Synthesis of a novel ligand containing phenyl pyridine

Article abstract of DOI:10.1080/00397910902923540

In this article, we provide a new, efficient route to synthesize 2-[3-(3,4-bis(2-ethylhexyloxy)phenyl]phenyl pyridine ligand from readily available starting materials. The target compound was obtained by a condensation reaction and Suzuki coupling reaction. Structures of compounds were demonstrated by 1H NMR, 13C NMR, and high-resolution mass spectrometry. The advantages of this synthetic route are simple operation, mild reaction conditions, and good yields.

Full text of DOI:10.1080/00397910902923540

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Synthesis of a Novel Ligand Containing
Phenyl Pyridine
Mingxin Yu a b , Haiyan Fang a , Youfeng Yue a , Yenchun Chen b
Showan Chen b
&
a Department of Chemistry, Zhejiang University, Hangzhou, China
b Chemical Engineering Department, National Tsing Hua University,
Hsinchu, Taiwan
Published online: 09 Dec 2009.
To cite this article: Mingxin Yu , Haiyan Fang , Youfeng Yue , Yenchun Chen & Showan Chen
(2009) Synthesis of a Novel Ligand Containing Phenyl Pyridine, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:1, 58-63, DOI:
10.1080/00397910902923540
To link to this article: http://dx.doi.org/10.1080/00397910902923540
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Synthetic Communications1, 40: 58–63, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902923540
SYNTHESIS OF A NOVEL LIGAND CONTAINING
PHENYL PYRIDINE
Mingxin Yu,1,2 Haiyan Fang,1 Youfeng Yue,1 Yenchun Chen,2
and Showan Chen2
1Department of Chemistry, Zhejiang University, Hangzhou, China
2Chemical Engineering Department, National Tsing Hua University,
Hsinchu, Taiwan
In this article, we provide
a
new, efficient route to synthesize 2-[3-(3,
4-bis(2-ethylhexyloxy)phenyl]phenyl pyridine ligand from readily available starting mate-
rials. The target compound was obtained by a condensation reaction and Suzuki coupling
reaction. Structures of compounds were demonstrated by 1H NMR, 13C NMR, and
high-resolution mass spectrometry. The advantages of this synthetic route are simple oper-
ation, mild reaction conditions, and good yields.
Keywords: 2-[3-(3,4-Bis(2-ethylhexyloxy)phenyl] phenyl pyridine; ligand; phenylboronic acid compounds;
Suzuki coupling reaction; synthesis
Among the heterocyclic compounds exhibiting high physiological activity,
nitrogen-containing substances, many of which belong to the class of materials exhi-
biting analgesic action, are of particular interest. The phenyl pyridine compounds
are known as compounds with antibacterial and antifungal properties.[1,2] Antican-
cer activity is more efficient using phenyl pyridine structures with lateral catena.[2,3]
They are of interest not only as medicinal products but also as ligands for the
preparation of coordination compounds exhibiting valuable specific properties, such
as high photoluminescence. Initiated by the pioneering work of Baldo et al.,[4] enor-
mous advances[5–14] in metal complexes have been made in pursuit of highly efficient
electrophosphorescent organic light-emitting diodes (OLEDs). It has been well
demonstrated that structural changes in the skeleton as well as the substituent
groups of the cyclometalating ligand afford significant color tuning of electropho-
sphorescence. Therefore, the design and synthesis of novel cyclometalating ligands
have been enthusiastically investigated.[15–19]
In recent years, many derivatives of pyridine have been prepared. Paulose
et al.[15] synthesized a series of 2-alkenyl pyridines in 2004. This was the first example
Received January 16, 2009.
Address correspondence to Mingxin Yu, Department of Chemistry, Zhejiang University,
Hangzhou 310027, China. E-mail: mingxinyu@zju.edu.cn
58

