Direct Hydroxylation of Benzene to Phenol Using Hydrogen Peroxide Catalyzed by Nickel Complexes Supported by Pyridylalkylamine Ligands

Article abstract of DOI:10.1021/jacs.5b01814

Selective hydroxylation of benzene to phenol has been achieved using H₂O₂ in the presence of a catalytic amount of the nickel complex [Ni^II(tepa)]²⁺ (2) (tepa = tris[2-(pyridin-2-yl)ethyl]amine) at 60°C. The maximum yield of phenol was 21% based on benzene without the formation of quinone or diphenol. In an endurance test of the catalyst, complex 2 showed a turnover number (TON) of 749, which is the highest value reported to date for molecular catalysts in benzene hydroxylation with H₂O₂. When toluene was employed as a substrate instead of benzene, cresol was obtained as the major product with 90% selectivity. When H₂¹⁸O₂ was utilized as the oxidant, ¹⁸O-labeled phenol was predominantly obtained. The reaction rate for fully deuterated benzene was nearly identical to that of benzene (kinetic isotope effect = 1.0). On the basis of these results, the reaction mechanism is discussed.

Full text of DOI:10.1021/jacs.5b01814

Communication
pubs.acs.org/JACS
Direct Hydroxylation of Benzene to Phenol Using Hydrogen Peroxide
Catalyzed by Nickel Complexes Supported by Pyridylalkylamine
Ligands
Yuma Morimoto, Shuji Bunno, Nobutaka Fujieda, Hideki Sugimoto, and Shinobu Itoh*
Department of Material and Life Science, Division of Advanced Science and Biotechnology, Graduate School of Engineering, Osaka
University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
S
* Supporting Information
date of intermolecular hydroxylation of externally added benzene
ABSTRACT: Selective hydroxylation of benzene to
phenol has been achieved using H2O2 in the presence of
a catalytic amount of the nickel complex [NiII(tepa)]2+ (2)
(tepa = tris[2-(pyridin-2-yl)ethyl]amine) at 60 °C. The
maximum yield of phenol was 21% based on benzene
without the formation of quinone or diphenol. In an
endurance test of the catalyst, complex 2 showed a
turnover number (TON) of 749, which is the highest value
reported to date for molecular catalysts in benzene
hydroxylation with H2O2. When toluene was employed
as a substrate instead of benzene, cresol was obtained as
the major product with 90% selectivity. When H218O2 was
utilized as the oxidant, 18O-labeled phenol was predom-
inantly obtained. The reaction rate for fully deuterated
benzene was nearly identical to that of benzene (kinetic
isotope effect = 1.0). On the basis of these results, the
reaction mechanism is discussed.
derivatives with transition-metal complexes supported by
pyridylalkylamine ligands, although a large number of active-
oxygen transition-metal complexes have been developed to
date.26−29 We herein report a benzene hydroxylation reaction
employing nickel complexes supported by pyridylalkylamine
ligands as the catalysts and H2O2 as the oxidant under mild
conditions.
