Highly Selective and Efficient Ring Hydroxylation of Alkylbenzenes with Hydrogen Peroxide and an Osmium(VI) Nitrido Catalyst

Article abstract of DOI:10.1002/anie.201705986

The Os^VI nitrido complex, Os^VI(N)(quin)₂(OTs) (1, quin=2-quinaldinate, OTs=tosylate), is a highly selective and efficient catalyst for the ring hydroxylation of alkylbenzenes with H₂O₂ at room temperature. Oxidation of various alkylbenzenes occurs with ring/chain oxidation ratios ranging from 96.7/3.3 to 99.9/0.1, and total product yields from 93 % to 98 %. Moreover, turnover numbers up to 6360, 5670, and 3880 can be achieved for the oxidation of p-xylene, ethylbenzene, and mesitylene, respectively. Density functional theory calculations suggest that the active intermediate is an Os^VIII nitrido oxo species.

Full text of DOI:10.1002/anie.201705986

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Accepted Article
Title: Highly Selective and Efficient Ring Hydroxylation of
Alkylbenzenes with H2O2 based on an Osmium(VI) Nitrido
Catalyst
Authors: Tai-Chu Lau, Hoi Ki Kwong, Po Kam Lo, Shek Man Yiu,
Hajime Hirao, and Kai Chung Lau
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10.1002/anie.201705986
Angewandte Chemie International Edition
COMMUNICATION
Highly Selective and Efficient Ring Hydroxylation of
Alkylbenzenes with H2O2 based on an Osmium(VI) Nitrido
Catalyst
Hoi-Ki Kwong,[a] Po-Kam Lo,[a] Shek-Man Yiu,[a] Hajime Hirao,*[a,b] Kai-Chung Lau,*[a] and Tai-Chu Lau*[a]
Dedicated to Professor Chi-Ming Che on the occasion of his 60th birthday
Abstract: The osmium(VI) nitrido complex, OsVI(N)(quin)2(OTs) (1,
quin = 2-quinaldinate, OTs = tosylate), is a highly selective and
efficient catalyst for the ring hydroxylation of alkylbenzenes with
H2O2 under ambient conditions. Oxidation of various alkylbenzenes
occurs with ring/chain oxidation ratios ranging from 96.7/3.3 to
99.9/0.1, and total product yields from 93% to 98%. Moreover,
turnover numbers (TONs) up to 6360, 5670 and 3880 can be
achieved for the oxidation of p-xylene, ethylbenzene and mesitylene
respectively. DFT calculations suggest that the active intermediate is
an OsVIII nitrido oxo species.
alkylbenzenes, with R/C oxidation products ranging from
96.7/3.3 to 99.9/0.1. Moreover, the catalytic reactions readily
occur within minutes at room temperature with the highest
product yields of 93-98% (based on H2O2 consumed).
Selective hydroxylation of alkylarenes to give the corresponding
alkylphenols is a challenging reaction since the sp3 C–H bonds
of the alkyl side-chain are in general much weaker than the sp2
C‒H bonds of the aromatic ring. Although various transition
metal-based catalysts, such as Fe, Cu, Mn, Co, V and Os have
been reported for the oxidation of alkylarenes with H2O2,[1] most
of these systems show low product yields/conversions and low
ring hydroxylation selectivity. Only a few more selective systems
were reported recently. For example Mizuno and co-workers
reported good chemoselectivity for the hydroxylation of
alkylbenzenes with H2O2 at 60 °C, with ring/chain (R/C)
oxidation ratios ranging from 98:2 for toluene to 86:14 for
ethylbenzene, and yields of 60 - 66%.[2] More recently Itoh and
Figure 1. Structure (left) and ORTEP plot of 1 (right). Thermal ellipsoids are
drawn at 50% probability; hydrogen atoms are omitted for clarity.
We previously reported the synthesis of OsVI(N)(quin)2Cl;[4]
treatment of this complex with Ag(OTs) in CH3CN afforded
OsVI(N)(quin)2(OTs) (1). The ESI/MS of 1 in CH3CN exhibits a
predominant peak at m/z = 550, which is assigned to the ion
[OsVI(N)(quin)2]+ (Figure S1). The X-ray crystal structure of 1
indicates that the complex has a distorted octahedral geometry
with the two quinaldinato ligands in a trans configuration (Figure
1).
coworkers reported that
a nickel(II) complex bearing a
tetradentate pyridylalkylamine ligand is also a chemoselective
catalyst for oxidation of alkylbenzenes using H2O2, with R/C
ratios ranging from 90:10 for toluene to 55:45 for ethylbenzene,
although a 500 fold excess of H2O2 and a temperature of 60 °C
The catalytic activity of 1 towards oxidation of alkylbenzenes
was first investigated by using p-xylene as substrate and H2O2
as oxidant. In a typical reaction, 30% aqueous H2O2 (62.5 mM)
was added over 30 min via a syringe pump to a yellow solution
were used.[3]
.
