Alkane oxygenation with H2O2 catalysed by FeCl 3 and 2,2′-bipyridine

Article abstract of DOI:10.1016/j.tetlet.2005.05.007

The H₂O₂-FeCl₃-bipy system in acetonitrile efficiently oxidises alkanes predominantly to alkyl hydroperoxides. Turnover numbers attain 400 after 1 h at 60°C. It has been assumed that bipy facilitates proton abstraction from a H₂O₂ molecule coordinated to the iron ion (these reactions are stages in the catalytic cycle generating hydroxyl radicals from the hydrogen peroxide). Hydroxyl radicals then attack alkane molecules finally yielding the alkyl hydroperoxide.

Full text of DOI:10.1016/j.tetlet.2005.05.007

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4563–4567
Alkane oxygenation with H2O2 catalysed
by FeCl3 and 2,20-bipyridine
Georgiy B. Shulꢀpin,a,* Camilla C. Golfeto,b Georg Suss-Fink,c
¨
Lidia S. Shulꢀpinad and Dalmo Mandellib
aSemenov Institute of Chemical Physics, Russian Academy of Sciences, ulitsa Kosygina, dom 4, Moscow 119991, Russia
b
´ ´
Pontifıcia Universidade Catolica de Campinas, Faculdade de Quımica, Rod. D. Pedro I, km 136, Pq. das Universidades,
´
13020-904, Campinas, SP 13086-900, Brazil
c
´
ˆ
ˆ
Institut de Chimie, Universite de Neuchatel, Avenue de Bellevaux 51, CH-2007 Neuchatel, Switzerland
dNesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ulitsa Vavilova, dom 28, Moscow 119991, Russia
Received 27 March 2005; revised 26 April 2005; accepted 4 May 2005
Available online 23 May 2005
Abstract—The H2O2–FeCl3–bipy system in acetonitrile efficiently oxidises alkanes predominantly to alkyl hydroperoxides. Turnover
numbers attain 400 after 1 h at 60 ꢀC. It has been assumed that bipy facilitates proton abstraction from a H2O2 molecule coordi-
nated to the iron ion (these reactions are stages in the catalytic cycle generating hydroxyl radicals from the hydrogen peroxide).
Hydroxyl radicals then attack alkane molecules finally yielding the alkyl hydroperoxide.
ꢁ 2005 Elsevier Ltd. All rights reserved.
Iron ions surrounded with certain N-containing ligands
can activate molecular oxygen and they play an extre-
mely important role in nature, particularly in oxidations
of alkanes and other hydrocarbons (see reviews1–7). Sur-
prisingly, in vitro ꢁsimpleꢀ iron derivatives are usually
poor catalysts for hydrocarbon oxidations with hydro-
gen peroxide.8,9 Iron complexes containing N-ligands
exhibit higher catalytic activity in comparison with ꢁsim-
pleꢀ salts, and amines added to the reaction solutions
either accelerate oxidations or/and significantly change
their selectivity.10–28
0.08
0.06
0.04
0.02
0
CyOOH
-one
In the course of our systematic studies of iron-
catalysed hydrocarbon oxygenations with per-
oxides4,5,7,12,23,24,27,28 we decided to explore the
possibility of enhancing the efficiency of the reaction
by addition of certain amines (see a review on the dra-
matic role of additives in metal-catalysed hydrocarbon
oxygenations in solutions4). In the present paper we
report that 2,20-bipyridine (bipy) added to iron(III)
x
x
-ol
x
x
x
x
0
1
2
3
4
Time / hours
Figure 1. Cyclohexane (0.55 mol dmꢀ3) oxidation with 35% aqueous
H2O2 (1.2 mol dmꢀ3) catalysed by FeCl3 (5 · 10ꢀ4 mol dmꢀ3) and bipy
(5 · 10ꢀ3 mol dmꢀ3). Accumulation of cyclohexyl hydroperoxide
(ROOH), cyclohexanol (–ol) and cyclohexanone (–one) (concentra-
tions of –ol and –one were measured twice before and after reduction
of the reaction mixture with PPh3) with time is shown. The
temperature was 60 ꢀC, and the solvent was acetonitrile.
