Oxidation of cycloalkanes by H2O2 using a copper-hemicryptophane complex as a catalyst

Article abstract of DOI:10.1039/c2cc37829a

Efficient alkane C-H bond oxidation was achieved using a newly designed Cu(ii)-hemicryptophane complex. Protection of the copper site in the inner cavity of the host leads to enhanced yields and allows discriminating cyclohexane from cyclooctane or adamantane in competitive experiments.

Full text of DOI:10.1039/c2cc37829a

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ARTICLE TYPE
Oxidation of Cycloalkanes by H O Using a Copper-Hemicryptophane
2
2
Complex as a Catalyst†
a
b
a
a
Olivier Perraud, Alexander B. Sorokin, Jean-Pierre Dutasta and Alexandre Martinez*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
Efficient alkane C–H bond oxidation was achieved using a
newly designed Cu(II)-hemicryptophane complex. Protection
catalyze the alkane oxidation with H
mild conditions. Turnovers and yields are doubled when
O as clean oxidant under
2 2
of the copper site in the inner cavity of the host leads to 50 compared to the model complex 2 with no cavity, demonstrating
the great potential of such an approach for the C-H oxidation.
enhanced yields and allows discriminating cyclohexane from
cyclooctane or adamantane in competitive experiments.
10
2+
It is now recognized that the confined space of a molecular cavity
can strongly modify the behaviour of an encapsulated molecule.
O
OMe
1
MeO
O
OMe
O
O
For instance, living systems involve the use of elaborated protein
binding pockets for designing efficient and selective enzyme
O
O
ClO4–
2+
2
H3C
H2O
Cu
CH3
NH
H3C
2
HN
15
20
25
30
35
40
45
catalysts. The design of bio-inspired supramolecular assemblies
HN
2 ClO4–
H2O
Cu
able to accomplish such efficient chemical transformations,
represents an important challenge. In this regard, host-guest
systems based on synthetic molecular receptors are very
attractive, provided that endohedral functionalization can be
achieved to mimic the protein functions.
HN
N
NH
HN
1
2
N
Chart 1 Structure of the complex 1 and the model complex 2.
The complex 1 was prepared from the hemicryptophane
ligand and Cu(ClO ) (H O) with high yield (ESI), and was
characterized by near-IR/vis and EPR spectroscopies, and their
electrochemical properties were investigated. The essential
feature of this novel supramolecular assembly is the localization
of the copper site inside the molecular cavity, where a substrate
molecule can also be accommodated. Complex 1 was first tested
in the oxidation of CyH by H O in MeCN at room temperature.
The total yield of CyOH and Cy=O of 31% was obtained (Table
, entry 5). Thus, 1 can be regarded as one of the most efficient
copper catalysts reported so far.
conditions on the efficiency of the oxidation was investigated. (i)
The amount of H O has a relevant effect since the overall yields
of CyOH and Cy=O are enhanced upon increasing the
oxidant/substrate ratio from 10 to 15 (22% and 30% yields,
respectively, entries 1 vs 2). However, further increase of H O
content leads to a lower product yield (Table 1, entry 3). Slow
addition of H O to the reaction mixture has often increased the
yield of oxidation products with iron-based catalysts. However,
no improvement was observed when we followed this procedure
with complex 1. When t-BuOOH was used as oxygen source, a
sharp drop of the yield was observed (<5%). (ii) Although the
presence of acid can improve the efficiency of copper catalysts in
Bio-inspired catalysts have been viewed as promising
candidates to carry out selective and efficient oxidations of C-H
19
55
60
65
70
75
80
4
2
2
6
3
bonds of alkanes, as does the copper containing particulate
20
4
methane monooxygenase (pMMO). The direct and efficient
oxidation of cheap and largely available alkanes remains an
5
-10
ambitious goal yet to be achieved.
In particular, the oxidation
products of cyclohexane (CyH), i.e. cyclohexanol (CyOH) and
2
2
11
cyclohexanone (Cy=O), are of industrial significance. Among
the various attempts to develop efficient and selective biomimetic
catalytic systems, those involving copper-based catalysts using
1
12-14
The influence of the reaction
1
2-14
H O as oxidant are of a high potential interest.
However, the
2
2
conversions and turnovers for the CyH oxidation, obtained with
copper-based synthetic systems, are still commonly low and new
approaches have to be proposed.
2
2
Although attention has been paid to design supramolecular
2
2
1
5
copper complexes, their use as catalysts for the oxidation of
alkanes, in particular for the conversion of CyH, still remains an
unexplored area of research. Among the catalysts based on
cyclodextrin, calixarene or curcubituril derivatives that can
2
2
1
6
enhance the catalytic activity by guest encapsulation, the
hemicryptophane hosts, combining a recognition and a catalytic
1
7,18
site in their inner molecular cavity, appear as very promising.
Herein we report the first use of a hemicryptophane copper
complex 1 (Chart 1) for the oxidation of CyH to CyOH and
Cy=O. Unlike most of the supramolecular metal catalysts, which
frequently suffer from products inhibition and require relatively
large catalyst loadings, we show that 1 is able to efficiently
This journal is © The Royal Society of Chemistry [year]
12
the CyH oxidation, no positive effect of the acid addition
HNO , AcOH) has been detected with our system. A similar
behavior has been observed for the oxidation of alkanes with t-
BuOOH catalyzed by tetracopper(II) complexes. (iii) The
(
3
21
[journal], [year], [vol], 00–00 | 1

