Silver ion promoted, PdII-catalyzed arylation of arenes with a free amine as directing group in aqueous medium

Article abstract of DOI:10.1002/chem.201301229

Palladium(II)-catalyzed arylation of arenes with aryl boronic acids and a free amine as directing group in aqueous medium has been developed. High reactivity and chemoselectivity for the formation of carbon-carbon bonds were achieved by the use of soluble

Full text of DOI:10.1002/chem.201301229

FULL PAPER
DOI: 10.1002/chem.201301229
II
Silver Ion Promoted, Pd -Catalyzed Arylation of Arenes with a Free Amine
as Directing Group in Aqueous Medium
[
a]
[a]
[a]
[a]
[a, b]
Zunjun Liang, Jinzhong Yao, Kai Wang, Haoran Li, and Yuhong Zhang*
Abstract: Palladium(II)-catalyzed arylation of arenes with aryl boronic acids and
a free amine as directing group in aqueous medium has been developed. High re-
activity and chemoselectivity for the formation of carbon–carbon bonds were ach-
ieved by the use of soluble silver salts. The addition of water is crucial to improve
the arylation yield.
Keywords: amines · CÀH activa-
tion · homogeneous catalysis · palla-
dium · silver
Introduction
the NÀH bond. In 2006, Daugulis and co-workers reported
II
Pd -catalyzed ortho arylation of benzyl amines with aryl io-
[10]
The development of general methods for selective transfor-
dides. They found that the amount of acid strongly influ-
enced the rate of the arylation reaction, and using five
equivalents of trifluoroacetic acid gave the best results, but
suffered from spontaneous conversion of free amine to tri-
fluoroacetamide. Later, Shi and co-workers reported an al-
ternative approach using amine derivatives, namely, N,N-di-
mation of CÀH bonds has aroused substantial interest in
[1]
recent years. Reactivity and selectivity are the most impor-
tant issues in these transformations. Chelation-assisted strat-
egies using transition metal catalysts have led to spectacular
advances in efficiency and selectivity of CÀH activation. Ni-
[11]
trogen-containing groups are among the most extensively
alkyl amines, as directing groups;
the binding ability of
studied chelating groups, and numerous CÀH-activating
the amino group was tuned by means of the acidity of the
reaction medium. In 2011, Gaunt et al. demonstrated that
transformations have been developed by the use of
[
2]
[3]
[4]
[5]
II
amides, imines, oximes, alkyl amines, and nitrogen-
arylÀNH is a very effective directing group in Pd -catalyzed
[6]
[12]
containing heterocycles as directing groups. Despite these
important advances, the directing-group limitations remain
a challenge in this field. For example, amines are impor-
tant N-containing functional groups and can be found in
many natural products and pharmaceuticals. However, the
CÀH functionalization of b-aryl ethyl amines. They pro-
posed that the introduction of an aryl group into an amine
[7]
would increase the acidity of the aryl NÀH bond and reduce
II
the likelihood of formation of bis-amino Pd complexes,
which is favorable for the formation of the cyclopalladated
complex.
[8]
utilization of amines, especially free amines, as directing
groups in transition metal catalyzed CÀH activation is often
We previously investigated free-amine-directed, palladi-
um-catalyzed alkenylation of arenes in the presence of
acetic acid, but the free amines subsequently underwent cy-
cloamination with the alkenes to generate phenanthridines
thwarted by catalyst poisoning, which is attributed to the
relatively strong bonding of amino groups to metal centers.
The excess of the amine is also unfavorable for the cyclome-
talation process. An equally important challenge for free-
amine strategies is to find a way for selective formation of
[13]
as the final products. Given the known strong coordina-
tive interaction between silver ions and amines, we speculat-
ed that the binding ability of the amino group could also be
tuned by employing the appropriate silver salt, which acts
like an acid. Herein, we report a palladium-catalyzed, free-
[9]
CÀC rather than CÀN bonds. It is important to develop
knowledge and associated strategies for overcoming these
hurdles.
