Synthesis of unsymmetrical, monosubstituted bis-terpyridine derivatives via suzuki-miyaura cross-coupling

Article abstract of DOI:10.1055/s-0030-1259986

As building blocks for metallo-supramolecular polymers, novel, unsymmetrical, monosubstituted bis-terpyridine derivatives with one electron-donating (OMe) or electron-withdrawing (CN or COOMe) group have been synthesized via the Suzuki-Miyaura cross-coupl

Full text of DOI:10.1055/s-0030-1259986

PAPER
1361
Synthesis of Unsymmetrical, Monosubstituted Bis-terpyridine Derivatives via
Suzuki–Miyaura Cross-Coupling
Synthesis
i
of
U
nsy
n
mmetrical,
M
onosubstitu
h
ted Bis-terp
u
yridine Deriv
a
atives Li,a Takashi Sato,b Hongfang Li,b Masayoshi Higuchi*a,b,c
a
Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba 305-8577, Japan
International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS),
Tsukuba 305-0044, Japan
b
Fax +81(29)8604721; E-mail: higuchi.masayoshi@nims.go.jp
JST-CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan
c
Received 26 January 2011; revised 7 March 2011
In this contribution, we present the design and synthesis of
novel, unsymmetrical, monosubstituted bis-terpyridine
derivatives with one electron-donating (OMe) or electron-
withdrawing (CN or COOMe) group at the 6-position of
Abstract: As building blocks for metallo-supramolecular poly-
mers, novel, unsymmetrical, monosubstituted bis-terpyridine deriv-
atives with one electron-donating (OMe) or electron-withdrawing
(CN or COOMe) group have been synthesized via the Suzuki–
Miyaura cross-coupling reaction. This method is quick, efficient the pyridine ring. The synthetic method is quick, efficient
and suitable for the introduction of various substituents at the pe-
riphery of pyridine.
and suitable for the introduction of various substituents at
the periphery of pyridine. In general, monosubstituted
Key words: terpyridines, bis-terpyridines, oxidation, borylation,
Suzuki–Miyaura cross-coupling
ligands are extremely difficult to synthesize and purify
due to poor solubility, high polarity and instability. Our
rationale for synthesizing this kind of unique ligand is to
explore the synthesis and application of hetero-metallo-
Metallo-supramolecular polymers have become of in- supramolecular polymers containing different metal ions.
creasing interest over the last few decades for constructing
The preparation of mono-terpyridine derivatives 1 and 4
macromolecular assembles and devices.1 Many research-
followed the modified Kröhnke method.4a,5 We have con-
ers have paid more attention to ditopic bis-terpyridines as
structed two kinds of functionalized systems to modify the
organic ligands of the polymers for their structural advan-
periphery of the terpyridine, by using electron-donating
tages. This type of ligand is generally chemically and ther-
(OMe) group modification and electron-withdrawing (CN
mally stable, and has very high binding affinity towards a
or COOMe) group modification. Thus, for further func-
large variety of transition metal ions by forming octahe-
tionalization, terpyridine 1 was oxidized with m-chloro-
dral coordination geometries.2 The metallo-supramolecu-
peroxybenzoic acid to provide the mono-N-oxide 2 in
lar polymers, which are prepared by complexation of the
ligands with metal ions, have potential applications, such
42% yield (Scheme 1).6a The resulting oxide 2 was then
subjected to a Reissert–Henze-type reaction to produce
as in energy and information storage, chemical reactions
the 6-carbonitrile 3.6b Oxidation of terpyridine 4 with mo-
and biorecognition.3
lecular oxygen in the presence of potassium tert-butoxide
We have reported symmetrical bis-terpyridine derivatives afforded the 6-carboxylic acid 5 in 60% yield.7 Hydrolysis
with methoxy, methyl, cyano or bromo groups at the 6-po- of terpyridine 3 under strong acid conditions can also pro-
sition of the pyridine rings, or without substituents,4,5 as duce carboxylic acid 5, which is then transformed to ester
well as unsymmetrical bis-terpyridines with two methoxy 6.6b The corresponding methoxy-substituted terpyridine
or cyano groups at one terpyridine moiety,4a which were [4¢-(4-bromophenyl)-6-methoxy-2,2¢:6¢,2¢¢-terpyridine
prepared using the Kröhnke method and cross-coupling (11)] was prepared according to the literature method.4a
reactions.
