Oxidation of Organic Molecules with a Redox-Active Guanidine Catalyst

Article abstract of DOI:10.1002/anie.201709809

Herein, we report the first examples of the use of redox-active guanidines as catalysts in the green oxidation of organic molecules with dioxygen. In one half-reaction, the oxidized form of the redox-active guanidine is converted into the reduced, protonated state, thereby enabling dehydrogenative oxidation of the substrate (3,5-di-tert-butylcatechol→ortho-benzoquinone, benzoin→benzil, and 2,4-di-tert-butylphenol→biphenol). In the other half-reaction, efficient re-oxidation of the guanidine to the oxidized state is achieved with dioxygen in the presence of a copper catalyst. These results pave the way for the broader use of redox-active guanidines as oxidation catalysts.

Full text of DOI:10.1002/anie.201709809

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Title: Oxidation of Organic Molecules with a Redox-Active Guanidine
Catalyst
Authors: Ute Wild, Florian Schön, and Hans-Jörg Himmel
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10.1002/anie.201709809
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Oxidation of Organic Molecules with a Redox-Active Guanidine
Catalyst
Ute Wild, Florian Schön and Hans-Jörg Himmel*
Hirao developed polyanilines as “synthetic metal” catalytic
systems.[11]
Abstract: Herein we report the first examples of the use of redox-
active guanidines as catalysts in the green oxidation of organic
molecules with dioxygen. In one half-reaction, the oxidized state of
the redox-active guanidine is converted to the reduced, protonated
state, thereby enabling dehydrogenative oxidation of the substrate
(3,5-ditertbutylcatechol → o-benzoquinone, benzoin → benzil, and
2,4-ditertbutylphenol → biphenol). In the other half-reaction, efficient
re-oxidation of the guanidine to the oxidized state is achieved with
dioxygen in the presence of a copper catalyst. The results pave the
way for a broader use of redox-active guanidines as oxidation
catalysts.
Redox-active guanidines are up to date unknown as organic
oxidation
catalysts.
Herein,
1,2,4,5-tetrakis(tetramethyl-
guanidino)-benzene (1, see Scheme 1),[12] being a quite strong
electron donor (E1/2 = -0.7 V vs. Fc+/Fc for the redox pair
12+/1),[ 13 ] is used in the first examples of such reactions.
Reduction of the oxidized form, 12+, by proton-coupled electron
transfer is favored by the strong Brønsted basicity of guanidines
and restoration of the aromatic system. First it is demonstrated
that (1+2H)2+ can be efficiently oxidized catalytically with
dioxygen to the dication 12+. Then 12+ is applied in
(stoichiometric) dehydrogenative oxidation reactions with three
organic substrates differing in their nucleophilicity and redox
potential (3,5-di-tert-butylcatechol → o-benzoquinone, benzoin
→ benzil, and 2,4-di-tert-butylphenol → biphenol, see SI). Finally,
these half-reactions are combined in a catalytic cycle, using
dioxygen as green oxidation reagent and 12+ as organo-catalyst
(see Scheme 1). Both involved guanidine species, 12+ and
(1+2H)2+, are readily available. In spite of its high nitrogen
content, 1 and its twofold-oxidized respectively diprotonated
versions, are also thermally stable (neutral 1 melts at ca. 205 °C
and sublimes at higher temperature without decomposition). The
salt 1(PF6)2 is prepared by reaction of neutral 1 with FcPF6 (Fc =
ferrocene),[14] and the salt (1+2H)(PF6)2 by reaction of 1 with
(NH4)(PF6).[12] Both 12+ and (1+2H)2+ are highly soluble in
CH3CN.
Catalytic, selective oxidation of organic compounds is one of the
top research themes in synthetic chemistry. The use of readily
available O2 as oxidation reagent, generally requiring an oxygen-
activating metal catalyst, is particularly attractive. Bäckvall and
others established the use of benzoquinones as redox mediators
for the oxidation of organic molecules by multistep electron
transfer.[1,2] Catalytic oxidation of catechols and p-hydroquinone
with O2 was thoroughly investigated, using dinuclear and also
mononuclear transition metal complexes (esp. of copper, cobalt
and iron) as catalysts.[3,4,5,6,7] Stahl and Hammes-Schiffer et al.
disclosed the mechanisms of such reactions and grouped
quinones in two families, those with a high redox potential, such
as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), and
bioinspired o-quinones resembling the o-quinone cofactor found
in amine oxidases and related enzymes, that have lower redox
potentials.[7, 8 ] Special o-quinones enable aerobic oxidation of
amines without the need for a metal cocatalyst.[910] The group of
Scheme 1. Catalytic cycle for oxidation of organic molecules with O2 using the redox-active guanidine 1,2,4,5-tetrakis(tetramethylguanidino)-benzene (1) as
catalyst (this work). Cocatalyst = CoII or CuII complexes (best results with CuCl2 / Cu(H2O)6(BF4)2)
[a]
U. Wild, F. Schön, Prof. Dr. H.-J.Himmel
Anorganisch-Chemisches Institut
Ruprecht-Karls-Universität Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
E-mail: hans-joerg.himmel@aci.uni-heidelberg.de
Supporting information for this article is given via a link at the end of
the document.
