Observations on the transition-metal catalysed oxidation of alkanes in trifluoroacetic acid: Urea-hydrogen peroxide/TFA as a convenient method for the oxidation of unactivated C-H bonds

Article abstract of DOI:10.1039/b003074k

Oxidation of cyclohexane in TFA using 30% aqueous H₂O₂ or urea-H₂O₂ (UHP) gives cyclohexyl trifluoroacetate in good yield, although the reaction is not accelerated by rhodium or ruthenium catalysts casting doubt

Full text of DOI:10.1039/b003074k

Observations on the transition-metal catalysed oxidation of alkanes in
trifluoroacetic acid: urea–hydrogen peroxide/TFA as a convenient method for
the oxidation of unactivated C–H bonds
Christopher J. Moody and Jenny L. O’Connell
School of Chemistry, University of Exeter, Stocker Road, Exeter, UK EX4 4QD. E-mail: c.j.moody@ex.ac.uk
Received (in Liverpool, UK) 17th April 2000, Accepted 22nd May 2000
Oxidation of cyclohexane in TFA using 30% aqueous H2O2
or urea–H2O2 (UHP) gives cyclohexyl trifluoroacetate in
good yield, although the reaction is not accelerated by
rhodium or ruthenium catalysts casting doubt on earlier
claims on the role of transition-metals in oxidations in
TFA.
did indeed occur as evidenced by gas chromatographic analysis
which clearly showed disappearance of the hydrocarbon and
formation of the ester over 12 h (Fig. 1). When the blank
experiment was run under identical conditions but in the
absence of the rhodium complex a very similar plot was
obtained (Fig. 1). The results show that this particular oxidation
of cyclohexane clearly proceeds in the absence of the metal
complex, and furthermore dirhodium tetraacetate does not
catalyse the reaction.
In order to obtain rate constants for the oxidation of
cyclohexane in TFA, aqueous H2O2 was replaced by the urea
hydrogen peroxide complex (UHP), a convenient solid source
of anhydrous H2O2. This enabled the use of a large excess of
peroxide to create pseudo-first order reaction conditions. Under
these conditions (2.5 mmol cyclohexane in 2 ml CH2Cl2, 22
mmol UHP, 10 ml TFA), rates for the oxidation of cyclohexane
in the presence (k = 2.9 3 1025 M21 s21) and absence (k = 3.3
3 1025 M21 s21) of dirhodium tetraacetate were readily
obtained (Fig. 2). Given the error in the determination of rate
constants (estimated as ±10%), the rates of these two reactions
are clearly similar. In both the 30% aqueous H2O2–TFA and
UHP–TFA oxidations, trace amounts of cyclohexanol were also
observed. In a separate blank experiment it was shown that
cyclohexanol is readily esterified in TFA, and therefore the
alcohol is presumably the initial product of oxidation.
We also investigated the use of ruthenium catalysts based on
the RuCl3–TFA system reported by Murahashi et al.,12 which
was also thought to involve a metal oxo complex as the oxidant.
Again it was evident that RuCl3 also had no effect on the rate of
cyclohexane oxidation in TFA (k = 3.1 3 1025 M21 s21).
Therefore, we conclude that claims of transition-metal catalysed
oxidations of hydrocarbons in peroxide–TFA systems should be
viewed with caution in cases where the appropriate blank
experiments have not been carried out. This view concurs with
that of Hogan and Sen who have independently concluded that
the role of the metal in C–H oxidation reactions carried out in
TFA needs to be reassessed.10,13
The oxidation of unactivated C–H bonds in alkanes is often
regarded as one of the Holy Grails of organic chemistry.1
Whereas in Nature such oxidations are efficiently carried out by
enzymes, there exists no single general laboratory or industrial
method, despite the undoubted commercial importance of such
a process. Nevertheless a number of methods have been
developed which do effect the oxidation of unactivated C–H
bonds: these include oxidations in superacid media,2 using
peroxide type reagents (including peracids, dioxiranes and
oxaziridines),3 ozone,4 various cytochrome P450 models,5 and
a range of metal mediated oxidations,6 including Gif chem-
istry.7 Much of the current work in this area focuses on the use
of transition-metal catalysed processes, and in view of our own
interest in reactions catalysed by dirhodium(II) carboxylates,8
we were intrigued to see a Chemical Communication in which
dirhodium tetraacetate was reported to catalyse the oxidation of
cyclohexane by hydrogen peroxide in TFA.9 As a prelude to
investigating the role of dirhodium(II) catalysts in other
oxidation reactions, we have reinvestigated this original work,
and report our results herein.
In their communication, Nomura and Uemura reported that a
variety of rhodium salts (0.1–0.3 mol%) catalysed the oxidation