We first examined the catalytic activity of [NiII(tmpa)]2+ (1)
(tmpa = tris[2-(pyridin-2-yl)methyl]amine), [NiII(tepa)]2+ (2)
(tepa = tris[2-(pyridin-2-yl)ethyl]amine), and [NiII(bepa)]2+
(3) (bepa = N,N-bis[2-(pyridin-2-yl)ethyl]-2-phenylethyl-
amine) in the benzene hydroxylation reaction with H2O2 (for
the ligand structures, see Chart 1).30,31,25 Treatment of benzene
Chart 1. Ligands for Ni-Based Hydroxylation Catalysis
henol and its derivatives are an important class of chemicals
P
as precursors of dyes, pharmaceuticals, polymers, etc.1
Phenol and cresol are currently produced in industry by the
cumene process, which consists of three chemical steps:
propylation of benzene or toluene, autoxidation to the cumene
hydroperoxide derivative, and Hock rearrangement.1,2 These
reactions are carried out under high temperature, high pressure,
and strongly acidic conditions, and an equimolar amount of
acetone is produced as a byproduct in the final step. In addition,
the overall yield of phenol from benzene is very low (5%). Thus, a
much simpler and more efficient process that proceeds under
mild conditions is desired. In particular, a direct aromatic
oxygenation reaction with an economically and environmentally
benign oxidant such as O2 or H2O2 has remained a focal point for
extensive research efforts.3−15 However, the direct introduction
of hydroxyl functionality into the aromatic C−H bond with such
oxidants is challenging because of the notoriously low reactivity
of aromatic C−H bonds and the low product selectivity caused
by overoxidation of phenols.16−18
(5.0 μmol) with H2O2 (2.5 mmol) in the presence of a catalytic
amount of 1, 2, or 3 (0.50 μmol, 10 mol %) and triethylamine
(TEA) (5.0 μmol) afforded phenol in 18%, 21%, or 2% yield
based on benzene, respectively, after 5 h (Table 1, entries 1−3).32
This is the first example of hydroxylation of benzene with H2O2
catalyzed by nickel complexes. When 1 was employed as the
catalyst, the overoxidation product benzoquinone (BQ) was also
obtained in 9% yield. In contrast, only a negligible amount (<1%
yield) of BQ was generated with catalyst 2 (Figure S1 in the
Supporting Information (SI)). The 21% yield of phenol without
formation of the overoxidation product (<1%) (entry 2) is the
best result reported to date for homogeneous systems using
H2O2 (Scheme 1; for other systems, see Table S1 in the SI).33,34
In the previous studies of transition-metal complexes of active
oxygen species, dinuclear complexes such as dicopper(II) μ-
η2:η2-peroxide, dicopper(III) bis(μ-oxo), and dinickel(III) bis(μ-
oxo) complexes supported by pyridylalkylamine ligands have
been demonstrated to exhibit hydroxylation reactivity toward
aromatic groups embedded in their supporting ligands.19−25 To
the best of our knowledge, however, there has been no report to
Received: February 18, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/jacs.5b01814
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Journal of the American Chemical Society
Communication
Table 1. Catalytic Activity of Ni(II) Complexes
Table 2. Product Distributions in Catalytic Oxidation of
Alkylbenzenes with 2
entry
cat
conv. (%)
yield (%)
selectivity (%)
1
2
3
4
5
1
2
3
4
5
27
23
25
7
18
21
2
66
>99
8
0
−
−
10
0
Conditions: benzene (5.0 μmol), H2O2 (2.5 mmol), catalyst (0.50
μmol), and TEA (5.0 μmol) in MeCN for 5 h at 60 °C.
Scheme 1. Catalytic Hydroxylation of Benzene with 2
Conditions: substrate (5.0 mmol), H2O2 (5 equiv), 2 (0.01 mol %),
a
and TEA (0.10 mol %) in CH3CN at 60 °C for 24 h. Ratio of
The reaction also proceeded at room temperature, but the yield
was lower (14% in 5 h). When phenol was employed as the
substrate (5.0 mol) with 2 under the same conditions, the
hydroxylation reaction hardly took place (phenol was recovered
almost quantitatively).
products given by aromatic hydroxylation (sp2), alkyl-substituent
b
oxygenation (sp3), and quinone derivatives (q). Ratio of products of
c
hydroxylation at the ortho, meta, para, and ipso positions. Selectivity
for aromatic hydroxylation products except phenol. Calculated on the
basis of the amount of aromatic hydroxylation products, except for
d
Nickel complexes supported by the tetraaza macrocyclic
ligands such as [NiII(12-tmc)]2+ (4) (12-tmc = 1,4,7,10-
tetramethyl-1,4,7,10-tetraazacyclododecane) and [NiII(14-
tmc)]2+ (5) (14-tmc = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacy-
clotetradecane) did not show any catalytic ability for the reaction
(entries 4 and 5).35,36 Nickel(II) acetate alone or with 2,2′-
bipyridine (bpy) as the ligand also did not work as the catalyst.