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1) Catalytic oxidation of (1+2H)2+ with O2. Oxidation of (1+2H)2+
A cocatalyst screening (see SI) shows that CuII salts speed up
further the reaction. With Cu(H2O)6(BF4)2 (4 mol%), more than
90% conversion is already reached after 280 min at room
temperature (see Figure 1). Further optimization shows that a
1:1 mixture of CuCl2 and Cu(H2O)6(BF4)2 as cocatalyst (ca. 3
mol%) gives the best results with 100 mol% conversion in only
22 min (see SI).
with dioxygen to give 12+ requires
a cocatalyst. Several
cocatalysts are tested (see SI), and conversion followed by NMR
spectroscopy at room temperature. In an O2 atmosphere, the
salt (1+2H)(PF6)2 and the cocatalyst (2-5 mol%) are dissolved in
acetonitrile (NMR tube experiments). The CoII complex of the
dianion
of
bis[3-(salicylideneimino)propyl]methylamine
(salmdptH2), Co(salmdpt),[2,7] an established cocatalyst for
catechol-oxidation, enables the reaction (see Figure 1). In the 1H
NMR spectra, the signals at δ = 2.78 (methyl protons) and 6.11
ppm due to (1+2H)2+ disappear completely, and the signals at
δ = 2.87 and 5.16 ppm due to 12+ grow in instead. Due to the
tendency of tetrakisguanidine electron donors to donate two
electrons simultaneously, O2 is reduced to water (similar to
catechol oxidation). To access the influence of O2 concentration
on the reaction rate, the experiment is repeated in a vial under
O2 atmosphere (vial method). Indeed, the reaction rate
considerably increases (see Figure 1 and SI).
2) Stoichiometric dehydrogenative oxidations with 12+. Next the
dication 12+ is applied in dehydrogenative oxidation of 3,5-
ditertbutylcatechol, benzoin and 2,4-ditertbutylphenol (see
Scheme 1). In an Ar atmosphere, one of the substrates and
1(PF6)2 are dissolved in acetonitrile, and the conversion followed
by NMR spectroscopy. Reaction of 3,5-ditertbutylcatechol with
1(PF6)2 (0.02 mol/l) at room temperature yields the o-
benzoquinone product almost quantitatively within 10 min (see
Figure 2). The fast rate argues for a concerted pathway. Indeed,
quantum chemical calculations find a complex between 3,5-
ditertbutylcatechol and 12+ with two O-H···N bridging interactions
(see SI), enabling simultaneous transfer of both hydrogen atoms.
The reaction is slowed down at lower concentrations, and can
then be monitored by UV/Vis spectroscopy. The benzoquinone
absorption near 400 nm can be neglected, since its extinction
coefficient (1900 L mol−1cm−1)[ 15 ] is much lower than that of
1(PF6)2 (27610 L mol−1cm−1).[14] The presence of an isosbestic
point (at 355 nm) confirms clean conversion (see Figure 2).
a)
b)
Figure 2. UV/Vis spectra recorded for the reaction between catechol and
1(PF6)2 in acetonitrile (band at 425 nm due to 12+). Inlet: conversion vs. time
plots for ca. 0.02 mol/l from NMR (red) and for 3.76·10-5 mol/l from UV/Vis
spectroscopy (blue).
Oxidation of benzoin to benzil is slower, ca. 85% conversion
being reached after 20 h. Keeping the concentration of 12+
constant at ca. 0.02 mol/l, a benzoin concentration higher than
0.02 mol/l accelerates the reaction, while a decrease of this
concentration slows down the reaction (see SI). These results
Figure 1. a) 1H NMR spectra for oxidation of (1+2H)2+ to 12+ with O2 and 4.5
mol% Co(salmdpt) as cocatalyst (spectra recorded at 10, 307, 511, 1758,
2913 and 3308 min reaction time), and b) conversion vs. time plot for
[Co(salmdpt)] (NMR and vial method, see text) and Cu(H2O)6(BF4)2 catalyzed
oxidation.
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are in line with those obtained for 3,5-ditertbutylcatechol and
also for oxidative coupling of thiols to disulfides and phosphines
to diphosphines with 12+.[14] Hence in all reactions the rate
increases with increasing concentrations of the two reactants. In
our experiments, we deliberately use low concentrations, leading
on the one hand to quite long reaction times, but on the other
hand maintaining optimal conditions for the NMR spectroscopic
monitoring of all reactions. 2,4-Ditertbutylphenol oxidation is still
slower under the chosen conditions, presumably due to
inhibition by formation of a stable complex between two of the
involved species (see below). It selectively leads to the biphenol
coupling product. The reaction rate and yield of coupling product
can be increased by applying an excess of phenol (see SI). With
6 eq. of phenol, ca. 20% conversion is reached after 45 h.
