Mechanistic diversity of the selective oxidations mediated by supported iron phthalocyanine complexes

Article abstract of DOI:10.1039/b511231a

Selective oxidations of (i) phenols and condensed aromatics to quinones and (ii) alkynes to α,β-acetylenic ketones mediated by supported iron phthalocyanine complexes exhibit very different mechanistic features as evidenced by ¹⁸O labelling and kinetic isotope effect studies. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2005.

Full text of DOI:10.1039/b511231a

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L E T T E R
Mechanistic diversity of the selective oxidations mediated by
supported iron phthalocyanine complexes
´ ´
Celine Perollier, Corinne Pergrale-Mejean and Alexander B. Sorokin*
Institut de Recherches sur la Catalyse, UPR 5401, 2 avenue A. Einstein, 69626 Villeurbanne
Cedex, France. E-mail: sorokin@catalyse.cnrs.fr; Fax: (þ33) 4 72 44 53 99;
Tel: (þ33) 4 72 44 53 37
Received (in Montpellier, France) 5th August 2005, Accepted 14th September 2005
First published as an Advance Article on the web 28th September 2005
Selective oxidations of (i) phenols and condensed aromatics to
quinones and (ii) alkynes to a,b-acetylenic ketones mediated by
supported iron phthalocyanine complexes exhibit very different
mechanistic features as evidenced by 18O labelling and kinetic
isotope effect studies.
phenols and alkynes are listed in Table 1. Except for the very
demanding oxidation of 2-methylnaphthalene, the FePcS–SiO2
catalyst in combination with TBHP was very efficient in
aromatic oxidation, providing quinones in 84–91% yields.
Importantly, even phenols containing other oxidizable groups,
e.g. methyl and acetamide groups, could be oxidized into
corresponding valuable quinones with high selectivity. For
example, trimethyl-1,4-benzoquinone, obtained by oxidation
of 2,3,6-trimethylphenol, is the precursor of vitamin E. A high
selectivity of this catalytic system was further demonstrated in
the a-oxidation of alkynes while the triple bond was left intact
(Table 1). Highly useful a,b-acetylenic ketones were obtained
in up to 84% yield. Such conjugated a,b-acetylenic ketones are
usually prepared by multistep synthesis. Only a few homo-
geneous methods have been reported using direct alkyne
oxidation.9 To the best of our knowledge this is the first
heterogeneous catalytic system for the selective oxidation of
alkynes to a,b-acetylenic ketones.
Catalytic homogeneous oxidation of alkanes and olefins
using metal complexes has been an object of numerous stu-
dies.1,2 By contrast, the reports on the selective catalytic
oxidation of aromatic compounds and alkynes are rather
scarce. The oxidation of aromatics provides quinones used
for the preparation of drugs and vitamins.3 a,b-Acetylenic
ketones obtained via selective oxidation of alkynes are valuable
precursors for the enantioselective total syntheses and prepara-
tion of heterocyclic compounds, nucleosides, etc.4,5 Halogen or
heavy metal based stoichiometric oxidants are usually applied
to perform these oxidations thus leading to severe environ-
mental problems. The quest for efficient catalytic methods that
use clean oxidants such as dioxygen or peroxides and hetero-
geneous catalysts still remains an important challenge. The
catalysts immobilized on solid supports are especially attrac-
tive because they allow easy separation from the reaction
mixture and possible recycling. Phthalocyanine metal com-
plexes resemble porphyrin complexes widely used by Nature
in the active sites of oxygenases. By contrast to porphyrins, a
cheap and facile preparation of phthalocyanines, their avail-
ability at a large scale as well as their chemical and thermal
stability make them industrially viable candidates for oxidation
catalysis. Indeed, we have recently shown that iron tetrasulfo-
phthalocyanine (FePcS–SiO2) and iron hexadecachlorophtha-
locyanine (FePcCl16–SiO2) covalently supported onto silica are
efficient catalysts in the selective oxidation of phenols6–8 and
Then the question arises: what mechanism is operating to
provide such a high selectivity in the oxidation of these
polyfunctionalized substrates? It should be noted that mechan-
ism(s) of oxidation by peroxides in the presence of iron
complexes is an important topic in oxidation catalysis and a
subject of numerous studies and discussions.10 We used 18O
labelling11,12 and isotope effects13 to gain insight on the
mechanism of the heterogeneous oxidation.