Since complex 2 showed the highest activity and selectivity, an
endurance test was performed using 0.01 mol % 2, 0.10 mol %
TEA, and 5.0 equiv of H2O2.37 In this case, the turnover number
(TON) of 2 reached 749 with a 7.5% yield of phenol after 216 h
without the formation of substantial amounts of the over-
oxidation products (Figure 1).38 This is the highest TON
phenol, which was calculated on the basis of the substrate.
It should be noted that the aromatic sp2 carbons were
preferentially oxygenated with a high selectivity of 90% (Scheme
S1 in the SI) despite the fact that the bond dissociation energy
(BDE) of the C−H bond of a benzylic sp3 carbon (90 kcal mol−1)
is much lower than that of an aromatic C−H bond (112 kcal
mol−1).39
Mizuno and co-workers reported selective aromatic oxygen-
ation of toluene with H2O2 using the POM catalyst [γ-
PW10O38V2(μ-OH)2]3−, where a high aromatic carbon to
benzylic carbon selectivity of 98:2 was obtained. However, the
total selectivity for cresol decreased to 86% as a result of
overoxidation of cresol to methyl-p-quinone. Thus, the present
system showed the highest selectivity for cresol formation from
toluene with H2O2.40 The regioselectivity of the present system
was also different from that of Mizuno’s system: with nickel
catalyst 2, the ortho position was mainly oxygenated, whereas the
para position of toluene was mainly oxygenated with Mizuno’s
system. Stimulated by this result, we examined the oxygenation
of other alkylbenzene derivatives with more reactive benzylic C−
H bonds, namely, ethylbenzene (BDE = 87 kcal mol−1) and
cumene (BDE = 84.5 kcal mol−1), in the presence of a catalytic
amount of 2 (0.01 mol %).39 To our delight, oxygenation of the
sp2 carbons of those substrates also proceeded, although the
selectivity for sp2 carbons slightly decreased (Table 2, entries 2
and 3; for a comparison with previous reports, see Tables S3−
S5). In these cases as well, no overoxidation products such as
hydroquinone or quinone derivatives were obtained (Schemes
S2 and S3). In the oxygenations of ethylbenzene and cumene, the
ortho position was mainly attacked, as in the case of toluene
oxygenation. However, the selectivity slightly decreased with
increasing bulkiness of the substituent, and the selectivity for the
ipso position to produce phenol increased.
Figure 1. Time course of the turnover number in the catalytic oxidation
of benzene (5.0 mmol) by H2O2 (25 mmol) in the presence of 2 (0.50
μmol) and TEA (5.0 μmol) in 3.0 mL of MeCN at 60 °C.
reported for benzene hydroxylation reactions using transition-
metal complexes as molecular catalysts; among molecular
catalysts showing high selectivity (>95%), the polyoxometalate
(POM) catalyst Py1−PMo10V2O40 showed a TON of 21, which
was the highest number reported previously (Table S1).
The system could also be applied to the hydroxylation of
toluene. In the presence of 5 equiv of H2O2 and 0.01 mol % 2, the
TON reached 96 after 24 h to give cresol as the major product
without the formation of quinone derivatives (Table 2, entry 1).
