Ullmann diaryl ether synthesis catalyzed by copper (I)/pyridine-functionalized silane

Article abstract of DOI:10.1080/10426507.2015.1119135

Ullmann-type diaryl ether synthesis was performed under mild conditions in DMF/K₂CO₃using a pyridinefunctionalized silane as a ligand. The productswere obtained in good yields. This method tolerates a variety of functional groups and is effective in the synthesis of hindered diaryl ethers and heteroaryl ethers.

Full text of DOI:10.1080/10426507.2015.1119135

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Ullmann Diaryl Ether Synthesis Catalyzed by
Copper (I) / Pyridine-Functionalized Silane
Baohua Zhang, Lanxiang Shi, Ruixia Guo & Sijie Liu
To cite this article: Baohua Zhang, Lanxiang Shi, Ruixia Guo & Sijie Liu (2016): Ullmann Diaryl
Ether Synthesis Catalyzed by Copper (I) / Pyridine-Functionalized Silane, Phosphorus, Sulfur,
and Silicon and the Related Elements, DOI: 10.1080/10426507.2015.1119135
To link to this article: http://dx.doi.org/10.1080/10426507.2015.1119135
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Ullmann Diaryl Ether Synthesis Catalyzed by Copper (I) / Pyridine-Functionalized Silane
Baohua Zhang, Lanxiang Shi*, Ruixia Guo and Sijie Liu
College of Chemical Engineering, Shijiazhuang University, Shijiazhuang 050035, China
*Address correspondence to Lanxiang Shi, College of Chemical Engineering, Shijiazhuang
University, Shijiazhuang 050035, China. E-mail: kedashilanxiang@126.com
Abstract Ullmann-type diaryl ether synthesis was performed under mild conditions in
DMF/K2CO3 using a pyridine-functionalized silane as the ligand. The products were obtained in
good yields. This method tolerates a variety of functional groups and is effective in the synthesis
of hindered diaryl ethers and heteroaryl ethers.
O
Si
Si
L2 -CuI (20 mol%)
Ar' X
+
O
Ar''OH
Ar'
Ar''
K2CO3 (2 equiv)
yield 30-89%
N
N
DMF, 100 ℃
L2
Key words: Diaryl ether, Copper, Pyridine-functionalized silane, Ullmann reaction
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INTRODUCTION
Diaryl ethers are an important class of compounds in pharmaceuticals and agricultural chemicals.
The most straightforward way to synthesize diaryl ethers involves the direct formation of an
aryl-oxygen bond from an aryl halide.1 Efficient copper-catalyzed arylations of phenols or their
sodium salts have been developed in recent years.2-5 However, the synthetic scope of this
reaction is strongly limited by the insolubility of copper (I) salts in organic solvents, the high
reaction temperatures required (~200oC). Another major drawback of this protocol is the use of
stoichiometric quantities of copper catalysts, which results in the production of large quantities
of waste.6 It is still desirable to develop more robust and more cost-effective processes for this
important reaction.
Various types of ligands and catalytic systems have been developed. It has been found
We thank the Hebei Province Science and Technology Support Programs (grant no. 13964002D，
15226601D).
that some bidentate N,N-, N,O-, O,O-, or N,S-ligand such as picolinic acid,7 diols, 8
diketone,9 ketone-ester,10 amino-alcohols,11 diamines,12 diimines,13 diethylsalicylamide,14
aminoarenethiolate,15were efficient ligands for the copper catalyzed Ullmann arylation reactions.
The high catalytic activities of Cu / bidentate ligands are ascribed to the abilities of these
bidentate compounds to form chelated Cu(I) species.16 The success of Cu-1,10-phenanthroline17
catalysts in O-arylation reactions promoted us to examine whether the pyridine-functionalized
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silanes L1-L5 (Figure 1) could be useful for the arylation of phenols under mild conditions. In
this article we report a practical and efficient arylation of phenols by using simple and easily
available pyridine-functionalized silanes as ligands.
RESULTS AND DISCUSSION
In the preliminary experiment, we used 20 mol% dimethyl di (2-pyridyl)silane L1 as the ligand
with 20 mol% CuI for the coupling of iodobenzene with p-cresol in DMF at 100oC in presence of
2 equiv of K2CO3. After 24 h the coupling reaction provided 52% yield for the corresponding
diaryl ether (Table 1, entry 1). Replacing L1 with L2-L5 respectively, provided products in
21-84% yields. L2 was the best among the ligands tested, and the diaryl ether was isolated in
84% yield (Table 1, entry 2). Ligands L4 and L5 also showed good activities under the same
conditions (Table 1, entries 4 and 5), whereas L3 gave a poor yield (21%) of the target product
within 24 h (Table 1, entry 3). The coupling reaction did not provide a trace amount of diaryl
ether when the reaction was carried out without L2 and CuI (Table 1, entry 13). When the
reaction was carried out with CuI without L2, the product was obtained only in 11% yield (Table
1, entry 14). This shows that ligand is required for a real quantitative yield of the product.
Among these copper sources, CuI was the most effective. Changing the solvent to acetonitrile
decreased the yield to 79% yield (Table 1, entry 11). The 1-Methyl-2-pyrrolidinone (NMP) gave
a similar yield to DMF. Both Cs2CO3 and K2CO3 were effective bases, whereas K3PO4 gave a
lower yield (Table 1, entry 10). The K2CO3 was chosen since it is much cheaper.