ChemComm
Page 2 of 3
increase of the reaction temperature or time did not lead to better
2 (14 % yield), the cage catalyst 1 showed the increased
yields. (iv) The oxidation of CyH occurred even if smaller 50 performance providing 2-fold higher yield (28%). This finding
amounts of the catalyst were used. With a half catalyst loading (4
mol%) similar yields were obtained (22% and 31%, entries 4 and
5, respectively, compared to entries 1 and 2). A decrease of the
catalytic activity was observed with 1 mol% catalyst loading.
strongly suggests that the cage structure prevents the degradation
of the catalyst. Self-oxidation reactions between two molecules of
the catalyst should be avoided because of the location of the
View Article Online
5
0
5
0
active site in the inner cavity, and 1 appears to be much more
Nevertheless, heating the reaction mixture at 35°C for two hours 55 robust under the strong oxidation conditions than the model
afforded a similar yield (28%; entry 6). Scale up of the procedure
was also performed leading to similar yield (29%, entry 7). A
turnover number of about 110-130 can be reached for a
sufficiently high [alkane]/[catalyst] ratio (1000), demonstrating
the efficiency of 1 in the oxidation of CyH. This result highlights
the relevance of the hemicryptophane host structure to design
supramolecular catalysts, as previously reported for the oxidation
catalyst 2. Similar protection from decomposition by
a
supramolecular structure and resulting to a remarkable catalytic
2
5
1
1
2
activity has been recently reported by Raymond et al.
1
7
of thioethers. Most of the supramolecular systems designed for
catalysis have turned to be inactive either due to their high
rigidity or should be used in stoichiometric amounts since the
reaction product remains in the cavity preventing the next
2
2
catalytic cycle.
In contrast, the hemicryptophane based
complexes are rather flexible, as previously observed from
60
Fig. 1 Time course of oxygenation of cyclohexane catalyzed by 1, 2 and
2
3
structural and molecular recognition studies. This allows a
greater lability of the host-guest association which could account
for their efficiency in catalysis.
Cu(ClO
4
)
2
(H
2
O)
(
6
. MeCN (250 µL), cyclohexane (3.2 µL, 30 µmol), H
300 µmol), catalyst (0.3 µmol), T = 35°C.
2 2
O
To further demonstrate the essential role of the cavity, we
examined the discriminating ability of 1 in concurrent oxidation
a
Table 1 Oxidation of cyclohexane (CyH).
b
65 of closely related cyclohexane and cyclooctane, which have the
same chemical properties but slightly different sizes. As expected
from the comparison of their C-H bond dissociation energies (less
than 3% difference), similar yields and conversions were
obtained in the oxidation of CyH and cyclooctane to
Entry Catalyst
H
2
O
2
Catalyst
(%)
Yield (%)
(
eq.)
10
15
30
10
15
10
10
10
10
10
c-hexanol c-hexanone Total
1
2
3
4
5
6
1
1
1
1
1
1
1
8
8
8
4
4
1
1
1
11
15
15
11
16
16
17
3
11
15
7.3
11
15
12
12
1
22
30
22
22
31
28
29
4
26
70
CyOH/Cy=O and cyclooctanol/cyclooctanone, respectively, in
the presence of 2 (Table 2). Using 1, a higher conversion was
observed with cyclooctane whereas a better product yield was
achieved in CyH oxidation (Table 2).
c
7
8
9
Cu(ClO
2
4
)
2
1
-
10
-
5
-
15
-
1
0
None
Table 2 Competitive oxidation experiments of CyH and cyclooctane (1:1
a
b
a
75 mixture), and CyH and adamantane (Ad) (1:1 mixture).
2
5
0
Conditions: Entries 1-5: MeCN (250 µL), CyH (3.2 µL, 30 µmol), H
300, 500 ou 1000 µmol), catalyst (1.2 or 2.4 µmol), T.A., 6h; Entries 6-
0: MeCN (250 µL), CyH (3.2 µL, 30 µmol), H (300 µmol), catalyst
0.3 µmol), 35°C, 2h. Yields were determined by GC using
chlorobenzene as external standard. conditions : MeCN (8.3 mL), CyH