To gain insight into the reaction mechanism, the kinetic
isotope effect (KIE) was examined using a 1:1 mixture of C6D6
and C6H6. From the ratio of phenol to phenol-d5, the KIE value
was determined to be 1.0, which is close to the KIE values for
intramolecular aromatic hydroxylation of the dicopper(II) μ-
B
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Communication
η2:η2-peroxide, dicopper(III) bis(μ-oxo), and dinickel(III) bis(μ-
oxo) complexes (0.9−1.0).21−23 Such a small or negligible KIE
value is typical in aromatic hydroxylation by metal−active oxygen
species via the electrophilic aromatic substitution mechanism.41
Such a KIE value also suggests that a Fenton-type reaction is not
likely to be involved, as the KIE value for the Fenton reaction was
reported to be 1.7.42 Metal insertion is not a plausible mechanism
either, as the KIE value for C−H bond activation via Pd(0)
insertion was reported to be 2.9−4.8.43
Scheme 3. Proposed Catalytic Mechanism
To verify the origin of the oxygen atom, benzene oxygenation
was carried out using H218O2 with 90% atom purity in H216O. In
this case, 18O was incorporated into the phenol product nearly
quantitatively (92%), whereas no 18O atom was incorporated
into the product when the reaction was carried out in H218O
using H216O2. These results unambiguously indicated that H2O2
is the oxygen source in the present reaction.44
A number of nickel complexes supported by pyridylalkylamine
ligands, including N,N-bis[(6-phenylpyridin-2-yl)methyl]-N-
[(pyridin-2-yl)methyl]amine (Ph2tmpa) and bepa have been
demonstrated to generate dinickel(III) bis(μ-oxo) complexes in
the reaction with H2O2. Moreover the Suzuki group and our
group have independently reported intramolecular aromatic
oxygenation in the dinickel(III) bis(μ-oxo) supported by
pyridylalkylamine ligands under low-temperature conditions
(Scheme 2).45 In fact, a nickel(II) complex supported by
tepa exhibited a prominent ability to produce phenol in 21% yield
based on benzene without the formation of any overoxidation
products. The total turnover number of the nickel complex
supported by tepa reached 749, which is the highest value ever
reported for molecular catalysts. The aromatic hydroxylation
method has been shown to be applicable to oxygenation of
alkylbenzene derivatives. The selectivity for cresol in the toluene
hydroxylation reached 90%, which is also the highest reported
value for direct hydroxylation of toluene to cresol with H2O2 and
a molecular catalyst. Details of the reaction mechanism and the
reason for the bizarre selectivity are now under investigation.53
ASSOCIATED CONTENT
■
S
* Supporting Information
Scheme 2. Intramolecular Aromatic Hydroxylation by a
Experimental details. The Supporting Information is available
free of charge on the ACS Publications website at DOI: 10.1021/
jacs.5b01814.
Dinickel(III) Bis(μ-oxo) Complex25
AUTHOR INFORMATION
Corresponding Author
*shinobu@mls.eng.osaka-u.ac.jp
■
Notes
The authors declare no competing financial interest.
Ph2tmpa could oxygenate benzene under the same reaction
conditions as shown in Table 1, although the yield of phenol was
only 3%. The low yield could be attributed to the competitive
intramolecular reaction, as the product of intramolecular
oxygenation of the phenyl group of the ligand was also found
in the electrospray ionization (ESI) mass spectrum of the final
reaction solution (Figure S2). Hydroxylation of aliphatic C−H
bonds has also been demonstrated to be a characteristic feature of
dinickel(III) bis(μ-oxo) complexes supported by pyridylalkyl-
amine ligands, whereas aliphatic hydroxylated products are
minor products in the present alkylbenzene oxygenation.46−49 By
contrast, nickel(II) complexes supported by the tetraaza
macrocyclic ligands 12-tmc and 14-tmc have been shown to
provide a mononuclear nickel(III) peroxide complex and a
nickel(II) superoxide complex, respectively, in the reaction with
H2O2; neither Ni(III) peroxide nor Ni(II) superoxide species are
known to have H-atom transfer reactivity.35,36,50−52 It should be
also noted that the reaction of ethylbenzene and m-
chloroperoxybenzoic acid catalyzed by complex 2 exclusively
provided 1-phenylethanol (sp3-carbon oxygenation product)
rather than ethylphenol, where we proposed that a Ni(II) oxyl
radical-type species is involved as the key reactive intermediate.31
On the basis of these results, we propose that a dinickel(III)
bis(μ-oxo) complex is the most plausible reactive intermediate in
the present reaction, as illustrated in Scheme 3.
ACKNOWLEDGMENTS
■
This work was partly supported by a JSPS Fellowship for Young
Scientists (Y.M.) and a Grant for Scientific Research on
Innovative Areas (22105007 to S.I.) from MEXT of Japan.
Y.M. and S.I. express their special thanks to the JSPS Japanese−
German Graduate Externship Program on “Environmentally
Benign Bio and Chemical Processes” for financial support of the
stay at RWTH Aachen. The authors also express their gratitude
to Prof. Takashi Hayashi and Dr. Koji Oohora at Osaka
University for their help with ESI mass spectrometry.
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D
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