[14]
In previous studies, extensive efforts were made to adjust
the binding ability of the amino group by introducing an
acidic medium into the reaction or increasing the acidity of
amine-directed Suzuki–Miyaura-type coupling reaction of
biaryl-2-amines with aryl boronic acids in the presence of
silver nitrate in aqueous media. The free amino groups are
not modified in the reaction. In addition to acting as oxi-
dants, two different roles of the silver ion were demonstrat-
ed, that is, increasing the reactivity and improving the che-
moselectivity. This methodology expands the scope of palla-
dium-catalyzed CÀH activation reactions and opens up
[
a] Dr. Z. Liang, J. Yao, K. Wang, H. Li, Prof. Y. Zhang
ZJU-NHU United R&D Center, Department of Chemistry
Zhejiang University, Hangzhou 310027 (P. R. China)
Fax : (+86)571-87953244
E-mail: yhzhang@zju.edu.cn
a new and efficient route for catalytic formation of carbon–
carbon bonds for free-amine substrates.
[
b] Prof. Y. Zhang
State Key Laboratory of Applied Organic Chemistry
Lanzhou University, Lanzhou 730000 (P. R. China)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201301229.
Chem. Eur. J. 2013, 19, 16825 – 16831
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
16825

Results and Discussion
also investigated, and Pd
ACHTUNGTNRENUNG( OAc) was clearly the best choice
2
(
Table 1, entries 12–14). No reaction took place without cat-
We initially employed the reaction conditions of our free-
alyst or oxidant in this system (Table 1, entries 15 and 16).
Oxygen was found to be ineffective (Table 1, entry 17). The
2
amine-directed alkenylation of C
A
H
U
G
R
N
N
(sp )ÀH by palladium catal-
ysis under acidic condition with copper salts as oxidant.
different bases and solvents were also screened; Na HPO4
2
However, all efforts to extend the catalyst system to the ary-
and DMSO are the most suitable for this transformation
(for details, see Supporting Information). Increasing or de-
creasing the reaction temperature is unfavorable for this re-
action. Thus, we established the optimized reaction condi-
2
[15]
lation of C
4
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(sp )ÀH failed, and only the N-arylated product
a was obtained in almost quantitative yield (Table 1,
tions as follows: 5 mol% of Pd ACHTUGNTERNN(UNG OAc) , two equivalents of
2
[
a]
Table 1. Optimization of reaction conditions.
AgNO , and two equivalents of Na HPO in 1.5 mL of
3
2
4
DMSO/H O (2:1 v/v) at 758C for 20 h.
2
Once the optimized reaction conditions were identified,
we explored the substrate scope and generality of the aryla-
tion reaction (Table 2). The reaction tolerates a wide variety
of functional groups, including Me, OMe, F, Cl, CF , and
3
[
b]
OH. Both electron-rich and electron-deficient aryl boronic
acids were accommodated with good to excellent efficiency.
In general, aryl boronic acids bearing electron-withdrawing
groups afforded the arylation products in higher yields (3d,
Entry Catalyst
Oxidant
Cu(OAc)
AgOAc
AgOAc
Additive
Yield [%]
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
Pd
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
PdCl
Pd(TFA)
Pd(dba)
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OAc)
2
2
2
2
2
2
2
2
2
2
2
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
2
HOAc
–
0 (99)
8 (0)
12 (0)
25 (0)
44 (0)
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
2
HPO
2
HPO
2
HPO
2
HPO
2
HPO
2
HPO
2
HPO
2
HPO
2
HPO
2
HPO
2
HPO
2
HPO
2
HPO
2
HPO
2
HPO
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
/
3
3
3
3
3
3
3
3
3
3
3
3
3
e, 3 f, 3j, and 3k) than those with electron-donating groups
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
2
·12H O
(
3a, 3b, 3c, 3g, and 3h). When 4-methoxyphenylboronic
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
/H
/H
/H
/H
/H
/H
/H
/H
/H
/H
/H
/H
2
2
2
2
2
2
2
2
2
2
2
2
O (10 mmol) 46 (0)
O (20 mmol) 55 (0)
O (25 mmol) 69 (0)
85 (0)
O (30 mmol) 72 (0)
acid was used as coupling partner, the corresponding prod-
uct 3c was obtained in lower yield, due to the formation of
a larger amount of homocoupling product than in the other
cases. 3-Hydroxyphenylboronic acid gave the desired prod-
uct 3i in moderate yield. 2-Naphthalenylboronic acid react-
ed smoothly to afford the corresponding product in 78%
yield (3l).
