DOI: 10.1002/chem.201001429
Selective Iron-Catalyzed Oxidation of Phenols and Arenes with Hydrogen
Peroxide: Synthesis of Vitamin E Intermediates and Vitamin K3
Konstanze Mçller, Gerrit Wienhçfer, Kristin Schrçder, Benoꢀt Join, Kathrin Junge, and
[
a]
Matthias Beller*
The selective oxidation of arenes to quinones constitutes
an important biological process and is of significant interest
the smooth oxidation of TMP with hydrogen peroxide in an
organic solvent. Here, the reaction proceeds in the presence
of a special heteropolyacid catalyst with yields of 70–85%.
[1]
[9]
to the chemical industry. Various quinone derivatives are
currently produced on ton-scale as fine chemicals and they
are common constituents of biologically relevant molecules,
However, the most common procedure in industry makes
use of a copper chloride mediated oxidation of TMP with
[2]
[10]
for example, vitamin K1 (phylloquinone). Notably, qui-
nones serve as electron acceptors in electron transport
molecular oxygen resulting in high yield.
Unfortunately,
stoichiometric amounts of copper are applied in this reac-
tion. This results in large amounts of copper waste and prod-
uct contamination. Thus, the development of more environ-
mentally friendly procedures for the oxidation of TMP is
still of actual interest.
[3]
chains in photosynthesis and aerobic respiration.
Among the industrially relevant quinones, 2,3,5-trimethyl-
p-benzoquinone 2 (TMBQ) represents one of the intermedi-
[4]
ates for the synthesis of vitamin E (a-tocopherol), which is
used extensively as antioxidant in food, medical treatments,
Based on our recent work in ruthenium-catalyzed oxida-
[5]
[11]
and cosmetics. While in nature, quinones are produced by
oxidation of aromatic amines, polyhydric phenols, and poly-
nuclear hydrocarbons or enzymatic oxidation of polyphe-
tion of arenes to the corresponding quinones,
we asked
ourselves whether iron complexes might be also suitable for
this task. Evidently, iron is an ideal candidate for catalysis,
because of its abundant availability and its relative non-tox-
[6]
nols, the key step in the synthesis of vitamin E is the con-
[12,13,14]
version of 2,3,6-trimethylphenol 1 (TMP) to 2 (Scheme 1).
icity compared to precious metals.
In addition, iron is
involved in manifold biological systems as fundamental key
element. Based on the development of iron-catalyzed epoxi-
[15]
dations,
we applied a three component catalyst system
consisting of FeCl ·6H O, pyridine-2,6-dicarboxylic acid
3
2
(
H pydic), and different benzylamines for the oxidation of
2
TMP with hydrogen peroxide. At this point it should be
noted, that next to air, H O is the most “green”, and waste-
avoiding oxidant.
2
2
Scheme 1. Oxidation of TMP 1 to its corresponding quinone TMBQ 2.
[16]
In preliminary tests we discovered that TMP is indeed
smoothly oxidized in the presence of different iron catalysts.
Best results are obtained in t-amyl alcohol as solvent with
7.5 mol% catalyst (FeCl ·6H O/H Pydic/amine=1/1/2.2)
To date several protocols have been established for the
[7]
direct oxidation of TMP to TMBQ, though few of them
are of industrial relevance. Notably, Schuster et al. reported
that Salcomin (a salencobalt(II) complex) catalyzed the oxi-
dation of TMP to the corresponding quinone in 80–95%
3
2
2
and 4 equivalents of H O (30%) at 08C. Notably, the co-
2
2
ligand (amine) controlled the chemoselectivity to a major
extent. In Table 1 the influence of the added co-ligands on
the model reaction is summarized in more detail. In all
cases high conversion is obtained (ꢀ90%) independent of
the amine co-ligand. However, without any amine added
only low conversion is achieved. While aliphatic amines
gave low selectivities (25%), the addition of benzylamine
led to 73% selectivity (Table 1, entries 1–3). Similar to ben-
zylamine, o-, m-, and p-chloro-substituted as well as p-hy-
[8]
yield. A process developed by Shimizu et al. is based on
[
a] K. Mçller, G. Wienhçfer, K. Schrçder, Dr. B. Join, Dr. K. Junge,
Prof. Dr. M. Beller
Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock
Albert-Einstein-Straße 29a, 18059 Rostock (Germany)
Fax : (+49)381-1281-5000
E-mail: matthias.beller@catalysis.de
10300
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 10300 – 10303