Triethanolamine as an inexpensive and efficient ligand for copper-catalyzed hydroxylation of aryl halides in water

Article abstract of DOI:10.1002/ejoc.201301370

The CuI/triethanolamine catalyst system efficiently promotes the direct hydroxylation of aryl iodides and bromides in water to provide the corresponding phenols in good to excellent yields. Moreover, the procedure avoids the use of toxic organic solvents and tolerates many functional groups. The CuI/triethanolamine catalyst system efficiently promotes the direct hydroxylation of aryl iodides and bromides in water to afford the corresponding phenols in good to excellent yields. Copyright

Full text of DOI:10.1002/ejoc.201301370

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201301370
Triethanolamine as an Inexpensive and Efficient Ligand for Copper-Catalyzed
Hydroxylation of Aryl Halides in Water
Deping Wang,*[a,b] Daizhi Kuang,[a,b] Fuxing Zhang,[a,b] Siping Tang,[a,b] and Wujiu Jiang[a]
Keywords: Copper / Hydroxylation / Phenols / N ligands / Water chemistry
The CuI/triethanolamine catalyst system efficiently promotes
the direct hydroxylation of aryl iodides and bromides in
water to provide the corresponding phenols in good to excel-
lent yields. Moreover, the procedure avoids the use of toxic
organic solvents and tolerates many functional groups.
Introduction
In spite of these developments, there remains a need for
economical and easily available ligands that lead to gen-
Phenols are structural scaffolds frequently found in nu- erally applicable, ecofriendly catalyst systems for the Cu-
merous pharmaceuticals, polymers, agrochemicals, and bio- catalyzed hydroxylation of aryl halides. As part of our en-
logically active natural products.[ Over the years, protocols deavors to find environmentally friendly protocols,
1]
[19]
for the oxidative and nonoxidative preparation of phenols herein we wish to report triethanolamine as an inexpensive,
have been developed, including nucleophilic aromatic sub- simple, and efficient ligand for the copper-catalyzed hydrox-
stitution of activated aryl halides, copper-promoted conver- ylation of aryl iodides and bromides in water.
sions of arene diazonium salts, and benzyne methodologies.
Unfortunately, these methods usually involve harsh reaction
conditions and starting materials that are not readily avail-
Results and Discussion
[
2]
able. Recently, Pd-catalyzed hydroxylation reactions of
aryl halides with hydroxide salts have been explored for the
synthesis of phenols in excellent yields under mild reaction
As shown in Table 1, we selected 4-iodoanisole as the
model substrate and CuI (5 mol-%) as the catalyst for opti-
mization of the reaction conditions. Initially, a series of li-
gands was examined by using potassium hydroxide
[
3]
[4]
conditions, even at room temperature. However, the use
of expensive palladium and elaborate phosphorated ligands
limits the further application of these hydroxylation reac-
tions to large- and industrial-scale production. Very re-
(4.0 equiv.) as the nucleophile, water as the solvent, and
nBu NBr (TBAB, 20 mol-%) as the phase-transfer catalyst.
4
[5]
Of the ligands screened, triethanolamine (L1) gave the best
result (87%). It should be noted that lower yields (66%)
were obtained if the amount of L1 was reduced to 20 mol-
%. The other ligands also worked well, except for L3 and
L6, whereas no product was isolated in the absence of li-
gands under similar reaction conditions. As L4 is more ex-
pensive than L1, L1 was chosen for further investigations.
The scope of the CuI/triethanolamine-catalyzed synthesis
of phenols was then explored under our optimal conditions.
As indicated in Table 2, various aryl iodides containing
both electron-donating (Table 2, entries 6, 8, 10) and elec-
tron-withdrawing groups (Table 2, entries 3, 9, 11–14) cou-
cently, the efficient Cu-catalyzed direct hydroxylation of
[
6]
aryl halides was reported under mild conditions (100–
80 °C) with the use of various ligands including 1,3-diket-
1
[
7]
[8]
[9]
ones, 1,10-phenanthroline, pyridine-2-aldoxime, lith-
ium pipecolinate, d-glucose, quinolin-8-ol, N,NЈ-di-
methylethylenediamine (DMEDA),
1
particles,
acid.
[
10]
[11]
[12]
[13]
8-hydroxyquinoline
[
14]
[15]
-oxide, 5-bromo-2-(1H-imidazol-2-yl)pyridine,
nano-
[
16]
[17]
N-heterocyclic carbenes,
and glycolic
[
18]
[
a] Department of Chemistry and Material Science, Hengyang
Normal University,
1
65# Huangbai Road, Hengyang 421008, Hunan Province, pled with KOH to afford the corresponding phenols in
P. R. China
good to excellent yields in water. Also, hydroxylation of
iodobenzene proceeded smoothly in good yields (85%) on
a gram scale (Table 2, entry 1). Notably, steric hindrance of
the substituent of the substrate had an unfavorable effect
on the hydroxylation reactions. For example, hydroxylation
of p-iodotoluene produced the desired phenol in a yield of
E-mail: wdping0119@gmail.com
wangdeping@hynu.cn
http://www.hynu.cn/
[
b] Key Discipline of Materials Physics and Chemistry of
Hengyang Normal University, 12th Five-Year Plan Key
Construction Disciplines of Hunan Province,
Hengyang 421008, P. R. China
http://hxx.hynu.cn/xkjs/index.asp
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301370.
87%, o-iodotoluene gave the corresponding product in a
lower yield of 61%, whereas if 2-iodo-m-xylene was used as
Eur. J. Org. Chem. 2014, 315–318
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
315

