Copper-catalyzed direct preparation of phenols from aryl halides

Article abstract of DOI:10.1016/j.catcom.2010.07.011

A method for direct preparation of phenols from aryl halides using microwave heating is reported. A catalyst system comprising a simple copper salt and a diamine ligand is used, together with tripotassium phosphate as base and water as the solvent. Heating at 180 °C for 30 min allows for the conversion of a range of aryl bromides and iodides to the corresponding phenols. Aryl chlorides prove less reactive.

Full text of DOI:10.1016/j.catcom.2010.07.011

Catalysis Communications 12 (2010) 64–66
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Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Copper-catalyzed direct preparation of phenols from aryl halides
Arshad Mehmood, Nicholas E. Leadbeater ⁎
Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269-3060, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 May 2010
Received in revised form 19 July 2010
Accepted 20 July 2010
Available online 29 July 2010
A method for direct preparation of phenols from aryl halides using microwave heating is reported. A catalyst
system comprising a simple copper salt and a diamine ligand is used, together with tripotassium phosphate
as base and water as the solvent. Heating at 180 °C for 30 min allows for the conversion of a range of aryl
bromides and iodides to the corresponding phenols. Aryl chlorides prove less reactive.
©
2010 Elsevier B.V. All rights reserved.
Keywords:
Copper
Phenol
Microwave heating
Aryl halide
Diamine
1
. Introduction
reaction at 200–300 °C in 30 min. While copper powder was a good
catalyst (10 mol%) for the reaction, the optimum catalyst system was
10 mol% CuI together with 5 mol% L-proline as an additive. A
drawback to the protocol is the very high temperatures required,
this leading in some cases to competitive decomposition of either the
substrates or phenol products. This limits the scope to highly
thermally stable substrates. Very recently, the groups of You [11],
Taillefer [12] and Fu [13] have reported copper-mediated methodol-
ogies for the conversion of a range of aryl halides to phenols. They use
either neat water [13] or a 1:1 water / DMSO solvent mix [11,12],
copper iodide as a catalyst and either 1,10-phenanthroline, a diketone
or an aldoxime as a ligand. A range of aryl iodides and bromides can
be used as substrates and reactions are complete within 20–48 h at
100–130 °C. An iron-catalyzed procedure has also very recently
Compared to the formation of diaryl ethers via a C–O bond forming
reaction between an aryl halide and a phenol or alcohol [1], the
conversion of aryl halides to phenols via a similar C–O bond forming
reaction using water as the nucleophilic coupling partner is not a
trivial synthetic challenge. Traditionally, radical [2] and photo-
chemical [3] reactions or fluoride displacement from electron-
deficient substrates [4] have been used. To circumvent these methods,
there have been numerous multi-step approaches reported [5]. More
recently copper- or palladium-catalyzed protocols have become the
methods of choice. In the area of palladium catalysis, catalyst systems
involving bulky phosphine ligands have appeared [6]. These require
performing the reaction under an inert atmosphere. Building on
these, Beller and co-workers have developed a methodology using
imidazole-based phosphine ligands, the advantage being that the
procedure can be performed in air [7]. Palladium nanoparticles
supported on polyaniline nanofibers can also be used for the reaction,
this offering a semi-heterogeneous approach [8].
3
been reported using FeCl as the catalyst in the presence of a
diamine ligand and using potassium phosphate as base [14]. With
the objective of improving on our previously reported procedure,
we too have recently developed a more versatile copper-catalyzed
protocol for the conversion of aryl halides to phenols and present our
results here.
One of the first reports using copper as a catalyst for the reaction
4
required heating the aryl halide, CuSO and base in water in a sealed
steel bomb for 1 1/2 days [9]. This is a theme that runs through most of
the direct copper-catalyzed methods; water as a solvent, copper salts
as catalysts, elevated temperatures and lengthy reaction times. In
2. Experimental
2
006 we developed a protocol using high-temperature or near-critical
2.1. General experimental
water as the solvent in conjunction with a copper catalyst and a
mineral base [10]. Using microwave heating we performed the
Unless otherwise noted, materials were obtained from commercial
sources and used without further purification. Reactions were
conducted using a CEM Discover microwave unit. Temperature and
pressure were monitored using commercially available software
provided by the microwave manufacturer.
⁎
Corresponding author. Tel.: +1 860 486 5076; fax: +1 860 486 2981.
E-mail address: nicholas.leadbeater@uconn.edu (N.E. Leadbeater).
1566-7367/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2010.07.011