t
The oxidation of several substrates by BuOOH was per-
formed in the presence of 18O2 (Table 1). Isotopic compositions
of products and dioxygen in the gas phase were constant
during all reaction courses indicating no side reactions, e.g.
t
dioxygen evolution from BuOOH or oxygen exchange be-
tween dioxygen and products. A dramatic difference of 18O
labelling in two groups of substrates was observed. The
oxidation of alkynes occurred with significant 18O incorpora-
tion from 18O2 in both oct-4-yn-3-one (61.7%) and 4-phenyl-
but-3-yn-2-one (85.1%). To the contrary, a very low labelling
of products was observed during oxidation of anthracene A to
anthraquinone AQ (8.3%), 2,3,6-trimethylphenol to trimethyl-
quinone (2.3%) and xanthene to xanthone (1.6%). GC-MS
analysis of the oxidation products of A indicated that
anthrone, the first oxidation product of A, contained only
16O. Importantly, the isotopic molecular cluster in the mass
spectrum of AQ consisted of 208 [M]1 and 210 [M þ 2]1
meaning that the 18O atom was unambiguously located only in
one carbonyl group of this quinone. These results are quite
surprising since radicals, easily formed via 1 eꢀ oxidation of
these substrates, were expected to result in a significant 18O
content in oxidation products. Two key points emerge from the
systematic labelling study: (i) a very small percentage of 18O in
oxidation products of anthracene, trimethylphenol and
t
alkynes9 by BuOOH (TBHP). Beyond the synthetic utility, in
particular a high product yield and an easy separation and
recycling of catalyst, mechanistic aspects of these oxidations
are also of importance, especially when hydroperoxide oxidant
is involved. We report herein the selective oxidation of con-
densed aromatics to quinones with high yields and experimen-
tal evidence for multiple pathways in the FePc–SiO2 catalyzed
oxidation of aromatic compounds and alkynes.
The heterogeneous catalysts FePcS–SiO2 and FePcCl16–SiO2
were prepared as previously described6 and characterized by
chemical analysis, surface area determination and the diffuse
reflectance UV-Vis spectroscopy that evidenced the effective
complex grafting. The contents of complexes were determined
by metal analysis using an inductively coupled plasma-mass
spectroscopy method to be 21–25 mmol gꢀ1 (for FePcCl16–
SiO2) and 35–40 mmol gꢀ1 (for FePcS–SiO2). Results of the
oxidations of three types of substrates, condensed aromatics,
T h i s j o u r n a l i s & T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 5
1400
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t
Table 1 Oxidations of aromatics and alkynes by BuOOH catalyzed by FePcS–SiO2
a
Substrate
Product
Conversion (%)
100b
Yield (%)
90
18O Content (%)
8.3 ꢁ 0.4
70c
97b
45
84
91
n.d.
2.3 ꢁ 0.8
n.d.
100d
100d
75d,e,f
80d,e,f
84d,e,f
99
62
71
84
1.6 ꢁ 0.1
85.1 ꢁ 2.0
61.7 ꢁ 0.3
n.d.
a
Reaction conditions: 4 mmol catalyst, 0.4 mmol substrate, 2.24 mmol tBuOOH in CH3CN at 40 1C. Reaction time: 2 h for phenols, 7 h
b
c
d
for xanthene, 24 h for other substrates. n.d. ¼ not determined. In 1,1-dichloroethane. With 16 mmol catalyst. With 8 mmol catalyst.
e
t
In BuOH. With 1.6 mmol BuOOH.
f
t
xanthene is consistent with the involvement of iron phthalo-
cyanine centered species; and (ii) a large 18O incorporation in
acetylenic ketones suggests a possible involvement of free
radicals.