D. Wang, D. Kuang, F. Zhang, S. Tang, W. Jiang
SHORT COMMUNICATION
Table 1. Optimization of ligands for CuI-catalyzed hydroxylation
of 4-iodoanisole in water.[
Table 2. CuI-catalyzed hydroxylation of aryl iodides in water.[a]
a]
Ligand
Yield [%][b]
L1
L2
L3
L4
L5
L6
–
87/66[c]
69
26
86
60
22
0
[
a] Reaction conditions: 4-iodoanisole (1 mmol), CuI (0.05 mmol),
ligand (0.4 mmol), KOH (4 mmol), TBAB (0.2 mmol),
1.0 mL), Ar, 24 h. [b] Yield of isolated product. [c] L1 (0.2 mmol).
2
H O
(
the substrate, the product was isolated in only 42% yield
under the same conditions (Table 2, entries 6, 7, 10). In ad-
dition, the catalytic system displayed a great tolerance to a
variety of functional groups, including aldehydes, bromides,
ketones, nitro groups, carboxylic acids, and hydroxy groups
(Table 2, entries 4, 5, 11–16).
Subsequently, we further applied the above conditions to
aryl bromides, but the products were only isolated in 35%
yield by using 4-bromoanisole as the substrate. After a sim-
ple optimization of the reaction conditions, we were pleased
to find that good yields (76%) were obtained if the reaction
was conducted with a combination of 10% CuI, 100% L1,
40% TBAB, and 400% CsOH at 145 °C in water (Table 3,
entry 1). Furthermore, these conditions efficiently pro-
moted the hydroxylation of aryl bromides bearing electron-
donating groups such as p- and m-methoxy and p-methyl
(
Table 3, entries 1–3) and electron-withdrawing groups, in-
cluding p-fluoro, p-phenyl, and p-nitro (Table 3, entries 7–
). However, the hydroxylation of less-active chlorobenzene
with the CuI/L1 catalyst under the optimal conditions was [a] Reaction conditions: ArI (1 mmol), CuI (0.05 mmol), L1
0.4 mmol), KOH (4 mmol), TBAB (0.2 mmol), H O (1.0 mL), Ar,
4 h. [b] Yield of isolated product. [c] ArI (10 mmol scale).
9
(
2
2
not successful, and the desired product was not isolated
(Table 3, entry 5).
On the basis of previous literature reports on Ullmann
[
20]
coupling reactions, we formulated a possible mechanism
of the Cu/L1-catalyzed hydroxylation of aryl halides. As
shown in Scheme 1, chelation of CuI with L1 forms five- nucleophilic substitution by hydroxy to afford intermediate
member reactive species I in the presence of KOH or III. This is followed by reductive elimination, which readily
CsOH, and subsequent oxidative addition of I with an aryl provides the hydroxylation product and regenerates active
III
I
halide produces transient Cu species II, which undergoes Cu species I.
316
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 315–318