Keywords: Alkanes; Alkyl hydroperoxides; Biomimetics; Homo-
geneous catalysis; Hydrogen peroxide; Hydroperoxidation; Iron com-
plexes; Oxygenation.
*
Corresponding author. Fax: +7 095 1376130; e-mail: Shulpin@
chph.ras.ru
URL: http://members.fortunecity.com/shulpin.
0040-4039/$ - see front matter ꢁ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.007

4564
G. B. Shul’pin et al. / Tetrahedron Letters 46 (2005) 4563–4567
chloride used as a catalyst dramatically accelerates oxi-
dation of alkanes with hydrogen peroxide in acetonitrile
solution. The oxidations were carried out in air in
thermostated (60 ꢀC) Pyrex cylindrical vessels with vig-
orous stirring. The total volume of the reaction solution
was 5 mL. In our experiments, aqueous solutions of
hydrogen peroxide were used: either 35% (ꢁFlukaꢀ) or
mL) were taken. Samples of the reaction solutions were
usually analysed by GC (instruments ꢁHP Series 6890ꢀ
and ꢁDANI-86.10ꢀ; fused silica capillary columns) twice,
before and after addition of an excess of solid triphenyl-
phosphine. Triphenylphosphine reduces hydrogen per-
oxide to water and the alkyl hydroperoxide to the
corresponding alcohol, and the comparison of the reac-
tion chromatograms before and after the reduction
allowed us to estimate the real concentrations of the
alkyl hydroperoxide, formed from the alkane, as well
as the concentrations of the alcohol and the ketone.
This method was developed and used by us previ-
ously.4,5,7,12,23,24,27–30 In the kinetic studies presented
below, we measured the concentrations of the cyclohex-
anone and cyclohexanol only after reduction with PPh3
because in this way we obtained more precise values of
the initial reaction rates.
´
70% (ꢁPeroxidos do Brasilꢀ). The catalyst, FeCl3Æ6H2O,
and the co-catalyst, bipy, were introduced into the reac-
tion mixture in the form of stock solutions in aceto-
nitrile. After given time intervals, samples (about 0.2
bipy / Fe = 0
-ol
bipy / Fe = 1
-ol
0.04
0.03
0.02
0.01
0.0
b
a
c
e
-one
-ol
-one
0.06
0.04
0.02
[FeCl3] = 0.5 × 10−4
[FeCl3] = 1 × 10−4
a
b
bipy / Fe = 1.5
0.04
0.03
0.02
0.01
0.0
d
-ol
-ol
-ol
bipy / Fe = 2
-one
-one
-one
0.0
-one
bipy / Fe = 4
-ol
c
0.06
[FeCl3] = 5 × 10−3
d
-ol
-ol
[FeCl3] = 5 × 10−4
bipy / Fe = 6
-ol
0.04
0.02
0.0
0.04
0.03
0.02
0.01
0.0
f
-one
-one
-one
0
1
2
3
0
1
2
3
-one
Time / hours
[bipy] / mmol dm−3
4 6
0
1
2
3
0
1
2
3
0
2
8
10 12
Time / hours
15
10
e
g
80
40
0
5
0
0
1
2
3
4
5
6
[FeCl3] / mmol dm−3
0
1
2
3
4
5
6
bipy / Fe
Figure 3. Cyclohexane (0.5 mol dmꢀ3) oxidation with 70% aqueous
H2O2 (0.5 mol dmꢀ3) catalysed by the ꢁFeCl3–bipyꢀ system at various
concentrations of both FeCl3 and bipy at constant ratio bipy/
FeCl3 = 2. Accumulation of cyclohexanol (–ol) and cyclohexanone
(–one) (concentrations were measured after reduction of the reaction
mixture with PPh3) (graphs a–d) and dependence of initial rate of
formation of all oxygenates W0 on the concentration of FeCl3 and bipy
(graph e) are shown. The temperature was 60 ꢀC, the solvent was
acetonitrile.
