Synthesis of diaryl ethers through the copper-catalyzed arylation of phenols with aryl iodides using KF/Al2O3

Article abstract of DOI:10.1080/00397910802044264

An efficient synthesis of diaryl ethers by the copper-catalyzed arylation of phenols with a variety of aryl iodide susing KF/Al2O3 as a suitable base and CuI and 1,3 diphenyl-1,3 propandione as the catalyst is described. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802044264

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Synthesis of Diaryl Ethers
Through the Copper-Catalyzed
Arylation of Phenols with Aryl
Iodides Using KF/Al2O3
Rahman Hosseinzadeh a , Mahmood Tajbakhsh
a , Maryam Mohadjerani a , Parizad Rezaei a &
Mohammad Alikarami a
a Faculty of Chemistry, Mazandaran University ,
Babolsar, Iran
Published online: 28 Aug 2008.
To cite this article: Rahman Hosseinzadeh , Mahmood Tajbakhsh , Maryam
Mohadjerani , Parizad Rezaei & Mohammad Alikarami (2008) Synthesis of Diaryl Ethers
Through the Copper-Catalyzed Arylation of Phenols with Aryl Iodides Using KF/Al2O3
, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 38:17, 3023-3031, DOI: 10.1080/00397910802044264
To link to this article: http://dx.doi.org/10.1080/00397910802044264
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Synthetic Communications1, 38: 3023–3031, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802044264
Synthesis of Diaryl Ethers Through the
Copper-Catalyzed Arylation of Phenols with
Aryl Iodides Using KF/Al2O3
Rahman Hosseinzadeh, Mahmood Tajbakhsh, Maryam
Mohadjerani, Parizad Rezaei, and Mohammad Alikarami
Faculty of Chemistry, Mazandaran University, Babolsar, Iran
Abstract: An efficient synthesis of diaryl ethers by the copper-catalyzed aryla-
tion of phenols with a variety of aryl iodide susing KF=Al2O3 as a suitable base
and CuI and 1,3 diphenyl-1,3 propandione as the catalyst is described.
Keywords: Aryl iodide, copper-catalyzed, diaryl ethers, KF=Al2O3, phenols
Diaryl ethers are valuable intermediates in organic synthesis[1] and are
found in substructures in a variety of many important natural pro-
ducts.[2–4] The Ullmann diaryl ether synthesis (Ullmann condensation)
and aromatic nucleophilic substitution (SNAr) reaction has been known
for almost a century for the coupling of phenols with aryl halides.[5] The
Ullmann condensation is usually carried out in neat phenol or polar sol-
vents such as dimethylformamide (DMF), dimethylacetamide (DMA),
pyridine, and dimethylsulfoxide (DMSO) at high temperature (150–
250 ꢀC) in the presence of stoichiometric quantities of copper salts. Besides
SNAr, reactions usually require electron-deficient aryl halides.[6–8] The dia-
ryl ether formation using palladium catalysis in the presence of phosphine
ligands has also been under intensive investigation.[9] However, the use of
high boiling-point organic solvents, expensive catalysts, and ligands that
are often not reusable may not be the preferred choice.[10] The formation
of carbon-heteroatom bonds by copper-catalyzed cross-coupling method-
ology reported by Buchwald et al. and others has been the subject of sig-
nificant interest during the past few years.[11] Although most studies
Received November 18, 2007.
Address correspondence to Rahman Hosseinzadeh, Faculty of Chemistry,
Mazandaran University, Babolsar, Iran. E-mail: r.hosseinzadeh@umz.ac.ir
3023

3024
R. Hosseinzadeh et al.
have focused on CꢁN bond-forming procedures, few reports have been
published for the formation of CꢁO bonds.[12,13] In most reported proce-
dures, Cs2CO3 has been used as a base in a sealed tube. Cs2CO3 is highly
hygroscopic compound, so its uses as a base in moisture-sensitive reactions
is undesirable. On the other hand, the application of KF=Al2O3 to organic
synthesis has provided new methods for a wide array of organic reactions,
many of which are staples of synthetic organic chemistry.[14] In many cases,
the use of this base provides milder conditions and simpler procedures
than previously reported methods. Recently, we have used copper iodide
as a catalyst, KF=Al2O3 as a base, and 1,10-phenanthroline as a suitable
ligand to form CꢁN and C-O bonds.[15] In the formation of CꢁO bond
in the synthesis of diaryl ethers, and aryl alkyl ethers we had to use excess
phenols or alcohols to obtain high yield of products.[15d] Buck, et al.
reported that 2,2,6,6-tetramethylheptane-3,5-dione (TMHD) serves as a
powerful ligand that accelerates the Ullmann coupling reaction more than
previously described ligands, allowing some of the electronically unfavor-
able substrates to undergo ether formation.[16]
Having these data in hand, we have joined the copper iodide and
KF=Al2O3 with 1,3-diphenyl-1,3 propanedione as a new, efficient, and
simple ligand and obtained a high yield of the diaryl ethers from the reac-
tion of phenols with aryl iodides (Scheme 1).
To find the optimum conditions, we chose the cross-coupling
reaction of iodobenzene and phenol in the presence of 1,3 diphenyl-1,3
propandione, KF=Al2O3, and CuI as a model reaction. Variation of sol-
vent, temperature, and molar ratio of the substrates revealed that a molar
ratio of 3:1 phenol to iodobenzene and 1,3-diphenyl-1,3 propandione (15
mol%), CuI (15 mol%), and KF=Al2O3 (5 equivalant) in toluene at 100–
110 ꢀC gives the highest yield of the diphenyl ether. To show the gener-
ality of this method, we subjected a series of aryl iodides to this reaction,
and the results are summarized in Table 1.
Scheme 1. Copper-catalyzed formation of diaryl ethers.