We then focused on a Suzuki–Miyaura cross-coupling
Complexation of monosubstituted bis-terpyridines with strategy for the preparation of unsymmetrical, monosub-
two kinds of metal ions has the possibility to lead to the stituted bis-terpyridines with a methoxy, cyano or meth-
alternative introduction of the two metal ions in the oxycarbonyl group. The Miyaura–Ishiyama borylation
metallo-supramolecular polymers, which are expected to reaction between terpyridine 1 and bis(pinacolato)diboron
show unique electronic properties. In particular, modifi- with catalyst [PdCl2(PPh3)2] afforded boronic ester 7
cation at the 6-position of pyridine is important, because without the homocoupled byproduct, the symmetrical bis-
it is close to the metal binding center. This will strongly terpyridine (Scheme 2).4a,8 In this process, potassium ace-
influence the binding ability of the terpyridine moiety in tate is the most suitable base because stronger bases (such
the complexation.
as K3PO4 and K2CO3) afford the symmetrical bis-terpyri-
dine. Then, preparative HPLC was used to obtain pure
ligand 7. Using Suzuki–Miyaura cross-coupling, the de-
sired unsymmetrical bis-terpyridines 8–10 with one
electron-donating (OMe) or electron-withdrawing (CN or
COOMe) group were formed (Scheme 2). It is very im-
SYNTHESIS 2011, No. 9, pp 1361–1364
Advanced online publication: 04.04.2011
DOI: 10.1055/s-0030-1259986; Art ID: F14811SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
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0
1
1

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J. Li et al.
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Br
Br
Br
TMSCN
AcCl
MCPBA
CH2Cl2, 42%
CH2Cl2, 98%
N
N
N
+
N
N
N
N
N
N
O–
1
2
CN
3
Br
Br
Br
O2, t-BuOK, DMF
r.t., 60%
SOCl2, MeOH
reflux, 45% (from 3)
N
N
N
N
N
N
N
N
N
4
COOH
5
COOMe
6
Scheme 1 Synthesis of the 2,2¢:6¢,2¢¢-terpyridine derivatives
b'
c
c'
b
d'
a'
a
d
N
N
N
e'
e
g'
f'
g
f
11 or 3 or 6
O
O
N
B
N
N
PdCl2(PPh3)2
K2CO3, DMSO
80–120 °C
e''
N
N
N
d''
R
18–20 h
c''
b''
8 R = OMe
9 R = CN
(62%)
(54%)
7
10 R = COOMe (20%)
Scheme 2 Synthesis of the unsymmetrical, monosubstituted bis-terpyridine derivatives
portant to avoid the formation of homocoupled byproduct, tion polymers with unsymmetrical bis-terpyridines and
which has a similar high polarity as the desired ligand and different metal ions are in progress.
is very difficult to remove.
1H NMR and 13C NMR spectra were recorded in CDCl3 on a JEOL
AL 300/BZ spectrometer operating at 300 and 75 MHz, respective-
ly. Chemical shifts are reported in ppm downfield from SiMe4 as an
internal standard. High-resolution mass spectra (HRMS) were re-
corded on a Micromass LCT-LCMS-IT-TOF mass spectrometer.
MALDI-MS data were recorded on a Shimadzu/Kratos TOF mass
spectrometer using AXIMA-CRF.
New ligands 2, 3, 5, 6 and 8 are readily soluble in common
organic solvents (such as CH2Cl2, CHCl3, THF and
DMSO) which allowed us to conveniently obtain their 1H,
13C and 2D-COSY NMR spectra, and MALDI-TOFMS
and HRMS data. In contrast, new ligands 9 and 10 show
relatively low solubility in common organic solvents.
In summary, we have synthesized novel, rigid, conjugat-
ed, unsymmetrical, monosubstituted bis-terpyridine de-
rivatives via Suzuki–Miyaura cross-coupling as the key
reaction. This method is quick and efficient. It should be
possible to synthesize versatile bis-terpyridines with dif-
ferent functional groups, such as esters and amides, by us-
ing the monosubstituted bis-terpyridine derivatives as
starting materials. The design and synthesis of coordina-
4¢-(4-Bromophenyl)-2,2¢:6¢,2¢¢-terpyridine Mono-N-oxide (2)
To 4¢-(4-bromophenyl)-2,2¢:6¢,2¢¢-terpyridine (1; 1.02 g, 2.62
mmol) in CH2Cl2 (26 mL) was added a soln of 70% MCPBA (647
mg, 2.62 mmol) in CH2Cl2 (26 mL), and the mixture was allowed to
stir at r.t. overnight. Then, the mixture was washed with 5% Na2CO3
soln (50 mL) and dried (MgSO4). The solvent was evaporated and
the residue was purified by column chromatography on activated
basic alumina (CH2Cl2, then EtOAc) to give a white solid; yield:
448 mg (42%).