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Using the above optimized conditions, we investigated the scope of the L2-CuI catalyzed
Ullmann-type coupling reaction, and the results are summarized in Table 2. Compared with
phenol, para- methyl phenol or m- methoxy phenol as the substrate, increased the reaction yields
by 9% and 6%, respectively (Table 2, entries 1 and 4). When replacing phenol with para- chloro
phenol, the product was obtained in 64% yield (Table 2, entry 5). This shows that phenol with an
electron-rich substituent is beneficial for reaction.
Though ortho-substituted phenols and aryl halides are usually difficult substrates for
Cu-catalyzed methods (in contrast to Pd-catalyzed reactions),7 2-methoxyphenol coupled
effectively with 4-iodobenzene and obtained 61% yield (Table 2, entry 3). 2,4-Dichlorophenol
proved to be a significantly less effective coupling partner, due to its poor nucleophilicity and its
steric hindrance (Table 2, entry 6), while 4-nitrophenol, which bears a strong
electron-withdrawing group, does not undergo the desired O-arylation reaction (Table 2, entry 7).
As expected, the presence of an electron-withdrawing group in the aryl iodide such as cyano and
trifluoromethyl groups are well tolerated (Table 2, entries 8 and 9). The electron-donating group
at the para position of iodobenzene gave good conversions (Table 2, entry 11). Aryl halides with
steric hindrance such as 2-methyl iodobenzene gave the corresponding diaryl ether in lower yield
(Table 2, entry 10). Bromobenzene also has good activity and could coupled effectively with
phenol，product yield can reach 72% (Table 2, entry 12). Heteroaryl halides also coupled with
electron-deficient, -neutral and hindered phenols obtained good yields (Table 2, entries 13-15).
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CONCLUSION
In summary, we have developed a new way to carry out the Ullmann diaryl ether synthesis,
which is applicable to a wide variety of substrates with different functional groups. The ligands
are readily available. Further studies are under way to search for more active
heteroarene-functionalized silane ligands and to expand the scope of this methodology.
EXPERIMENTAL
13
1H and C spectra were recorded in CDCl 3 on a 300 MHz instrument at 300 MHz (1H) and 75
MHz (13C) with TMS as internal standard. Pyridine-functionalized silanes L1-L5 were obtained
according to the literature. 18-20 The Supplemental Materials contains full characterization data
for the known products presented in Table 2
General Procedure for Preparation of Diaryl Ether
Aryl iodide or bromides (1 mmol), ArOH (1 mmol), CuI (20 mol %) and dimethyl di
(2-pyridyl)silane (20 mol %) were placed in a small round-bottomed flask. DMF (3 mL) and
K2CO3 (276 mg, 2 mmol) were then added together. The mixture was stirred for 24h at 100℃ in
nitrogen atmosphere. The reaction mixture was cooled to room temperature. Ethyl acetate (10
mL) and H2O (1 mL) were added and the mixture was stirred. The organic layer was separated
and the aqueous layer was extracted twice more with ethyl acetate (10 mL). Combined organic
layer was dried over Na2SO4 and filtered. The filtrate was concentrated and the resulting residue
was purified by silica gel chromatography and afforded the desired products.
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REFERENCES
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5241-5244.
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16. Zhang, S. L.; Liu, L.; Fu, Y.; Guo. Q. X. Organometallics. 2007, 26, 4546-4554.
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2004, 361-362.
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Table 1 Effect of Ligand, Catalyst, Base, and Solvent on the Coupling of p-Cresol with
iodobenzenea
[Cu] (20 mol%)
ligand (20 mol%)
OH
I
O
+
base (2 equiv)
H3C
CH3
solvent, 100℃,
24h
entry
1
2
3
4
[Cu]
CuI
CuI
CuI
CuI
ligand
base
solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
MeCN
NMP
DMF
DMF
yield (%)b
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
K3PO4
K2CO3
K2CO3
K2CO3
K2CO3
52
84
21
77
77
72
68
53
86
41
79
85
0
L1
L2
L3
L4
L5
L2
L2
L2
L2
L2
L2
L2
-
5
CuI
6
7
8
9
10
11
12
13
14
CuBr
CuO
Cu(OAc)2
CuI
CuI
CuI
CuI
-
CuI
-
11
a
Reaction conditions: iodobenzene (1 mmol), catalyst (20 mol%), ligand (20 mol%), solvent (3
mL), base (2 mmol), p-cresol (1 mmol), 100℃, 24h; b Isolated yield.
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Table 2 Cu/L2 Catalyzed Coupling Reaction of Aryl Halides with phenolsa
L2-CuI (20 mol%)
O
Ar"OH
+
Ar' X
Ar'
Ar"
K2CO3 (2 equiv)
1a-1n
DMF, 100℃
Yield (%)b
84
Ar"OH
Ar' X
Entry
1
Product
O
OH
I
H3C
H3C
1a
O
I
OH
2
3
75
61
1b
O
OH
OCH3
I
OCH3
1c
H3CO
O
I
I
H3CO
OH
4
5
81
64
1d
O
OH
Cl
Cl
Cl
1e
O
OH
Cl
I
I
6
7
30
0
Cl
Cl
1f
O
OH
NO2
O2N
1g
NC
O
NC
I
OH
8
89
86
41
71
1h
F3C
O
F3C
I
OH
OH
OH
9
1i
O
I
10
11
CH3
1j
CH3
O
I
H3CO
H3CO
1k
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O
OH
Br
12
13
14
15
72
80
70
85
1b
O
N
I
OH
N
N
N
1l
O
I
OH
S
H3C
CH3
S
N
1m
CN
OH
NC
N
O
NC
Br
NC
1n
a
Reaction conditions: aryl iodide or bromide (1 mmol), CuI/L2 (20 mol%), DMF (3 mL),
K2CO3 (2 mmoL), ArOH (1 mmol), 100℃, nitrogen atmosphere;
b Isolated yield.
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O
Si
Si
Si
Si
Si
Si
Si
Si
N
N
N
N
N
N
N
N
N
N
L1
L2
L3
L4
L5
Figure 1 The ligands used for arylation of phenols
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