Triethanolamine as a Ligand Cu-Catalyzed Hydroxylations
Table 3. CuI-catalyzed hydroxylation of aryl bromides in water.[a]
Conclusions
In conclusion, we used triethanolamine (L1) as a simple,
efficient, and economical ligand for the direct copper-cata-
lyzed synthesis of phenols from a series of aryl iodides and
bromides in water. In addition, this procedure avoids the
use of toxic organic solvents and tolerates various func-
tional groups such as aldehydes, nitro groups, carbonyls,
carboxylic acids, fluoride groups, bromide groups, and
hydroxy groups.
Experimental Section
General Procedure for the Hydroxylation of Aryl Iodides: A 10 mL
Schlenk tube equipped with a magnetic stirring bar was charged
with the solid aryl iodide (1.0 mmol), CuI (0.05 mmol, 9.5 mg),
KOH (4 mmol), and TBAB (0.2 mmol, 65 mg). The tube was evac-
uated and backfilled with argon. Under a counter flow of argon,
2
H O (1.0 mL), the aryl iodide (1.0 mmol, if liquid) and triethanola-
mine (0.4 mmol, 60 mg) were added by syringe. The tube was evac-
uated twice and backfilled with argon. The tube was sealed and
put into a preheated oil bath at 120 °C for 24 h. After the mixture
solution was cooled to room-temperature, HCl was added to acid-
ify the solution (pH 2–3), and the solution was extracted with ethyl
acetate (3ϫ 5 mL). The combined organic phase was dried with
Na SO , filtered, and concentrated under vacuum; the remaining
2 4
residue was purified by column chromatography on silica gel to
provide the desired product.
General Procedure for the Hydroxylation of Aryl Bromides: A
10 mL Schlenk tube equipped with a magnetic stirring bar was
charged with the solid aryl bromide (1.0 mmol), CuI (0.1 mmol,
19 mg), CsOH (4 mmol), and TBAB (0.4 mmol, 130 mg). The tube
was evacuated and backfilled with argon. Under a counter flow of
[
(
1
a] Reaction conditions: ArBr (1 mmol), CuI (0.1 mmol), L1
1.0 mmol), CsOH (4 mmol), TBAB (0.4 mmol), H O (1.0 mL), Ar,
45 °C, 24 h. [b] Yield of isolated product. [c] 4-Bromoanisole
1 mmol), CuI (0.05 mmol), L1 (0.4 mmol), KOH (4 mmol), TBAB
0.2 mmol), H O (1.0 mL), Ar, 120 °C, 24 h. [d] Chlorobenzene was
2
2
argon, H O (1.0 mL), the aryl bromide (1.0 mmol, if liquid), and
(
(
triethanolamine (1.0 mmol, 149 mg) were added by syringe. The
tube was evacuated twice and backfilled with argon. The tube was
sealed and put into a preheated oil bath at 145 °C for 24 h. After
the mixture solution was cooled to room temperature, HCl was
added to acidify the solution (pH 2–3), and the solution was ex-
tracted with ethyl acetate (3*5 mL). The combined organic phase
2
used as substrate.
2 4
was dried with Na SO , filtered, and concentrated under vacuum;
the remaining residue was purified by column chromatography on
silica gel to provide the desired product.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, characterization data, and copies of the
1
13
H NMR and C NMR spectra of all key intermediates and final
products.
Acknowledgments
The authors thank the National Natural Science Foundation of
China (NSFC) (grant numbers 21202041, 21102040) and the Scien-
tific Research Foundation of Hengyang Normal University (grant
number 11B39) for their financial support.
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Scheme 1. Proposed mechanism for the Cu/L1-catalyzed hydroxyl-
ation of aryl halides.
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317

D. Wang, D. Kuang, F. Zhang, S. Tang, W. Jiang
SHORT COMMUNICATION
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