Oxidation of 3,5-di-tert-butylcatechol and 2-aminophenol by molecular oxygen catalyzed by an organocatalyst

Article abstract of DOI:10.1039/c5nj01405k

1,3,2-Oxazaphospholes are able to catalyze the oxidation of 3,5-di-tert-butylcatechol with ³O₂ to the corresponding o-quinone and 2-aminophenol to 2-aminophenoxazine-3-one in methanol. In both the cases, an overall third order reacti

Full text of DOI:10.1039/c5nj01405k

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Oxidation of 3,5-di-tert-butylcatechol and 2-
aminophenol by molecular oxygen catalyzed by an
organocatalyst†
Cite this: DOI: 10.1039/c3nj00000x
a
a
a
a
Gábor Székely, Nárcisz Bagi, József Kaizer * and Gábor Speier *
Received 00th XXXXX 2013,
Accepted 00th XXXXX 2013
DOI: 10.1039/c3nj00000x
www.rsc.org/njc
1
3
,3,2-Oxazaphospholes are able to catalyze the oxidation of Iodometric titration of the oxygenated solutions resulted in a
3
,5-di-tert-butylcatechol with O2 to the corresponding
o-
quinone and 2-aminophenol to 2-aminophenoxazine-3-one in
methanol. In both cases an overall third order reaction rate
equation and a new type of biomimetic organocatalyst for
oxidation reactions was found. A one electron transfer of the
phenolate, which is formed through deprotonation of
substrates by the catalyst, to dioxygen seems to be rate-
determining.
peroxide content in the range of 10-30%.11 This reminds one to
Oxidation reactions are widely applied in organic synthesis and in Scheme 1 General scheme for hydroperoxide formation and
oxidation/oxygenation with O .
2
chemical industry. Triplet dioxygen would be an economically and
1
environmentally successful candidate as primary oxidant, however
2
3
flavin models in which N,N,N-3,5,10-trialkylated flavins in its
spin restriction and thermodynamic burden lower its reactivity
and so its use in oxidation/oxygenation reactions is rather limited.
3
flavin hydroperoxides were observed.12 Pterins13
reaction with O
2
or even deprotonated uric acid14 form also hydroperoxides with
3O
. Since former studies of the reaction of 2,3-dihydro-2,2,2-
triphenylphenanthro[9,10- -oxazaphosphole 1) with
]1,3,2 5
triplet dioxygen evidenced that methanol is the best-suited solvent.
The reaction time for the oxygenation of the catalyst ( ) was below
(Eqn. 1) was formed under
Unfortunately, not just triplet dioxygen but also hydroperoxides
4
2
2
(even H O
2
) are sluggish oxidants and they need activation either
with the help of metalloenzymes (metal complexes)5 or organic
d
λ
(
compounds. Much work has been carried out the activation of
for
3O
6
7
1
2
or H
2
O by metal complexes, mainly of copper, iron, and other
2
8
5 min and an unstable hydroperoxide
ambient conditions.10
2
metals. Some organic co-factors and their mimics are also able to
9
form hydroperoxides, which oxidize various organic compounds.
We were interested to find organic compounds, which react with
3O
to hydroperoxides, just mimicking organic co-factors, and these
2
can oxidize several organic compounds either in a two or in a four
electron oxidation as shown in Scheme 1.
Recently we found that 1,3,2-oxazaphospholes under ambient
condition pick up molecular oxygen and form hydroperoxides (Eqn.
1
), which can transfer oxygen to triphenylphosphine forming the
oxide.10 The peroxide formed is not stable at room temperature.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2013
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DOI: 10.1039Jo/C
u
5
r
N
n
J
a
0
l
14
N
0
a
5Kme
-2 -1
As a continuation of our work on studies of models of organic of 0.76±0.11 and 0.62±0.03 M s respectively. The rates of the
cofactors in oxidation reactions we studied the reactions of some
phenolic compounds, namely 3,5-di-ter -butylcatechol (3a) and
aminophenol (3b), which are isoelectronic, with triplet dioxygen
catalyzed by 2,3-dihydro-2,2,2-triphenylphenantro [9,10- ]1,3,2- concentration (Fig. S2-S3†), on catalyst concentration (Fig. S4-S5†),
λ5-oxazaphosphole (
). Much work has been done until now on the the log 3b vs time of 3b oxidation (Fig. S6†) and on the initial
reaction were followed by UV-Vis spectroscopy at 400 (3a) (Fig. 2)
t
o-
and 434 (3b) (Fig. S1†) nm. A typical time plot of the oxidation of
3a and 3b can be seen in Fig. 1. The dependence on the dioxygen
d
1
oxidation of 3,5-di-tert-butylcatechol15 just to gain insight into the concentrations on 3a (Fig. S7†) and 3b (Fig. S8†) plotted against
possible mechanism of intra and extradiol cleavage of catechol the reaction rate gave straight lines, clearly evidenced that both
dioxygenases.
