PEG-OSO3H as an efficient and recyclable catalyst for the synthesis of β-amino carbonyl compounds via the Mannich reaction in PEG-H2O

Article abstract of DOI:10.1016/j.cclet.2012.01.016

Sulfuric acid-modified polyethylene glycol 6000 (PEG-OSO₃H) was applied as an efficient and recyclable catalyst for the synthesis of β-amino carbonyl compounds via the Mannich reaction between aldehydes, aromatic ketones and aromatic amines at room temperature using PEG400-H ₂O (1:1) as environment-friendly solvents. The reactions were completed in short times and mild reaction conditions with good to excellent yields.

Full text of DOI:10.1016/j.cclet.2012.01.016

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 423–426
www.elsevier.com/locate/cclet
PEG-OSO3H as an efficient and recyclable catalyst for the
synthesis of b-amino carbonyl compounds via the
Mannich reaction in PEG–H2O
*
Xi Cun Wang , Li Jia Zhang, Zhang Zhang, Zheng Jun Quan
Gansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering, Northwest Normal University,
Lanzhou 730070, China
Received 7 November 2011
Available online 3 March 2012
Abstract
Sulfuric acid-modified polyethylene glycol 6000 (PEG-OSO3H) was applied as an efficient and recyclable catalyst for the
synthesis of b-amino carbonyl compounds via the Mannich reaction between aldehydes, aromatic ketones and aromatic amines at
room temperature using PEG400–H2O (1:1) as environment-friendly solvents. The reactions were completed in short times and
mild reaction conditions with good to excellent yields.
# 2012 Xi Cun Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Mannich reaction; b-Amino carbonyl compounds; PEG-OSO3H; Environmentally benign
The Mannich reaction is an important carbon–carbon bond forming reaction in organic synthesis for the preparation
of b-amino carbonyl compounds constitute various pharmaceuticals, natural products, and versatile synthetic
intermediates used for the synthesis of amino alcohols, peptides and lactams, and as precursors for optically active
amine acids [1–4]. Over the past decades, the research on the new operationally simple, efcient, recyclable and
environmentally benign catalysts for the Mannich reaction has gained popularity in synthetic chemistry. Nowadays, it
has been noted that this reaction can also be promoted by a wide array of catalysts, such as GuHCl [5], CeCl3Á7H2O [6],
proline [7–10], Bronsted ionic liquids [11–14], rare earth peruorooctane [15–17], salts [18–27], etc. Green solvent
reactions are of great importance in organic synthesis. PEG, poly(ethylene glycol), is known to be inexpensive,
thermally stable, recoverable, biological compatible, and non-toxic [28]. However, most of the reported procedures for
the Mannich reaction suffer from drawbacks such as low yields of the products, long reaction times, and the use of
hazardous and often expensive catalysts, the use of volatile and hazardous organic solvents and no compliance with the
green chemistry protocols. Consequently, development of the efficient, inexpensive and environmentally benign
methods for the Mannich reaction is in demand.
We previously reported the preparation and utilization of polyethylene glycol bound sulfonic acid (PEG-OSO3H) in
the multicomponent reaction for the synthesis of 3,4-dihydropyrimidinones [29]. PEG-OSO3H is a mild, non-volatile
* Corresponding author.
E-mail address: wangxicun@nwnu.edu.cn (X.C. Wang).
1001-8417/$ – see front matter # 2012 Xi Cun Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2012.01.016

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X.C. Wang et al. / Chinese Chemical Letters 23 (2012) 423–426
R1
O
CHO
CH3
NH2
PEG-SO3H (5 mol%)
PEG400/H2O (1:1), r.t.
O
R3
+
+
N
H
R2
R1
R2
R3
2
1
3
4
Scheme 1. The Mannich reaction catalyzed by PEGOSO3H.
and non-corrosive organic acid. It also combines the advantageous features of homogeneous catalysis such as high
reactivity, lack of diffusion phenomena and analytical simplicity, as well as solid phase methods [30]. Then the PEG-
OSO3H has been used for the regioselective ring opening of epoxides with thiocyanate anion in water [31], Beckmann
¨
rearrangement, dehydration of oximes [32], Friedlander synthesis of poly-substituted quinolines [33] and one-pot
three-component synthesis of triazolo[1,2-a]indazoletriones [34]. As part of our ongoing research program on the
synthesis of polymer supported catalyst and it is utilization in organic reaction using green solvents [29,35]. We herein
reported the synthesis of b-amino carbonyl compounds catalyzed by PEG-OSO3H in PEG400–H2O (V:V = 1:1) at
room temperature (Scheme 1).
1. Results and discussion
Initially, we chosed the reaction of aniline, benzaldehyde with acetophenone using PEG-OSO3H as catalyst at room
temperature for the synthesis of compound 4a (Scheme 1, R1, R2, R3 = H) as a model reaction to optimize the reaction
conditions [36]. The reaction could occur in EtOH, MeCN, CH2Cl2, PhMe, H2O, PEG400, and the mixture of PEG400
with H2O to give 4a in yield 43–91% (Table, entries 1–7). Interestingly, the best yield of 4a (91%) was obtained when
the mixture of PEG400/H2O (V:V = 1:1) as the solvent (Table 1, entry 8). Moreover, we found that the yield was
obviously affected by the amount of PEG-OSO3H loaded (entries 8–10). It was found that 5 mol% of PEG-OSO3H
was sufficient and excessive amount of catalyst did not increase the yield.
Based on the above observations, we conducted the same reactions using various aromatic aldehydes, aromatic
ketone and aromatic amines in the presence of 5 mol% PEG-OSO3H. All of the reactions took place in PEG400/H2O
(V:V = 1:1) at room temperature conditions. The reactions were completed for periods ranging from 8 to 24 h to
provide good yields (76–95%) of b-amino carbonyl compounds (Table 2).
After completion of each reaction, ice was added to the reaction mixture and the crude product (insoluble in water)
was filtered and recrystallized from hot ethanol/water. In order to recover the catalyst, H2O was evaporated under
reduced pressure giving a mixture of PEG-OSO3H with PEG-400. Then hot water (2 mL) was added and the solution
was cooled to r.t. to give the pure PEG-OSO3H. The recovered catalyst was reused seven times in the condensation for
the synthesis of compound 4a and smooth decline of product yield was observed (the yield was 90% for 1st run, and
88%, 85%, 78%, 67%, 55%, 42% for 2nd to 7th run, respectively), which due to the loss of the amount of recovered
PEG-OSO3H. Compared with traditional liquid acid catalysts, PEG-OSO3H had an attractive property in that it can be
easy recover and recycled.
Table 1
Optimization of the PEG-OSO3H catalyzed the Mannich reaction.a
Entry
Solvent
PEGOSO3H/mol%
Yield (%)b
Entry
Solvent
PEGOSO3H/mol%
Yield (%)b
1
2
3
4
5
EtOH
MeCN
CH2Cl2
PhMe
H2O
5
5
5
5
5
69
64
55
43
75
6
7
PEG400
5
72
83
91
85
90
PEG400/H2O (V:V 1:2)
PEG400/H2O (V:V 1:1)
PEG400/H2O (V:V 1:1)
PEG400/H2O (V:V 1:1)
5
8
5
9
2.5
7.5
10
a
Reaction conditions: benzaldehyde (1 mmol), acetophenone (1 mmol) and aniline (1 mmol), PEG-OSO3H (5 mol%), time (10 h), r.t.
Isolated yields.
b