A. Mehmood, N.E. Leadbeater / Catalysis Communications 12 (2010) 64–66
65
2
.2. Experimental procedures
entry 1). We changed the base to tripotassium phosphate. This had
the effect of more than doubling the product conversion to 95%
(Table 1, entry 2). Changing the copper salt used to copper(II)acetate
had a deleterious effect on the reaction as did decreasing the reaction
time or temperature (Table 1, entries 3–5). Reducing the CuI:DMEDA
stoichiometric ratio from 1:5 to 1:2.5 resulted in a drop in catalytic
activity and, in the absence of the diamine ligand, no product was
All reactions were carried out following an identical procedure. All
products are known and spectral data are consistent with the assigned
structures.
2
.2.1. Representative procedure: preparation of p-methoxyphenol (Table 2,
entry 1)
Copper iodide (19 mg, 0.1 mmol), DMEDA (50 μL, 0.5 mmol), and
Table 2
a
water (2 mL) were placed in a 10 mL glass tube (Table 2, entry 1). The
Direct conversion of phenols to aryl halides.
mixture was stirred for 3–5 min. To this blue solution was added to
4
3 4
-bromoanisole (187 mg, 1.0 mmol) and K PO (212 mg, 1 mmol).
The vessel was sealed with a septum and placed into the microwave
®
cavity (CEM Discover ). An initial microwave irradiation of 25 W was
used, the temperature being ramped from rt to 180 °C where it was
held for 30 min. The reaction mixture was stirred continuously
throughout. After allowing the mixture to cool to rt, the reaction
vessel was opened and the contents acidified to pH 5–7 with 2 M
hydrochloric acid. The aqueous layer was extracted with ethyl acetate
(
4
3×10 mL). The organic washings were combined, dried over MgSO ,
and then the ethyl acetate was removed in vacuo. The crude product
was purified by flash column chromatography (petroleum ether:
dichloromethane, 30:70) giving 4-methoxyphenol in 81% yield
1
(
(
102 mg) as light brown solid. H NMR (CDCl
3
): δ 6.74 (s, 4H), 5.73
br s, 1H), 3.72 (s, 3H); 13C NMR (CDCl
): 153.4, 149.5, 116.1, 114.9,
3
5
5.8.
3
. Results and discussion
In the copper-catalyzed formation of diaryl ethers from aryl
halides and phenols, diamine ligands have been found to have a highly
beneficial effect [1]. We wanted to determine whether a catalyst
system comprising of a copper salt and a diamine ligand could prove
effective for the direct conversion of aryl halides to phenols in
basic aqueous media. As a starting point we chose as a test substrate
4
-bromoanisole. Performing the reaction in a sealed vessel at 180 °C
for 30 min in water using CuI (20 mol%) as the catalyst NaOH (1 eq) as
base and 1 eq. N,N′-dimethylethylenediamine (DMEDA) as ligand
resulted in a 45% conversion to the corresponding phenol (Table 1,
Table 1
Optimization of conditions for the direct conversion of 4-bromoanisole to 4-
a
methoxyphenol.
Entry
1
Conditions
Yield (%)b
45
CuI (20 mol%), DMEDA (1 mmol),
NaOH (1 mmol), 180 °C, 30 min
CuI (20 mol%), DMEDA (1 mmol),
2
3
4
5
6
7
8
9
95 (82)c
K
3
PO
Cu(OAc)
PO (1 mmol), 180 °C, 30 min
CuI (20 mol%), DMEDA (1 mmol),
PO (1 mmol), 180 °C, 15 min
CuI (20 mol%), DMEDA (1 mmol),
PO (1 mmol), 140 °C, 30 min
CuI (20 mol%), DMEDA (0.5 mmol),
PO (1 mmol), 180 °C, 15 min
CuI (20 mol%), no ligand,
PO (1 mmol), 180 °C, 30 min
CuI (10 mol%), DMEDA (0.5 mmol),
PO (1 mmol), 180 °C, 30 min
CuI (5 mol%), DMEDA (0.25 mmol),
PO (1 mmol), 180 °C, 30 min
4
(1 mmol), 180 °C, 30 min
2
(20 mol%), DMEDA (1 mmol),
72
K
3
4
70
K
3
4
20
K
3
4
65
K
3
4
0
K
3
4
96 (81)c
70
K
3
4
K
3
4
a
Conditions: 2.0 mL water as solvent. Reaction mixture heated to target temperature
and held for allotted time.
aConditions: 1.0 mmol (hetero)aryl halide, CuI (10 mol%), DMEDA (50 mol%), K
PO
3 4
b
(1 mmol), 2 mL water. Reaction mixture heated to 180 °C and held at this temperature
Yield determined by NMR using an internal standard.
b
c
for 30 min. Isolated yield.
Isolated yield.

66
A. Mehmood, N.E. Leadbeater / Catalysis Communications 12 (2010) 64–66
4
. Conclusion
In conclusion, we present here a methodology for direct
preparation of phenols from aryl halides. The catalyst system
comprises a simple copper salt, a diamine ligand, tripotassium
phosphate as base and water as the solvent. Heating at 180 °C for
3
0 min allows for the conversion of a range of aryl bromides and
iodides to the corresponding phenols. Aryl chlorides prove less
reactive. Thiophene-derived substrates form a catalytically inactive
complex with copper and are therefore incompatible with the
methodology.
Scheme 1.
obtained (Table 1, entries 6 and 7). Decreasing the catalyst loading
to 10 mol%, while keeping the CuI:DMEDA stoichiometric ratio from
Acknowledgements
1
:5, did not affect the outcome of the reaction (Table 1, entry 8).
This work was funded by the National Science Foundation
CAREER award CHE-0847262). The authors thank CEM Corp. for
microwave equipment support.
Reducing the loading further resulted in a concomitant drop in
product conversion (Table 1, entry 9). Thus, optimal conditions were:
CuI (10 mol%) as catalyst, DMEDA (0.5 mmol) as ligand, K
as base, water as solvent; 180 °C for 30 min.
(
3 4
PO (1 eq)
With optimized conditions in hand, we next screened a represen-
tative range of aryl halide substrates. The results are shown in Table 2.
Most of the aryl bromides screened could be converted to the cor-
responding phenols in good to excellent yields (Table 2, entries 1–5).
Exceptions include bulky or sterically crowded examples (Table 2,
entries 6 and 7). In the case of 4-bromobenzonitrile, while the reac-
tion was successful, the nitrile functionality was hydrolyzed
in the hot basic aqueous medium, the product of the reaction being
References
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1
(
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[
[
[
[
[
If the 2-bromothiophene was simply unreactive, we would expect
to obtain 4-methoxyphenol as the sole product in the reaction. If the
2
-bromothiophene was forming a catalytically inactive complex with
[
[
[
the copper, no reaction would be expected with the 4-bromoanisole
and thus no phenol would be formed. The latter is indeed the case,
no 4-methoxyphenol being obtained (the 4-bromoanisole being
recovered), this showing that the protocol is incompatible with
thiophene-derived substrates.