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
O (0.5 mL)
1
1
1
1
1
1
1
1
ACHTUNGTRENNUNG
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
O (1.0 mL)
O (0.5 mL)
O (0.5 mL)
O (0.5 mL)
O (0.5 mL)
O (0.5 mL)
O (0.5 mL)
19 (0)
63 (0)
75 (0)
51 (0)
0 (0)
2
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
2
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
2
–
We next studied the generality of this reaction by varying
the electronic and steric properties of the arenes. The elec-
tronic property of the arenes had a significant impact on
this arylation reaction (Table 3). Arenes with electron-do-
nating substituents (e.g., OMe) at the meta position showed
better reactivity to deliver the desired product 3m in moder-
ate yields than those with electron-withdrawing substituents,
such as F and Cl (3n and 3o). These results suggested that
electrophilic palladation/deprotonation might be involved in
this arylation reaction. 2-(Naphthalen-2-yl)aniline could also
tolerate the reaction conditions to give 3p in 64% yield.
Moderate yields were obtained for both electron-rich and
electron-deficient aniline substrates (3q and 3r). Steric hin-
drance retarded the reaction. For example, the ortho-substi-
tuted arene delivered the arylated product 3s in lower yield
than its meta analogues. When two meta positions were sub-
stituted by a methyl group, the reaction failed (3t). Biphen-
yl-2-amine was arylated by phenylboronic acid to give a mix-
ture of mono- and diarylation products in 2:1 molar ratio
(3v/3v’). We got similar results for 4’-substituted biphenyl-2-
amines: a mixture of mono- and diarylated products was
generated. We also tested a substrates bearing substituents
with different electronic properties, but only a moderate
Pd
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OAc)
2
2
0 (0)
0 (0)
[
c]
Pd(OAc)
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
O
2
[
(
(
a] Reaction conditions: 1a (0.5 mmol), 2a (3.0 mmol), Pd catalyst
0.025 mmol), oxidant (1 mmol, 2 equiv), additive (1.0 mmol), DMSO
1.0 mL), 758C for 20 h. [b] GC yields of 3a based on biphenyl amine 1a;
2
the yields of 4a are in parentheses. [c] O (1.0 atm).
entry 1). Intriguingly, when AgOAc was used as oxidant, the
2
C
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(sp )ÀH arylation product 3a was observed in 8% GC
yield and N-aryl product 4a was not found (Table 1,
entry 2). The addition of Na HPO further improved the re-
action to give 3a in 12% GC yield (Table 1, entry 3). Unex-
pectedly, AgNO showed better efficiency than AgOAc to
give 3a in 25% GC yield (Table 1, entry 4). It is noteworthy
that the use of Na HPO ·12H O led to a sharp increase of
the yield to 44% (Table 1, entry 5). It appeared that water
might be the key factor in this arylation reaction. Therefore,
we carefully examined the effect of the amount of water
Table 1, entries 6–11). Indeed, the incremental addition of
water led to a very rapid increase in activity, and a maximum
yield (85%) was observed when the amount of water was
2
4
3
2
4
2
(
0
.5 mL (ꢀ28 mmol, Table 1, entry 9). Further addition of
water decreased the yield (Table 1, entries 10 and 11).
