L-proline promoted Ullmann-type reaction of vinyl bromides with imidazoles in ionic liquidst

Article abstract of DOI:10.1039/b501628b

The Ullmann-type coupling reaction of vinyl bromides and imidazoles in ILs at 90-110 °C gave the corresponding N-vinylimidazoles in good to excellent yields by using L-proline as the ligand; the double bond geometry of the vinyl bromides was retained under the reaction conditions. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b501628b

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L-Proline promoted Ullmann-type reaction of vinyl bromides with
imidazoles in ionic liquids{
Zhiming Wang, Weiliang Bao* and Yong Jiang
Received (in Cambridge, UK) 3rd February 2005, Accepted 6th April 2005
First published as an Advance Article on the web 21st April 2005
DOI: 10.1039/b501628b
The Ullmann-type coupling reaction of vinyl bromides and
imidazoles in ILs at 90–110 uC gave the corresponding
N-vinylimidazoles in good to excellent yields by using L-proline
as the ligand; the double bond geometry of the vinyl bromides
was retained under the reaction conditions.
(entry 2). Without the addition of L-proline the reaction gave only
9% yield for the same reaction time and temperature (entry 3).
4
Among the solvents tested, [Bmim]BF gave the best result, ILs
with other different anions and MeCN provided slightly lower
yields, while DMSO and DMF delivered little desired coupling
product (compare entries 4–9). Furthermore, when the same anion
IL based on the pyridine was used as the reaction medium, a
similar result was obtained for the same reaction time and
temperature (entry 10). It seems that different anions of the ILs
have different effects on the reaction rate or yield, and the cation
has little effect on them in our novel reaction system.
N-Vinylimidazoles are valuable intermediates in organic synthesis.
They have been widely employed as building blocks in the
synthesis of metal complexes, and also as intermediates in the
synthesis of various heterocycles and poly(N-vinylimidazole)s
which have found growing applications in metals separation,
polar compounds extraction, cosmetics and coloring matter
After optimized reaction conditions were obtained, the reaction
scope was explored with various vinyl bromides and other
imidazoles. The results are summarised in Table 2. It was found
that either electron-rich or electron-deficient vinyl bromides were
suitable for this reaction, giving the desired coupling products in
good to excellent yields. We found, however, that Z-vinyl
bromides were not suitable substrates, most likely because of their
increased level of steric hindrance. In contrast, this protocol was
less sensitive to the size of imidazoles used. For example,
benzimidazole performed well under the reaction conditions and
1
refinement. In addition, N-vinylimidazoles have found antifungal
2
and antiparasitic applications in medicine and agriculture.
Conventionally, protocols for their preparation include direct
3
addition of imidazoles to alkynes, N-vinylation of imidazole with
4
vinyl halides or acetates, copper-catalyzed C–N bond cross-
5
coupling with vinylboronic acid, and olefination of b-hydro-
6
xyimidazoles. Although these protocols provide access to
N-vinylimidazoles, they suffer from either harsh reaction condi-
tions or lack of stereocontrol of the double bond geometry.
On the other hand, in recent years, great interest has been shown
7
in the metal-catalyzed C–N bond formation of aryl halides. Most
of the work has concentrated on the formation of aromatic C–N
bonds, with only one example of the palladium-catalyzed
8
vinylation of azoles reported. In contrast, vinylic C–N cross-
coupling reactions have been demonstrated using copper as the
9
catalyst or promoter. Surprisingly, although the copper-catalyzed
coupling of aryl halides with imidazoles has been extensively
Scheme 1 CuI-catalyzed coupling reaction of b-bromostyrene 1 with
imidazole 2.
10
