, J.;
Bustos, E.; Newkome, G. R. Chem. Commun. 2005, 4672-4674.
(8) Hovinen, J.; Hakala, H. Org. Lett. 2001, 3, 2473-2476.
10.1021/jo052036l CCC: $33.50 © 2006 American Chemical Society
Published on Web 01/10/2006
J. Org. Chem. 2006, 71, 1009-1014
1009

Eryazici et al.
SCHEME 1. Preparation of the 4-Substituted 2-Acetylpyridines and Their Pyridinium Iodide Saltsa
a (i) H2O/CH2Cl2, AgNO3, MeCOCO2H, H2SO4, (NH4)2S2O8, 3 h; (ii) MeCN, paraldehyde, TFA, t-BuOOH, 3 h; (iii) I2, pyridine, 3 h, N2.
modern Pd0-mediated cross-coupling procedures;29-33 further
chemical modifications of substituents have also been re-
ported.33-35 The two-step Kro¨hnke26 synthesis, using modified
2′-azachalcones and pyridinium iodide salts of 2-acetylpyridines,
facilitates the potential to create unsymmetrical and symmetrical
mono- and disubstituted 4′-phenyl-2,2′:6′,2′′-terpyridines; how-
ever, few examples of these procedures are found in the
literature.36-38
Herein we report the first microwave-assisted solid-state aldol
condensation procedure for the preparation of -CO2Me and
-CN substituted 2′-azachalcones, 4a-b, and the facile synthesis
of new mono- and disubstituted 4′-(4-bromophenyl)terpyridines
(5a-j; Figure 1) via the two-step Kro¨hnke26 method. Different
FIGURE 1. Substituted 2,2′:6′,2′′-terpyridines (5a-j).
methyl-, methoxycarbonyl-, and cyano-substitution patterns on
the 4,4′′-positions of 4′-arylterpyridine were initially chosen
because these functionalities afforded simple routes to a variety
SCHEME 2. Preparation of 4-Bromo-2′-azachalcones by
Claisen-Schmidt Aldol Condensationa
of useful substituted building blocks for higher-ordered supra-
macromolecular architectures. The X-ray crystal structures for
terpyridines 5a, 5c, 5g, and 5j and the crystal packing of diester
5a and the intermediary 2′-azachalcones 4a and 4b are also
presented.
Results and Discussion
The initial well-known pyridinium iodide salts of 2-acetylpy-
ridines (3a, 3c, 3d; Scheme 1) were prepared according to
a (i) MeOH, 1 M NaOH, 1 h; (ii) acidic Al2O3, MW 250 W, 60 °C, 15
min; (iii) basic Al2O3, MW 250 W, THF (2 mL), 15 min.
(22) Newkome, G. R.; Hager, D. C.; Kiefer, G. E. J. Org. Chem. 1986,
51, 850-853.
literature procedures,36,37,39 whereas the salt of 2-acetyl-4-
cyanopyridine (3b) was prepared starting with a radical carbo-
nylation at the 2 position of 4-cyanopyridine, 1b, followed by
addition to dry pyridine and iodine to give (85%) the new
pyridinium iodide salt (3b) of 2-acetyl-4-cyanopyridine. Support
for the structure of salt 3b included the appearance of peaks at
6.58 (COCH2) and 66.4 (COCH2) ppm in the 1H and 13C NMR,
respectively, and an upfield shift of the COCH2-pyridine
resonance (198.1 f 190 ppm, 13C NMR) that agreed with that
of similar conversions in the literature;36-39 a peak at m/z )
224.0836 [M - I]+ in the HRMS spectrum also confirmed the
transformation.
(23) Kozhevnikov, V. N.; Kozhevnikov, D. M.; Nikitina, T. V.; Rusinov,
V. L.; Chupakhin, O. N.; Zabel, M.; Ko¨nig, B. J. Org. Chem. 2003, 68,
2882-2888.
