Ligand free, highly efficient synthesis of diaryl ether over copper fluorapatite as heterogeneous reusable catalyst

Article abstract of DOI:10.1016/j.tetlet.2012.01.124

A novel ligand-free, highly efficient, and an inexpensive method has been developed by using ecofriendly, heterogeneous reusable copper fluorapatite (CuFAP) catalyst for the synthesis of diaryl ethers from the cross coupling reaction of the various substituted aryl halides (fluoride, chloride, bromide, and iodide) with the potassium salts of various substituted phenols in the presence of N-methyl 2-pyrrolidone (NMP) as a solvent at 120 °C. The protocol obtained the corresponding cross coupling products in good to excellent yield. The CuFAP catalyst was recovered by simple filtration from the reaction mixture and reused several times without the loss of catalytic activity.

Full text of DOI:10.1016/j.tetlet.2012.01.124

Tetrahedron Letters 53 (2012) 1826–1829
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Ligand free, highly efficient synthesis of diaryl ether over copper fluorapatite
as heterogeneous reusable catalyst
⇑
Shafeek A. R. Mulla , Suleman M. Inamdar, Mohsinkhan Y. Pathan, Santosh S. Chavan
Chemical Engineering and Process Development Division, National Chemical Laboratory, Pashan Road, Pune 411 008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel ligand-free, highly efficient, and an inexpensive method has been developed by using ecofriendly,
heterogeneous reusable copper fluorapatite (CuFAP) catalyst for the synthesis of diaryl ethers from the
cross coupling reaction of the various substituted aryl halides (fluoride, chloride, bromide, and iodide)
with the potassium salts of various substituted phenols in the presence of N-methyl 2-pyrrolidone
Received 12 December 2011
Revised 25 January 2012
Accepted 28 January 2012
Available online 4 February 2012
(NMP) as a solvent at 120 °C. The protocol obtained the corresponding cross coupling products in good
to excellent yield. The CuFAP catalyst was recovered by simple filtration from the reaction mixture
and reused several times without the loss of catalytic activity.
Keywords:
Copper fluorapatite
Ullmann coupling
Phenol
Ó 2012 Elsevier Ltd. All rights reserved.
Diaryl ethers
Arylhalide
1a
Diaryl ether motifs are present in the natural products and
medicinally important compounds.1 Diaryl ether molecules are
not only important in biological systems but also key moieties in
particles,1 Nano Ceria,11b KF/supported on natural nano-porous
12a
12b
13,14
Zeolite,
Ullmann and Goldberg reactions,
copper
and
1
5
palladium complexes in the presence of ligands. Moreover, phos-
phine–palladium complexes are air sensitive and other complexes
with palladium are expensive compared to copper or copper com-
plexes. Even though significant improvements have been achieved,
almost all these methods reported so far lack general applicability.
The use of metals and/or noble metals as catalysts with highly
expensive ligands along with harsh reaction conditions limits to
implement their application for the commercial-scale productions.
However, the development of more general and cost effective
ligand-free catalysts for the O-arylation of phenol, which is equally
applicable to electron-deficient, electronically neutral, and elec-
tron-rich aryl halides is still challenging and an active research area,
which enable aryl ether formation under much milder, more effi-
cient, environment friendly conditions compared to the classical
2
pharmaceutical, agricultural, polymer, industrial, and life science.
However, carbon–carbon and carbon–heteroatom bond forming
reactions catalyzed by transition metals are an important funda-
3
mental transformation in synthetic chemistry. The most simplest
and straightforward way to synthesize diaryl ethers involves the
4
direct formation of aryl–oxygen bond from an aryl halide. The
classical copper catalyzed Ullmann coupling reaction for ether
synthesis has been extensively used for the formation of diaryl ether
5
on industrial scale in polar solvents (pyridine, DMF, collidine).
However, application on industrial scale synthesis has been limited
due to harsh reaction conditions such as high reaction temperature
(
125–300 °C), longer reaction time at which many functional groups
are unstable hence lower yield of the desire product. In addition, the
requirement of excess or stoichiometric quantities of copper
complexes leads to the problem of waste disposal.6
1
2b
Ullmann and Goldberg reactions.
Herein, we report ligand-free,
highly efficient, an inexpensive, and general method for the synthe-
sis of diaryl ethers in good to excellent yield from the cross coupling
reactions of a wide range of electron-deficient, electronically neu-
tral, and electron-rich aryl halides with the potassium salts of vari-
ous substituted phenols over ecofriendly, heterogeneous reusable
copper fluorapatite (CuFAP) catalyst in the presence of N-methyl
2-pyrrolidone (NMP) as a solvent at 120 °C (Scheme 1).
To develop the protocol for O-arylation cross coupling reaction,
bromobenzene, and potassium salt of phenol catalyzed by CuFAP
catalyst, prepared as per reported procedure in the literature16
was selected as a model reaction to optimize the reaction condi-
Owing to the importance of diaryl ether moieties in life sciences,
pharmaceutical, agricultural, polymer, world-wide efforts have
been made in the last few decades to develop various methods for
the synthesis of Ullmann diaryl ethers using varieties of reagents.
The catalysts in combination with the various ligands have been
reported as catalytical processes,7 a palladium catalyzed coupling
reaction in the presence of ligand between sodium phenoxide and
electron deficient aryl bromide,10 microwave assisted Cu(0)nano
–9
⇑
Corresponding author. Tel.: +91 20 25902316; fax: +91 20 25902676.
E-mail address: sa.mulla@ncl.res.in (S.A. R. Mulla).
1
7
tions. Initially, we studied the effect of solvent on the cross
0
040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.01.124

