Iron-catalyzed oxidation of cycloalkanes and alkylarenes with hydrogen peroxide

Article abstract of DOI:10.1002/adsc.200404315

An iron-catalyzed process for the oxidation of saturated hydrocarbons (cycloalkanes and alkylarenes) to alcohols and ketones with aqueous H ₂O₂ in acetonitrile at room temperature is reported. Addition of a carboxylic acid increases

Full text of DOI:10.1002/adsc.200404315

FULL PAPERS
Iron-Catalyzed Oxidation of Cycloalkanes and Alkylarenes with
Hydrogen Peroxide
Chiara Pavan, Julien Legros, Carsten Bolm*
Institut fꢀr Organische Chemie der RWTH Aachen, Landoltweg 1, 52056 Aachen, Germany
Fax: (þ49)-241-809-2391; e-mail: carsten.bolm@oc.rwth-aachen.de
Received: October 12, 2004; Accepted: January 24, 2005
Abstract: An iron-catalyzed process for the oxidation tained with ethylbenzene as substrate and acetic
of saturated hydrocarbons (cycloalkanes and alkylar- acid as additive, affording acetophenone as the main
enes) to alcohols and ketones with aqueous H2O2 in product.
acetonitrile at room temperature is reported. Addi-
tion of a carboxylic acid increases the selectivity to- Keywords: C H activation; homogeneous catalysis;
wards the ketone formation. Best results were ob- hydrogen peroxide; iron; oxidation
ꢀ
Introduction
with 30% aqueous H2O2 and catalytic amounts
(10 mol %) of various iron complexes easily available
The synthesis of functionalized compounds, such as al- in bulk at reasonable, or even low, prices. As suggested
cohols and ketones, via CH oxidation generally requires by previous reports,[6] acetonitrile was used as solvent.
drastic conditions and non-benign oxidants and met- The results of this initial metal salt screening are sum-
als.[1] Oxidation processes involving green oxidants marized in Table 1.
and non-toxic metals are urgently needed. In this line,
Iron(II) acetate, iron(II) acetylacetonate, iron(III)
iron catalysts in combination with hydrogen peroxide[2] chloride, iron(II) oxalate and iron(II) bromide gave
are highly desirable systems to be tested and developed. poor conversions of the starting material (ꢁ20%) and
In fact, many studies have been devoted towards this led to the rapid decomposition of hydrogen peroxide.
goal and investigations on the use of iron complexes In contrast, by using iron(II) chloride, iron(III) nitrate,
for the oxidation of saturated hydrocarbons[3] have iron(II) tetrafluoroborate and iron(II) perchlorate,
been exemplified by Fenton chemistry[4] and Gif sys- more than 60% of ethylbenzene was converted into oxi-
tems,[5] to name only two. Most reports in this area, how- dized products and no significant decomposition of hy-
ever, focus on elucidating mechanistic and kinetic de- drogen peroxide was observed. Moreover, the latter
tails rather than on using the catalysts for synthetic pur- iron salts showed a pronounced selectivity for the oxida-
poses. Here, we report a very simple iron-catalyzed oxi- tion of the benzylic position (ꢂ50%), with acetophe-
dation of hydrocarbons giving alcohols and ketones un- none being the major product.
der mild reaction conditions using H2O2 as terminal
oxidant (Scheme 1).
An important drawback of the protocol described
above was the pronounced exothermicity of the reac-
tion, which could become a severe safety issue in
large-scale reactions. We presumed that the use of addi-
tives could improve the behavior and increase the effi-
ciency of the catalytic system. In the field of iron-cata-
lyzed oxidations, carboxylic acids have been shown to
be particularly effective.[2d,7] In the system described
here, simple carboxylic acids (20 mol %), typically acetic
and benzoic acid, were added to the reaction medium
prior tothe addition ofthe oxidant. The reactionbecame
very well-behaved and the undesirable exothermicity
was no longer observed. Moreover, without any de-
crease in conversion (>50%) the only detected benzylic
Scheme 1.
Results and Discussion
For the first experiments, ethylbenzene was chosen as oxidation product was acetophenone.[8,9]
the model substrate. Its oxidation to 1-phenylethanol
Acetic acid, benzoic acid and 4-nitrobenzoic acid
and acetophenone was performed at room temperature proved to be the most effective additives for increasing
Adv. Synth. Catal. 2005, 347, 703–705
DOI: 10.1002/adsc.200404315
ꢁ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
703