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Synthesis of Unsymmetrical, Monosubstituted Bis-terpyridine Derivatives
1363
1H NMR (300 MHz, CDCl3): d = 9.30 (d, J = 1.7 Hz, 1 H), 8.73 (m,
2 H), 8.54 (dd, J = 1.1, 0.9 Hz, 1 H), 8.44 (dd, J = 2.2, 2.2 Hz, 1 H),
8.36 (d, J = 6.6 Hz, 1 H), 7.86 (ddd, J = 1.8, 1.9, 1.8 Hz, 1 H), 7.75
(dd, J = 2.2, 2.2 Hz, 2 H), 7.63 (dd, J = 2.2, 1.7 Hz, 2 H), 7.38 (m,
3 H).
13C NMR (75 MHz, CDCl3): d = 156.30, 155.70, 149.52, 149.22,
148.52, 147.36, 140.87, 137.13, 136.92, 132.16, 129.00, 128.13,
125.66, 125.28, 124.06, 123.65, 123.12, 121.27, 119.16.
15 min, then the above precipitate was added and the mixture was
refluxed for 24 h. After concentration, CHCl3 (21 mL) was added,
and the solution was washed with 5% NaHCO3 soln (50 mL) and
dried (Na2SO4). The solvent was evaporated, and the residue was
purified by silica gel column chromatography (CH2Cl2–MeOH,
99:1), then recrystallized (toluene); yield: 84.1 mg (45%).
1H NMR (300 MHz, CDCl3): d = 8.86 (dd, J = 1.1, 1.1 Hz, 1 H),
8.75 (m, 3 H), 8.65 (dd, J = 0.9, 0.9 Hz, 1 H), 8.19 (dd, J = 1.1, 1.1
Hz, 1 H), 8.03 (dd, J = 7.9, 7.7 Hz, 1 H), 7.89 (ddd, J = 1.8, 1.8, 1.8
Hz, 1 H), 7.77 (dd, J = 2.0, 2.4 Hz, 2 H), 7.66 (dd, J = 2.0, 2.0 Hz,
2 H), 7.37 (dddd, J = 1.1, 1.3, 1.1, 1.1 Hz, 1 H), 4.06 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 165.83, 156.45, 156.19, 155.94,
155.25, 149.32, 149.18, 147.68, 137.75, 137.42, 136.82, 132.13,
128.95, 125.09, 124.54, 123.93, 123.54, 121.31, 119.13, 52.74.
MALDI-MS: m/z (%) = 445.04 (100) [M+].
HRMS: m/z [M + H]+ calcd for C23H17BrN3O2: 446.0504; found:
MALDI-MS: m/z (%) = 403.94 (100) [M + H+].
HRMS: m/z [M + H]+ calcd for C21H15BrN3O: 404.0398; found:
404.0405.
4¢-(4-Bromophenyl)-2,2¢:6¢,2¢¢-terpyridine-6-carbonitrile (3)
To mono-N-oxide 2 (750 mg, 1.86 mmol) in CH2Cl2 (22 mL) was
added TMSCN (256 mg, 2.58 mmol). After the solution had been
stirred for 20 min, AcCl (79.5 mg, 0.992 mmol) was added drop-
wise and stirring was continued for 24 h. Then, the mixture was con-
centrated to half volume; 10% K2CO3 soln (45 mL) was added and
the mixture was stirred for 1 h. The precipitate was collected by fil-
tration and washed with H2O; yield: 752 mg (98%).
1H NMR (300 MHz, CDCl3): d = 8.91 (dd, J = 1.1, 1.1 Hz, 1 H),
8.75 (m, 3 H), 8.62 (dd, J = 0.9, 1.1 Hz, 1 H), 8.01 (dd, J = 7.7, 7.7
Hz, 1 H), 7.89 (ddd, J = 1.8, 1.9, 1.8 Hz, 1 H), 7.73 (m, 5 H), 7.38
(dddd, J = 1.1, 1.1, 1.1, 1.1 Hz, 1 H).