S. A. R. Mulla et al. / Tetrahedron Letters 53 (2012) 1826–1829
1827
Table 2
X KO
+
O
CuFAP
without ligand
NMP, 120 C
Diaryl etherification of potassium phenoxide with substituted haloarenesa (X = F, Cl,
Br, I)
R'
R'
R
R
o
X KO
+
O
X= Cl, Br, I
CuFAP
NMP, 120 C
R, R'= H, Me, OMe, NO , t-Bu, Ph, Naphthyl, Halogen, etc
2
o
R
R
Scheme 1. CuFAP catalyzed Ullmann diaryl etherification of potassium salt of
substituted phenol with substituted halo-arene.
Yieldb
Entry Aryl halide
Product
Time
(
h)
(%)
Br
O
1
8
5
N.R.c
91
coupling reaction. The reactions were carried out in various
solvents at a different temperature by taking bromobenzene
Cl
Br
I
O
O
O
(
1 mmole) and potassium salt of phenol (1.1 mmole) in the pres-
2
ence of 100 mg CuFAP catalyst, however, only NMP at 120 °C gives
the cross-coupling product in a 93% isolated yield (Table 1, entry 8)
whereas DMF, DMSO, and diglyme give 8%, 10% and 15% yields
O N
O N
2
2
(
Table 1, entries 5–7), respectively. The desired cross-coupling
product formation was not observed during the reaction in THF,
CH CN, toluene, and dioxane (Table 1, entries 1–4).
Results on the cross coupling product of bromobenzene and
3
4
94
O2N
O N
2
3
4
3
3
94
93
potassium salt of phenol in NMP solvent using CuFAP catalyst at
optimized reaction conditions17 encourage us to investigate the
application of CuFAP catalyst for Ullmann diaryl etherification.
Therefore, a variety of electron-deficient, electron-rich, and elec-
tronically neutral substituted haloarenes (Fluoro, chloro, bromo,
and iodo) possessing a wide range of the functional group reacted
with potassium phenoxide in NMP to obtain cross-coupling prod-
uct in good to excellent yield; the results are shown in Table 2.
The formation of the desired cross-coupling product was not
observed in the absence of CuFAP catalyst (Table 2, entry 1). The
electron-deficient aryl halide such as 4-nitrochlorobenzene, 4-
nitrobromobenzene, 4-nitroiodobenzene, 4-chlorobromobenzene,
and 3-bromo, 4-fluoro benzaldehydeacetal reacted with potassium
phenoxide to provide an excellent yield to the desired cross cou-
pling product in the short reaction time (Table 2, entries 2–6).
However, the electron-rich and electronically neutral aryl halides
such as 4-bromoanisole, 3-bromotoluene, 4-iodoanisole, (Table 2,
entries 7–9) and bromobenzene, iodobenzene, (Table 2, entry 12
and 13) respectively, coupled with potassium phenoxide without
any difficulties to obtain the corresponding cross coupling prod-
ucts in moderate to good yield with longer reaction time; while
chlorobenzene provides very poor yield, (Table 2, entry 11) fluoro-
benzene gave no coupled product (Table 2, entry 10).
O N
O N
2
2
Br
O
5
Cl
Cl
O
Br
Br
O
O
6
O
5
92
F
F
O
O
7
5
5
4
87
90
89
MeO
MeO
H C
Br
I
H C
O
O
3
3
8
9
MeO
MeO
F
O
O
O
O
1
1
1
1
0
1
2
3
15
15
5
N. R.
18
Cl
Br
I
93
To explore the scope of this methodology over CuFAP catalyst
for electron-deficient, electronically neutral, and electron-rich
4
93
a
Reaction conditions: aryl halide (1 mmol), potassium phenoxide (1.1 mmol),
Table 1
NMP (1 ml), CuFAP (100 mg), 120 °C.
a
b
Effect of solvent on the Ullmann diaryl etherification
Isolated yields.
c
No reaction without CuFAP catalyst.
O
Br KO
+
CuFAP
Solvent,
potassium salt of various substituted phenols such as 4-methoxy-
phenol, 4-methylphenol, 3-methylphenol, 2-methylphenol, 4-
ter-butylphenol, alpha-naphthol, beta-naphthol, 4-phenylphenol,
4-nitrophenol, 4-chlorophenol were successfully coupled with
bromobenzene to give the corresponding diaryl ethers in good to
excellent yield (Table 3, entries 1–10), however, poor yield was
obtained in the case of potassium salt of 4-nitro phenol in long
reaction time (Table 3, entry 9).
The recyclability of CuFAP catalyst for the Ullmann diaryl
etherification was investigated using bromobenzene and potas-
sium phenoxide as substrate in NMP solvent at 120 °C, the results
are summarized in Table 4. The CuFAP catalyst was recovered
Entry
Solvent
THF
CH CN
Toluene
Dioxane
DMF
DMSO
Diglyme
NMP
Temperature (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
70
80
N.R.
N.R.
N.R.
N.R.
8
10
15
93
3
110
100
140
150
150
120
a
Reaction conditions: bromobenzene (1 mmol), potassium phenoxide
1.1 mmol), solvent (1 ml), CuFAP (100 mg).
Isolated yields.
(
b