(105.6 µL, 1.0 mmol), H (10 mmol), catalyst (0.01 mmol), 35°C, 2h.
2 2
O
(
1
(
c
c
Catalyst.
Conversion (%)
Yield (%)
2 2
O
b
C6
C8
C10
c-hexane c-octane
Ad
c
products products products
1
2
1
2
52
31
61 (50)
50 (42)
65
33
-
-
-
26
15
16
5
21
15
-
-
45
15
3
2
O
2
d
d
d
d
The influence of the structure of the ligand on the catalytic
activity was then studied in more details: (i) Much lower activity
56 (10)
29 (29)
-
-
a
of Cu(ClO ) (H O) (4% yield, Table 1, entry 8) shows the
importance of the tren ligand. (ii) To examine the role of the cage
4
2
2
6
Conditions: MeCN (250 µL), CyH (1.6 µL, 15 µmol), cyclooctane (1.6
b
µL, 15 µmol), H
Conditions: MeCN (500 µL), CyH (1.6 µL, 15 µmol), adamantane (2 mg,
15 µmol), H O (300 µmol), catalyst (0.3 µmol), 35°C, 4h. Conversions
2 2
and total yields were determined by GC using chlorobenzene as external
2 2
O (300 µmol), catalyst (0.3 µmol), 35°C, 4h.
35
40
45
structure on the catalytic activity, a direct comparison between 1
c
2
4
and the model complex 2, which lacks cavity, was performed.
Under the same conditions, a much better yield was obtained with
the cage complex 1 than with the model compound 2 (28% and
80
d
standard (averages of at least two runs). Conversion at t = 2h.
The higher hydrophobicity of cyclooctane could account for its
higher reactivity since it can interact more strongly with the
cavity of 1, close to the active site. Similarly, cyclooctanol and
cyclooctanone products are more hydrophobic than their
cyclohexane counterparts and their expected higher residence
times inside the cavity would result in over-oxidation and lower
product yields. The hydrophobicity of these alkane derivatives is
indeed closely related to their respective partition coefficients.
These findings show that 1 is able to discriminate cyclohexane
from cyclooctane (yields and conversions are 20% higher for
1
5%, respectively; Table 1, entries 6 and 8). To determine
whether the high yield was related to the increase of the reaction
rate or to the protection of the active site within the cage against
deactivation, kinetic studies were performed. The time course for
the oxidation of CyH to CyOH and Cy=O with 1, 2 and
Cu(ClO ) (H O) is shown in Fig. 1. The reaction rates in the
presence of 1 or 2 were higher than that obtained with
Cu(ClO ) (H O) . Thus, the tren ligand is essential for the high
catalytic activity and both 1 and 2 showed similar initial reaction
8
5
4
2
2
6
2
7
4
2
2
6
90
rates. However, whereas the reaction stopped after one hour with
2
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This journal is © The Royal Society of Chemistry [year]

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0
1
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2
2
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2
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6
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1
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1
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a
Laboratoire de Chimie, CNRS, Université Lyon 1, École Normale
Supérieure de Lyon, 46 Allée d'Italie, F-69364 Lyon, France. Fax: +33 4
7272 8860; Tel: +33 4 7272 8863; E-mail: alexandre.martinez@ens-
lyon.fr
1
1
1
1
15
45
50
55
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1
b
IRCELYON, UMR 5256, CNRS – Université Lyon 1, 2 av. A. Einstein,
2
2
2
3
F-69626 Villeurbanne, France. Tel: +33 4 7244 5337; E-mail:
alexander.sorokin@ircelyon.univ-lyon1.fr
† Electronic Supplementary Information (ESI) available: Experimental
conditions and procedures. See DOI: 10.1039/b000000x/
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Journal Name, [year], [vol], 00–00 | 3