species in the catalytic cycle were identified and characterized
by different spectroscopic techniques, the catalytic chemistry of
metallophthalocyanines is practically not developed in terms of
oxidation mechanisms and active species involved. When using
tBuOOH as an oxidant one can suggest the initial formation of
PcSFeIII–OOtBu. By analogy with iron porphyrin chemistry,
To further probe the mechanisms of oxidation of the two
types of substrates, we have determined deuterium kinetic
isotope effects (KIE) in the oxidations of anthracene and oct-
4-yne. The KIE in anthracene oxidation was determined in
intermolecular competitive experiments using a 50 : 50 A-h10–
A-d10 mixture. Isotopic compositions of compounds were
determined by GC-MS, substrate conversions were obtained
by HPLC and KIEs were calculated as described.14 Analysis of
the reaction mixture after 2 h reaction (conversion being 68%)
indicated a preferential consumption of A-d10 resulting in a
KIE of 0.90 ꢁ 0.02 for the initial reaction step. This inverse
KIE cannot be interpreted as a primary KIE involving C–H(D)
bond cleavage in the rate determining step and excluded an
oxygen rebound type mechanism which involves H atom
abstraction from the substrate by an electrophilic high-valent
oxo-iron complex to give a short-life radical followed by a
rapid recombination step. Inverse KIEs are usually associated
with secondary KIEs when no C–H(D) is cleaved, but this
bond located at the reaction site itself (a-secondary KIE)
changes its parameters in the transition state (TS).14 Based
on calculations with model systems, the a-secondary KIEs
have been interpreted as reflecting the changes in the out-of-
plane bending motion, i.e. hybridization change or differences
in the loose/tight character of the TS.15,16 The activation
energy for sp2-to-sp3 hybridization change is lower for the
deuterated substrate compared to the non-deuterated analo-
gue, creating then an inverse KIE.17 The aromatic hydroxyla-
tion of o- and p-xylene, catalyzed by cytochrome P-450,
showed also an inverse a-secondary KIE (0.83–0.94) which
has been explained by an addition reaction of an oxo-iron
species onto an sp2-hybridized carbon atom.18 Similarly, the
inverse KIE observed in anthracene oxidation strongly sug-
gests the formation of a s-complex between the substrate and
putative oxo-iron phthalocyanine species. It should be noted
that, in contrast with well-documented iron porphyrin chem-
istry relevant to cytochrome P-450, where intermediate active
this peroxo complex can undergo homolytic cleavage of the
O–O bond to give PcSFeIV O and a BuOd radical, or to
t
Q
produce PcSFeV O via heterolytic O–O cleavage. A low
Q
incorporation of 18O in AQ and no 18O labelling of anthrone
(the first oxidation product of A) observed by GC-MS, coupled
with an inverse KIE in the first oxidation step favor an FePcS-
based active species having two redox equivalents above the
FeIII state. An electrophilic attack of this species at an sp2 C9
atom of A to give a s-complex is probably the first step
(Scheme 1).
The inverse KIE indicative of a sp2-to-sp3 rehybridization in
the TS, no 18O incorporation into anthrone and the location of
8.3% of labelled oxygen only in one carbonyl position of
quinone are consistent with the proposed mechanism. An
intramolecular eꢀ transfer can lead to an intermediate carboca-
tion which cannot react with 18O2 and should be further
t
oxidized by BuOOH or FePcS-based species to give 91.7% of
unlabelled AQ. Otherwise, the intermediate radical s-complex
can be trapped by 18O2 to produce a small amount of labelled
AQ. A similar mechanism should also be operating in the
oxidations of 2,3,6-trimethylphenol and xanthene where smaller
18O incorporations, 2.3 and 1.6%, respectively, were observed
suggesting shorter lifetimes for intermediate radical species.
Oct-4-yne-1,2,3-d7 (98% isotope purity) having C–D and
C–H bonds in the same stereochemical environments was
prepared from pent-1-yne and 1-iodopropane-d7 for intramo-
lecular KIE determination:
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Scheme 1 Proposed mechanism of anthracene oxidation. ‘‘FeV O’’ stands for FePcS-based species having two redox equivalents above the
Q
FeIII state.