A
fair number of model oxidations of
o
-
reactions follow an overall third order rate equation. The activation
aminophenol16 have also been carried out as model reaction for 2- parameters for 3a oxidation are
ꢀ
E‡ = 34.03±03 kJmol-1,
ꢀ
H‡
=
aminophenoxazine-3-one synthase. The former enzyme contains
two copper ions in their active site,17 while 2-aminophenoxazine-3-
one synthase is a multicopper enzym
was obvious that we
triphenylphenanthro[9,10-
]1,3,2λ5-oxazaphosphole
e
catalyzed reaction.18 So it
tried 2,3-dihydro-2,2,2-
as
d
(
1)
a
bioinspired catalyst for catechol oxidation and a model reaction for
the flavin co-factor in the case of 2-aminophenoxazine-3-one
synthase. In their stoichiometric reactions beside of the
corresponding
beside of 2-aminophenoxazine-3-one (
). That was evidenced by O -uptake experiments (Fig. 1) and
iodometric titration of the solution.
o
-quinone (
4
) H
2
O
2
and in the case of
o-aminophenol
5
) H O is formed (Eqn. 2 and
2
3
2
1
1
ꢀ
2
Figure 2 Time dependence of the oxidation of 3a. [DTBCH
M, [1,3,2ꢀoxazaphosphole] = 12.5×10 M, [O
2
] = 12.5 × 10
ꢀ4
ꢀ3
2
] = 9.5 × 10 M, T = 298 K,
1
0 mL MeOH.
Kinetic studies of both reactions resulted in an overall third order 31.47±0.30 kJmol-1 and
rate equation (Eqn. 4) for 3a and and 3b with
obs values oxidation
E‡ = 38.08±0.41 kJmol-1,
S‡ = -129.58±0.66 Jmol K (Fig. S9-S10†).
ꢀ
S‡ = -142.04±0.55 Jmol K , and for 3
-1 -1
b
k
ꢀ
ꢀ
H‡ = 35.62±0.40 kJmol-1 and
-1
-1
ꢀ
reaction rate =
k
obs [catalyst] [O
2
] [3]
(4)
The KIE (Kinetic Isotope Effect) data of 1. 048 (3a) and 1.46 for 3b
oxidation (SFig. S11-S12†) are very small and also suggest that
protons are not involved in the rate-determining steps. We know
from earlier studies that there is an equilibrium between the ring
form 1,3,2-oxazaphosphole
(
1)
and the iminophosphorane
tautomer ( ) (Eqn. 5). The equilibrium in solution shifted to the
6
iminophosphorane tautomer
iminophosphorane tautomer (
(
6
).
Studies have shown that
6
) can be deprotonated by itself19,20
or it is able to deprotonate the substrates 3a and especially 3b to
the anion and to the protonated iminophosphorane 7.
8
Figure 1 Dioxygen-uptake of the oxidation of 3a (●) and 3b (■) catalyzed by
This proceeds probably via a charge transfer complex beetween
6
-
2
-3
1
. [3a] = 8.9 × 10 M, [catalyst] = 8.9 × 10 M, V = 10 mL, T = 60 °C; [3b] =
and (Scheme 2). This reaction is a fast pre-equlibrium (K ), which
3
1
-
2
-
3
8
.9 × 10 M, [catalyst] = 8.9 × 10 M, V = 10 mL, T = 60 °C.
is largely shifted to the site of the starting components. This
2
| J. Name., 2012, 00, 1-3
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DOI: 10.1039/C5NJ01405K
phenolate anion (
organic radical and superoxide anion. Phenolate anions are The use of 2,3-dihydro-2,2,2-triphenylphenanthro[9,10-
energyꢀrich molecules21 and can give up one electron to the ground oxazaphosphole (1) as an organic catalyst in the oxidation of 3,5-di-
8) reacts then in the rate-determining step to the good and the reactions can have preparative significance.
9
d -
]1,3,2λ5
state dioxygen to form the phenoxyl radical
anion.
9
and superoxide tert-butylcatechol
(
3a
)
and
o
-aminophenol
(
3b
)
to the
corresponding -quinone (
o
4
) and 2-aminophenoxazine-3-one (5)
by triplet dioxygen are preparative useful and kinetic
measurements resulted in an overall third order rate equation. The
single electron transfer fr
to the dioxygen forming
anion. These dismutase to
o
m
the deprotonated substrates 3a and 3b
-centered radical ) and superoxide
and 10 in fast reactions and also H is
ꢀaminophenol and subsequent
oxidation leads to 2ꢀaminophenoxazineꢀ3ꢀone ( ) (Eqn. 6).
