Nafion-H: A recyclable and diastereoselective solid acid catalyst for three-component mannich reaction

Article abstract of DOI:10.1134/S0023158412060079

One-pot, three-component Mannich reactions of ketones, aldehydes and amines are efficiently catalyzed by heterogeneous Nafion-H at ambient temperature to give the corresponding β-amino ketones compounds in good to excellent yields. The catalyst can be easily recovered and reused without any decrease of activity for at least four times. Diastereoselective products can be obtained in Mannich reaction of aliphatic ketone. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S0023158412060079

ISSN 0023ꢀ1584, Kinetics and Catalysis, 2012, Vol. 53, No. 6, pp. 689–693. © Pleiades Publishing, Ltd., 2012.
Published in Russian in Kinetika i Kataliz, 2012, Vol. 53, No. 6, pp. 733–737.
®
NafionꢀH : A Recyclable and Diastereoselective Solid Acid Catalyst
for ThreeꢀComponent Mannich Reaction1
Yang Sulinga, Li Ganga, and Long Yunlingb
a College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang 455002, China
b Department of Life Science and Technology, Xinxiang Medical University, Xixiang 453000, China
eꢀmail: lgorgchem@126.com
Received November 22, 2011
Abstract—Oneꢀpot, threeꢀcomponent Mannich reactions of ketones, aldehydes and amines are efficiently
®
catalyzed by heterogeneous NafionꢀH at ambient temperature to give the corresponding ꢀamino ketones
β
compounds in good to excellent yields. The catalyst can be easily recovered and reused without any decrease
of activity for at least four times. Diastereoselective products can be obtained in Mannich reaction of aliphatic
ketone.
®
Keywords: Mannich reaction, NafionꢀH , diastereoselectivity, recyclability
DOI: 10.1134/S0023158412060079
1. INTRODUCTION
comparable to that of 96–100% sulfuric acid (Н0 ≈ 12)
[23, 24]. Due to its strong acidity, high mechanical
strength, favorable thermostability, chemical stability,
easy recoverability and high catalytic activity, it has
been widely used to catalyze various reactions such as
esterification [25], acetylation of alcohols [26], tranꢀ
salkylation (Friedel–Crafts reaction) [27–29], ether
synthesis [30, 31], aldol condensation [32], Fries rearꢀ
rangements [33], and oxidations [34].
The Mannich reaction is one of the most important
multicomponent carbon–carbon bondꢀforming reacꢀ
tions in organic synthesis and one of the most fundaꢀ
mental and classical routes to prepare
βꢀamino
ketones compounds and their derivatives, which are
versatile synthetic intermediates for various pharmaꢀ
ceuticals, natural products and biologically active
compounds [1–4]. Because of the ubiquitous nature of
nitrogenꢀcontaining compounds including proteins,
nucleic acids and most biologically active molecules
there is an increasing interest in the Mannich reaction.
The reaction can can be conducted using either twoꢀ
component system or threeꢀcomponent system. Howꢀ
ever, the preferable route is oneꢀpot threeꢀcomponent
Mannich reaction of ketones, aldehydes, and amines.
To date, many protocols have been developed for
threeꢀcomponent Mannich reaction [5–12]. Various
catalysts including Lewis acids [13–15], Lewis bases
[16, 17], Brønsted acids [18, 19], rare metal salts
[20, 21], and small organic molecules are used to proꢀ
mote the Mannich reaction [22]. However, most of the
catalysts suffer from evident drawbacks, for example
toxicity, corrosivity, nonꢀrecovery, deactivation of catꢀ
alyst and nondiastereoselectivity. Therefore, it is
important to develop a Mannich reaction method in
which the catalyst can be recycled and diastereoselecꢀ
In this paper, we report that oneꢀpot threeꢀcompoꢀ
nent Mannich reaction of ketones, aldehydes
and amines in ethanol under mild conditions is effiꢀ
®
ciently catalyzed by Nafionꢀ
ing ꢀamino ketones compounds in good to excellent
yields. The Mannich reactions using aliphatic ketone as
Н to give the correspondꢀ
β
®
the substrate are diastereoselective. Nafionꢀ
Н can be
easily recovered and reused without any loss of catalytic
activity.
2. EXPERIMENTAL
2.1. Materials and Methods
All the chemicals and reagents used were of analytꢀ
ical grade and they were used without further purificaꢀ
®
tion. The Nafionꢀ
Н
(ion exchange capacity:
0.8 mmol Н+/g) was purchased from Aldrich Chem.
