PEG 1000-based dicationic acidic ionic liquid as an efficient catalyst for mannich-type reaction in water

Article abstract of DOI:10.1080/00397911.2014.907424

GRAPHICAL ABSTRACT PEG₁₀₀₀-based dicationic acidic ionic liquid (PEG₁₀₀₀-DAIL) was found to be an efficient and recyclable catalyst for Mannich-type reaction of different ketones with various aromatic aldehydes and aromatic amines in water to give various β-arylamino ketones in good yields. The catalytic system could be easily recovered and reused for at least six runs only with slight decrease in its activity.

Full text of DOI:10.1080/00397911.2014.907424

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PEG1000-Based Dicationic Acidic Ionic
Liquid as an Efficient Catalyst for
Mannich-Type Reaction in Water
a
a
a
a
Yi-Ming Ren , Juan-Juan Shao , Zhi-Chuan Wu , Ren-Chun Yang
a
a
,
a
Ze Zhang & Ting-Xian Tao
Department of Biochemical Engineering , Anhui Polytechnic
University , Wuhu , Anhui , China
Accepted author version posted online: 28 Apr 2014.Published
online: 01 Jul 2014.
To cite this article: Yi-Ming Ren , Juan-Juan Shao , Zhi-Chuan Wu , Ren-Chun Yang , Ze Zhang & Ting-
Xian Tao (2014) PEG1000-Based Dicationic Acidic Ionic Liquid as an Efficient Catalyst for Mannich-Type
Reaction in Water, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 44:17, 2529-2534, DOI: 10.1080/00397911.2014.907424
To link to this article: http://dx.doi.org/10.1080/00397911.2014.907424
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Synthetic Communications , 44: 2529–2534, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2014.907424
PEG1000-BASED DICATIONIC ACIDIC IONIC LIQUID
AS AN EFFICIENT CATALYST FOR MANNICH-TYPE
REACTION IN WATER
Yi-Ming Ren, Juan-Juan Shao, Zhi-Chuan Wu,
Ren-Chun Yang, Ze Zhang, and Ting-Xian Tao
Department of Biochemical Engineering, Anhui Polytechnic University,
Wuhu, Anhui, China
GRAPHICAL ABSTRACT
Abstract PEG1000-based dicationic acidic ionic liquid (PEG1000-DAIL) was found to be an
efficient and recyclable catalyst for Mannich-type reaction of different ketones with various
aromatic aldehydes and aromatic amines in water to give various b-arylamino ketones in
good yields. The catalytic system could be easily recovered and reused for at least six runs
only with slight decrease in its activity.
Keywords b-Arylamino ketones; ionic liquid; Mannich reaction; multicomponent
reactions; poly(ethylene glycol)
INTRODUCTION
With the increasing public concern over environmental degradation, the use of
environmentally benign solvents such as water is a very powerful green chemical
technology from both the economical and synthetic points of view. They have many
advantages, such as reduced pollution, lower cost, and simplicity in processing,
[
1]
which are beneficial to the industry as well as to the environment. Furthermore,
the other tool used to combine economic and environmental aspects is multicompon-
nent reactions (MCRs). MCRs allow the creation of several bonds in a single oper-
ation and are attracting increasing attention as one of the most powerful emerging
[
2]
synthetic tools for the creation of molecular diversity and complexity.
Received January 7, 2014.
Address correspondence to Yi-Ming Ren, Department of Biochemical Engineering, Anhui
Polytechnic University, Wuhu, Anhui 241000, China. E-mail: yimingren@ahpu.edu.cn
2
529

2530
Y.-M. REN ET AL.
Scheme 1. PEG1000-DAIL-catalyzed Mannich-type reaction.
b-Amino carbonyl compounds are important synthetic intermediates for
[
3]
various pharmaceuticals and natural products. Thus the synthesis of b-amino
carbonyl compounds is of much importance to organic chemists. The most straight-
forward synthesis of these compounds involves the three-component condensation
of ketones, aldehydes, and amines in the presence of various catalysts, such as
[
4]
[5]
[6]
[7]
[8]
ZrOCl ꢀ 8H O, ionic liquid, GuHCl, Cs2.5H0.5PW O , RE(OPf)3, and
2
2
12 40
[
9]
adenine. However, due to the drastic reaction conditions, severe side reactions,
and substrate limitations, the classical intermolecular Mannich reaction is plagued
by a number of serious disadvantages. Therefore, it is desirable to develop a new
efficient system for Mannich-type reactions.
Recently, poly(ethylene glycol)-linked dicationic acidic ionic liquids (PEG-DAILs)
[10]
have been explored as a powerful catalyst for various organic transformations. To
the best of our knowledge, there is no report on the application of PEG1000-DAIL as
[11]
acid catalysts for Mannich-type reaction. As part of our ongoing interest in ILs
[2,12]
and MCRs,
we report herein a simple and efficient procedure for Mannich-type
reaction of different ketones with various aromatic aldehydes and aromatic amines
in water using PEG1000-DAIL as an effective and reusable catalysts (Scheme 1).
RESULTS AND DISCUSSION
First, the reaction of benzaldehyde, acetophenone, and aniline in the presence
PEG1000-DAIL in water media was selected as a model reaction. The results showed
Table 1. Studies on the reaction of benzaldehyde, aniline, and acetophenone
ꢁ
a
Entry
PEG1000-DAIL (mol%)
T ( C)
t (h)
Yield (%)
1
2
3
4
5
0
1
rt
rt
rt
rt
rt
rt
rt
rt
40
80
4
4
4
4
3
2
2
2
2
2
Trace
45
56
2
3
81
93
4
b
6
5
94, 94, 92, 91, 90, 89
7
8
9
6
94
93
83
53
10
5
1
0
5
a
b
Isolated yields.
2
The system of H O= PEG1000-DAIL was run for six consecutive cycles.