of cyclohexane by 30% aqueous hydrogen peroxide in TFA.
The yields of cyclohexyl trifluoroacetate were consistently
62–65% irrespective of the rhodium salt used, and the authors
suggested a mechanism involving a highly reactive oxorhodium
species.9 The use of strongly acidic media is quite common in
metal catalysed oxidations of hydrocarbons since (a) the
conjugate base of a strong acid is a poor s-donor and therefore
enhances the electrophilicity of the metal ion, and (b) the
esterification of the alcohol, the primary product of alkane
oxidation, protects it from further oxidation.10 However, it
appears that the authors did not carry out a blank reaction in
TFA in the absence of the rhodium salt.9 This is somewhat
surprising since many years earlier Deno and Messer also
reported the oxidation of cyclohexane to cyclohexyl tri-
fluoroacetate (73% yield) under more or less identical condi-
tions (30% aqueous H2O2 in TFA) but in the absence of any
metal salt.11 Therefore our initial experiments were designed to
investigate this apparent anomaly (Scheme 1). When cyclohex-
ane (5 mmol) was treated with 30% aqueous H2O2 (15 mmol) in
TFA (12 ml) in the presence of dirhodium tetraacetate (1 mol%)
at room temperature, oxidation to cyclohexyl trifluoroacetate
Fig. 1 Cyclohexane consumption and cyclohexyl trifluoroacetate formation
vs. time in 30% aqueous hydrogen peroxide–TFA in the absence (2/Ω) or
presence (5/:) of dirhodium tetraacetate.
Scheme 1
DOI: 10.1039/b003074k
Chem. Commun., 2000, 1311–1312
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Table 1 Preparative scale hydrocarbon oxidation using UHP–TFA
Fig. 2 Oxidation of cyclohexane by UHP–TFA in absence (2) or presence
(5) (1 mol%) of dirhodium tetraacetate, and oxidation of cyclohexane-d12
(.), where [A]0 is the initial concentration of cyclohexane.
In the work of Deno et al. using 30% aqueous H2O2 in
TFA,11,14 it was assumed that the active oxidant was peroxytri-
fluoroacetic acid which participated in a concerted oxidation
mechanism via a cyclic transition state, the electrophilic nature
of the oxidant being further enhanced by protonation (Scheme
2). To shed further light on the mechanism of the UHP–TFA
oxidation, we compared the rate of oxidation of cyclohexane
with its perdeuterated analogue (k = 1.4 3 1025 M21 s21) (Fig.
2). The observed kinetic isotope effect of 2.3 ± 0.2 is in accord
with previous studies using peracids as oxidants, and is possibly
indicative of a concerted (cf. Scheme 2) or oxenoid type
mechanism.3a Unfortunately alternative mechanisms involving
radical hydrogen abstractions cannot be completely ruled out,
since although such reactions usually exhibit a significantly
larger deuterium isotope effect (kH/kD ≈ 4–8),15 the isotope
effect can be as low as 1.16
The preparative oxidation of hydrocarbons was briefly
investigated, and some illustrative examples are shown in Table
1. Cyclohexane, cycloheptane (k = 6.4 3 1025 M21 s21) and
cyclooctane were all oxidized to the corresponding esters;
norbornane gave the ester of exo-norborneol as the major
product, and although adamantane was rapidly oxidized to the
tertiary ester, with no sign of the secondary ester by GC, the
product was unstable under the reaction conditions. n-Hexane
gave a mixture of 2- and 3-hexyl trifluoroacetates (ratio =
47 53) with no evidence for oxidation at the terminal methyl
group. Compounds containing aromatic rings (n-propylben-
zene, cumene, tetralin) were completely decomposed in either
30% aqueous H2O2–TFA or in UHP–TFA.17
catalysts, and therefore claims of metal catalysis of related
reactions in TFA should be viewed with caution.
This work was supported by the EPSRC.
Notes and references
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10 A. Sen, Acc. Chem. Res., 1998, 31, 550.
In summary, we have shown that UHP–TFA is a simple
system for the oxidation of unactivated C–H bonds in alkanes;
such reactions are not accelerated by rhodium or ruthenium
11 N. C. Deno and L. A. Messer, J. Chem. Soc., Chem. Commun., 1976,
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12 S. Murahashi, Y. Oda, N. Komiya and T. Naota, Tetrahedron Lett.,
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14 N. C. Deno, E. J. Jedziniak, L. A. Messer, M. D. Meyer, S. G. Stroud and
E. S. Tomezsko, Tetrahedron, 1977, 33, 2503.
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17 Cf. N. C. Deno, B. A. Greigger, L. A. Messer, M. D. Meyer and S. G.
Stroud, Tetrahedron Lett., 1977, 1703.
Scheme 2
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Chem. Commun., 2000, 1311–1312