2,3ꢀdihydroꢀ2,2,2ꢀtriphenylphenanthro[9,10ꢀ
ꢀoxazaphosphole (1) is a new organic oxidation catalyst,
O
s (9
4
2 2
O
formed. 10b reacts then further with
o
5
The
compound
5
d
]1,3,2λ
which mimics biologically important organic cofactors. In these
reactions the formation of the hydroperoxide ( ) does not play a role,
the catalyst, as a strong base, deprotonate the substrates (3a, 3b
2
)
forming energyꢀrich phenolates, which give an electron to molecular
oxygen in the rateꢀdetermining steps. These reactions represent a new
type of dioxygen activation by phenolates, which lead to well defined
endproducts in good yields.
Scheme 2 Proposed mechanism of the oxidation of 3a and 3b with dioxygen
catalyzed by 1.
Experimental
2
ꢀAminophenol (24 mg, 0.223 mmol) or 3,5ꢀdiꢀtertꢀbutylcatechol (49
The color of the reaction mixture is red, which may be due to the mg, 0.223 mmol) and 2,3-dihydro-2,2,2-triphenylphenanthro[9,10-
]1,3,2 5
-oxazaphosphole ( (104 mg, 0.223 mmol) were dissolved
relative persistent phenoxyl radical or also to 3,5-di-tert
butylbenzoquinone (4a). It was interesting to observe that radical in 10 mL methanol in a Schlenk tube and stirred under dioxygen at
does not react with triplet dioxygen in a radical radical reaction. 60°C for 5 h. The solvent was distilled off the residue treated with ether
However, it reacts with superoxide anion (added KO ) and not with and recrystallized from benzene or isooctane. Yields: 2ꢀ
molecular oxygen. If we start with the substrate 3,5-di-tert- aminophenoxazineꢀ3ꢀon: 87 and 51%, 3,5ꢀdiꢀtertꢀbutylbenzoquinone:
butylcatechol (3a) the corresponding quinone is formed together 85 and 53% (UVꢀVis and preparative, identification see ESI, Fig. S13ꢀ
with hydrogen peroxide. The last one could be determined S18). Kinetics: into Schlenk vessel the substrates 3,5-di-tert
quantitatively by iodometry or O -compsumtion measurement butylcatechol or
-aminophenol were weighed in under an argon
Fig.1) and was found to be in the range of 85 – 90%. In the case of atmosphere, where already 10 or 20 mL methanol as solvent was
-aminophenol (3b) imino- -quinone 4b and hydrogen peroxide present. Thereafter, the catalyst, 1,3,2-oxazaphosphole, was added
is formed, which comes from 9b and HO
disproportion.22 The and the argon replaced by dioxygen. The temperature was adjusted
product of -aminophenol oxidation the formed imino- -quinone with a water bath, the solution stirred with magnetic bar and
0b is not stable. It reacts with the starting aminophenol (3b) to samples were taken at regular intervals through a septum. In the
the compound 11 in a 1,4-addition reaction. A similar compound to samples the formed amount of 3,5-di-tert-butylquinone and 2-
9
-
d
λ
1)
9
2
4
-
2
o
(
o
o
(
)
2
o
o
1
2
4
1
1
was characterized by UV-vis spectroscopy recently when the 5- aminophenoxazine-3-one were measured at 400 (log
ε = 3.21) and
o
-aminophenol was used.23 This is then further 434 (log
ε = 3.743) nm. The initial rates of the reactions were
25
methyl derivative of
oxidized t compound 12 and then to the endproduct
formed (Eqn. 6). The yields of both products (
o
5
by O
and
2
or the determined.
5) are
H
2
O
2
4
Notes and references
a
Department of Chemistry, University of Pannonia, H-8200 Veszprém,
Hungary. Fax: 336 88 624 469; Tel: +36 88 624 720; E-mail:
speier@almos.uni-pannon.hu
†
Electronic Supplementary Information (ESI) available: general
experimental part and kinetic measurements. See
DOI: 10.1039/b000000x/
The financial support of the Hungarian National Research Fund (OTKA
K108489, TÁMOPꢀ4.2.2.Aꢀ11/1/KONVꢀ2012ꢀ0071, TÁMOPꢀ4.2.4.A/
ꢀ11ꢀ1ꢀ2012ꢀ0001) (grants to J. K.), and the European Cooperation in
‡
2
Science and Technology (CMST COST actions CM1003, CM1201 and
CM1205 is gratefully acknowledged.
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