Maybe, the addition of water was favorable to increasing
yield was obtained (3u). In all cases, the substrates under-
2
went direct C
A
H
U
G
R
N
N
(sp )ÀH arylation with complete selectivity
the solubility of aryl boronic acid and AgNO . Other palla-
over a possible competitive Buchwald–Hartwig N-arylation
3
[9]
dium salts, such as PdCl , Pd
A
H
U
G
R
N
N
(TFA) (TFA=trifluoroacetate)
pathway.
2
2
and Pd ACHTUNGTRENNUNG( dba) (dba=trans,trans-dibenzylideneacetone) were
2
16826
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Chem. Eur. J. 2013, 19, 16825 – 16831

II
Pd -Catalyzed Arylation of Arenes
FULL PAPER
2
[a]
Table 2. Arylation of
C
A
H
U
G
E
N
N
(sp )ÀH with various aryl boronic acids.
Table 2. (Continued)
Entry ArB(OH)
[
b]
2
2
Product 3
Yield [%]
1
1
1
0
1
2
91
[
b]
Entry
1
ArB(OH)
2
2
Product 3
Yield [%]
83
82
78
2
3
4
5
6
7
8
9
77
42
87
84
90
83
85
68
[
a] Reaction conditions: 1a (0.5 mmol),
2
(3.0 mmol), Pd
(1.0 mmol), DMSO
O (0.5 mL), 758C, 20 h. [b] Yields of isolated compounds,
ACHTUNGTRENNUNG( OAc)
2
(
(
0.025 mmol), AgNO
1.0 mL), H
3
2 4
(1.0 mmol), Na HPO
2
based on biphenyl amine 1a.
[
a]
Table 3. Arylation of various biaryl-2-amines.
[
a] Reaction conditions:
1
(0.5 mmol),
2
(3.0 mmol), Pd ACHTUNGTRENNUNG( OAc)
2
(
(
0.025 mmol), AgNO
1.0 mL), H
3
(1.0 mmol), Na
O (0.5 mL), 758C, 20 h. Yields of isolated products based on
2
HPO
4
(1.0 mmol), DMSO
2
biphenyl amine 1.
Chem. Eur. J. 2013, 19, 16825 – 16831
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16827

Y. Zhang et al.
To understand the mechanism of this new CÀH arylation
reaction, the effect of silver salts was first examined in some
detail (Figure 1). Ag O and Ag CO , which are commonly
2
2
3
II
Figure 2. Performance of silver ions. Reaction conditions: (
mediate C (0.15 mmol), 2a (1.8 mmol), DMSO/H
58C, no AgNO ; (&) Pd(OAc) (0.3 mmol, 1.0 equiv), 1a (0.3 mmol), 2a
1.8 mmol), AgNO (0.6 mmol), DMSO/H O (2:1 v/v, 1.0 mL), 758C;
~) Pd intermediate C (0.15 mmol), 2a (1.8 mmol), AgNO
(0.6 mmol),
O (2:1 v/v, 1.0 mL), 758C; (*) Pd
(OAc) (0.6 mmol, 2.0 equiv),
a (0.3 mmol), 2a (1.8 mmol), DMSO/H O (2:1 v/v, 1.0 mL), 758C, no
(0.3 mmol, 1.0 equiv), 1a (0.3 mmol), 2a
O (2:1 v/v, 1.0 mL), 758C, no AgNO
&
) Pd inter-
2
O (2:1 v/v, 1.0 mL),
7
(
(
3
A
H
U
G
R
N
N
2
3
2
II
3
DMSO/H
1
AgNO
2
A
H
U
G
R
N
U
2
Figure 1. The effect of various silver salts. Reaction conditions: 1a
2
3
;
(*) Pd
ACHTUNGETRNNUNG( OAc)
2
(
0.5 mmol), 2a (3.0 mmol), Pd
1.0 mmol), Na HPO (1.0 mmol), DMSO (1.0 mL), H
0 h.