Figure 2. Cyclohexane (0.5 mol dmꢀ3) oxidation with 70% aqueous
H2O2 (0.5 mol dmꢀ3 catalysed by FeCl3 (1 · 10ꢀ4 mol dmꢀ3
at
various concentrations of added bipy. Accumulation of cyclohexanol
(–ol) and cyclohexanone (–one) (concentrations were measured after
reduction of the reaction mixture with PPh3) (graphs a–f) and
dependence of initial rate of formation of oxygenates W0 on the
bipy/Fe ratio (graph g) are shown. The temperature was 60 ꢀC, the
solvent was acetonitrile.
)
)

G. B. Shul’pin et al. / Tetrahedron Letters 46 (2005) 4563–4567
4565
Oxidation of cyclohexane by the H2O2–FeCl3–bipy sys-
tem gave rise to formation of cyclohexyl hydroperoxide
predominantly which was transformed in the course of
the reaction into cyclohexanol and cyclohexanone
(Fig. 1). Turnover numbers (total moles of products
produced per one mole of a catalyst; TONs) attained 205
was ca. 35 times higher in the reaction co-catalysed by
bipy in comparison with the reaction in the absence of
bipy (compare graphs a, d and e in Fig. 2).
Figure 3 demonstrates reaction profiles for cyclohex-
ane oxidations at various catalyst concentrations (with
fixed ratio bipy/Fe = 2). Maximum initial rate was
attained at [FeCl3] = 2 · 10ꢀ3 mol dmꢀ3 and [bipy] =
4 · 10ꢀ3 mol dmꢀ3 (graph e). It is interesting that at
high concentrations of the catalytic system, the cyclo-
hexyl hydroperoxide formed in the alkane oxygenation
process decomposed extensively to produce substantial
amounts of the corresponding ketone (compare graph
a with graph c and especially with graph d). Thus, it
after 2.5 h at [FeCl3] = 5 · 10ꢀ4 mol dmꢀ3
.
When the concentration of FeCl3 was lower
(1 · 10ꢀ4 mol dmꢀ3) we measured TON = 410 after 1 h
(Fig. 2, graph d). At this catalyst concentration, the
maximum initial rate of the cyclohexane oxygenation
was found for the ratio bipy/Fe = 2–4 (Fig. 2, graph
g). It should be noted that the initial oxidation rate
Table 1. Selectivities of alkane oxidations by various systems in MeCNa
Entry
System
Hydrocarbon oxidised (the selectivity parameter)
n-Hexane
1:2:3
3-MH
2,4,4-TMP
MCH
cis-1,2-DMCH
1ꢀ:2ꢀ:3ꢀ
1:2.0:8.8
1ꢀ:2ꢀ:3ꢀ
1ꢀ:2ꢀ:3ꢀ
1:4.7:14.7
trans/cis
1
2
3
4
5
6
H2O2–FeCl3–bipy
H2O2–FeCl3
1:5.1:6.7
1:3.7:10.5
1:7:57
1:5: 45
1:2:6
0.85
1.0b
H2O2–Fe(ClO4)3
H2O2–hm
1:9:9
1:10:7
1:4:30
1:4:12
1:4:30
0.9
H2O2–VOꢀ3 –PCAc
H2O2–[LMnIV(O)3MnIVL]2+d
1:8:7
1:42:37:34e
1:5.7:22
1:22:200
1:4:9
1:5:55
1:6:22
1:26:200
0.75
0.34
a The concentrations of alcohols formed in the reaction were measured after reduction with PPh3. Substrates: 3-methylhexane, 3-MH; 2,4,4-
trimethylpentane, 2,4,4-TMP (isooctane); methylcyclohexane, MCH; cis-1,2-dimethylcyclohexane, cis-1,2-DMCH. Parameter 1:2:3 is normalised
(i.e., calculated taking into account the number of hydrogen atoms at each position) relative reactivities of hydrogen atoms in positions 1, 2 and 3 of
the hydrocarbon chain, respectively. Parameter 1ꢀ:2ꢀ:3ꢀ is the normalised relative reactivities of hydrogen atoms at primary, secondary and tertiary
carbons, respectively. Parameter trans/cis = [trans-ol]/[cis-ol] is the ratio of concentrations of tertiary alcohols trans-ol and cis-ol formed in the
oxidation of cis-1,2-dimethylcyclohexane.
