Iridium-catalyzed aerobic oxidation of alkylarenes with excellent turnover numbers

Article abstract of DOI:10.1016/j.catcom.2013.01.020

A highly efficient catalyst system has been developed for the aerobic oxidation of alkylarenes under solvent free conditions. The combination of iridium complex, nitrogen ligand and iodobenzene was found to be crucial for catalytic activity. Excellent turnover numbers were achieved for the preparation of benzoic acids and aryl ketones. This finding may provide useful clues for improving commercially important oxidation processes.

Full text of DOI:10.1016/j.catcom.2013.01.020

Catalysis Communications 35 (2013) 64–67
Contents lists available at SciVerse ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Iridium-catalyzed aerobic oxidation of alkylarenes with excellent
turnover numbers
a
a
a,
a
b
Yunyun Yan , Yanyan Chen , Ming Yan ⁎, Xingshu Li , Wei Zeng
a
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly efficient catalyst system has been developed for the aerobic oxidation of alkylarenes under solvent
free conditions. The combination of iridium complex, nitrogen ligand and iodobenzene was found to be
crucial for catalytic activity. Excellent turnover numbers were achieved for the preparation of benzoic acids
and aryl ketones. This finding may provide useful clues for improving commercially important oxidation
processes.
Received 29 December 2012
Received in revised form 31 January 2013
Accepted 31 January 2013
Available online 15 February 2013
©
2013 Elsevier B.V. All rights reserved.
Keywords:
Aerobic oxidation
Alkylarenes
Iridium complex
Iodobenzene
1
. Introduction
Iridium complexes have been found to be efficient catalysts for a
number of oxidation reactions [18]. Some iridium complexes also
show excellent activity toward the dehydrogenative oxidation of
alcohols with dioxygen [19–22]. Crabtree and co-workers recently
reported that Cp*Ir (Cp*=pentamethylcyclopentadienyl) complexes
could catalyze C\H oxidation with ceric ammonium nitrate [23,24].
To the best of our knowledge, iridium-catalyzed oxidation of saturat-
ed C\H bonds with dioxygen has not been explored. Herein we
report iridium-catalyzed aerobic oxidation of benzylic C\H bonds.
The novel catalyst system exhibits extremely high catalytic activity.
The selective oxidations of alkanes are of great scientific and
commercial values for the manufacture of alcohols, ketones, alde-
hydes and acids [1–4]. Traditionally strong oxidants such as KMNO
4
,
PCC, peroxide acid and fuming sulfuric acids are applied to the trans-
formations. In response to the requirement of sustainable industrial
processes, the application of green oxidants including hydrogen
peroxide, air or molecular oxygen has received increasing attention.
The oxidations of methylarenes and tertiary alkanes with molecular
oxygen (generally named as “autoxidation”) have been extensively
developed. Today millions' tons of terephthalic acid, benzonic acid
and other commodity chemicals are manufactured via autoxidation
processes [5,6]. Because autoxidation processes are typically slow in
the absence of the catalysts, various heterogeneous and homoge-
neous transition metal catalysts have been used to accelerate the
2. Results and discussion
During a study of iridium-catalyzed oxidative benzylic C\H arylation
of xylene with aryl iodides [25], we unexpectedly found that the reaction
generated p-toluic acid efficiently while [Cp*IrCl ] /picolinic acid was
2 2
reactions. The Co(OAc)
2
/Mn(OAc)
2
/HBr/AcOH system (MC process)
used as the catalyst (Scheme 1). The examination of the reaction
mixture indicated the concurrent formation of p-tolylmethanol and
p-methylbenzaldehyde, which are characteristic products from an
autoxidation process. The radical scavenger such hydroquinone
and 4-hydroxyl-2,2,6,6-tetramethylpiperidinooxy inhibited the reaction
completely. The fact also supported a radical oxidation mechanism.
A detailed examination of this transformation was carried out and
the results are summarized in Table 1. Better yield could be obtained
using pure dioxygen instead of air (Table 1, entry 1–2). The use of
iodobenzene is crucial for the catalyst system. The reaction led to signif-
icantly lower yield and different product distribution in the absence of
iodobenzene (Table 1, entry 3). Iodobenzene was expected to decom-
pose under the reaction condition. The generated phenyl radical
works as the initiator of the reaction [26,27]. Iodine and sodium iodide
is the most successful industrial process for the production of
terephthalic acid and other aromatic acids [7]. However due to the
strong corrosion of metal/bromine/acetic acid mixtures under high
temperature, the expensive titanium clad equipments must be used.
In addition, the decarboxylation of acetic acid under the reaction
condition is also troublesome. Continuous efforts have been made
to develop more efficient catalysts [8–17]. Considering the great
commercial values of these reactions, further improvements in cata-
lytic efficiency and product distribution are highly desirable.
⁎
Corresponding author. Tel./fax: +86 20 39943049.
E-mail address: yanming@mail.sysu.edu.cn (M. Yan).
1566-7367/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2013.01.020