X.C. Wang et al. / Chinese Chemical Letters 23 (2012) 423–426
425
Table 2
PEGOSO3H catalyzed the Mannich reaction between aldehyde, ketone and amine.a
Entry
R1
R2
R3
Time (h)
Product
Yield (%)b
Mp/(8C) (Lit.)
1
2
C6H5
4-OCH3
4-CH3
4-NO2
4-Cl
4-F
H
H
H
10
8
4a
4b
4c
4d
4e
4f
91
95
93
78
89
83
92
78
87
85
90
76
81
77
169–170 (169–171 [6])
147–149 (148–150 [6])
129–130 (127–129 [5])
103–105 (104–106 [5])
114–117 (115–116 [5])
107–108 (108–110 [5])
165–168 (167–171 [27])
185–188 (184–186 [6])
181–183 (183–185 [15])
130–132 (132–134 [6])
163–165 (165–168 [6])
132–135 (138–139 [15])
109–110 (110–113 [27])
115–117 (116–118 [27])
H
H
3
H
H
9
4
H
H
12
9
5
H
H
6
H
H
10
9
7
H
4-CH3
4-NO2
4-Br
3-Cl
4-OCH3
H
4g
4h
4i
8
H
H
12
10
9
9
H
H
10
11
12
13
14
H
H
4g
4k
4l
H
H
9
H
4-CH3
4-NO2
4-Cl
24
12
24
H
H
4m
4n
H
H
a
Reaction conditions: benzaldehyde (1 mmol), acetophenone (1 mmol) and aniline (1 mmol), PEG-OSO3H (5 mol%), PEG-400/H2O
(2.5 mL:2.5 mL), r.t.
b
Isolated yield.
2. Conclusion
An efficient method was developed for the synthesis of b-amino carbonyl compounds via the Mannich reaction
using recyclable PEG-OSO3H as an eco-friendly and recyclable catalyst. This method is bestowed with several unique
merits, such as high conversions, simplicity in operation, cost efciency and used PEG400/H2O as green solvents.
Acknowledgments
We are thankful for the financial support from the National Nature Science Foundation of China (Nos. 20902073
and 21062017), the Natural Science Foundation of Gansu Province (No. 096RJZA116), and the Scientific and
Technological Innovation Engineering program of Northwest Normal University (Nos. nwnu-kjcxgc-03-64, nwnu-
lkqn-10-15).
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[36] General procedure: PEG-OSO3H (0.31 g, 0.05 mmol –SO3H) was added to a mixture of aniline (1 mmol), benzaldehyde (1 mmol) and
acetophenone (1 mmol) in PEG400 (2.5 mL) and H2O (2.5 mL). The mixture was stirred at room temperature for a certain time (Table 2) and
monitored by TLC. After the completion of the reaction, ice (30 g) was added and the crude product was slowly separated out. The insoluble
crude product was filtered and recrystallized from EtOH/H2O (V:V = 4:1) affording 4a. All the products were characterized by comparison of
their melting points, IR, 1H NMR and 13C NMR spectra with those of authentic samples. Selective data: 4a: mp 169–170 8C; IR (KBr): n 3385,
167, 1599, 1512, 1291, 746, 687, 579 cmÀ1; 1H NMR (400 MHz, CDCl3): d 3.45 (d, 1H, J = 6.0 Hz), 3.54 (d, 1H, J = 6.0 Hz), 5.02 (m, 1H),
6.57 (d, 2H, J = 8.0 Hz), 6.57–6.68 (m, 1H), 7.01–7.10 (m, 2H), 7.25 (d, 1H, J = 5.9 Hz), 7.26–7.34 (m, 2H), 7.42–7.58 (m, 2H), 7.90 (d, 2H,
J = 8.0 Hz); 13C NMR (100 MHz, CDCl3): d 46.3, 54.7, 113.7, 117.7, 126.3, 127.3, 128.2, 128.7, 128.8, 129.1, 133.4, 136.6, 142.9, 147.0,
198.2.