b cis-Decalin was used instead of cis-1,2-DMCH.
c PCA, pyrazine-2-carboxylic acid. For this system, see Refs. 1,2,4,5,23,29,31,32.
d Complex [LMnIV(O)3MnIVL]2+, where L = 1,4,7-trimethyl-1,4,7-triazacyclononane. The oxidation at 20 ꢀC proceeds only in the presence of
CH3COOH in low concentration. For this system, see Refs. 2,4,5,33–38.
e
n-Heptane was used instead of n-hexane.
H2O2
OH
OH
OH
OH
H
N
N
FeIII
FeIII
FeIII
FeIII
N
N
N
O
OH
O
OH
O
OH
N
H
N
H
N
B
C(2)
C(1)
A
HOH
FeIII
HO
H2O2
HOO
H2O
N
N
FeII
FeII
FeII
N
N
N
O
OH
O
OH
O
OH
N
N
H
N
H
G
D
F
E
N
is bipy
N
Scheme 1. Catalytic cycle proposed for hydroxyl radical generation from hydrogen peroxide catalysed by an iron(III) complex and assisted with
bipyridine.

4566
G. B. Shul’pin et al. / Tetrahedron Letters 46 (2005) 4563–4567
2. Shilov, A. E.; Shulꢀpin, G. B. Activation and Catalytic
Reactions of Saturated Hydrocarbons in the Presence of
Metal Complexes; Kluwer Academic: Dordrecht/Boston/
London, 2000, Chapter X (Homogeneous catalytic oxida-
tion of hydrocarbons by peroxides and other oxygen atom
donors).
can be concluded that the FeCl3–bipy combination in
acetonitrile is a catalyst for transformation of alkyl
hydroperoxides into the corresponding ketones.
Selectivity parameters for the oxidation of certain
hydrocarbons by H2O2–FeCl3–bipy are given in Table
1, which also summarises the corresponding data for
other alkane-oxygenating systems, particularly for the
H2O2–VOꢀ3 –PCA reagent which is known to generate
hydroxyl radicals,1,2,4,5,23,29,31,32 and for H2O2–LMnIV-
(O)3MnIVL–CH3COOH (where L = 1,4,7-trimethyl-1,4,
7-triazacyclononane) system2,4,5,33–38 which is believed
to oxidise alkanes via attack of Mn(V)@O species on a
C–H bond. It can be seen that oxidations of all the test
hydrocarbons proceeded with low selectivity parameters
which are close to the parameters determined for the hy-
3. Dunford, H. B. Coord. Chem. Rev. 2002, 233–234, 311–
318.
4. Shulꢀpin, G. B. J. Mol. Catal. A: Chem. 2002, 189, 39–66.
5. Shulꢀpin, G. B. C. R. Chim. 2003, 6, 163–178.
6. Friesner, R. A.; Baik, M.-H.; Gherman, B. F.; Guallar, V.;
Wirstam, M.; Murphy, R. B.; Lippard, S. J. Coord. Chem.
Rev. 2003, 238–239, 267–290.
7. Shulꢀpin, G. B. Oxidations of C–H Compounds Catalyzed
by Metal Complexes, 2nd ed. In Transition Metals for
Organic Synthesis; Beller, M., Bolm, C., Eds.; Wiley–
VCH: Weinheim/New York, 2004; Vol. 2, pp 215–242,
Chapter 2.2.
droxyl-generating systems: H2O2–hm and H2O2–VOꢀ–
3
PCA. The oxidation of a disubstituted cyclohexane
was not a stereoselective reaction.