1
828
S. A. R. Mulla et al. / Tetrahedron Letters 53 (2012) 1826–1829
Table 3
a
Ullmann diaryl etherification of bromobenzene with substituted potassium phenoxides
Br KO
+
O
CuFAP
NMP, 120 C
o
R
R
Entry
1
Substituted phenoxide
Product
Time (h)
4
Yieldb (%)
93
KO
O
OMe
KO
OMe
O
2
3
4
5
6
5
92
90
87
CH3
CH3
CH3
CH3
KO
KO
O
O
H C
3
H C
3
KO
O
5
6
5
6
88
89
KO
O
KO
O
7
8
6
4
86
87
O
KO
KO
O
O
9
16
6
15
82
NO2
Cl
NO2
Cl
KO
1
0
a
Reaction conditions: bromobenzene (1 mmol), substituted potassium phenoxide (1.1 mmol), NMP (1 ml), CuFAP (100 mg), 120 °C.
Isolated yields.
b
quantitatively by simple filtration and reused for several times
without the loss of catalytic activity (Table 4, entries 1–5). The
isolated yield obtained for cross coupling product even after the
fourth recycle of CuFAP catalyst (Table 4, entries 2–5) is very much
consistent with fresh CuFAP catalyst (Table 4, entry 1). The consis-
tent catalytic activity of reused CuFAP catalyst for coupling product
indicates that the reused catalyst shows excellent performance for
the Ullmann diaryl etherification and no leaching and loss of
copper occurred during the course of reaction, which was also con-
firmed by atomic absorption spectroscopy.
According to the previous research work over CuFAP catalyst for
the N-arylation of heterocycles,16 the possible mechanism pro-
posed in Scheme 2 for O-arylation may involve the CuFAP cata-
lyzed nucleophilic substitution that proceeds via the formation of
the complex (a) with potassium phenoxide and then subsequently
onto the oxidative addition of aryl halide via the formation of
another complex (b) followed by the instantly in situ reductive
elimination to release the diaryl ether product (c) as well as CuFAP
catalyst in its original form (to recycle again).
heterogeneous reusable copper fluorapatite (CuFAP) catalyst for
the synthesis of Ullmann diaryl ethers from the cross coupling
reaction of the various substituted aryl halides with the potassium
salts of various substituted phenols in the presence of N-methyl
Table 4
Recyclability studies of CuFAP catalyst for the Ullmann diaryl
a
etherification
Br KO
+
O
CuFAP
o
NMP, 120 C
Cycle
Yieldb (%)
1
2
3
4
5
93
92
93
92
92
a
Reaction conditions: bromobenzene (1 mmol), potassium
In conclusion, a novel ligand-free, highly efficient, and an
inexpensive method has been developed by using ecofriendly,
phenoxide (1.1 mmol), NMP (1 ml), CuFAP (100 mg), 120 °C, 5 h,
b
Isolated yields