applied to synthesize the N-arylimidazoles, the application of the
same cross-coupling reaction to vinyl halides has not been
described. Herein, we wish to report the synthesis of
N-vinylimidazoles by using CuI as the catalyst and L-proline as
the ligand.
Table 1 Formation of 3 under different catalytic conditions
a
Entry
Solvent
T/uC
t/h
Yield (%)
Ionic liquids (ILs) as the novel ‘‘solutions’’ for transition metal
1
1
catalysis have been widely studied in recent years. Various metal-
1
2
3
4
5
6
7
8
9
[Bmim]BF
[Bmim]BF
[Bmim]BF
4
4
4
90
110
110
110
110
110
reflux
110
110
110
30
20
20
20
30
30
36
30
30
20
c
80
87
9
catalyzed reactions, including copper-catalyzed Ullmann–type
b
1
2
reaction, have been demonstrated in ILs and excellent results
have been obtained. Our experiment was first conducted by
coupling b-bromostyrene and imidazole catalyzed by 10 mol% CuI
and 20 mol% L-proline (Scheme 1). This reaction proceeded well at
[Bmim]PF
[Bmim]Br
[Bmim]I
MeCN
6
70
78
60
25
c
DMSO
DMF
[Bpy]BF
—
—
9
0 uC in IL [Bmim]BF
4
in the presence of K CO
2
3
to produce
c
N-styrylimidazole in 80% yield (Table 1, entry 1). Higher yield and
10
a
4
85
b
shorter time were obtained by raising the reaction temperature
Isolated yield. L-proline was not used. Little coupling product
d
was determined. Bmim 5 1-butyl-3-methylimidazolium, Bpy 5
e
N-butylpyridinium. Reaction conditions: b-bromostyrene (2 mmol),
{
Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b5/b501628b/
wbao@hzcnc.com
imidazole (2.2 mmol), CuI (0.2 mmol), L-proline (0.4 mmol), K
(
2 3
CO
5 mmol) in 4 mL suitable solvent.
*
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Table 2 N-Vinylimidazoles synthesized with CuI/L-proline/IL system
the reaction, b-bromostyrene, imidazole, CuI, L-proline and
CO in [Bmim]BF were allowed to react in the ionic solvent
a
K
2
3
4
Entry Vinyl bromide
1
Imidazole Product
t/h Yield (%)
for 20 h and then the products were extracted with ethyl acetate
(3 6 2 mL). After the recovered ionic solvent was concentrated in
vacuo (5.0 torr for 1.5 h at 60 uC), further amounts of reactants
and K CO (2 mmol) were added and the process was repeated up
20 87
2
3
to four times, until the build-up of KBr rendered the mixture solid-
1
3
2
3
20 88
30 60
like at room temperature. It seems that there is little effect on the
rate or yield of the reaction during each cycle (Table 3).
In summary, we have developed a mild and efficient method for
the copper-catalyzed coupling of imidazoles with vinyl bromides.
The use of ionic liquids as excellent media for the coupling reaction
has been demonstrated. The mild reaction conditions and high
stereoselectivity relative to previous methods, the operational
simplicity, and recyclable metal-catalyzed reaction system should
render this protocol attractive to synthetic chemists.
4
5
20 75
20 86
Zhiming Wang, Weiliang Bao* and Yong Jiang
Department of Chemistry, Zhejiang University, Xi Xi Campus,
Hangzhou, Zhejiang, 310028, P. R. China. E-mail: wbao@hzcnc.com;
Fax: +86-571-88911554
Notes and references
6
7
20 86
20 93
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a
b
Isolated yield. Reaction conditions: vinyl bromide (2 mmol),
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4
6
longer reaction time was required to consume the starting material,
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11,12
metal catalysts immobilized in these media can be reused.
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6
7
Table 3 Reuse of CuI/L-proline/IL reaction system
a
a
Cycle
Yield (%)
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1
2
a
87
85
b
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82
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Isolated yield. Reaction conditions: b-bromostyrene (2 mmol),
imidazole (2.2 mmol), CuI (0.2 mmol), L-proline (0.4 mmol), K
2 3
CO
9
(
5 mmol) in 4 mL [Bmim]BF at 110 uC for 20 h.
4
2
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