A
H
U
G
R
N
U
G
2
(0.025 mmol), silver salt
(
1.8 mmol), DMSO/H
2
3
.
(
2
4
2
O (0.5 mL), 758C,
2
used in CÀH activation showed,
very poor effects on the aryla-
tion reaction. In contrast,
AgNO , which is rarely used in
3
these transformations, exhibited
the best efficiency and afforded
3
a in high yield. AgF and
AgSbF also worked under the Scheme 1. Study on the key palladacyclic intermediate.
6
reaction conditions, but deliv-
ered lower yields. AgOTf gave
the arylated product in moderate yield. AgTFA and AgOAc
showed good efficiency. In general, the effect of silver salt is
in accordance with their relative solubilities.
tween palladium and free amine in intermediate E to make
the reductive-elimination process easier (Figure 3, Path I).
We performed the arylation reaction of 0.15 mmol of palla-
We suppose that silver ions could influence this arylation
dacyclic intermediate C with and without AgNO (Figure 2).
3
II
in two ways: 1) by acting as an oxidant to complete the Pd /
Surprisingly, the reaction without AgNO3 is much faster
than that with 2.0 equivalents of silver nitrate (Figure 2,
plots 1 and 3). The results clearly demonstrated that silver
ions have very limited impact on improving the transmetala-
tion and reductive elimination process.
To probe the effect of silver ion further, we performed
the reaction between substrate 1a and phenylboronic acid
(2a) in the presence of a stoichiometric amount of Pd-
0
Pd catalytic cycle (see Figure 3 below); 2) by serving as
a
(
promoter to facilitate the cyclopalladation process
Figure 3, Path b). Under our standard reaction conditions,
silver ion is in equilibrium with the amine. Formation of
[
16]
II
silver amine complex F
can decrease formation of Pd
II
amine complex A. This is favorable to the formation of Pd
amino complex B, which is a required precursor of the cy-
[17]
clopalladation intermediate.
ACHTUNGTNERNU(GN OAc) with and without AgNO (Figure 2, plots 2 and 5). A
2 3
Firstly, we prepared palladacyclic complex C according to
ref. [18] and treated it with phenylboronic acid (2a) under
standard reaction conditions in the absence of Ag salts.
Indeed, we obtained the arylated product 3a in 89% yield
prominent effect of silver ions was noted in this reaction. In
the absence of silver nitrate, the efficiency of the transfor-
mation was much lower than with 2.0 equivalents of AgNO3.
In addition, the nitrate anion may also influence the reac-
tion. We performed reactions with one equivalent of Pd-
(
Scheme 1), which indicated that the palladacyclic complex
C is a key intermediate during this catalytic cycle. Next, we
examined the effect of silver ions on the reductive-elimina-
tion process. Perhaps they can facilitate the interaction be-
ACHTUNGTENRNUNG( OAc) in the presence of 2.0 equiv NaNO3 and without
2
NaNO , which resulted in almost the same yields of the ary-
3
lated products (Scheme 2). These results showed that the re-
16828
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ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 16825 – 16831

II
Pd -Catalyzed Arylation of Arenes
FULL PAPER
coordinates
amine
with
substrate
1
to give palladium
amine complex A, which is
known to be stable due to the
strong binding ability of the
amino group. The subsequent
formation of intermediate B,
which is relatively active, may
proceed in two ways. One is the
direct formation of intermedi-
ate B, which is not favored in
the absence of silver ion
(
Figure 3, Path a). In this
regard, we demonstrated that
the arylation reaction was slug-
gish without the use of AgNO3
(
Figure 2, plots 4 and 5). In the
presence of silver ion, the for-
mation of intermediate B is
promoted by the formation of
[18]
silver amine complex
F
(
Figure 3, Path b). We indeed
found that the arylation reac-
tion was much faster in the
presence of AgNO3 (Figure 2,
plot 2). The electrophilic cyclo-
[19]
palladation occurs at the less
hindered ortho position of the
arenes to generate the inter-
Figure 3. A plausible mechanism.