(24) Kozhevnikov, V. N.; Kozhevnikov, D. M.; Shabunina, O. V.;
Rusinov, V. L.; Chupakhin, O. N. Tetrahedron Lett. 2005, 46, 1521-1523.
(25) Pabst, G. R.; Pfu¨ller, O. C.; Sauer, J. Tetrahedron 1999, 55, 5047-
5066.
(26) Kro¨hnke, F. Synthesis 1976, 1-24.
(27) Potts, K. T.; Cipullo, M. J.; Ralli, P.; Theodoridis, G. J. Org. Chem.
1982, 47, 3027-3038.
(28) Jameson, D. L.; Guise, L. E. Tetrahedron Lett. 1991, 32, 1999-
2002.
(29) Lehmann, U.; Henze, O.; Schlu¨ter, A.-D. Chem.sEur. J. 1999, 5,
854-859.
(30) Fallahpour, R.-A. Synthesis 2000, 1665-1667.
(31) Cuperly, D.; Gros, P.; Fort, Y. J. Org. Chem. 2002, 67, 238-241.
(32) Loren, J. C.; Siegel, J. S. Angew. Chem., Int. Ed. 2001, 40, 754-
757.
(33) Heller, M.; Schubert, U. S. J. Org. Chem. 2002, 67, 8269-8272.
(34) El-ghayoury, A.; Ziessel, R. J. Org. Chem. 2000, 65, 7757-7763.
(35) Thompson, A. M. W. C. Coord. Chem. ReV. 1997, 160, 1-52.
(36) Gelling, A.; Orrell, K. G.; Osborne, A. G.; Sˇik, V. J. Chem. Soc.,
Dalton Trans. 1998, 937-945.
(37) Mikel, C.; Potvin, P. G. Polyhedron 2002, 21, 49-54.
(38) Snow, R. A.; Delecki, D. J.; Shah, C. R.; Hollister, K. R. U.S. Patent
5,350,696, 1994.
The 4-bromo-2′-azachalcones (4a-d; Scheme 2) were pre-
pared by Claisen-Schmidt aldol condensation. Synthesis of the
ester- and cyano-substituted 2′-azachalcones, 4a and 4b, was
achieved using microwave irradiation with little or no solvent
in the presence of either acidic or basic Al2O3, respectively, as
a catalyst and solid support.38,40 These protocols were employed
(39) Polin, J.; Schmohel, E.; Balzani, V. Synthesis 1998, 321-324.
(40) Husson, J.; Migianu, E.; Beley, M.; Kirsch, G. Synthesis 2004, 267-
270.
1010 J. Org. Chem., Vol. 71, No. 3, 2006

4,4′′-Functionalized 4′-(4-Bromophenyl)-2,2′:6′,2′′-terpyridines
SCHEME 3. Preparation of 4,4′′-Functionalized 4′-(4-Bromophenyl)-2,2′;6′,2′′-terpyridines by the Kro1hnke Methoda
a (i) MeOH, NH4OAc, 8 h; (ii) AcOH, NH4OAc, 6 h.
instead of using NaOH as a result of potential side reactions,
for example, saponification. The reaction mixture of 4-bro-
mobenzaldehyde and ester 2a was heated to 60 °C, whereas
the cyano 2b was dissolved in a small amount (1-2 mL) of
THF to obtain homogeneous mixtures. Then the addition of
Al2O3 and irradiation in the microwave at 250 W for 15 min
afforded (56%) the desired azachalcones 4a and 4b, respec-
tively.41,42 Methyl-substituted 2′-azachalcone 4c was prepared
by the NaOH-promoted aldol condensation, similar to the
literature procedure for 4-bromo-2′-azachalcone (4d).43
Azachalcones 4a-c were characterized (1H NMR) by two
doublet absorptions (7.78-8.19 ppm) assigned to COCHAd
CHB with large coupling constants (JA,B ) 15.9-16.2 Hz)
indicative of the trans double bond and a single carbonyl (13C
NMR) resonance for such constructs in the range of 187.5 to
189.7 ppm.43 The spectral assignment of 4d agreed with the
literature.43 HRMS spectra further confirmed the 4-bromo-2′-
azachalcone structures with peaks at m/z ) 367.9899 [M + Na]+
(4a), m/z ) 334.9812 [M + Na]+ (4b), and m/z ) 323.9992
[M + Na]+ (4c); NaI was used in the positive-ion mode.