8. Gozzo, F. J. Mol. Catal. A: Chem. 2001, 171, 1–22.
9. Buda, F.; Ensing, B.; Gribnau, M. C. M.; Baerends, E. J.
Chem. Eur. J. 2003, 9, 3436–3444.
10. Nam, W.; Valentine, S. New J. Chem. 1989, 13, 677–682.
11. Fish, R. H.; Konings, M. S.; Oberhausen, K. J.; Fong, R.
H.; Yu, W. M.; Christou, G.; Vincent, J. B.; Coggin, D.
K.; Buchanan, R. M. Inorg. Chem. 1991, 30, 3002–3006.
12. Shulꢀpin, G. B.; Nizova, G. V. React. Kinet. Catal. Lett.
1992, 48, 333–338.
13. Perkins, M. J. Chem. Soc. Rev. 1996, 229–236.
14. Kulikova, V. S.; Gritsenko, O. N.; Shteinman, A. A.
Mendeleev Commun. 1996, 119–120.
All these data clearly testify that the mechanism of al-
kane oxidation by the H2O2–FeCl3–bipy system in ace-
tonitrile includes the formation of free hydroxyl
radicals. Scheme 1 shows a catalytic cycle which we pro-
pose for hydroxyl radical generation by the system
under consideration. One can assume that the role of
bipy is proton transfer (via protonation–deprotonation
steps of the N-atom) of a coordinated H2O2 molecule
(structure B) to an –OH ligand resulting in the forma-
tion of a hydroperoxyl derivative E. Bipyridine could
also assist the transformation of F to G. Species G gen-
erates a hydroxyl radical with the simultaneous conver-
sion into the starting species A.
15. Liu, C.; Ye, X.; Zhan, R.; Wu, Y. J. Mol. Catal. A: Chem.
1996, 112, 15–22.
´
16. Menage, S.; Vincent, J. M.; Lambeaux, C.; Fontecave, M.
J. Mol. Catal. A: Chem. 1996, 113, 61–75.
´
17. Duboc-Toia, C.; Menage, S.; Lambeaux, C.; Fontecave,
M. Tetrahedron Lett. 1997, 38, 3727–3730.
18. Nishino, S.; Hosomi, H.; Ohba, S.; Matsushima, H.;
Tokii, T.; Nishida, Y. J. Chem. Soc., Dalton Trans. 1999,
1509–1513.
Acknowledgements
´
19. Mekmouche, Y.; Duboc-Toia, C.; Menage, S.; Lambeaux,
C.; Fontecave, M. J. Mol. Catal. A: Chem. 2000, 156, 85–89.
20. Roelfes, G.; Lubben, M.; Hage, R.; Que, L., Jr. Chem.
Eur. J. 2000, 6, 2152–2159.
The authors thank the Swiss National Science Founda-
tion, the State of Sa˜o Paulo Research Foundation (Fun-
dac¸a˜o de Amparo a Pesquisa do Estado de Sa˜o Paulo,
FAPESP), the Brazilian National Council on Scientific
and Technological Development (Conselho Nacional
´ ´
21. Breheret, A.; Lambeaux, C.; Menage, S.; Fontecave, M.;
Dallemer, F.; Fache, E.; Pierre, J.-L.; Chautemps, P.;
´
´
´
Averbusch-Pouchot, M.-T. C. R. Acad. Sci. Paris, Serie
IIc, Chem. 2001, 4, 27–34.
22. Chen, K.; Que, L., Jr. J. Am. Chem. Soc. 2001, 123, 6327–
´
de Desenvolvimento Cientifico e Tecnologico, CNPq,
Brazil) and the Russian Basic Research Foundation
for support. This work was also supported by a grant
from the Section of Chemistry and Material Science of
the Russian Academy of Sciences (Program ꢁA theoreti-
cal and experimental study of chemical bonds and mech-
anisms of main chemical processesꢀ).