Chiara Pavan et al.
TON
FULL PAPERS
Table 1. Oxidation of ethylbenzene to acetophenone and phenylethanol.
Catalyst
Conversion[a] [%]
Selectivity[a, b] [%]
Ketone:Alcohol
FeBr2
FeCl2
FeCl3
20
60
–
15
15
–
88: 12
90: 10
–
0.3
0.9
–
Fe(OAc)2
Fe(acac)2
FeC2O4
Fe(NO3)3
Fe(BF4)2
Fe(ClO4)2
–
–
–
63
60
65
–
–
–
50
59
64
–
–
–
–
–
–
3.2
3.5
4.2
83: 17
89: 11
90: 10
[a]
Based on substrate. Determined by GC/MS and GC analysis using nitrobenzene as internal standard.
Selectivity towards benzylic oxidation: (mmol acetophenoneþmmol phenylethanol)/mmol substrate converted.
[b]
Table 2. Iron-catalyzed oxidation of saturated hydrocarbons.
Substrate
Major product
Yield[a] [%]
Conversion [%]
Selectivity[%]
TON
Ethylbenzene (1)
Acetophenone (6)
(4-Nitro)acetophenone (7)
Benzophenone (8)
Cyclooctanone (9)
Cyclohexanol (10)
Cyclohexanone (11)
50
67
65
48
55
–
75
74
73
80
–
5.0
4.8
3.5
4.4
2.0
2.0
(4-Nitro)ethylbenzene (2)
Diphenylmethane (3)
Cyclooctane (4)
48[b]
35[b]
44[b]
20[c]
20[c]
Cyclohexane (5)
–
–
[a]
Based on substrate.
[b]
Determined by GC analysis using internal standard.
[c]
1
Determined by H NMR analysis.
the selectivity towards ketone formation [>60% with (48%). More challenging oxidations of fully saturated
Fe(ClO4)2]. 4-Methoxybenzoic acid, on the other hand, cycloalkanes were also attempted. To our delight we
showed a detrimental effect [only 43% with Fe(ClO4)2]. found that cyclooctane (4) was smoothly oxidized, giv-
Since the results do not correlate with the strength of the ing a ratio of ketone/alcohols of 8.8 with cyclooctanone
acid (acetic acid<4-methoxybenzoic acid<benzoic (9) as the major product (44% yield). Other compounds
acid<4-nitrobenzoic acid) the additive effect does not were detected by GC/MS analysis and their masses indi-
seem to be a simple consequence of an acidity change cated the formation of diketones. Finally, the less reac-
of the reaction medium. Other acids such as CF3CO2H[10] tive cyclohexane (5) was converted giving an equimolar
and 2-picolinic acid (which is known to be very efficient mixture of cyclohexanol (10) and cyclohexanone (11) in
in the Gif systems[5]) gave unsatisfactory results. Solvents 40% yield. This result is remarkable and can be com-
other than acetonitrile were also examined. When the re- pared well with the best ones reported so far in the liter-
action was performed in ethyl acetate, dichloromethane or ature for systems involving Fe species as catalyst and
methanol, decomposition of the oxidant occurred and no aqueous hydrogen peroxide as terminal oxidant.[11]
oxidation of the substrate was observed. Decreasing the
catalyst loading (5 mol %) had also a clear negative effect
on the conversion (<40%), while the selectivity remained Conclusion
unchanged.
After having established the best conditions for the In summary, we report an iron-catalyzed oxidation of sa-
oxidation of ethylbenzene, we focused our attention turated hydrocarbons, using aqueous hydrogen perox-
on the substrate scope. The conversion of a series of hy- ide as terminal oxidant. The process exhibits great ad-
drocarbons was assessed applying a combination of vantages: the reaction proceeds under truly catalytic
Fe(ClO4)2 (10 mol %) and AcOH (20 mol %) for the conditions, the catalyst does not require any ligand,
CH activation. The results are presented in Table 2. and water is the only by-product formed. These features,
(4-Nitro)ethylbenzene (2) afforded the corresponding combined with the mild reaction conditions (aerobic at-
ketone 6 with a conversion and selectivity comparable mosphere and room temperature), make the system a
to the ones observed for ethylbenzene. Diphenylme- promising tool for large-scale applications and provide
thane (3) gave benzophenone (8) with a good selectivity a simple method to access alcohols and ketones starting
(73%), although the conversion was only moderate from unfunctionalized substrates.
704
ꢁ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2005, 347, 703–705