The pyridinium iodide salts of the modified 2-acetylpyridines,
3a-d, were next reacted via a Michael-type addition with the
functionalized 4-bromo-2′-azachalcones, 4a-d, followed by the
ring-closure of the resulting diketone using ammonium acetate
in either AcOH or MeOH to afford (33-73%) the desired
unsymmetric and symmetric 4′-(4-bromophenyl)-2,2′;6′,2′′-
terpyridines (5a-j; Scheme 3). Most of the reactions proceeded
with a higher yield in MeOH than in AcOH as a result of the
potential side reactions of the substituents in an acidic and high-
temperature environment.
3,3′′-pyrH (pyr ) pyridine) resonance for diester 5a (7.93, 8.87,
and 9.18 ppm) and dicyano 5b (7.63, 8.92, and 8.89 ppm) as
well as upfield shifts for the same signals assigned to the
dimethyl terpyridine 5c (7.19, 8.58, and 8.47 ppm) compared
to those of known terpyridines, such as 5d43 (7.35, 8.72, and
8.66 ppm) and 4′-phenylterpyridine44 (7.33, 8.74, and 8.68 ppm).
Dimethyl terpyridine, 5c, showed a similar 1H NMR pattern as
that of 4′-(4-chlorophenyl)-4,4′′-dimethylterpyridine,36 but to
confirm the proper assignments, two-dimensional 2D COSY
NMR experiments (Supporting Information) were conducted.
HRMS spectra also supported the structural assignments of the
diester 5a, m/z ) 526.0375 [M + Na]+; dicyano 5b, m/z )
438.0364 [M + H]+, 460.0194 [M + Na]+; and dimethyl
terpyridine 5c, m/z ) 438.0582 [M + Na]+.
1H NMR spectra of the unsymmetrical monosubstituted 4′-
(4-bromophenyl)terpyridines (5g, 5i, 5j; Supporting Information)
show unique proton resonances for each pyridine ring as a result
of the diminished symmetry. The 5-pyrH resonance (1H NMR)
of ester 5g, cyano 5i, and methyl 5j appears as a doublet,
whereas the 5′′-pyrH resonance appeared as a doublet of
doublets as a result of coupling (J5′′,6′′ ) 7.5 Hz, J5′′,4′′ ) 4.8
Hz) with the adjacent protons. Moreover, the 5-pyrH resonance
shifted downfield for ester 5g (7.9 f 7.35 ppm) and cyano 5i
(7.56 f 7.4 ppm) but upfield for the methyl construct 5j (7.21
f 7.38 ppm). The 3-pyrH resonance follows the same pattern;
it shifts downfield for ester 5g (9.14 f 8.72 ppm) and cyano
5i (8.9 f 8.63 ppm) and upfield for methyl 5j (8.49 f 8.66
ppm) when compared to the 3′′-pyrH resonance as well as
changing from a singlet (3-pyrH) to a doublet (3′′-pyrH).
Rationale for these shifts is rooted in the deshielding effect of
the electron-withdrawing groups for ester 5g and cyano 5i and
the shielding effect caused by the electron-donating methyl
group in terpyridine 5j. These assignments have been confirmed
by 2D COSY NMR experiments (Supporting Information).
Furthermore, 1H and 2D COSY NMR (Supporting Information)
spectra of the monosubstituted 4′-(4-bromophenyl)terpyridines
1
The H NMR spectra of the symmetric disubstituted 4′-(4-
bromophenyl)terpyridines (5a, 5b, 5c; Supporting Information)
revealed downfield shifts for the 5,5′′-pyrH, 6,6′′-pyrH, and
(41) Esmaeili, A. A.; Tabas, M. S.; Nasseri, M. A.; Kazemi, F. Monatsh.