Y. Yan et al. / Catalysis Communications 35 (2013) 64–67
65
Scheme 1. Unexpected formation of p-toluic acid during an oxidative benzylic C\H
arylation reaction.
Fig. 1. Effect of the loading of iodobenzene. Reaction conditions: p-xylene (16 mmol),
[Cp*IrCl (0.0025 mmol), 2-picolinic acid (0.005 mmol), 1 atm O , 120 °C, 12 h.
2
]
2
2
were found to be completely inefficient for the transformation. For a
comparison, radical initiators AIBN (azobisisobutyronitrile) and BPO
6). Phenanthroline derivative L6 provided good yield and selectivity
(Table 2, entry 7). Readily available picolinic acid L7 was identified as
the best ligand. It provided the optimal yield and favorable product
distribution (Table 2, entry 8). 6-Methyl picolinic acid L8 is less efficient
than L7 (Table 2, entry 9). The reaction temperature also exerted the
strong effect. When the reaction was carried out at 90 °C, poor yield
was obtained (Table 2, entry 10). Higher reaction temperature
(150 °C) also decreased the yield and selectivity (Table 3, entry 11).
Increasing the pressure of dioxygen showed an unfavorable effect
(
benzoyl peroxide) were examined, however poor yields and unfavor-
able product selectivities were observed (Table 1, entries 4–5).
Bromobenzene also promoted the oxidation process, but lower yields
was obtained (Table 1, entry 6). Chlorobenzene is much less efficient
(Table 1, entry 7). Low yield and inferior product selectivity were also
obtained in the absence of Ir complex (Table 1, entry 8). Although the
exact catalytic mechanism is still unclear, the combination of Ir complex
and iodobenzene appears to provide the most efficient catalyst system
2 2
(Table 2, entry 12). [Cp*IrCl ] /picolinic acid was found to be highly
[
28]. Ir complex may promote the decomposition of iodobenzene to
active. Even the use of 1/10 catalyst loading still provided good yield
and selectivity (Table 2, entry 13).
release the phenyl radical and initiate the auto-oxidation process. In
addition, it also affects the product distribution during the decomposing
of peroxide intermediate.
The effect of the amount of iodobenzene was examined and the
results are illustrated in Fig. 1. Increasing the loading of iodobenzene
gave better yields. A ratio of PhI/[Ir]=120 was found to be optimal.
Further increase of the loading of iodobenzene led to inferior results.
A series of nitrogen ligands was investigated and the results are
summarized in Table 2. The reaction gave very low yield in the absence
of ligand (Table 2, entry 1). 5-Trifluoromethyl-2-hydroxylpyridine
L1 provided low yield (Table 2, entry 2) [29–31]. Bipyridine L2 and
pyridin-2-ylmethanamine L3 gave better yields and selectivities
Table 2
Effect of nitrogen ligands on aerobic oxidation of xylene.
(
Table 2, entries 3–4). Pyridin-2-ylmethanamine derived imine
L4 provided improved yield and selectivity (Table 2, entry 5).
-Hydroxylquinine L5 appeared to inhibit the reaction (Table 2, entry
8
Table 1
Effect of Ir complex and radical initiator.
Entrya
Ligand
Yield (%)
Products distribution (%)
\
OH
\CHO
\COOH
1
2
3
4
5
6
7
8
9
10
11
12
13
–
2.5
13.4
23
24.6
26.5
0
23.3
27.6
20.8
3.1
14.6
17.3
22.1
27.4
10
8.9
10.1
6.0
–
72.6
21.4
13.2
13.2
10.7
–
Trace
68.6
77.9
76.7
83.3
–
L1
L2
L3
L4
L5
L6
L7
L8
L7
L7
L7
L7
Entrya
Catalyst
Initiator
Yield (%)
Product distribution (%)
9.8
5.9
9.6
34.8
8.1
14.3
9.7
13.2
10.7
15.3
65.2
22.9
11.3
14.2
77
\
OH
\CHO
\COOH
83.4
75.1
Trace
69.0
74.4
76.1
1
2
3
4
5
6
7
8
(in air)
[Ir]
[Ir]
[Ir]
[Ir]
[Ir]
[Ir]
[Ir]
–-
PhI
PhI
9.8
14.6
5.7
3.3
3.6
10.6
3.8
5.6
20.2
12.1
35.1
35.8
38.6
14.9
39.9
34.1
23.3
19.6
47.3
64.2
61.4
23.3
60.1
65.9
56.5
68.3
17.6
Trace
Trace
61.8
Trace
Trace
b
c
–
d
AIBN
BPO
PhBr
PhCl
PhI
e
a
Reaction conditions: p-xylene (16 mmol), [Cp*IrCl
]
2 2
(0.0025 mmol), L1–L7
(
0.005 mmol), PhI (0.3 mmol),
O
2
balloon at 120 °C for 12 h. The yields of
p-tolylmethanol and p-methylbenzaldehyde were detected by GC using n-dodecane as
the internal standard. The yield of p-toluic acid was determined based on the isolated
product.
a
Reaction conditions: p-xylene (16 mmol), [Cp*IrCl
2 2
] (0.0025 mmol), 2-picolinic acid
(
0.005 mmol), initiator (0.0075 mmol), O
2
balloon at 120 °C for 12 h. The yields of
b
p-tolylmethanol and p-methylbenzaldehyde were detected by GC using n-dodecane as
the internal standard. The yield of p-toluic acid was determined based on the isolated
product. The trace amounts of p-tolyl 4-methylbenzoate (generallyb1%) generated from
p-toluic acid and p-tolylmethanol were observed by GC–MS.
The reaction was carried out at 90 °C.
The reaction was carried out at 150 °C.
The reaction was carried out under 5 atm oxygen pressure.
2 2
[Cp*IrCl ] (0.00025 mmol)2–picolinic acid (0.0005 mmol) were used.
c
d
e