Co. (China). The structure and syn/anti ratio of prodꢀ
tive product obtained in the process.
1
1
®
Н ) is
ucts were determined by HNMR. H NMR spectra
were obtained from solution in CDCl3 with TMS as
internal standard using a Varian Scimitar Series 800
(400 MHz) spectrometer.
Perfluorinated resin sulfonic acid (Nafionꢀ
an important solid superacid catalyst, which acidity is
1
The article is published in the original.
689

690
SULING et al.
Table 1. Direct threeꢀcomponent Mannich reactions cataꢀ
Encouraged by the remarkable result, we explored
®
®
lyzed by NafionꢀH in different solvents
the generality and scope of Nafionꢀ
Н
catalyzed
threeꢀcomponent Mannich reaction. The reaction
was examined with various ketones, aldehydes and
amines under the same condition as shown in Table 2.
The following conclusions emerge from the dada
NH2
CHO
O
CH3
1 mmol
NH
+
+
related to the Mannich reaction conducted with variꢀ
1 mmol 1 mmol
®
ous substrates and catalyzed by the Nafionꢀ
Н :
®
Ph
(1) The NafionꢀН can efficiently catalyze Manꢀ
8 mol % NafionꢀH
1 mL solvent, r t
O
nich reactions of equal amount of various structural
ketones, aldehydes and amines at ambient temperaꢀ
ture;
Ph
Ph
Yield, %
Entry
Solvent
(2) For aromatic amines with various substitution
groups, including nitroaniline bearing strong elecꢀ
tronꢀwithdrawing group –NO2, the reaction is effiꢀ
1
2
3
4
5
6
EtOH
CH2Cl2
CH3CN
Cl2CHCH3
MeOH
92 (86a, 93b)
45
72
cient to give the corresponding ꢀamino ketones comꢀ
β
pounds in good to excellent yields (entries 4, 9);
(3) Activity of anisaldehyde bearing strong elecꢀ
tronꢀdonating group CН3О– is lower than that of benꢀ
52
84
zaldehyde, but the corresponding ꢀamino ketones
β
H2O
trace
the reaction can be also obtained in a moderate yields
(entry 2);
Note: Reaction conditions: benzaldehyde (1 mmol), aniline
®
(1 mmol), acetophenone (1 mmol), NafionꢀH (8 mol %),
(4) In general, reactivity of pꢀmethylacetophenone
a
®
b
®
room temperature 18 h. Isolated yield, 5 mol % NafionꢀH ,
is slightly lower (entries 7ꢀ9) than that of acetophenone
(entries 1–6). Reactivity of open alkyl chain 3ꢀpenꢀ
tanone is less (enries 15, 16) than that of cyclic ketone
cyclohexanone (entries 10–14);
c
10 mol % NafionꢀH .
®
2.2. General Procedure for the NafionꢀH ꢀCatalyzed
Mannich Reaction
(5) A good to excellent diastereoselectivity can be
obtained in Mannich reaction of aliphatic ketone cataꢀ
Aldehyde (1 mmol), amine (1 mmol), ketone
®
lyzed by NafionꢀН (entries 15, 16). For the reactions
®
(1 mmol) and NafionꢀН (8 mol %) were added to
using cyclohexanone as the substrate, anti/3ꢀamino
ketone isomer is the major product (entries 10–14).
For the reactions with 3ꢀpentanone (entries 15, 16)
ethanol (1 mL) placed in a 25 mL oneꢀnecked roundꢀ
bottom flask. Then, the reaction mixture was stirred
vigorously with a magnetic stirrer under a nitrogen
atmosphere at ambient temperature for the time.
Intervals indicated in Tables 1–3. After reaction comꢀ
pletion, the system was dissolved in acetone to sepaꢀ
rate catalyst by vacuum filtration. The catalyst recovꢀ
ered from system was directly reused in next cycle. A
rotary evaporator removed the solvent in filtrate. The
mixture obtained was either purified by silica gel chroꢀ
matography (petroleum ether/ethyl acetate mixtures)
or recrystallization from ethanol or ethanol–acetone
use as the substrate, syn
major product.
β
ꢀamino ketone isomer is the
®
Н for Mannich reaction
Reusability of Nafionꢀ
was also investigated using the same model reaction.