Chem. 2005, 136, 571-576.
(42) Sharma, U.; Bora, U.; Boruah, R. C.; Sandhu, J. S. Tetrahedron
Lett. 2002, 43, 143-145.
(43) Korall, P.; Bo¨rje, A.; Norrby, P.-O.; Åkermark, B. Acta Chem.
Scand. 1997, 51, 760-766.
(44) Constable, E. C.; Lewis, J.; Liptrot, M. C.; Raithby, P. R. Inorg.
Chim. Acta 1990, 178, 47-54.
J. Org. Chem, Vol. 71, No. 3, 2006 1011

Eryazici et al.
with small meta coupling constants (J3′,5′ ) 1.5-2.1 Hz). The
HRMS spectra also support the structural assignments of the
terpyridines: 5e, m/z ) 493.0274 [M + Na]+; 5f, m/z )
482.0471 [M + Na]+; and 5h, m/z ) 449.0384 [M + Na]+.
X-ray crystal structures of ester 4a and cyano azachalcone
4b (Supporting Information) confirmed the proposed structures.
The data showed that ester 4a and azachalcone 4b crystallized
in a monoclinic cell with a P21/n space group and in a triclinic
cell with a P1 space group, respectively. Also, the X-ray data
of ester 4a and azachalcone 4b revealed a trans double bond
configuration with bond lengths (Å) of C(7)sC(8) ) 1.312(5)
and C(7)sC(8) ) 1.342(4), respectively, which is similar to
that of the 2′-azachalcone45 and chalcones45,46 [1.321(2)s1.329-
(4) Å]. Furthermore, the CdO bond lengths (Å) of ester 4a,
O(1)sC(9) ) 1.224(4) Å and azachalcone 4b, O(1)sC(9) )
1.219(3) Å, were in agreement with the literature.45,46
FIGURE 2. Molecular structure of diester 5a with thermal ellipsoids
drawn at 50% probability.
X-ray crystal data of the diester 5a (Figure 2), dimethyl 5c,
ester 5g, and methyl 5j (Supporting Information) confirm the
proposed structures. The three pyridine rings showed a transoid
arrangement about the interannular CsC bonds, which was also
in agreement with the literature.44,47-49 This configuration mini-
mizes electrostatic interactions between the nitrogen lone pairs
and the van der Waals interactions between the meta protons.44
The interannular CsC bond lengths of 5a, 5c, 5g, and 5j [1.481-
(8)s1.494(4) Å] are comparable with those of the 2,2′;6′,2′′-
terpyridines [1.480(1)s1.498(3) Å] found in the literature.44,47,48
Moreover, the three pyridine rings are not exactly coplanar and
the torsion angles of the two terminal rings with the central
pyridine ring are 5.16 and 3.88° for diester 5a, 9.48 and 1.06°
for methyl 5c, 2.65 and 3.05° for ester 5g, and 6.59 and 0.97°
for methyl 5j, which is comparable to those of 4′-phenylterpy-
ridine44 (5.7°) and 4′-(4-anilino)terpyridine48 (2.7 and 7.4°).
Furthermore, the 4′-bromophenyl ring connected to the terpy-
ridine is distorted with torsion angles of 22.83° for diester 5a,
39° for dimethyl 5c, 27.48° for ester 5g, and 39.75° for methyl
5j, which are higher than that of 4′-phenylterpyridine44 (10.9°),
comparable to that of 4′-(4-anilino)terpyridine48 (27.5°), and
lower than those of 4′-(2,4,6-trimethylphenyl)terpyridine50
(67.5°) and 4′-(2,5-dimethoxyphenyl)terpyridine51 (50.4°).
