Palladium-catalysed and phosphine-promoted synthesis of diaryl ethers through self-coupling

Article abstract of DOI:10.3184/174751916X14768086301069

An efficient, palladium acetate-catalysed, tributylphosphine-promoted direct synthesis of symmetrical diaryl ethers through the self-coupling of aryl fluorides has been developed with K₂CO₃/ZrO₂ as a base. This provides an alternative method to prepare aromatic polymers, important synthetic intermediates and natural products for use in the field of pharmaceuticals and industrial materials.

Full text of DOI:10.3184/174751916X14768086301069

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 40 NOVEMBER, 691–693
RESEARCH PAPER 691
Palladium-catalysed and phosphine-promoted synthesis of diaryl ethers
through self-coupling
Dawei Wang, Zhaojun Xu, Xiaoli Yu, Yongliang Li and Huida Wan*
The Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122,
Jiangsu Province, P.R. China
An efficient, palladium acetate-catalysed, tributylphosphine-promoted direct synthesis of symmetrical diaryl ethers through the self-
coupling of aryl fluorides has been developed with K2CO3/ZrO2 as a base. This provides an alternative method to prepare aromatic
polymers, important synthetic intermediates and natural products for use in the field of pharmaceuticals and industrial materials.
Keywords: self-coupling, phosphine, symmetrical diaryl ethers, aryl fluorides
Over several decades, aromatic polyimides have been generally
recognised to possess excellent mechanical properties and
outstanding thermal stability. A variety of symmetrical diaryl
ether compounds have been used as the precursor of aromatic
polyimides and widely applied to the pesticide, medicine and
material fields.1 In addition, symmetrical diaryl ethers have
been applied in the microelectronic and aerospace industries on
account of their high thermal stability, chemical resistance and
electronic properties.2 Therefore, the synthesis of symmetrical
diaryl ether derivatives is still of interest today.
The classical method for the synthesis of diaryl ether
derivatives is a C–O coupling reaction of phenolic derivatives
with a C–X bond.3–6 In most cases, transition metals have
played a key role in this transformation. Many transition
metals, such as Fe, Ir, Rh, Pd and Cu, have shown excellent
catalytic activity in this area.7,8 For example, a versatile sol-
gel immobilised copper catalyst for the Ullmann arylation of
phenols has been shown to be effective by Monnier, Taillefer
and others.9–14 Magnetic copper ferrite nanoparticles have
also been used as catalysts for this transformation.15–17 Other
syntheses of diaryl ether derivatives have been reported.18–26
Recently, we developed iridium-catalysed C–F activation of
fluoroarenes with the use of bis(pinacolato)diboron (B2pin2)
as an additive for a B–F bond activation.27 This provides a
convenient method to convert fluoride aromatic compounds
into symmetrical diaryl ethers. However, we found that iridium
catalysts, ligands and B2pin2 reagent are all expensive for this
transformation (Scheme 1). Herein, we describe a palladium
acetate-catalysed and tributylphosphine-promoted synthesis of
diaryl ether derivatives by the self-coupling of aryl fluorides
in moderate to high yields in the presence of the basic K2CO3/
ZrO2 conditions.
In the start of the investigation, the reaction of
p-fluoronitrobenzene (1a) was used to establish the reaction by
using a phosphine as an additive28 with palladium acetate as a
catalyst. Interestingly, the self-coupling product was obtained,
although in a low yield. Next, the reaction conditions were
modified to obtain a better yield (Table 1). Only a low yield
was obtained, even by changing the solvents, phosphine and
metals. Interestingly, quite a good yield was obtained when a
supported solid base was used for this reaction. We examined
several supported solid bases under different reaction
conditions, including K2CO3/ZrO2, K2CO3/Al2O3 and Cs2CO3/
ZrO2. These are easily prepared following known methods.29–32
As listed in Table 1, the results showed that the simple K2CO3/
ZrO2 could promote this reaction with good yield, although
K2CO3/Al2O3 gave disappointing results. A blank experiment
showed that the reaction did not occur without a phosphine or
base.