S. A. R. Mulla et al. / Tetrahedron Letters 53 (2012) 1826–1829
1829
PhOK
P
P
O
Cu
P
P
O
O
Cu
OPh
O
K
(
a)
Ar-X
-
KX
O
Ar
Ph
Reductive Elimination
Oxidative Addition
Ph
(
c)
P
P
O
Cu
O
O
KX
(b)
Scheme 2. Plausible mechanism for the Ullmann diaryl etherification reaction over CuFAP catalyst.
2
-pyrrolidone (NMP) as a solvent at 120 °C. The protocol obtained
9. (a) Kidwai, M.; Mishra, N. K.; Bansal, V.; Kumar, A.; Mazumdar, S. Tetrahedron
Lett. 2007, 48, 8883; (b) Miao, T.; Wang, L. Tetrahedron Lett. 2007, 48, 95; (c)
Zhang, J.; Zhang, Z.; Wang, Y.; Zheng, X.; Wang, Z. Eur. J. Org. Chem. 2008, 5112.
the corresponding cross coupling products in good to excellent
yield. The CuFAP catalyst was recovered by simple filtration from
the reaction mixture and reused several times without the loss of
catalytic activity.
1
0. Mann, G.; Hartwig, J. F. Tetrahedron Lett. 1997, 38, 8005.
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2
.
.
2
700; Evan, D. A.; Dinsmore, C. J.; Watson, P. S.; Wood, M. R.; Richardson, T. I.;
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3
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4
.
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17. General experimental procedure for Ullmann diaryl etherification: Arylhalide
(1 mmol), potassium salts of phenol (1.1 mmol), NMP (1 ml) and CuFAP
catalyst (100 mg) were taken in a 10 ml round bottomed flask and stirred in
nitrogen atmosphere at 120 °C for 3–16 h (Table 2 and 3) and the progress of
the reaction was monitored by TLC. After the completion of the reaction,
reaction mixture was cooled to room temperature and diluted with 20 ml ethyl
acetate followed by filtration to recover the catalyst. The filtrate was
concentrated in vacuo to get the crude product, which was further purified
by column chromatography on silica gel (hexane/ethyl acetate, 80:20) to
obtain diaryl ether product.
1
974, 43, 679.
5
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6
.
.
(a) Ullmann, F. Chem. Ber. 1904, 37, 853; (b) Sawyer, J. S. Tetrahedron 2000, 56,
5
045.
7
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Spectral data for diphenylether (Table 2, entry 12): Colorless liquid; Yield: 93%;
À1
1
8
.
3 3
IR (CHCl ) m 660, 725, 1240, 1498, 1610, 3021 cm ; H NMR (200 MHz, CDCl )
13
3
d 7.32–7.24 (m, 4H), 7.08–6.93 (m, 6H). C NMR (200 MHz, CDCl ) d 157.21,
129.71, 123.19, 118.86.