Herein we report the catalytic hydroxylation of alkylbenzenes
with H2O2 at ambient conditions using an osmium(VI) nitrido
complex bearing two trans quinaldinato ligands as the catalyst,
OsVI(N)(quin)2(OTs) (1, quin = 2-quinaldinate, OTs = tosylate)
(Figure 1). This catalytic system shows the highest
chemoselectivity towards ring hydroxylation of a variety of
of
1
(0.625 mM) and excess p-xylene (1.25 M) in
CH2Cl2/CH3CO2H (5:2, v/v) at 23 °C. After stirring for an
additional 25 min, analysis by GC/FID and GC/MS revealed the
presence of 98% of oxidized products (Scheme 1 and Table 1,
entry 8). More significantly the R/C oxidized products is 99.9/0.1,
despite the much higher bond dissociation energy of an aromatic
C-H bond (ca. 112 kcal mol-1) than that of a benzylic C-H bond
(ca. 85 kcal mol-1).[5] The predominant products are the
corresponding phenols (97.2% selectivity) generated from the
hydroxylation of the benzene ring. A small amount of 2,5-
dimethyl-p-benzoquinone (2.7% selectivity) could also be
detected, which was derived from further oxidation of the phenol
product. Only a trace amount of the side-chain oxidation product
4-methylbenzaldehyde (0.1% selectivity) was formed. The
presence of 2,4-dimethylphenol indicates the occurrence of a
NIH shift of the methyl substituent during oxidation of the
[a]
Dr. H. K. Kwong, Dr. P. K. Lo, Dr. S. M. Yiu, Dr. H. Hirao, Dr. K. C.
Lau, Prof. T. C. Lau
Department of Biology and Chemistry and Institute of Molecular
Functional Materials
City University of Hong Kong
Tat Chee Avenue, Kowloon Tong, Hong Kong, China
E-mail: bhtclau@cityu.edu.hk, kaichung@cityu.edu.hk,
hhirao@cityu.edu.hk
[b]
Dr. H. Hirao
Division of Chemistry and Biological Chemistry, School of Physical
and Mathematical Sciences
Nanyang Technological University
aromatic ring. NIH shift refers to the 1,2-migration of
a
substituent to the adjacent carbon atom of the aromatic ring,
21 Nanyang Link, Singapore 637371
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/anie.201705986
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COMMUNICATION
which has been observed in the oxidation of arenes by
cytochrome P-450.[6]
CF3CH2OH), the product yields and rates are greatly enhanced
by the presence of acetic acid.
When the oxidation of p-xylene by 1/H2O2 was done in air
instead of under argon, the same product yields were obtained
(Table S4, entry 2). When the reaction was carried out in the
presence of BrCCl3, which is an effective scavenger for carbon-
centered radicals, there was a slight decrease in product yield
but no significant change in product distribution was observed
and no brominated products could be detected in the reaction
mixture (entry 3). These results indicate that no long-lived
carbon-centered radicals are generated in the catalytic oxidation.
Scheme 1. Catalytic oxidation of p-xylene with 1/H2O2
The catalytic oxidation of various alkylbenzenes by 1/H2O2 was
investigated (Table 1). These reactions all showed excellent
selectivity towards ring oxidation (96.7% – 99.9%), with the
corresponding phenols obtained as the major products. Over
95% yields of products were obtained for substrates possessing
two or three electron-donating substituents (entries 8 - 12). The
lowest product yield of 47% was obtained in the oxidation of
benzene, which gave a mixture of 76.2% phenol and 23.8%
benzoquinone (entry 1). The relative amount of phenol
increased to 93.6% when a higher concentration of benzene
was used (entry 2). Independent experiments showed that
phenol is readily oxidized by 1/H2O2 to give predominantly
benzoquinone (Table S5). These results indicate the
involvement of an electrophilic active intermediate in the
catalytic oxidation. In the oxidation of benzenes with two or more
substituents, products arising from NIH shift could also be
detected. For instance, the oxidation of o-xylene also generated
2,6-dimethylphenol and 2,6-dimethyl-p-benzoquinone (entry 10).