[17c]
mediate C’,
which undergoes
transmetalation with the aryl
boronic acid to produce inter-
mediate D with the assistance
of Na HPO . Reductive elimi-
2
4
nation results in the arylated
0
product and liberates Pd ,
II
which is oxidized to Pd by
silver salt to restart the cycle.
Polycyclic aromatics have
been widely studied for their
unique properties in material
3
Scheme 2. The action of NaNO .
[20]
science;
for example, they
À
[20a]
action was not influenced by the addition of NO . In the
are important d-conjugated functional materials.
The ary-
3
0
II
I
Pd /Ag system, silver nitrate may oxidize the Pd and thus
lated product 3a can be easily transformed into triphenylene
derivative 5a by diazotization and subsequent removal of ni-
II
makes the concentration of Pd higher than that without
I
II
[21]
Ag . To investigate the effect of Pd concentration, we per-
formed the reaction in the presence of two equivalents of
trogen by heating (Scheme 3).
Pd
was faster than with one equivalent of Pd
plot 5), but much lower than with a combination of one
equivalent of Pd(OAc) and 2.0 equivalents of AgNO3
Figure 2, plot 2). All of these results demonstrated that
ACHTUNGTRENNUNG( OAc) without AgNO (Figure 2, plot 4). The reaction
2
3
AHCTUNGTNERN(GU OAc) (Figure 2,
2
ACHTUNGTRENNUNG
2
(
silver ions play a key role in the reaction besides acting as
an oxidant.
Based on these preliminary results and related studies on
[17]
the ortho metalation of primary amines, a plausible reac-
tion mechanism was proposed (Figure 3). First, Pd(OAc)
Scheme 3. Synthesis of triphenylene 5a.
AHCTUNGTRENNUNG
2
Chem. Eur. J. 2013, 19, 16825 – 16831
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16829

Y. Zhang et al.
Conclusion
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We have developed an efficient free-amine-directed aryla-
tion reaction of arenes by palladium catalysis in aqueous
medium. By employing soluble silver salt, the poisoning
II
effect of the free amine on Pd is eliminated, which allows
significant improvement of regioselectivity and reactivity to
2
give the C
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(sp )ÀH arylation products in high yields. Further
2
008, 130, 16474; l) M. Wasa, K. M. Engle, J.-Q. Yu, J. Am. Chem.
mechanistic investigations to reveal the detailed effects of
silver salts and application of this new protocol to other
amine-directed CÀH activations are currently ongoing.
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1, 2247.
5
Experimental Section
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boronic acids: A round bottom flask (10 mL) with a magnetic stir bar
and reflux condenser was charged with Pd
A
H
U
G
R
N
U
G
2
(0.025 mmol, 6 mg,
HPO (1.0 mmol,
5
1
(
mol%), AgNO
3
2
4
3.0 mmol, 6.0 equiv), DMSO (1.0 mL), and H
2
was stirred at 758C for 20 h. After cooling to room temperature, the mix-
ture was filtered through a plug of Celite and the residue washed with
2 3
ethyl acetate (2ꢁ20 mL). Then saturated Na CO (30 mL) was added,
and the organic layer was collected. The aqueous phase was extracted
with ethyl acetate (3ꢁ20 mL). The combined organic phases were
washed with brine (40 mL), dried over anhydrous sodium sulfate, filtered
and concentrated. The residue was purified by flash column chromatogra-
phy with ethyl acetate and petroleum ether as eluent to afford the corre-
sponding products.
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Received: April 1, 2013
Revised: August 28, 2013
Published online: October 25, 2013
Chem. Eur. J. 2013, 19, 16825 – 16831
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16831