Ullmann reaction in tetraethyl orthosilicate: A novel synthesis of triarylamines and diaryl ethers

Article abstract of DOI:10.1039/b706449g

A novel synthesis of triarylamines and diaryl ethers is reported; a feature of this process is the ligand-free copper-catalysed C-N and C-O bond formation in tetraethyl orthosilicate. The Royal Society of Chemistry.

Full text of DOI:10.1039/b706449g

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Ullmann reaction in tetraethyl orthosilicate: a novel synthesis of
triarylamines and diaryl ethers{
Yuanhong Zhao, Yunsong Wang, Hongwei Sun, Liang Li and Hongbin Zhang*
Received (in Cambridge, UK) 30th April 2007, Accepted 9th May 2007
First published as an Advance Article on the web 29th May 2007
DOI: 10.1039/b706449g
A novel synthesis of triarylamines and diaryl ethers is reported;
a feature of this process is the ligand-free copper-catalysed C–N
and C–O bond formation in tetraethyl orthosilicate.
To our disappointment, besides low yields (5% in DMF and
25% in DMSO), the purification of diarylamines from the residue
4
of DMF or DMSO was troublesome. In the literature, tetraethyl
orthosilicate (TEOS) has been utilized as a dehydration reagent for
4b
the synthesis of enaminoesters and sterically-hindered imines.
4a
High boiling point solvents are frequently required as reaction
media for better yields in organic synthesis. These solvents
generally provide the high temperature that is sometimes crucial
for the synthesis of triarylamines, an important type of electronic
We perceived that TEOS could be used as a solvent for Ullmann
reactions. As shown in Scheme 1, when switching to TEOS, the
desired triarylamine, which was generally obtained by the utiliza-
tion of a ligated palladium or copper complex-catalysed Ullmann
1
2
materials, by a copper-promoted Ullmann reaction. Although
numerous high boiling point organic solvents have been used as
reaction media for this transformation, relatively few are in general
use. As a consequence, the utilization of high boiling point solvents
suffers from the difficulty of purifying the desired products and is
occasionally problematic, with several chromatographic separa-
tions being required to separate a desired product from the residue
of a high boiling point solvent. As reaction ‘‘media’’, solvents are
used in large excess. Unavoidably, this brings the environmental
problem of atmospheric emissions and the contamination of
aqueous effluents. It is therefore highly desirable to find suitable
solvents for high-temperature Ullmann reactions that don’t suffer
the shortcomings of traditional high boiling point solvents such as
DMF and DMSO.
5
reaction, was obtained in one step with high yield in the presence
6
of copper(I) iodide.{ No ligand was necessary in this new solvent.
Encouraged by this result, we carried out a number of reactions
in TEOS in order to optimise the reaction conditions (Table 1). We
found that the copper-catalysed amination of aryl iodide in TEOS
could lead to triarylamines in good yield, even in the presence of
only a 10% equivalent amount of copper(I) iodide (Table 1, entry
4). In order to understand the role that TEOS plays, we also
carried out reactions in traditional solvents, but with TEOS as an
additive. It is worthwhile noting that TEOS might serve as a
promoting ligand for Ullmann coupling (Table 1, entries 8 and 9).
The yields of triarylamines dramatically decreased when bromo-
benzene was used instead of iodobenzene.
In our studies towards the synthesis of triarylamines, we decided
to carry out a proline–copper complex-catalysed Ullmann
amination, as indicated in Scheme 1. Although proline–copper
complex-promoted amination had been successfully applied to the
Although the palladium complex-catalysed ‘‘one-pot’’ synthesis
5h
of triarylamines has been realized by Buchwald, to the best of
a
Table 1 Studies on the CuI-catalysed formation of triarylamines
3
preparation of diarylamines in the literature, no examples
concerning triarylamines have been reported.
Entry
Base
Solvent
Aryl halide
Yield (%)
t
1
2
3
4
5
6
7
8
9
a
BuOK
Si(OEt)
Si(OEt)
Si(OEt)
Si(OEt)
Si(OEt)
DMF
DMSO
DMF
DMSO
4
Iodobenzene
Iodobenzene
Iodobenzene
Iodobenzene
Bromobenzene
Iodobenzene
Iodobenzene
Iodobenzene
Iodobenzene
(complex)
K
2
CO
3
4
4
4
4
65
82
Cs
Cs
Cs
Cs
Cs
Cs
Cs
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
b
67
5
7
5
70
55
c
Scheme 1 Attempts towards the synthesis of triarylamines.
c
Reaction conditions: Aryl halide (3 mmol), CuI (20% mol equiv.), aryl
Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan
University), Ministry of Education, School of Chemical Science and
Technology, Yunnan University, Kunming, Yunnan 650091, P. R. China.
E-mail: zhanghb@ynu.edu.cn
amine (1 mmol) and base (2 mmol) in commercially available organic
solvents (4 mL) were de-gassed and purged with nitrogen, and then
b
stirred at 145 uC (oil bath) for 20 h. Reactions were carried out
under identical conditions, except with less CuI (10% mol equiv.).
{
Electronic supplementary information (ESI) available: Experimental
c
Reactions were carried out under identical conditions, except in the
presence of TEOS (1.0 mmol). Yields quoted are isolated yields.
1
13
section, H NMR, C NMR and HRMS spectra of all new compounds.
See DOI: 10.1039/b706449g
3
186 | Chem. Commun., 2007, 3186–3188
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Table 2 CuI-catalysed synthesis of triarylamines in TEOS with
primary arylamines and aryl iodides
our knowledge, our procedure represents the first general method
for the one-step synthesis of triarylamines with catalytic amounts
of copper (20%) in the absence of a promoting additive ligand
under relatively mild reaction conditions (145 uC oil bath and
a
Cs
easily realized by treatment of the reaction mixture with freshly
prepared aqueous NH F (6.25%) absorbed onto silica gel in the
2 3
CO as a base). Complete removal of the solvent (TEOS) was
4
presence of ethanol. The solvent was completely converted to silica
gel, and the desired product was obtained by filtration and
washing with a regular organic solvent. With a 20% amount of
copper(I) iodide as the catalyst, a number of triarylamines were
prepared with TEOS as the reaction media. The results are
summarised in Table 2.
Entry
Product
Time/h Yield (%)
1
48
42
61
70
Table 2 CuI-catalysed synthesis of triarylamines in TEOS with
primary arylamines and aryl iodides (Continued )
a
2
3
4
5
Entry
Product
Time/h Yield (%)
40
24
30
75
85
83
1
0
30
81
1
1
1
2
24
24
94
85
1
3
4
120
87
84
6
7
18
24
89
90
1
32
1
1
5
6
28
24
93
88
8
9
40
24
81
80
a
Reagents and conditions: Aryl iodide (3 mmol), CuI (38 mg,
.2 mmol), aryl amine (1 mmol) and Cs CO (652 mg, 2 mmol) in
0
2
3
commercially available TEOS (3–5 mL) were de-gassed and purged
with nitrogen, and then stirred at 145 uC (oil bath) for 18–120 h.
Yields quoted are isolated yields.
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Chem. Commun., 2007, 3186–3188 | 3187