[a]
Table 1. Catalytic oxidation of various alkylbenzenes by 1/H2O2
Selectivity (%)
Phenols
Total
yield
(%)
Entry
Substrate
R/C
Quinone
23.8
1
-
-
76.2
93.6
47
51
2[d]
6.4
99.8/
0.2
(o/m/p
57.2:7.0:35.8)
=
=
=
=
=
=
=
=
=
=
3
94.8
5.0
4.9
4.9
5.3
0
74
96
84
87
79
98
95
95
96
98
98.5/
1.5
(o/m/p
53.4:7.2:39.4)
4
93.6
93.8
94.7
100
98.7/
1.3
(o/m/p
46.1:6.8:47.1)
5
(o/m+p
44.8:55.2)
6
100/0
100/0
The observed >95% R/C chemoselectivity and product yields for
the oxidation of various alkylbenzenes by 1/H2O2 are the highest
among all reported systems (Table S6). By increasing the
H2O2/catalyst ratio, TONs of up to 6360, 5670 and 3880 could
be achieved for the oxidation of p-xylene, ethylbenzene and
mesitylene, respectively, with no change in product distributions
(Table S7). These TONs are also the highest among all
molecular catalysts for alkylbenzene oxidation.
(o/m/p
50.8:0:49.2)
7
99.9/
0.1
(2,5/2,4[b]
87.8:12.2)
8
97.2
98.9
97.8
99.3
93.3
2.7
1.0
2.1[c]
0
99.9/
0.1
(2,4/2,6/3,5/2,3[b]
76.1:22.9:0.6:0.4)
9
99.9/
0.1
(2,3/3,4/2,6[b]
36.4:55.8:7.8)
10
11
12
This catalytic system is also able to oxidize alkanes such as
cyclohexane under ambient conditions, and the product is a
mixture of cyclohexanol (58.4% yield) and cyclohexanone (9.5%
yield) (Table S8, entry 2). In a competitive experiment using an
equimolar mixture of benzene and cyclohexane as the substrate,
the yields of products arising from benzene and cyclohexane
oxidation are 73.8% and 26.2% respectively (Table S9). When
an equimolar mixture of toluene and cyclohexane was used as
substrate, 97.3% of oxidized products are derived from toluene,
with only 2.7% of cyclohexanol detected (Table S10). This result
is close to the 99.8/0.2 intramolecular selectivity found in toluene.
A closer agreement is expected if we take into account the
statistical factor; there are 12 sp3 C-H bonds in cyclohexane
compared to only 3 in toluene. These results further establish
that the oxidation of aromatic C-H bonds occurs more readily
than that of aliphatic C-H bonds.
99.3
/0.7
(2,4,6/2,3,5[b]
99.6:0.4)
96.7/
3.3
(2,5/2,4[b]
80.1:19.9)
3.4
[a] Reaction conditions: 1 (0.625 mM), substrate (1.25 M), H2O2 (62.5 mM) (slow
addition for 30 min using syringe pump). All reactions were carried out in
CH2Cl2/CH3CO2H (5:2) under argon, T = 23 °C, reaction time = 25 min. [b]
Products derived from NIH shift. [c] 2,3-dimethyl-p-benzoquinone:2,6-dimethyl-p-
benzoquinone = 82.8:17.2. [d] [Benzene ] = 5.0 M.
The effects of solvents on the catalytic oxidation of p-xylene
were studied (Table S3). The best solvent system is
CH2Cl2/CH3CO2H (5:2, v/v), which gives the highest product
o
yield of 98% and the shortest reaction time of 25 min at 23 C
(entry 1). For all solvents tested (CH2Cl2, CH3CN and
Kinetic isotope effects (KIEs) for the catalytic oxidation of
benzene have been determined by competitive oxidation of
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benzene and d6-benzene. The KIEs for the formation of phenol
and p-benzoquinone are 0.96 ± 0.1 and 1.10 ± 0.2, respectively.
This result indicates that a H-atom abstraction mechanism for
the oxidation of benzene is unlikely, but is more consistent with
an electrophilic active intermediate that interacts with a sp2
carbon of the aromatic ring.[7] In the catalytic oxidation of
ethylbenzene and d10-ethylbenzene, the KIE for the side-chain
oxidation product 1-phenylethanol is 4.5 ± 0.4, while the KIEs for
the aromatic ring oxidation products benzoquinone and phenols
are both 1.1 ± 0.2. These results suggest that side-chain
hydroxylation has a different mechanism from ring hydroxylation,
with the rate-determining step involving the cleavage of a
benzylic C-H bond.
Competitive oxidation experiments between arenes with
electron-withdrawing and electron-donating groups have also
been carried out; the substrates include toluene versus 4-
chlorotoluene, p-xylene versus benzene and mesitylene versus
benzene. The yields of ring hydroxylation products arising from
toluene and 4-chlorotoluene are 96.7% and 3.3%, respectively;
those from p-xylene and benzene are 95.9% and 4.1%,
respectively; while the yields for mesitylene and benzene are
99.1% and 0.9%, respectively (Tables S11 - S13). The observed
product enhancement by electron-donating methyl groups and
product suppression by the electron-withdrawing chloro
substitutent further support an electrophilic mechanism for the
ring hydroxylation of arenes.
the 2-quinaldinate ligands occupies the axial position.