Hence, the rates for dehydrogenative oxidation reactions with
12+ cover a large range.
after 50 h obtained with the NMR method (with 10 mol% of
1(PF6)2 and ca. 10 mol% NEt3) is increased to more than 80%
with the vial method.
Scheme 2. Selected results of catalytic oxidations with 1(PF6)2 as organo-
catalyst and O2 as oxidation reagent (vial method). Please note that the
reaction rates depend on the concentrations (higher concentrations speed up
the reactions). In our experiments we deliberately use relatively small
concentrations to follow the reactions with NMR spectroscopy (see conversion
vs. time plots in the SI).
3) Catalytic reactions. The results of the previous two sections
are now combined to elaborate catalytic reactions. As catalysts,
1(PF6)2 as dehydrogenative oxidation catalyst (with catalyst
loadings between 2 and 20 mol%) and {CuCl2+Cu(H2O)6(BF4)2}
(3 mol% with respect to 1(PF6)2) for dioxygen activation are used.
Some Na2SO4 is added to remove the water, that otherwise
causes broad, perturbing signals in the NMR spectra. Control
experiments show that Na2SO4 addition has no influence on the
reaction. Two series of experiments are carried out. In the first
one (termed “NMR method” in the following), the solutions are
saturated with O2 and transferred in an O2 atmosphere into NMR
tubes. Reaction in the NMR tube at a temperature of 60 °C is
then followed. In the second series of experiments (termed “vial
method” in the following), the O2 supply is increased by carrying
out the reaction in a sealed vial (20 ml) under O2 atmosphere.
In similarity with the stoichiometric reactions, the catalytic
reaction of catechol proceeds fastest and takes only 2 h with the
vial method (see Scheme 2). The time for quantitative
conversion is reduced to ca. 30 min with 10 mol% of 1(PF6)2 and
to less than 2 h with 5.5 mol% of 1(PF6)2 by applying the vial
method (see Scheme 2 and SI). Using the NMR method,
quantitative conversion is achieved within 23 h with 10 mol% of
1(PF6)2. For benzoin oxidation, the NMR method leads to more
than 70% conversion in 50 h with 10 mol% of 1(PF6)2. With 20
mol% of 1(PF6)2, the yield increases to more than 80%. Almost
quantitative conversion is achieved with the vial method and 20
mol% of 1(PF6)2. The 2,4-ditertbutylphenol oxidation is not only
very selective, leading only to the biphenol product, but also
provides the product in quite high yield. The addition of 10 mol%
NEt3 is found to accelerate this particular reaction (in line with
previous studies on phenol oxidation [16-23]). The yield of 70%
In all cases, blank tests are run without 1(PF6)2. Only in the case
of benzoin, a significant conversion is observed in these blank
tests (ca. 36% conversion with the NMR method and 22% with
the vial method after 50 h reaction time, see SI). In additional
experiments, the catalyst loadings are varied. If the catalyst
loading is reduced, the reaction rate decreases. Nevertheless,
with only
2
mol% 1(PF6)2 and 0.07 mol% {CuCl2+
Cu(H2O)6(BF4)2}, still more than 65% 2,4-ditertbutylphenol are
converted in 25 h with the vial method. To further clarify the role
of copper on the overall reaction mechanism, the copper
cocatalyst was added in the stoichiometric reaction between 12+
and 2,4-ditertbutylphenol (see SI). A low product yield of ca.
16 % was obtained after 45 h, much lower than the yield of more
than 80% obtained in the catalytic reaction. This result confirms
that the copper is mainly responsible for dioxygen activation
(Scheme 1).
In summary, the results of this work show that redox-active
guanidines are valuable catalysts for the green oxidation of
organic molecules with dioxygen. The following points highlight
the advantages of redox-active guanidine catalysts.
1) Oxidation of the twofold protonated guanidine, (1+2H)2+, with
dioxygen at room temperature to give 12+ is very efficient with
simple, commercially available CuII cocatalysts, enabling
quantitative conversion in less than half an hour.
2) The redox-active guanidine used in this work is
environmentally benign, readily available and thermally stable,
making it an attractive organo-catalyst.
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3) The key properties of the redox-active guanidine, its redox
potential and its basicity, can easily be tuned, as demonstrated
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Entry for the Table of Contents
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U. Wild, F. Schön, H.-J. Himmel*
Page No. – Page No.
Oxidation of Organic Molecules with
a Redox-Active Guanidine Catalyst
Due to the combination of high Brønsted basicity and electron donor properties,
redox-active guanidines are superior organic redox catalysts. Herein we report the
first catalytic oxidation reactions with dioxygen.
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