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a
Table 3 CuI-catalysed formation of diarylethers in TEOS
In summary, a versatile reaction medium for the synthesis of
triarylamines and diaryl ethers by a ligand-free copper-catalysed
Ullmann reaction, tetraethyl orthosilicate (TEOS), is disclosed.
TEOS can serve as a promoting ligand in copper-catalysed
Ullmann coupling reactions. Separation of the desired product
from the solvent medium is also greatly facilitated. For applica-
tions in industry, TEOS could be recycled by distillation under
reduced pressure, while the TEOS residue could be hydrolysed
easily to silica gel and ethanol, therefore making it an economic
and green process. Utilization of this solvent in other organic
reactions is currently under way in our laboratory.
Entry
1
Product
Yield (%)
79
This work was supported by a grant (706052) from the
Foundation of the Chinese Ministry of Education for fostering
important scientific programs. We would like to thank the
National Natural Science foundation of China for partial financial
support (20662011).
2
3
4
86
89
84
Notes and references
{
(
General procedure for the synthesis of triarylamines: A mixture of CuI
38 mg, 0.2 mmol), Cs CO (652 mg, 2 mmol, 2.0 equiv.), primary aryl
2
3
amine (1 mmol) and aryl iodide (3 mmol) in TEOS (3–5 mL) was de-gassed
and purged with nitrogen (2 times). The resulting mixture was then stirred
at 145 uC (oil bath) under nitrogen. The reaction was monitored by thin
layer chromatography (TLC). After cooling to room temperature, the
residue was diluted with ethyl acetate (5 mL) and 95% ethanol (10 mL).
4 2 4
NH F–H O on silica gel [5 g, pre-prepared by the addition of NH F (10 g)
in water (150 mL) to silica gel (50 g, 100–200 mesh)] was added, and the
resulting mixture was kept at room temperature for 3–5 h. The solidified
material was filtered and washed with ethyl acetate. After removal of the
solvents, the residue was chromatographed on silica gel (ethyl acetate–
petroleum ether) to afford the products.
5
78
1
2
3
4
5
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Reagents and conditions: Aryl bromide (1 mmol), CuI (95 mg,
.5 mmol), respective phenol (1.2–1.3 mmol) and Cs CO (652 mg,
mmol) in commercially available TEOS (3–5 mL) were de-gassed
0
2
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3
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1
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8–20 h. Yields quoted are isolated yields.
6
7
There is only one reported example of the ligand-free copper-catalysed
synthesis of a triarylamine, namely the preparation of triphenylamine by
the reaction of aniline with iodobenzene in the presence of BuOK in a
high pressure autoclave, see: A. A. Kelkar, N. M. Patil and R. V.
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(a) B. H. Lipshutz, J. B. Unger and B. R. Taft, Org. Lett., 2007, 9, 1089;
The synthesis of diaryl ethers by copper-catalysed Ullmann
t
coupling reactions are of current interest, and a number of new
7
protocols have recently been developed. To our pleasant surprise,
our triarylamine synthetic process could also be applied to the
synthesis of diarylether by the direct coupling of phenols with
aryl bromides. A notable feature of our method is that it is
free of a promoting additive ligand. A number of diaryl ethers
were synthesized with high yields. The results are shown in
Table 3.
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Chem., Int. Ed., 2006, 45, 4321; For reviews of diaryl ether synthesis by
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3
188 | Chem. Commun., 2007, 3186–3188
This journal is ß The Royal Society of Chemistry 2007