The intrinsic KIEs of the first oxidation step were measured
by GC-MS using the ratio of oct-4-yn-6-ol-d7 (C–H oxidation
Experimental
Solvents and chemicals were obtained from Sigma-Aldrich and
used without purification unless indicated. Anthracene-d10
product, major ion at m/z ¼ 104 corresponding to [M ꢀ
C2H5]1) and oct-4-yn-3-ol-d6 (C–D oxidation product, major
ion at m/z ¼ 98: [M ꢀ C2D5]1). The KIEs for the acetylenic
ketone formation were determined using the ratio of oct-4-yn-
6-one-d7 (C–H oxidation product, major ion m/z ¼ 102: [M ꢀ
C2H5]1) and oct-4-yn-3-one-d5 (C–D oxidation product, major
ion m/z ¼ 95: [M ꢀ C2D5]1). High KIEs obtained with the two
catalysts are consistent with C–H bond cleavage in the rate
limiting step (Table 2). The dependence of intramolecular KIE
on the catalyst structure strongly suggests the involvement of
FePc-based active species. The formation of ketone proceeds
via the cleavage of two C–H bonds. Higher KIE on ketone
formation indicates that oxidation of alcohol to ketone also
proceeds with significant isotope effect. These results, coupled
with high 18O incorporation in the reaction products from 18O2
(61.7% for oct-4-yne), may be rationalized as follows. At the
first rate limiting step, an FePc-based active species abstracts
an H atom from an a-position of the alkyne (Scheme 2). The
radical formed reacts with O2 to give an intermediate peroxo
radical leading to acetylenic ketones. The alkyne radical could
also react with an FePc-based species to give unlabelled
propargylic alcohol that can be rapidly converted to ketone.
To summarize, the oxidation of anthracene, 2,3,6-trimethyl-
phenol and xanthene by the FePcS–SiO2–tBuOOH catalytic
system occurs with a very low 18O incorporation from 18O2 to
products and an inverse KIE, indicating 2 eꢀ oxidation as a
principal pathway consistent with a high yield of quinones,
while coupling products should be obtained if a 1 eꢀ pathway is
operating. The oxidation of alkynes occurs with a significant
18O incorporation from 18O2 to reaction products and a high
KIE, suggesting an involvement of radical intermediates cor-
responding to one electron oxidation. The reason for this dual
reactivity is not yet clear. This finding might be reminiscent of
the involvement of multiple reaction pathways in the cyto-
chrome P-450 mediated oxidations explained by two-oxi-
dants19 and two-state reactivity models.20 The results
obtained indicate that a complexity of oxidation reactions is
a feature not only for porphyrin19,20 or non-heme complexes21
but probably a more general phenomenon. Further research is
in progress in order to understand whether two different
species could be involved or if one active species would be
able to adapt its mechanism of action depending on the
substrate.
(Acros, 99þ atom% D) was purified by sublimation. 1-Iodo-
propane-d7 (Eurisotope, 98% isotope purity) was used as
received. 18O2 (98.5 atom%) was purchased from Eurisotope.
The reaction products were identified and quantified by
NMR spectroscopy (AM 250 Bruker spectrometer), GC-MS
(Hewlett Packard 5973/6890 system; electron impact ionization
at 70 eV, He carrier gas, 30 m ꢂ 0.25 mm cross-linked 5%
PHME siloxane [0.25 mm coating] capillary column, HP-5MS),
GC (Agilent 4890D system, N2 carrier gas, 15 m ꢂ 0.25 mm
cross-linked 5% PHME siloxane [0.25 mm coating] capillary
column, HP-5MS) and HPLC (Agilent Series 1100, Eclipse
XDB-C8 column, MeCN–water ¼ 70 : 30, 0.8 mL minꢀ1, UV-
Vis detection) methods. The reaction courses were monitored
by GC and substrate conversions and product yields were
determined using an internal standard. Control experiments
in the absence of FePc under otherwise identical reaction
conditions showed a minor non-selective oxidation of oct-4-
yne (13% conversion, 5% ketone yield), 1-phenylbut-1-yne
(15% conversion, 8% ketone yield), anthracene (after 7 h: no
reaction; after 24 h: 30% conversion, 8% quinone yield),
trimethylphenol (21% conversion, 4% quinone yield). Other
substrates were completely stable under the reaction conditions
in the absence of the catalyst.