LIGAND CONTAINING PHENYL PYRIDINE
59
Scheme 1. Synthesis of BEPPP.
of alkenyl pyridines as organic ligands for phosphorescent iridium complexes.
You[19] designed and synthesized ligands by changing the fused ring conjugation
of pyridine- and pyrazine-based ligand structures. Herein, we prepared 2-[3-(3,
4-bis(2-ethylhexyloxy)phenyl]phenyl pyridine (BEPPP) as a novel ligand.
BEPPP can be used as electron transporter and luminescence host
material for phenyl pyridine, and it also leads to fine solubility because it is
connected to the hydrocarbon chain. We chose 1-bromo-3,4-dihydroxy benzene,
1-bromo-2-ethylhexane, 2-bromopyridine, and 3-bromophenylboronic acid as
the basic raw materials. The target compound was obtained by the conden-
sation reaction and Suzuki coupling reaction (Scheme 1). Synthetic procedures
are described in the Experimental section. Structures of compounds were
demonstrated by 1H NMR, 13C NMR and high-resolution mass spectrometry
(HRMS). The advantages of this synthetic route are simple operation, mild
reaction conditions, and good yields.
In conclusion, we provide a new, efficient route to the BEPPP ligand in good
yields from readily available starting materials. BEPPP can be used as electron trans-
porter and luminescence host material for metal complexes, and it also leads to fine
solubility because it is connected to the hydrocarbon chain.
EXPERIMENTAL
All chemicals were used as supplied. All melting points were determined
with a WRS-1A melting-point apparatus and were uncorrected. 1H NMR and
13C NMR spectra were recorded using a Bruker AV-500 NMR instrument in
CDCl3 with tetramethylsilane (TMS) as internal standard. Mass spectra (MS)
were obtained on a Jeol JMS-S ꢀ 102A HRGC=LC=MS instrument operating in
EI mode at 70 eV.

60
M. YU ET AL.
Synthesis of 1,2-Bis(2-ethylhexyloxy)-4-bromobenzen
A mixture of 1-bromo-2-ethyl-hexane (6.2 g, 32.0 mmol), 1-bromo-3,4-dihydroxy
benzene (2.26 g, 12.0 mmol), and potassium hydroxide (1.7 g, 30 mmol) in ethanol
(EtOH, 60 mL) was heated under reflux at 80ꢁC for 16h. The reaction mixture was
allowed to cool to room temperature, and the inorganic material was filtered off.
The filtrate was concentrated under reduced pressure, and crude oil was chromato-
graphed on silica gel using ethyl acetate and hexane as eluent to yield 3.38 g (85%)
of colorless oil.
1
Colorless oil; H NMR (500 MHz, CDCl3): 6.97–6.95 (m, 2H), 6.71 (d, 1H,
J ¼ 9.0 Hz), 3.83 (s, 2H), 3.80 (s, 2H), 1.76–1.70 (m, 2H), 1.54–1.25 (m, 16H),
0.93–0.86(m, 12H); 13C NMR (500 MHz, CDCl3): 150.34 (C), 148.68 (C), 123.17
(CH), 116.54 (CH), 114.75 (CH), 112.56 (C), 71.76 (CH2), 71.55 (CH2), 39.45
(CH), 39.44 (CH), 30.52 (2CH2), 29.07 (CH2), 29.06 (CH2), 23.85 (2CH2), 23.03
(2CH2), 14.05 (2CH3), 11.12 (2CH3). HRMS (m=z): Calcd. for C22H37BrO2,
412.1977, found 412.1982.
Synthesis of 2-(3-Bromophenyl)pyridine
A degassed mixture of 2-bromopyridine (1.92 mL, 20 mmol), Na2CO3 (4.6 g,
44 mmol), water (22 mL), EtOH (16 mL), dimethoxyethane (50 mL), 3-bromophenyl-
boronic acid (4.0 g, 20 mmol), and Pd(PPh3)4 (230 mg, 0.2 mmol) was heated at reflux
for 18 h. The reaction mixture was allowed to cool to room temperature, and the
inorganic material was filtered off. The filtrate was concentrated under reduced
pressure, and crude oil was chromatographed on silica gel to afford 3.21 g (68.6%)
of 2-(3-bromophenyl) pyridine (eluent: ethyl acetate and hexane).
Colorless oil[20]; 1H NMR (500 MHz, CDCl3): 8.67 (d, 1H, J ¼ 5.0 Hz), 8.15 (s,
1H), 7.88 (d, 1H, J ¼ 7.0 Hz), 7.73 (dd, 1H, J ¼ 8.5, 6.5 Hz), 7.66 (d, 1H, J ¼ 8.5 Hz),
7.51 (d, 1H, J ¼ 7.0 Hz), 7.31 (dd, 1H, J ¼ 7.0, 7.5 Hz), 7.23 (dd, 1H, J ¼ 6.0, 7.0 Hz);
13C NMR (500 MHz, CDCl3): 155.57 (C), 149.59 (CH), 141.21 (C), 136.75 (CH),
131.69 (CH), 130.10 (CH), 129.84 (CH), 125.23 (CH), 112.90 (C), 122.53 (CH),
120.40 (CH).
Synthesis of 3-(Pyridine-2-yl)phenylboronic Acid
A 2.5 M solution of n-butyllithiium in hexane (4.8 ml, 6 mmol) was added drop-
wise to a solution of 2-(3-bromophenyl)pyridine (2.34 g, 10.0 mmol) in tetrahydro-
furan (THF, 50 mL) at ꢂ 78ꢁC. The mixture was maintained at this temperature
for 1 h before trimethylborate (8.6 mL, 50 mmol) was added slowly to the mixture.
The reaction mixture was stirred for 1 h at ꢂ 60ꢁC and allowed to warm to room
temperature overnight. After addition of aqueous 3 M hydrochloric acid (40 mL),
the mixture was stirred for 30 min. The organic layer was concentrated under
reduced pressure. The residue was recrystallized from hexane to yield 1.0 g (50.2%)
of a white solid.
1
Mp 77–78ꢁC[21]; H NMR (500 MHz, CDCl3): 8.54–8.39 (m, 2H), 8.00–7.10
(m, 6H), 5.78 (s,b, 2H); 13C NMR (500 MHz, CDCl3): 155.12 (C), 149.58 (CH),