Table 1 Screening of reaction conditionsa
O
Pd(OAc)2, Phosphine
O2N
F
Solvent, Base
N
O2
NO2
2a
1a
Previous work
Phosphine Base
Solvent
DMF
DMF
DMF
DCE
Yield/%b
Entry
1
2
3
4
5
6
7
8
X
X
OH
O
O
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PBu3
P(OMe)3
Cs2CO3
K2CO3
K3PO4
Cs2CO3
Cs2CO3
13
<5
<5
<5
<5
16
15
73
27
<5
77
82
<5
Strong base
X = I, Br, Cl
Cu, Pd, Fe
OH
THF
Cs2CO3
Cs2CO3
Toluene
Xylene
Toluene
Toluene
Toluene
Xylene
Xylene
Xylene
O
B(OH)2
F
Cu(OAc)2/Et3N
K2CO3/ZrO2
K2CO3/Al2O3
Cs2CO3/ZrO2
K2CO3/ZrO2
K2CO3/ZrO2
K2CO3/ZrO2
O
[(COD)IrCl]2/dppe
9
H2O, B2pin2/Cs2CO3
10
11
12
13
This work
O
F
PBu3, K2CO3/ZrO2
Pd, DMF
aReaction conditions: 1a (1.0 mmol), Pd(OAc)2 (2 mol%), phosphine (2.0 equiv.), base
(1.5 equiv.), 24 h, 110 °C or reflux.
bIsolated yields based on 1a.
Scheme 1 Synthesis of diaryl ether derivatives promoted by boron
and phosphine.
* Correspondent. E-mail: huidawan@jiangnan.edu.cn

692 JOURNAL OF CHEMICAL RESEARCH 2016
Table 2 Substrate expansion of aryl fluoridesa
tetramethylsilane. Proton coupling patterns are described as singlet (s),
doublet (d), triplet (t) and multiplet (m).
O
Pd(OAc)2, PBu3, K2CO3/ZrO2
Xylene, Reflux, N2
R
R
F
Preparation of diaryl ethers; general procedure
R
A mixture of fluorobenzene (1.0 mmol), PBu3 (2.0 mmol), Pd(OAc)2
(2 mol%), K2CO3/ZrO2 (1.5 equiv., based on K2CO3, 2.070 g) in xylene
(10 mL) was stirred at reflux under nitrogen for 24 h or according
to the TLC. On completion, the resulting mixture was filtered and
washed with DCM. The combined organic solvent layers were
separated, the solvent evaporated and the product purified by column
chromatography with dichloromethane/n-hexane (1:1–1:2) as the
eluent to provide the corresponding product 2.
2
1
Melting point/°C
Reported
143
Entry
R
Yield/%b
Measured
141–142
113
Ref.
33
34
35
none
36
none
37
38
39
none
1
2
3
4
5
6
7
8
9
10
p-NO2
o-NO2
p-CN
o-CN
82 (2a)
77 (2b)
71 (2c)
68 (2d)
85 (2e)
76 (2f)
74 (2g)
65 (2h)
114
179–181
noned
103–104
noned
154–156
154
177–178
c
–
4,4′-oxybis(nitrobenzene) (2a): 1H NMR (400 MHz, CDCl3): δ 8.31
(d, J = 9.0 Hz, 2H), 7.19 (m, J = 9.0 Hz, 2H); 13C NMR (101 MHz,
CDCl3): δ 160.7 (s), 144.2 (s), 126.2 (s), 119.3 (s).
o-CN–p-NO2
o-NO2–p-F
o-Cl–p-NO2
o-NO2–p-Cl
o-NO2–p-NO2 83 (2i)
o-Br–p-NO2 69 (2j)
103
97–99
153
150–152
136–137
158–159
2,2′-oxybis(nitrobenzene) (2b): 1H NMR (400 MHz, CDCl3): δ 8.05
(d, J = 7.8 Hz, 2H), 7.61 (t, J = 7.6 Hz, 2H), 7.33 (t, J = 7.8 Hz, 2H), 7.10
(d, J = 7.6 Hz, 2H); 13C NMR (101 MHz, CDCl3): δ 149.2 (s), 141.2 (s),
134.6 (s), 126.2 (s), 124.7 (s), 120.9 (s).