After the separation of catalyst from the system, it was
directly reused in the next cycle without further purifiꢀ
®
cation. It can be seen from Table 3 that Nafionꢀ
Н can
be recycled at least four times without any loss of catꢀ
®
alytic activity. Excellent reusability of Nafionꢀ
Н
should be attributed to its highly mechanical strength
and stability. It is also not crushed by stirrer during the
reaction.
(
v/v
= 1 : 1) to afford the corresponding compounds.
3. RESULTS AND DISCUSSION
Initially, oneꢀpot Mannich reaction of benzaldeꢀ
hyde, aniline, and acetophenone catalyzed by the
4. CONCLUSIONS
®
®
Nafionꢀ
Н
is selected as a model reaction to investiꢀ
In conclusion, NafionꢀН can efficiently catalyze
gate the effect of solvents at ambient temperature as oneꢀpot threeꢀcomponent Mannich reactions of variꢀ
shown in Table 1. The results show that among organic ous aldehydes, amines and ketones at ambient temꢀ
solvent used, ethanol is the most appropriate solvent perature. Not only the catalyst can be easily recovered
®
for Mannich reaction catalyzed by the Nafionꢀ
The reaction can hardly take place in water. The reacꢀ activity, but also the Mannich reactions using aliphatic
tion could proceed efficiently with 8 mol % of catalyst. ketone as the substrate are diastereoselective. Anti
Н
.
and reused several times without any loss of catalytic
βꢀ
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®
NAFIONꢀH : A RECYCLABLE AND DIASTEREOSELECTIVE SOLID
691
®
Table 2. NafionꢀH catalyzed oneꢀpot threeꢀcomponent of various ketones, aldehydes and amines
O
Ar1
O
Ar2
Ar3
Ar3
N
8 mol % NafionꢀH
1 mL EtOH, r t
Ar2 NH2
Ar1 CHO
H
+
+
O
O
Ar1
Ar2
N
H
1 mmol
1 mmol
1 mmol
Entry
(No.)
Yield, %a
Tmp., °C
Ketones
Aldehydes
Amines
Time, h
18
(syn/anti)b
O
1
2
3
93
167–168
148–150
161–162
CHO
NH2
CH3
O
24
14
62
95
CH3O
CHO
NH2
CH3
O
CHO
CH3
NH2
CH3
O
NH2
4
18
90
144–146
CHO
CH3
NO2
O
5
6
7
8
24
8
78
93
82
82
148–150
168–171
128–130
150–151
CHO
CHO
CHO
CHO
CH3O
Cl
NH2
CH3
O
NH2
CH3
O
H3C
H3C
24
20
NH2
CH3
O
CH3O
NH2
CH3
O
NH2
H3C
9
17
2
78
130–132
CHO
CHO
CH3
NO2
O
10
94 (27:73) 136–138
NH2
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692
SULING et al.
Table 2. (Contd.)
Entry
(No.)
Yield, %a
T
mp., °C
Ketones
Aldehydes
O
Amines
Time, h
15
(syn/anti)b
O
O
O
O
11
92 (34:66)
86–89
NH2
CHO
12
13
14
4
8
95 (35:65) 138–140
90 (18:82) 116–117
CHO
Cl
NH2
CHO
CH3
CH3
NH2
NH2
12
84 (4:96)
124–126
Cl
CHO
O
O
15
16
16
24
64 (72:28) 123–125
CHO
CHO
NH2
56 (82:18) 138–140
Cl
NH2
®
Note: Reaction conditions: aldehyde (1 mmol), amine (1 mmol), kenone (1 mmol), NafionꢀH (8 mol %), room temperature. Isoꢀ
a
b
1
lated yield, anti/syn ratio was determined by H NMR spectroscopy analysis of the crude reaction mixture.
amino ketone isomer is the major product employing compounds using easily recoverable and ecoꢀfriendly
®
Nafionꢀ
Н
as a catalyst.
cyclohexanone as the substrate, and syn
βꢀamino
ketone isomer is the major product employing 3ꢀpenꢀ
mtanone as the substrate. Therefore, it is an attractive
and promising method to synthesize βꢀamino ketone
ACKNOWLEDGMENTS
The authors thank Nature Science Foundation of
Anyang Normal University for financial support.
®
Table 3. Reusability of NafionꢀH for Mannich reaction
Run
Yield, %
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92
92
93
92
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