Preparation of oct-4-yne-d7
To a cold (ꢀ78 1C) stirred solution of pent-1-yne (600 mL, 6.1
mmol) in anhydrous THF (25 mL) was added n-BuLi (1.6 M in
hexane, 4 mmol) under argon. The solution was allowed to
t
Table 2 KIEs in the oxidation of oct-4-yne-d7 by BuOOHa
Catalyst
Alcohol kH/kD
Ketone kH/kD
FePcS–SiO2
FePcCl16–SiO2
3.5 ꢁ 0.7
6.5 ꢁ 0.3
9.3 ꢁ 0.7
18.1 ꢁ 0.6
a
t
T ¼ 40 1C, BuOH, 2 h, catalyst : substrate : oxidant ¼ 1 : 100 : 400.
Scheme 2 Proposed mechanism for alkyne oxidation.
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warm to room temperature before adding 1-iodopropane-d7
(328 mg, 1.9 mmol). The reaction mixture was stirred for two
hours at room temperature, then heated to 38 1C for 42 hours
until 1-iodopropane-d7 was consumed (GC control). The mix-
ture was cooled to 0 1C and quenched with saturated NH4Cl.
The product was then extracted with diethyl ether and purified
by distillation to give a pure product. GC-MS analysis indi-
cated 98% isotope purity (98.0% of oct-4-yne-d7 and 2.0% of
oct-4-yne). MS (EI) m/z (relative int.): 117 (100, [M]1), 102
(11, [M ꢀ CH3]1), 99 (14, [M ꢀ CD3]1), 88 (41, [M ꢀ C2H5]1),
83 (57, [M ꢀ C2D5]1).
substrate conversion was monitored by HPLC and isotopic
compositions of products and gas phase were analyzed by GC-
MS. Isotopic compositions of substrates left were determined
during 2 h of the reaction from the intensities of molecular
peaks at m/z ¼ 178/188.
Acknowledgements
The authors are grateful to French Ministry of Education,
Research and Technology for financial support and for doc-
toral (CPM) and postdoctoral (CP) fellowships.
18O2 experiments
References
18O incorporations in products were corrected on 18O natural
abundance and purity of 18O2. Reactions were carried out in
triplicate using an 18O2 (98.5 atom%) mixture with argon in a
ratio of 45 : 55 according to the following procedure. A 25 mL
flask was charged with 2 mL of 20 mM substrate solution in
acetonitrile and solid catalyst [1 mol% for anthracene and
trimethylphenol oxidation and 2 mol% for oxidation of
xanthene and alkynes]. The reaction mixture was submitted
to 3 freeze–pump–thaw cycles and the reaction flask was filled
up with the mixture containing about 45% of 18O2 (98.5
atom%) and 55% of argon. The reaction was started by the
addition of 3.5 M TBHP solution in PhCl. The reaction
temperature was 30 1C for TMP oxidation and 40 1C for other
substrates. The substrate conversion was monitored by HPLC
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for anthrone (tautomeric form of 9-hydroxyanthracene), m/z ¼
210/212 for oxanthrone (tautomeric form of 9,10-dihydro-
9,10-dihydroxyanthracene), m/z ¼ 208/210 for anthraquinone,
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xanthone (9-xanthenone). Isotopic compositions of the oxida-
tion of oct-4-yne and 1-phenylbut-1-yne were calculated as
described.9
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Oxidation of anthracene
Reactions were carried out in triplicate using an anthracene-
h10/anthracene-d10 mixture in 50 : 50 molar ratio. A 25 mL flask
was charged with 2 mL of 20 mM anthracene solution in 1,1-
dichloroethane and 1 mol% of solid catalyst. The reaction was
started by the addition of 3.5 M TBHP solution in PhCl. The
N e w J . C h e m . , 2 0 0 5 , 2 9 , 1 4 0 0 – 1 4 0 3
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