138
noned
1
aReaction conditions: 1 (1.0 mmol), Pd(OAc)2 (2 mol%), P(nBu)3 (2.0 equiv.), base
4,4′-oxydibenzonitrile (2c): H NMR (400 MHz, CDCl3): δ 7.12 (d,
J = 8.6 Hz, 4H), 7.70 (d, J = 8.6 Hz, 4H); 13C NMR (101 MHz, CDCl3):
δ 108.0 (s), 118.3 (s), 119.7 (s), 134.5 (s), 159.2 (s).
(1.5 equiv.), 24 h, reflux.
bIsolated yields based on 1.
cOil was obtained.
dM.p. was not in the literature.
1
2,2′-oxydibenzonitrile (2d); H NMR (400 MHz, CDCl3): δ 7.73 (d,
J = 8.2 Hz, 2H), 7.60 (t, J = 8.2 Hz, 2H), 7.30 (t, J = 8.2 Hz, 2H), 6.99
(d, J = 8.6 Hz, 2H); 13C NMR (101 MHz, CDCl3): δ 157.4 (s), 134.6
(s), 134.2 (s), 124.9 (s), 118.8 (s), 115.0 (s), 105.3 (s). HRMS calcd for
C14H9N2O [M + H]+:221.0715; found: 221.0712.
4,4′-oxybis(3-fluoro-1-nitrobenzene) (2e): 1H NMR (400 MHz,
CDCl3): δ 8.16 (d, J = 9.8 Hz, 2H), 8.11 (d, J = 9.0 Hz, 2H), 7.21 (t,
J = 8.2 Hz, 2H); 13C NMR (101 MHz, CDCl3): δ 113.6 (s), 113.8 (s),
119.9 (s), 120.8 (s), 120.8 (s), 144.5 (s), 144.5 (s), 148.1 (s), 148.2 (s),
151.1 (s), 153.6 (s).
O
Pd(OAc)2, K2CO3/ZrO2
N
F
O2
Xylene, Reflux, N2
N
O2
NO2
1a
2a
: <5%
Scheme 2 Control experiment.
4,4′-oxybis(1-fluoro-3-nitrobenzene) (2f): 1H NMR (400 MHz,
CDCl3): δ 8.43 (s, 2H), 8.17 (d, J = 8.6 Hz, 2H), 7.04 (d, J = 9.0 Hz,
2H); 13C NMR (101 MHz, CDCl3): δ 113.4 (s), 113.6 (s), 121.8 (s),
122.0 (s), 122.2 (s), 122.3 (s), 141.1 (s), 141.2 (s), 145.5 (s), 145.5 (s),
156.7 (s), 159.2 (s). HRMS calcd for C12H7F2N2O5 [M + H]+: 297.0323;
found: 297.0324.
4,4′-oxybis(3-chloro-1-nitrobenzene) (2g): 1H NMR (400 MHz,
CDCl3): δ 8.01 (s, 2H), 7.62 (d, J = 8.2 Hz, 2H), 6.95 (d, J = 8.2 Hz,
2H); 13C NMR (101 MHz, CDCl3): δ 119.3 (s), 123.9 (s), 126.3 (s),
127.0 (s), 144.6 (s), 155.9 (s).