Only the diester 5a crystal packing revealed π-π interactions
(interlayer distances smaller than 3.5 Å).52 Molecules of diester
5a (approximately coplanar) are stacked by the overlap of the
(5g, 5i, and 5j) revealed splitting of the singlet (3′,5′-pyrH) in
the symmetric terpyridines (5a, 5b, and 5c) resulting in two
doublets with small meta coupling constants (J3′,5′ ) 1.5 Hz).
1
The ester 5g and methyl 5j showed similar H NMR patterns
as that of 4′-(p-toluyl)-4-(methoxycarbonyl)terpyridine37 and 4′-
(4-chlorophenyl)-4-methylterpyridine,36 respectively. HRMS
spectra also supported the structural assignments of ester 5g,
cyano 5i, and methyl terpyridine 5j with a peak at m/z )
468.0331 [M + Na]+, m/z ) 435.0235 [M + Na]+, and m/z )
424.0424 [M + Na]+, respectively.
1
The H NMR spectra of the unsymmetric disubstituted 4′-
(4-bromophenyl)terpyridines (5e, 5f, 5h; Supporting Informa-
tion) showed unique proton resonances for each pyridine ring
similar to those of the above monosubstituted counterparts.
Moreover, the 5-pyrH resonance shifts downfield in the cases
of the ester-cyano 5e (7.95 f 7.61 ppm), ester-methyl 5f (7.9
f 7.2 ppm), and cyano-methyl 5h (7.58 f 7.25 ppm) when
compared to the 5′′-pyrH and 3-pyrH resonances that show the
same pattern; it shifts downfield for the ester-cyano 5e (9.08
f 8.9 ppm), ester-methyl 5f (9.16 f 8.5 ppm), and cyano-
methyl 5h (8.93 f 8.47 ppm) when compared to the 3′′-pyrH
1
resonance. Furthermore, the H and 2D COSY NMR spectra
(Supporting Information) of these unsymmetric compounds, 5e,
5f, and 5h, revealed the splitting of the 3′,5′-pyrH peaks in
symmetric terpyridines (5a, 5b, and 5c) resulting in two doublets
FIGURE 3. (a) Stacking of diester 5a in the crystal lattice with the distances (Å) between the central pyridine rings and (b) the orientation of
diester 5a in adjacent planes in the lattice, viewing along the c axis. Hydrogen atoms are omitted for clarity.
1012 J. Org. Chem., Vol. 71, No. 3, 2006

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
(45) Turowska-Tyrk, I.; Grzesniak, K.; Trzop, E.; Zych, T. J. Solid State
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(46) Toda, F.; Tanaka, K.; Kato, M. J. Chem. Soc., Perkin Trans. 1 1998,
1315-1318.
(47) Fallahpour, R.-A.; Neuburger, M.; Zehnder, M. Polyhedron 1999,
18, 2445-2454.
(48) Storrier, G. D.; Colbran, S. B.; Craig, D. C. J. Chem. Soc., Dalton
Trans. 1997, 3011-3028.
(49) Constable, E. C.; Housecroft, C. E.; Neuburger, M.; Phillips, D.;
Raithby, P. R.; Schofield, E.; Sparr, E.; Tocher, D. A.; Zehnder, M.;
Zimmermann, Y. J. Chem. Soc., Dalton Trans. 2000, 2219-2228.
(50) Leslie, W.; Batsanov, A. S.; Howard, J. A. K.; Williams, J. A. G.
Dalton Trans. 2004, 623-631.
(51) Storrier, G. D.; Colbran, S. B.; Craig, D. C. J. Chem. Soc., Dalton
Trans. 1998, 1351-1363.
(52) Hunter, C. A.; Sanders, J. K. M. J. Am. Chem. Soc. 1990, 112,
5525-5534.
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J. Org. Chem, Vol. 71, No. 3, 2006 1013

Eryazici et al.