446.0508.
Monosubstituted Bis-terpyridines 8–10; General Procedure
A reaction vessel was charged with boronic ester 7 (0.301 mmol),
K2CO3 (125 mg, 0.903 mmol), terpyridine 3 or 6 or the correspond-
ing methoxy derivative 11 (0.301 mmol), and PdCl2(PPh3)2 (5
mol%), then DMSO (9 mL) was added. The mixture was then heat-
ed at 80–120 °C for 18–20 h. The catalyst was removed by filtration
and washed with CHCl3 and H2O. The separated organic layer was
concentrated and purified by silica gel column chromatography
(EtOAc–MeOH, 1:1) and recycling preparative HPLC to give 8–10.
13C NMR (75 MHz, CDCl3): d = 157.66, 156.40, 155.67, 154.01,
149.48, 149.28, 137.87, 137.00, 136.94, 133.29, 132.30, 128.87,
128.28, 124.47, 124.14, 123.84, 121.29, 119.60, 119.02, 117.40.
MALDI-MS: m/z (%) = 412.03 (100) [M+].
HRMS: m/z [M + H]+ calcd for C22H14BrN4: 413.0402; found:
6-Methoxy-4¢-[4¢-(2,2¢:6¢,2¢¢-terpyridin-4¢-yl)-1,1¢-biphenyl-4-
yl]-2,2¢:6¢,2¢¢-terpyridine (8)
Yield: 120 mg (62%).
413.0422.
1H NMR (300 MHz, CDCl3): d = 8.82 (s, 2 H, He), 8.76 (m, 5 H,
e¢,e¢¢,a,a¢), 8.70 (d, J = 7.9 Hz, 3 H, Hd,d¢), 8.30 (d, J = 7.3 Hz, 1 H,
4¢-(4-Bromophenyl)-2,2¢:6¢,2¢¢-terpyridine-6-carboxylic Acid (5)
A two-neck flask fitted with a stirrer bar and an oxygen gas inlet and
outlet was charged with terpyridine 4 (76.7 mg, 0.19 mmol) and an-
hyd DMF (0.57 mL). A soln of t-BuOK (53.3 mg, 0.48 mmol) in
DMF (1.9 mL) was added dropwise and the yellow mixture was
stirred at r.t. for 1 h. Oxygen was then bubbled into the reaction mix-
ture for 6 h and the resulting mixture was poured onto ice, diluted
with H2O (50 mL), neutralized with 0.1 mM HCl and extracted with
CHCl3 (5 × 30 mL). The combined organic layers were dried
(MgSO4) and concentrated under reduced pressure. The solid was
washed with EtOAc and cystallized in CHCl3 to give white 5; yield:
50.3 mg (60%).
H
Hd¢¢), 8.05 (dd, J = 8.3, 8.4 Hz, 4 H, Hg,g¢), 7.84 (m, 8 H, Hc,c¢,f,f¢,c¢¢),
7.37 (m, 3 H, Hb,b¢), 6.84 (d, J = 8.3 Hz, 1 H, Hb¢¢), 4.12 (s, 3 H,
OMe).
13C NMR (75 MHz, CDCl3): d = 163.59, 156.34, 156.27, 156.03,
155.98, 155.95, 153.62, 149.68, 149.57, 149.17, 149.13, 141.02,
141.00, 139.36, 138.04, 137.70, 136.88, 127.86, 127.83, 127.78,
127.67, 127.58, 123.85, 123.82, 121.43, 121.40, 118.72, 118.61,
114.07, 111.18, 53.35.
MALDI-MS: m/z (%) = 646.97 (100) [M + H]+.
HRMS: m/z [M + H]+ calcd for C43H31N6O: 647.2559; found:
1H NMR (300 MHz, CDCl3): d = 8.88 (dd, J = 1.1, 1.3 Hz, 2 H),
8.71 (m, 3 H), 8.21 (m, 2 H), 8.03 (ddd, J = 1.5, 1.7, 1.8 Hz, 1 H),
7.92 (d, J = 8.4 Hz, 2 H), 7.80 (d, J = 8.4 Hz, 2 H), 7.53 (dd, J = 7.7,
7.7 Hz, 1 H).
647.2568.