Subsequently, there is a peroxydase-like heterolytic O–O bond
cleavage, which leads to the formation of a water molecule and
an OsVIII nitrido oxo species (2). 2 is highly reactive and it attacks
the ortho position of p-xylene (path A) with a tiny barrier, to form
the major hydroxylated product 2,5-dimethylphenol (Figure 2
and Figure S3a). 2 can also attack the ipso position of p-xylene
(path B, Figure S3b), but the corresponding transition state (TS)
is slightly less stable than the TS for path A (18.1 vs. 17.1 kcal
mol-1, Figure S3), in agreement with the observed selectivity
trends (85.3 vs. 11.9). After the ipso-attack in path B, a NIH shift
occurs via a 1,2-methyl transfer to form the product 2,4-
dimethylphenol (Figure S3b). The attack of species 2 on the
methyl side-chain has an even higher barrier (19.5 kcal mol-1,
Figure S3c), again consistent with the observed selectivity trend
(ring/chain = 99.9/0.1). Interestingly, DFT calculations show that
the side-chain hydroxylation can occur via hydride transfer,
which directly forms a hydroxylated product without any rebound
barrier (Figure S3c).
In summary, we have reported a highly active and selective
catalyst for the oxidation of alkylbenzenes by the green oxidant
H2O2 under ambient conditions. To the best of our knowledge,
this catalytic system exhibits the highest chemoselectivity
towards ring oxidation, the highest TONs and product yields
reported to date among molecular catalysts for the oxidation of
alkylbenzenes. DFT calculations suggest that the excellent ring
hydroxylation selectivity arises from a highly electrophilic OsVIII
nitrido oxo active species. Our group has previously reported
To gain more insight into this catalytic process, the oxidation of
p-xylene by 1/H2O2 has been studied theoretically using density
functional theory (DFT). Key results are presented in Figure 2,
while other details are given in the Supporting Information. DFT
results show that the first step involves the binding of H2O2 to
Os(VI) in the equatorial position. Consequently, the coordination
geometry changes in such a way that the oxygen atom of one of
that d2 nitrido complexes such as
[OsVI(N)(salchda)(OH2)]+ [9] and [MnV(N)(CN)4]2
[OsVI(N)Cl4]–,[8]
[10-11]
–
are highly
efficient and selective catalysts for the hydroxylation of aliphatic
C-H bonds by H2O2, with yields >95% and TON >1,000 for the
oxidation of cyclohexane. These catalytic systems go through
Figure 2. (a) DFT-derived mechanism for the reaction of p-xylene. (b) Geometries of transition states (key distances in Å) for the reactions of 2, along with the
reaction sites and respective relative free energies in kcal/mol.
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10.1002/anie.201705986
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similar d0 OsVIII or MnVII nitrido oxo species as active
intermediates, which activate aliphatic C-H bonds by initial one-
electron hydrogen atom transfer followed by O-rebound. In this
work, we demonstrate that by suitable choice of ligands, we can
switch the selectivity of the catalytic system from aliphatic to
aromatic C-H bond hydroxylation. The catalyst 1 prefers to
oxidize C-H bonds by two-electron process, which is probably
the cause for its high selectivity towards ring over side-chain
hydroxylation. These results should provide insights into the
design of selective arene hydroxylation catalysts. We are
currently investigating a series of osmium(VI) nitrido catalysts
bearing various ancilliary ligands in order to understand the
factors that determine the selectivity and the hydroxylation
mechanism.
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This work was supported by the Hong Kong Research Grants
Council (CityU 11336816) and the Hong Kong University Grants
Committee Area of Excellence Scheme (AoE/P-03-08). H.H.
thanks startup grants from City University of Hong Kong
(7200534 and 9610369).
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Keywords: alkylbenzenes • hydroxylation • hydrogen peroxide •
osmium complexes • nitrido
[1]
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10.1002/anie.201705986
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COMMUNICATION
Entry for the Table of Contents
Layout 1:
COMMUNICATION
The osmium(VI) nitrido complex
OsVI(N)(quin)2(OTs) catalyses the
hydroxylation of alkylbenzenes by
H2O2, with ring/chain ratio of up to
99.9/0.1 and TON of >6,300.
Hoi-Ki Kwong, Po-Kam Lo, Shek-Man
Yiu, Hajime Hirao,* Kai-Chung Lau*
and Tai-Chu Lau*
Page No. – Page No.
Highly Selective and Efficient Ring
Hydroxylation of Alkylbenzenes
with H2O2 Based on an Osmium(VI)
Nitrido Catalyst
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