LIGAND CONTAINING PHENYL PYRIDINE
61
138.84 (C), 138.30 (CH), 135.48 (CH), 132.80 (CH), 128.96 (CH), 128.74 (CH),
128.09 (C), 126.92 (CH), 122.27 (CH).
Synthesis of 2-[3-(3,4-Bis(2-ethylhexyloxy)phenyl]phenyl Pyridine
A degassed mixture of 1,2-Bis(2-ethylhexyloxy)-4-bromobenzen (0.413 g,
1.0 mmol), Na2CO3 (0.233 g, 2.2 mmol), water (1.1 mL), EtOH (0.8 mL), dimethox-
yethane (2.5 mL), 3-(pyridine-2-yl)phenylboronic acid (0.2 g, 1.0 mmol), and
Pd(PPh3)4 (11.5 mg, 0.01 mmol) was heated at reflux for 18 h.The reaction mixture
was allowed to cool to room temperature, and the inorganic material was filtered
off. The filtrate was concentrated under reduced pressure, and crude oil was chroma-
tographed on silica gel to afford 0.34 g (69.8%) of 2-[3-(3,4-bis (2-ethylhexyloxy)phe-
nyl]phenyl pyridine (eluent: ethyl acetate and hexane).
1
Colorless oil; H NMR (500 MHz, CDCl3): 8.71 (d, 1H, J ¼ 5.0 Hz), 8.16 (s,
1H), 7.90 (d, 1H, J ¼ 7.5 Hz), 7.76–7.75 (m, 2H), 7.60 (d, 1H, J ¼ 7.5 Hz), 7.51
(dd, 1H, J ¼ 7.5, 7.5 Hz), 7.25–7.22 (m, 1H), 7.20–7.17 (m, 2H), 6.95 (d, 1H,
J ¼ 8.5 Hz), 3.95 (s, 2H), 3.92 (s, 2H), 1.82–1.78 (m, 2H), 1.59–1.25 (m, 16H),
0.92–0.86 (m, 12H);13C NMR (500 MHz, CDCl3): 157.54 (C), 149.64 (CH), 149.28
(C), 141.77 (C), 139.82 (C), 136.72 (CHmic), 133.92 (C), 129.04 (CH), 128.71 (C),
127.48 (CH), 125.47 (CH), 125.28 (CH), 122.13 (CH), 120.74 (CH), 119.61 (CH),
113.72 (CH), 112.93 (CH), 71.76 (CH2), 71.64 (CH2), 39.63 (CH), 39.55 (CH),
30.57 (2CH2), 29.13 (CH2), 29.10 (CH2), 23.89 (2CH2), 23.06 (2CH2), 14.08
(2CH2), 11.18 (CH3), 11.16 (CH3); HRMS (m=z): calcd. for C33H45NO2 487.3450;
found 487.3456.
ACKNOWLEDGMENT
We thank the Key Industrial Catalysis Subject of Zhejiang Province, China, for
financial support.
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