Encouraged by such promising results, we applied this
methodology to a variety of substrates to determine the scope
and limitations of the method. Almost all the substrates reacted
smoothly and produced the corresponding products with moderate
to good yields. As expected, when the substrate with a Br group
was used to test this reaction, the self-coupling reaction took place
successfully, providing the desired product in 69% yield (Table 2).
To reveal the possible reaction mechanism, a control
experiment involving no phosphine was tested for this reaction.
The result showed that the reaction did not happen without a
phosphine reagent (Scheme 2).
In summary, we have developed a palladium acetate-catalysed
and tributylphosphine-promoted diaryl ether synthesis in
moderate to high yields using K2CO3/ZrO2 as a base. The
reaction involves oxygen insertion and then self-coupling of
aryl fluorides. This provides an alternative method to prepare
some aromatic polymers, important synthetic intermediates
and natural products for use in the field of pharmaceuticals and
industrial materials.
4,4′-oxybis(1-chloro-3-nitrobenzene) (2h): 1H NMR (400
MHz, CDCl3): δ 8.47 (s, 2H), 8.19 (d, 2H, J = 8.6 Hz), 7.07 (d,
2H, J = 8.8 Hz); 13C NMR (101 MHz, CDCl3): δ 113.4 (s), 113.6
(s), 121.8 (s), 122.0 (s), 122.2 (s), 122.3 (s), 141.1 (s), 141.2 (s),
145.5 (s), 145.5 (s), 156.78 (s), 159.2 (s).
1
4,4′-oxybis(1,3-dinitrobenzene) (2i): H NMR (400 MHz, CDCl3):
δ 7.45 (d, 2H, J = 8.0 Hz), 7.35 (t, 2H, J = 8.0 Hz), 6.99 (d, 2H,
J = 9.0 Hz); 13C NMR (101 MHz, CDCl3): δ 115.3 (s), 117.9 (s), 120.7
(s), 135.7 (s), 139.0 (s), 159.0 (s).
4,4′-oxybis(3-bromo-1-nitrobenzene) (2j): 1H NMR (400
MHz, CDCl3): δ 8.62 (s, 2H), 8.24 (d, 2H, J = 8.6 Hz), 7.02 (d, 2H,
J = 9.0 Hz); 13C NMR (101 MHz, CDCl3): δ 105.3 (s), 115.0 (s),
118.8 (s), 124.9 (s), 134.2 (s), 134.6 (s), 157.4 (s). HRMS calcd for
C12H7Br2N2O5 [M + H]+:416.8722; found: 416.8717.
Experimental
All solvents were dried and purified by known procedures and freshly
distilled under nitrogen from appropriate drying agents before use.
The products were isolated by column chromatography on silica gel
(200–300 mesh or 100–200 mesh) using petroleum ether (60–90 °C)
and ethyl acetate as eluents. Silica gel for column chromatography
was purchased from Qingdao Haiyang Chemical Co. Ltd. All yields
described herein are the isolated yields after column chromatography.
Reaction progress and product mixtures were routinely monitored by
TLC using TLC SiO2 sheets, and compounds were visualised under
ultraviolet light. Melting points were determined using a WRS-1B
Electronic Supplementary Information
Detailed experimental procedures and 1H NMR and 13C
NMR data for compounds 2 are available in the ESI through:
stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data.
Acknowledgements
1
digital melting point apparatus. H NMR and 13C NMR spectra were
We gratefully acknowledge financial support for this work from
the National Natural Science Foundation of China (21401080),
the Natural Science Foundation of Jiangsu Province of China
(BK20130125), Jiangsu Talents Project (2013-JNHB-027),
recorded on a 400 or 600 NMR spectrometer. 1H NMR chemical
shifts are referenced to tetramethylsilane (TMS) (0 ppm). Chemical
shifts are reported in parts per million (ppm, δ) downfield from

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Received 10 September 2016; accepted 4 October 2016
Paper 1604199 doi: 10.3184/174751916X14768086301069
Published online: 24 October 2016
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