4¢-[4¢-(2,2¢:6¢,2¢¢-Terpyridin-4¢-yl)-1,1¢-biphenyl-4-yl]-2,2¢:6¢,2¢¢-
terpyridine-6-carbonitrile (9)
Yield: 104 mg (54%).
13C NMR (75 MHz, CDCl3): d = 165.70, 155.69, 154.79, 154.76,
154.61, 149.23, 148.37, 147.73, 138.82, 137.33, 136.53, 132.16,
129.03, 124.93, 124.50, 124.10, 123.01, 120.87, 118.32, 118.12,
79.08.
MALDI-MS: m/z (%) = 431.03 (100) [M+].
HRMS: m/z [M – H]+ calcd for C22H13BrN3O2: 430.0191; found:
1H NMR (300 MHz, CDCl3): d = 8.91 (d, J = 8.1 Hz, 1 H, Hd¢¢), 8.87
(d, J = 1.5 Hz, 1 H, He¢¢), 8.83 (m, 3 H, He,e¢), 8.75 (m, 3 H, Ha,a¢),
8.69 (d, J = 7.9 Hz, 2 H, Hd), 8.63 (d, J = 8.1 Hz, 1 H, Hd¢), 8.02 (m,
5 H, Hg,g¢,c¢¢), 7.87 (m, 7 H, Hf,f¢,c,c¢), 7.74 (d, J = 7.7 Hz, 1 H, Hb¢¢),
7.36 (m, 3 H, Hb,b¢).
13C NMR (75 MHz, CDCl3): d = 158.06, 156.50, 156.20, 156.07,
154.05, 150.22, 149.35, 149.23, 141.51, 141.04, 138.00, 137.77,
137.39, 136.78, 133.49, 128.15, 128.14, 127.91, 127.85, 127.81,
127.67, 124.48, 123.98, 123.77, 121.41, 121.31, 120.24, 119.86,
119.26, 118.85.
430.0188.
Methyl 4¢-(4-Bromophenyl)-2,2¢:6¢,2¢¢-terpyridine-6-carboxy-
late (6)
A mixture of terpyridine 3 (174 mg, 0.42 mmol), concd H2SO4 (1.89
mL), AcOH (1.89 mL) and H2O (0.42 mL) was stirred at 90–100 °C
for 24 h, then the solution was added to ice water (16 mL). The pre-
cipitate was collected by filtration, washed with H2O and MeCN,
and dried in vacuo. To cooled (ice water bath) MeOH (12 mL) was
added dropwise SOCl2 (504 mg). The solution was stirred at r.t. for
MALDI-MS: m/z (%) = 641.23 (100) [M+].
HRMS: m/z [M + H]+ calcd for C43H28N7: 642.2406; found:
642.2397.
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J. Li et al.
PAPER
Methyl 4¢-[4¢-(2,2¢:6¢,2¢¢-Terpyridin-4¢-yl)-1,1¢-biphenyl-4-yl]-
2,2¢:6¢,2¢¢-terpyridine-6-carboxylate (10)
Yield: 40.6 mg (20%).
References
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H
H
e,e¢), 8.76 (d, J = 3.1 Hz, 3 H, Ha,a¢), 8.69 (dd, J = 7.9, 5.9 Hz, 3 H,
d,d¢), 8.20 (dd, J = 0.9, 0.9 Hz, 1 H, Hb¢¢), 8.04 (m, 5 H, Hg,g¢,c¢¢), 7.87
(m, 7 H, Hf,f¢,c,c¢), 7.37 (m, 3 H, Hb,b¢), 4.08 (s, 3 H, COOMe).
13C NMR (75 MHz, CDCl3): d = 165.96, 156.75, 156.48, 156.29,
156.17, 155.30, 150.06, 149.75, 149.25, 149.21, 147.85, 141.20,
141.11, 137.88, 137.78, 137.70, 136.78, 127.93, 127.86, 127.63,
125.01, 124.56, 123.84, 123.75, 121.70, 121.40, 121.36, 119.38,
119.35, 118.82, 52.70.
MALDI-MS: m/z (%) = 674.24 (100) [M+].
HRMS: m/z [M + Na]+ calcd for C44H30N6NaO2: 697.2321; found:
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Acknowledgment
We thank the Ministry of Education, Culture, Sports, Science and
Technology, Japan, for financial support.
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Synthesis 2011, No. 9, 1361–1364 © Thieme Stuttgart · New York