Fe-Catalyzed Oxidation of Cycloalkanes and Alkylarenes with H2O2
FULL PAPERS
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Experimental Section
Materials
All the chemicals are commercially available and have been
[2] For overviews on the use of hydrogen peroxide in oxida-
tion reactions, see: a) Catalytic Oxidations with Hydro-
gen Peroxide as Oxidant, (Ed.: G. Strukul), Kluwer Aca-
demic, Dordrecht, 1992; b) C. W. Jones, Applications of
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Sato, Chem. Commun. 2003, 1977; d) B. S. Lane, K. Bur-
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[3] Reviews on iron-catalyzed oxidations: a) M. Fontecave,
S. Menage, C. Duboc-Toia, Coord. Chem. Rev. 1998,
178–180, 1555; b) M. Costas, K. Chen, L. Que Jr., Coord.
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346, 317 and references cited therein.
used as provided, without further purification. Acetonitrile
with HPLC grade purity has been used.
General Procedure for the Oxidation of Cycloalkanes
or Alkylarenes
To a stirred solution of the substrate 1–5 (1 mmol), Fe(ClO4)2 ·
6 H2O (36.6 mg, 0.1 mmol), acetic acid (12.0 mg, 0.2 mmol)
and nitrobenzene (as internal standard, 0.2 mmol, 24.6 mg) in
MeCN (5 mL) was added 30% aqueous H2O2 (5 mmol,
567 mg) over 4 h (1 mmol/h). After 5 h, the reaction was
quenched with MnO2, filtered on Na2SO4 and analyzed. Com-
pounds 6–11 were isolated by column chromatography (pen-
tane/diethyl ether, 3:1).
Analyses
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[6] For the use of acetonitrile in oxidation reactions see, for
example: a) J. T. Groves, M. Van Der Puy, J. Am. Chem.
Soc. 1976, 98, 5290; b) R. H. Fish, M. S. Konings, K. J.
Oberhausen, R. H. Fong, W. M. Yu, G. Christou, J. B.
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NMR and GC analyses were performed on a Varian Inova 400
(400 MHz) and a Hewlett-Packard HP 5890 Series II gas chro-
matograph, respectively. Authentic samples of 6–11 were used
to assign the peaks in chromatograms.
Alkylarenes (1–3): GC analyses were conducted using a FS-
Phenyl-Silcapillary pre-column (3 mꢃ0.250 mm) and a Cyclo-
dex b-I/P capillary column (25 mꢃ0.250 mm), with N2 as the
carrier gas.
Cycloalkanes (4, 5): GC analyses were conducted using a HP
Ultra 2capillarycolumn (25 mꢃ0.2 mm), withN2 asthe carrier
gas.
The yield of compound 5 was determined by 1H NMR (CD3
CN) using benzene as internal standard.
Acknowledgements
[7] a) M. C. White, A. G. Doyle, E. N. Jacobsen, J. Am.
Chem. Soc. 2001, 123, 7194; b) J. Legros, C. Bolm, An-
gew. Chem. Int. Ed. 2004, 43, 4225.
[8] Noteworthy is the fact that this system is also capable of
oxidizing alcohols to ketones. For example, 1-phenyl-
ethanol was converted into acetophenone with an excel-
lent selectivity (>90%). For a recent report on FeBr2-
mediated oxidations of alcohols, see: E. Martin, A. Gar-
rone, Tetrahedron Lett. 2003, 44, 549.
We are grateful to the Fonds der Chemischen Industrie and the
Deutsche Forschungsgemeinschaft (SPP 1118) for financial
support. C. P. thanks the Graduiertenkolleg (GRK 440) for a
predoctoral stipend, and J. L. acknowledges the Alexander
von Humboldt Foundation for a postdoctoral fellowship.
References and Notes
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aromatic ring have also been detected by GC analysis.
[10] Non-catalyzed oxidations of alkanes with H2O2 in pure
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Chem. Soc. Chem. Commun. 1976, 1051; b) N. C. Deno,
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Adv. Synth. Catal. 2005, 347, 703–705
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