IONIC LIQUID–CATALYZED MANNICH-TYPE REACTION
2531
that an appreciable amount of PEG1000-DAIL was 5 mol% to benzaldehyde (Table 1,
entry 6). A longer reaction time would be necessary and lower yield was obtained
with less PEG1000-DAIL. An increase in the amount of PEG1000-DAIL did not lead
to an improvement in yield (Table 1, entries 7 and 8). However, in the absence of
PEG1000-DAIL, the few products were synthesized (Table 1, entry 1). The reaction
temperature had a great influence on the reaction. A poor yield was obtained when
the reaction proceeded at high temperature, possibly because the Mannich base is
[
7,8]
unstable at elevated temperatures (Table 1, entries 9 and 10).
The condensation of benzaldehyde, acetophenone, and aniline under the con-
ditions described in Table 1 with PEG1000-DAIL as catalysts was run for six consecu-
tive cycles with satisfying results (Table 1, entry 6). After completion of the reaction,
the reaction mixture was extracted with diethyl ether or EtOAc. The resultant
residues H O containing ionic liquid were reused directly without further treatment
2
for the next run after being charged with fresh starting materials.
Under the optimized reaction conditions, we investigated the reaction of a var-
iety of ketones, aromatic aldehydes, and aromatic amines (Table 2). It was found that
the reaction was not affected by the electronic effect of substituent groups of aniline
(
Table 2, entries 1–6). However, when o-substituted anilines were performed as sub-
strate, the reaction gave no desired product due to the hindrance of ortho substituents
Table 2, entries 7–9). Table 1 showed that p-nitrobenzaldehyde is most inactive for
(
the reaction (Table 2, entry 10). This is because rich electron-withdrawing groups
þ
degrades the activity of the intermediate (RC H C HNHC H ), which does not
5
6
4
6
favor the following reaction. Cyclopentanone and cyclohexanone were also employed
Table 2. Mannich-type reactions of different ketones with various aromatic aldehydes and aromatic
amines
1
Ketone (R )
2
Amine (R )
3
Aldehyde (R )
a
Entry
t (h)
Yield (%)
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
2
1.5
3
94
96
89
92
85
95
—
—
—
82
91
97
90
89
92
93
85
83
85
80
2 6 4
4-NO C H
Ph
Ph
4-MeC H
6 4
4-ClC
4-MeOC
6
H
4
2
Ph
Ph
6
H
4
3
3-NO
2-NO
2
C
C
6
H
H
4
2
Ph
Ph
2
6
4
5
2-ClC
6
H
4
5
Ph
Ph
2-MeC
Ph
6
H
4
5
1
1
1
1
1
1
1
1
1
1
2
0
1
2
3
4
5
6
7
8
9
0
4-NO
2
C
6
H
4
4
Ph
Ph
Ph
Ph
4-ClC
6
H
4
3
4-MeC
4-MeOC
Ph
6
H
4
3
Ph
Ph
Ph
6
H
4
3
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclopentanone
Cyclopentanone
Cyclopentanone
4
4-MeC
6
H
4
Ph
Ph
5
4-ClC
4-ClC
6
H
4
5
6
H
4
4-MeOC
Ph
6
H
4
4
5
Ph
4-ClC
4-ClC
4
6
H
H
4
4
Ph
4-MeOC
3
6
6
H
5
a
Isolated yields.

2532
Y.-M. REN ET AL.
for the reaction, and the reactions were finished within 5 h and good yields were
obtained. However, the catalyst PEG1000-DAIL appeared to show no catalytic
activity for the reaction in which the aliphatic amines such as butylamine and
aliphatic aldehydes such as isovaleraldehyde were performed as substrates.
In conclusion, we have successfully developed an easy and efficient method to
prepare a variety of b-arylamino ketones from the reaction of different ketones, aro-
matic aldehydes, and aromatic amines in the presence of PEG1000-DAIL. The advan-
tages of the present reaction are the elimination of the metals, short reaction times,
operational simplicity, and excellent yields of products. Moreover, the use of water
as a solvent and the excellent recyclability of the PEG1000-DAIL make this procedure
cleaner, which is a good example of green chemistry technology.
EXPERIMENTAL
[
10a]
The PEG1000-DAIL was prepared by the procedure given in the literature.
All the other chemicals and reagents are obtained from commercial sources. Com-
1
mercially available reagents were used without further purification. H NMR spectra
were measured on Bruker Advance RX500. All products were known compounds
1
and were identified by their mp and H NMR.
PEG1000-DAIL (0.05 mmol) was added to a solution of aldehydes (1 mmol),
ketones (1 mmol), and amines (1 mmol) in H O (2 mL). The reaction mixture was
2
vigorously stirred at room temperature for the period of time and monitored by
thin-layer chromatography (TLC). Then the reaction mixture was extracted with
diethyl ether or EtOAc. The combined organic extracts were dried over anhydrous
Na SO and concentrated to generate the crude product. The crude products were
2
4
purified by column chromatography on silica gel using ethyl acetate=hexane
as eluent. The resultant residues H O containing ionic liquid were reused directly
2
without further treatment for the next run after being charged with fresh starting
materials.
FUNDING
The project sponsored by the Anhui Polytechnic University for Young Elite
Talents (No. 2013RZR002ZD) and the National Innovation Program for University
Students (Nos. 201210363036 and 201310363065).
SUPPLEMENTARY DATA
Supplemental data for this article can be accessed on the publisher’s website.
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