Angewandte
Chemie
DOI: 10.1002/anie.201306850
Homogeneous Catalysis Very Important Paper
Selective Methylation of Amines with Carbon Dioxide and H **
2
Yuehui Li, Ivꢀn Sorribes, Tao Yan, Kathrin Junge, and Matthias Beller*
Carbon dioxide is the most abundant carbon source respon-
sible for the construction of all organic compounds in nature.
Because of the rising anthropogenic emission of CO , its use
2
as a cheap and renewable C1 feedstock is of increasing
interest for the production of value-added bulk chemicals
such as methanol, polycarbonates, as well as fine chemi-
[
1–3]
cals.
In recent years, important developments to convert
the thermodynamically stable CO molecule into formates,
2
methanol, and methane have been reported using different
[4–15]
reductants.
In addition to these methods, very recently
interesting methylations using CO were reported by Cantat
2
[
16]
[17]
et al. and us. Unfortunately, in both cases hydrosilanes
had to be used as the reductant for the production of
methylated amine products in the presence of either a Zn/
Figure 1. A) Known methods for N-methylation. B) N-methylation
using CO and H . Tf=trifluoromethanesulfonyl.
2
2
NHC or Ru/BuPAd catalyst.
2
Since methyl-substituted amines exist frequently as bio-
active compounds and have been widely utilized as key
intermediates and important chemicals, the development of
more efficient methylation methods continuously attracted
conversion with 96% yield of N,N-dimethylaniline (3a) and
4% of N-methylaniline (2a) in the presence of a catalytic
amount of a Brønsted acid (Table 1, entry 8). This combi-
nation was found to be critical (Table 1, entries 1–7, 9–14).
[29]
[18]
the attention of chemists in the last decades. Still, the most
common methylation of amines in industry makes use of toxic
formaldehyde, whereas in organic synthesis less benign
methylation reagents, for example, methyl iodide, and
Interestingly, the pressure of CO could be lowered to only
2
2 atm, thus generating 88% of 2a and 4% of 3a, and
indicating methylation of 1a is favored over methylation of 2a
(Table 1, entry 15). Notably, this reaction system is robust and
not sensitive to air. Hence, it is not necessary to work under
inert conditions before introducing carbon dioxide.
[
19,20]
dimethyl sulfate, prevail.
Thus, the application of more
sustainable reagents with good selectivity (e.g. functional-
group tolerance and monomethylation) is highly desired.
Obviously, catalytic methylations using CO and H represent
To understand the mechanism of this methylation reac-
tion, control experiments were studied to identify the key
intermediates. Since it is known that CO2 can be hydro-
genated to formic acid and methanol in the presence of
ruthenium complexes, the reduction of the formamide 5a and
methylation from methanol were investigated. As shown in
Scheme 1a, 5a was fully converted and 2a was the major
2
2
an elegant and viable method with H O as the only byproduct
2
[
21]
(
Figure 1).
Herein we describe a general and selective
ruthenium-catalyzed methylation of both aromatic and ali-
phatic amines using carbon dioxide/hydrogen to N-methy-
lated products.
The present work was motivated by the efficiency of
[30a]
ruthenium-catalyzed hydrogenation of CO and carboxylic
product in 64% yield.
Meanwhile, it was found that
2
acid derivatives as well as N-alkylation from alcohols
methanol can also act as the source of the methyl group.
Interestingly, this reaction occurred in low yield in the
presence of H2 (Scheme 1b). To further understand the
methylation process, a reaction profile of 1a was performed
(see Figure S1 in the Supporting Information). Under the
standard reaction conditions, no obvious incubation period
was observed. During the reaction, 5a is not detected as an
intermediate. However, significant amounts of methanol were
generated (up to 9.5 mmol MeOH produced). In contrast, at
[
14,22–28]
previously reported by us and other groups.
Initially,
we investigated the reaction of carbon dioxide, H , and aniline
2
(1a) in the presence of in situ formed ruthenium complexes as
a model system (Table 1 and Tables S1–S4 in the Supporting
Information). The most active catalyst was formed from
ruthenium acetylacetonate [Ru(acac) ] and 1,1,1-tris(diphe-
3
nylphosphinomethyl)ethane (triphos; 4 f), and afforded full
a lower pressure of H (30 atm), 5a is detected in low yield
2
[
*] Dr. Y. Li, Dr. I. Sorribes, T. Yan, Dr. K. Junge, Prof. Dr. M. Beller
Leibniz-Institut fꢀr Katalyse e.V.
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
E-mail: matthias.beller@catalysis.de
Homepage: http://www.catalysis.de
(< 5%). Under the same reaction conditions, using benzyl
amine as the substrate, only traces of the corresponding
methylated product can be obtained with a significant amount
of formamide byproduct. These results are consistent with the
work of Cole-Hamilton and Leitner et al. for the reduction of
[
**] This work was supported by the state of Mecklenburg-Vorpommern
[26]
and the BMBF. We thank Prof. Kuiling Ding for fruitful discussions.
N-aliphatic amides compared to that of N-aromatic amides.
To understand the influence of electronic effects, the
competition reaction of para-substituted aniline derivatives
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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