3025

3026

3027

3028
R. Hosseinzadeh et al.
From Table 1, it can be observed that the Ullmann coupling
reactions under optimum conditions (entry 1) follow the general trend
that electron-donating groups on the phenol and electron-withdrawing
groups on the aryl iodides make the reaction favorable and faster (entries
3 and 6). Stronger electron-donating groups such as methoxy on the aryl
iodide make the reaction slower and give lower yields of the correspond-
ing diaryl ethers (entries 4 and 8). On the other hand, substitution in the
ortho-position of the aryl iodides afforded lower yield of the product
(entries 9, 10, and 13), which could be due to the steric effect of the sub-
stitution in the formation of intermediate from oxidative addition of aryl
iodide to copper-ligand complex, as we have seen in our previous work in
the preparation of diaryl ethers.[15d] However, ortho-substituted diaryl
ethers can be prepared by the reaction of aryl iodides with ortho-
substituted phenols in moderate yields (entries 11 and 12). In addition,
b-naphtol and 2-phenylphenol coupled with iodobenzene and 4-
iodotoluene to give high yield of the parent diaryl ethers (entries 14–16).
In summary, we have developed an operationally simple and efficient
method for the copper-catalyzed coupling of a variety of aryl iodides with
phenols using KF=Al2O3 as a base and CuI and 1,3-diphenyl-1,3 propan-
dione as the catalyst. We believe that potassium fluoride supported on
alumina (KF=Al2O3) provides an excellent complement to the other base
such as Cs2CO3 in copper-catalyzed methodology that has already been
utilized in a number of applications.
EXPERIMENTAL
Melting points were recorded on an electrothermal melting-point appar-
atus and are uncorrected. The NMR spectra were recorded in CDCl3
with TMS as an internal standard on Bruker Advance DPX 500-MHz
(GmbH, Germany) and JNM-Ex 90A-MHz NMR spectrometers. Purity
determination of the products was accomplished by thin-layer chromato-
graphy (TLC) on silica-gel polygram SIL G=UV 254 plates. Products
were separated and purified by different chromatographic techniques
and were also identified by the comparison of their melting points and
NMR spectra with those reported for authentic samples.
General Procedure for the Copper-Catalyzed O-Arylation of
Aryl Iodides in the Presence of KF/Al2O3 (Table 1)
To a solution of aryl iodide (1 mmol) and phenol (3 mmol) in toluene
(5 ml) under an argon atmosphere, CuI (15 mol%) and 1,3-diphenyl-1,3
[17]
propanedione (15 mol%) followed by KF=Al2O3
(5 equiv.) were

Synthesis of Diaryl Ethers
3029
added, and the reaction was stirred at 100–110 ꢀC for the specified
time (Table 1). The progress of the reaction was monitored by TLC.
The reaction mixture was allowed to cool to room temperature, diluted
with ethylacetate (30 ml), and filtered off. The filtrate was concentrated
under reduced pressure. The desired product was isolated by column
chromatography on silica gel using hexane as eluent to afford the pure
product. The spectroscopic data and melting points for the known
products agreed well with the reported data.
Data
1-Methyl-4-(4-methylphenoxy)benzene (entry 7, Table 1).
White solid. Mp: 48–50 ꢀC (lit.[7] mp: 50 ꢀC); 1H NMR (500 MHz, CDCl3)
d (ppm) ¼ 7.10 (d, J ¼ 8.4 Hz, 4H), 6.88–6.85 (m, 4H), 2.30 (s, 6H).
1-Methoxy-4-(4-methylphenoxy)benzene (entry 8, Table 1).
ꢀ
ꢀ
1
White solid. Mp: 45 C (lit.[7] mp: 63 C); H NMR (500 MHz, CDCl3) d
(ppm) ¼ 7.08 (d, J ¼ 8.4 Hz, 2H), 6.94–6.92 (m, 2H), 6.86–6.82 (m, 4H),
3.78 (s, 3H), 2.29 (s, 3H).
1-Methyl-(2-phenoxy)benzene (entry 11, Table 1).
Colorless oil; 1H NMR (90 MHz, CDCl3): d (ppm) ¼ 7.5–6.7 (m, 9H), 2.2
(s, 3H).
2-Naphtyl-phenyl ether (entry 14, Table 1).
ꢀ
ꢀ
1
White solid. Mp: 45–47 C (lit.[18] mp: 45–46 C); H NMR (500 MHz,
CDCl3): d (ppm) ¼ 7.81 (t, J ¼ 7.5 Hz, 2H), 7.68 (d, J ¼ 8.1 Hz, 1H),
7.44 (t, J ¼ 7.0 Hz 1H), 7.40–7.24 (m, 5H), 7.12 (t, J ¼ 7.4 Hz 1H),
7.06 (d, J ¼ 8.1 Hz, 2H).
2-(4-Methylphenoxy)-biphenyl ether (entry 16, Table 1).
White solid. Mp: 48–49 ꢀC, 1H NMR (500 MHz, CDCl3): d (ppm) ¼ 7.61
(br d, J ¼ 7.7 Hz, 2H), 7.49 (dd, J ¼ 7.5, 1.5 Hz, 1H), 7.40 (t, J ¼ 7.5 Hz,
2H), 7.35–7.30 (m, 2H), 7.24– 7.22 (m, 1H), 7.11 (d, J ¼ 8.4 Hz, 2H),
7.02 (br d, J ¼ 8.1 Hz, 1H), 6.88 (d, J ¼ 6.5 Hz, 2H), 2.34 (s, 3H).

3030
R. Hosseinzadeh et al.
ACKNOWLEDGMENT
Financial support of this work from the Research Council of
Mazandaran University is gratefully acknowledged.
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