121.1, 123.3, 123.9, 129.1, 132.5, 137.4, 138.8, 149.5, 150.1, 155.9,
157.3, 166; HRMS (EI): [M + Na]+ calcd for C25H18BrN3O4Na,
526.0378; found, 526.0375.
(s, 3H, pyrCO2CH3), 7.35 (dd, 1H, 5′′-pyrH, J1 ) 7.5 Hz, J2 ) 4.8
Hz), 7.65 (d, 2H, 3,5-ArH, J ) 8.4 Hz), 7.76 (d, 2H, 2,6-ArH, J )
8.4 Hz), 7.9 (m, 2H, 5,4′′-pyrH), 8.72 (m, 4H, 3′,5′,3′′,6′′-pyrH),
8.84 (d, 1H, 6-pyrH, J ) 5.1 Hz), 9.14 (s, 1H, 3-pyrH); 13C NMR
δ 52.9, 118.8, 119, 120.8, 121.7, 123, 123.8, 124.2, 129, 132.3,
137.1, 137.4, 138.6, 149.16, 149.27, 150, 155.4, 155.9, 156.4, 157.4,
166. HRMS (EI): [M + Na]+ calcd for C23H16BrN3O2Na, 468.0323;
found, 468.0331.
4′-(4-Bromophenyl)-4-methoxycarbonyl-4′′-cyano-2,2′;6′,2′′-
terpyridine (5e). To a stirred solution of 3b (469 mg, 1.33 mmol)
and 4a (462 mg, 1.33 mmol) in MeOH (20 mL) was added excess
NH4OAc (3.47 g). Then, via route A, the product, 5e, was isolated
1
as a white solid: 240 mg (38%); mp 253-254 °C; H NMR δ
4.08 (s, 3H, pyrCO2CH3), 7.61 (dd, 1H, 5′′-pyrH, J1 ) 3.3 Hz, J2
) 1.5 Hz), 7.68 (d, 2H, 3,5-ArH, J ) 8.7 Hz), 7.75 (d, 2H, 2,6-
ArH, J ) 8.7 Hz), 7.95 (dd, 1H, 5-pyrH, J1 ) 3.3 Hz, J2 ) 1.8
Hz), 8.74 (d, 1H, 5′-pyrH, J ) 1.8 Hz), 8.78 (d, 1H, 3′-pyrH, J )
1.8 Hz), 8.9 (m, 3H, 6,6′′,3′′-pyrH), 9.08 (dd, 1H, 3-pyrH, J1 )
0.9 Hz, J2 ) 0.6 Hz); 13C NMR δ 53.1, 117, 119.4, 120, 120.7,
121.7, 123.36, 123.45, 124.1, 125.3, 128.9, 132.5, 137, 138.9, 149.6,
150.2, 154.5, 156, 156.8, 157.4, 170. HRMS (EI): [M + Na]+ calcd
for C24H15BrN4O2Na, 493.0276; found, 493.0274.
Acknowledgment. The authors gratefully acknowledge the
National Science Foundation (DMR-0401780, CHE0116041),
the Air Force Office of Scientific Research (F496200-02-1-
0428,03), and the Ohio Board of Reagents for financial support.
Supporting Information Available: 1H, 13C, and COSY NMR
spectra of all compounds, experimental details of 5b, 5c, 5f, 5h,
5i, and 5j, general remarks, crystallographic data, and CIF files of
4a, 4b, 5a, 5c, 5g, and 5j. This material is available free of charge
via the Internet at http://pubs.acs.org.
4′-(4-Bromophenyl)-4-methoxycarbonyl-2,2′;6′,2′′-terpyri-
dine (5g). To a stirred solution of 3d (496 mg, 1.52 mmol) and 4a
(526 mg, 1.52 mmol) in MeOH (25 mL) was added excess NH4-
OAc (4.41 g). Then, via route A, the product, 5g, was isolated as
1
a white solid: 250 mg (37%); mp 173-174 °C; H NMR δ 4.04
JO052036L
1014 J. Org. Chem., Vol. 71, No. 3, 2006