G. B. Shulꢀpin expresses his gratitude to the Swiss
National Science Foundation (Grant No. 20-64832.01),
the FAPESP (Grant No. 2002/08495-4), the CNPq
6337.
23. Shulꢀpin, G. B.; Kozlov, Y. N.; Nizova, G. V.; Suss-Fink,
¨
G.; Stanislas, S.; Kitaygorodskiy, A.; Kulikova, V. S. J.
Chem. Soc., Perkin Trans. 2 2001, 1351–1371.
24. Nizova, G. V.; Krebs, B.; Suss-Fink, G.; Schindler, S.;
¨
Westerheide, L.; Gonzalez Cuervo, L.; Shulꢀpin, G. B.
Tetrahedron 2002, 58, 9231–9237.
´
25. Balogh-Hergovich, E.; Speier, G.; Reglier, M.; Giorgi, M.;
´
Kuzmann, E.; Vertes, A. Eur. J. Inorg. Chem. 2003, 1735–
´
´
(Grant No. 300601/01-8), Institut de Chimie, Universite
de Neuchatel and the Faculdade de Quımica, Pontifıcia
1740.
26. Paczesniak, T.; Sobkowiak, A. J. Mol. Catal. A: Chem.
ˆ
´
´
´
2003, 194, 1–11.
´
Universidade Catolica de Campinas for making it
possible for him to stay at these Universities as invited
Professor and to perform a part of the presentwork.
27. Shulꢀpin, G. B.; Stoeckli-Evans, H.; Mandelli, D.; Kozlov,
Y. N.; Tesouro Vallina, A.; Woitiski, C. B.; Jimenez, R. S.;
Carvalho, W. A. J. Mol. Catal. A: Chem. 2004, 219, 255–
264.
28. Shulꢀpin, G. B.; Nizova, G. V.; Kozlov, Y. N.; Gonzalez
References and notes
Cuervo, L.; Suss-Fink, G. Adv. Synth. Catal. 2004, 346,
317–332.
¨
1. Shilov, A. E.; Shulꢀpin, G. B. Chem. Rev. 1997, 97, 2879–
2932.
29. Shulꢀpin, G. B.; Attanasio, D.; Suber, L. J. Catal. 1993,
142, 147–152.

G. B. Shul’pin et al. / Tetrahedron Letters 46 (2005) 4563–4567
4567
30. Shulꢀpin, G. B.; Nizova, G. V.; Kozlov, Y. N. New J.
Chem. 1996, 20, 1243–1256.
35. Shulꢀpin, G. B.; Nizova, G. V.; Kozlov, Y. N.; Pechenk-
ina, I. G. New J. Chem. 2002, 26, 1238–1245.
31. de la Cruz, M. H. C.; Kozlov, Y. N.; Lachter, E. R.;
Shulꢀpin, G. B. New J. Chem. 2003, 27, 634–638.
32. Kozlov, Y. N.; Nizova, G. V.; Shulꢀpin, G. B. J. Mol.
Catal. A: Chem. 2005, 227, 247–253.
36. Nizova, G. V.; Bolm, C.; Ceccarelli, S.; Pavan, C.;
Shulꢀpin, G. B. Adv. Synth. Catal. 2002, 344, 899–905.
37. Woitiski, C. B.; Kozlov, Y. N.; Mandelli, D.; Nizova, G.
V.; Schuchardt, U.; Shulꢀpin, G. B. J. Mol. Catal. A:
Chem. 2004, 222, 103–119.
38. Shulꢀpin, G. B.; Nizova, G. V.; Kozlov, Y. N.; Arutyunov,
V. S.; dos Santos, A. C. M.; Ferreira, A. C. T.; Mandelli,
D. J. Organomet. Chem., in press.
33. Shulꢀpin, G. B.; Suss-Fink, G.; Lindsay Smith, J. R.
¨
Tetrahedron 1999, 55, 5345–5358.
34. Shulꢀpin, G. B.; Suss-Fink, G.; Shulꢀpina, L. S. J. Mol.
¨
Catal. A: Chem. 2001, 170, 17–34.