66
Y. Yan et al. / Catalysis Communications 35 (2013) 64–67
Table 3
Table 4
Areobic oxidation of methylarenes.
Oxidation of secondary and tertiary C\H bonds.
Entrya
1
Methylarene
Product
TONb
Entrya
Substrate
Product
TON
12,350
\OH
\CO\
\OH
\CO\
1
5376
13,696
2
3
4
5
11,760
7940
3600
1750
2
3
4
10,240
16,192
20,352
18,944
0
14,656
5b
180
77
6
7
1300
6b
101
12,070
a
Reaction conditions: substrate (16 mmol), [Cp*IrCl
2 2
] (0.00025 mmol), picolinic
acid (0.0005 mmol), PhI (0.3 mmol), O
2
balloon at 120 °C for 12 h. TON is calculated
as the molar ratio of the products to the catalyst as determine by GC analysis using
8
–
n-dodecane as the internal standard.
b
[
2 2
Cp*IrCl ] (0.0025 mmol) and picolinic acid (0.005 mmol) were used in this case.
a
Reaction conditions: methylarene (16 mmol), [Cp*IrCl
]
2 2
(0.00025 mmol), picolinic
acid (0.0005 mmol), PhI (0.3 mmol), O
2
balloon at 120 °C for 12 h.
however with low TON (Table 4, entry 5). Cyclohexene was transformed
to cyclohexenone and cyclohexenol with low TON (Table 4, entry 6).
The recycle ability of the catalyst for the oxidation of p-xylene was
also studied. After p-toluic acid was filtered, the residue was supplied
with fresh p-xylene and stirred under an oxygen balloon at 120 °C for
12 h. The catalytic activity was found to decrease with every recycle
(TONs 10294, 8824, 3529, and 0 for 1–4 recycles respectively). The
partially decomposition of the catalyst during every recycle may
account for the observed result.
b
TON is calculated as the molar ratio of isolated product to the catalyst.
The aerobic oxidation of a series of methylarenes was examined and
the results are summarized in Table 3. The reaction provided the acids,
alcohols and aldehydes as the major products. Excellent turnover
numbers (TON) were achieved for p-xylene and o-xylene (Table 3,
entries 1–2). Lower TON was obtained for m-xylene (Table 3, entry
3
). Mesitylene was transformed to 3,5-dimethylbenzoic acid efficiently
(
Table 3, entry 4). None of the diacids was observed in these cases.
3
. Conclusions
Toluene could be oxidized to benzoic acid, however TON is significantly
lower in comparison with p-xylene (Table 3, entry 5). 1-Methoxy-
In conclusion, we have developed a highly efficient catalyst system
4
-methylbenzene was transformed to 4-methoxyl-benzoic acid in the
similar TON with toluene (Table 3, entry 6). On the other hand,
-chloro-4-methylbenzene was smoothly oxidized with excellent TON
Table 3, entry 7). 2-Methyl pyridine could not be oxidized by the
for the aerobic oxidation of alkylarenes under solvent free conditions.
Excellent TONs were achieved for the preparation of benzoic acids and
aryl ketones. The combination of iridium complex, nitrogen ligand and
iodobenzene is crucial for achieving excellent catalytic activity. This
finding provides a new clue for the development of more efficient
autoxidation catalyst systems.
1
(
present catalyst system (Table 3, entry 8). It may bind to Ir complex
and inhibit the catalytic activity.
Furthermore a number of substrates with secondary and tertiary
C\H bonds were examined and the results are summarized in
Table 4. Excellent TONs were achieved for the oxidation of ethylbenzene
and tetrahydronaphthalene. The corresponding ketones were obtained
together with fewer amounts of alcohols (Table 4, entries 1–2). The
oxidation of diphenylmethane led to benzophenone with extremely
high TON and selectivity (Table 4, entry 3). To the best of knowledge,
the TON is the best among the ever developed catalyst system. The
oxidation of isopropylbenzene provided 1-phenylethanol and aceto-
phenone efficiently (Table 4, entry 4). Such a demethylation reaction
was also previously observed in autoxidation of isopropylbenzene
Acknowledgments
Financial supports from National Natural Science Foundation of
China (Nos. 20972195, 21172270) and Guangdong Engineering
Research Center of Chiral Drugs are gratefully acknowledged.
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://
dx.doi.org/10.1016/j.catcom.2013.01.020.
[32,33]. Methylcyclohexane could be oxidized to 1-methylcyclohexanol,

Y. Yan et al. / Catalysis Communications 35 (2013) 64–67
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