Recyclable polymeric π-acid catalyst effective on Mannich-type reaction in water

Article abstract of DOI:10.1248/cpb.54.591

Polymer-supported dicyanoketene acetal (poly-DCKA-1), synthesized by copolymerization of a DCKA bearing a 4-vinylbenzyl group with ethyleneglycol dimethacrylate, was found to be an excellent recyclable catalyst for the three-component Mannich-type reaction of aldehydes, aromatic amines, and TMS enolate of ethyl isobutyrate in water as the sole solvent.

Full text of DOI:10.1248/cpb.54.591

April 2006
Communications to the Editor
Chem. Pharm. Bull. 54(4) 591—593 (2006)
591
ciently in water have emerged recently. In our project on the
creation of new polymer-modified DCKA catalysts working
in water, we have investigated the catalytic activities of poly-
DCKA-1 and a new solid catalyst (poly-DCKA-2) of the
ether type, which were developed from DCKA-3 with a pri-
mary hydroxyl group that appears versatile for functionaliza-
tion, in Mannich-type reactions. We now report on poly-
DCKA-1 as a highly efficient and recyclable catalyst promot-
ing aqueous Mannich-type reactions of various imines in-
cluding unstable imines prepared in situ from aromatic and
aliphatic aldehydes.
First, the new DCKAs (DCKA-1 and DCKA-2) were pre-
pared as monomeric standard DCKAs (Chart 1). DCKA-1
was obtained from tetracyanoethylene (TCNE) and 2-benzyl-
1,3-propanediol according to the general procedure42);
DCKA-2 by benzylation of DCKA-3, which was prepared
from TCNE and 2-hydroxy-2-methyl-1,3-propanediol; and
DCKA-4 by alkylation of DCKA-3 with 4-vinylbenzylchlo-
ride, respectively.43) A polymer-supported DCKA (poly-
DCKA-2) was prepared by copolymerization of DCKA-4
with EGDMA in the presence of AIBN as a radical initiator
in refluxing toluene.44)
p
Recyclable Polymeric -Acid Catalyst
Effective on Mannich-Type Reaction in
Water
Yukio MASAKI, ,a,b Kouichi YAMAZAKI,a Hyouei KAWAI,a
*
Tomoyasu YAMADA,a Akichika ITOH,a Yoshitsugu ARAI,a
b
and Hiroshi FURUKAWA
a Gifu Pharmaceutical University; 5–6–1 Mitahora-Higashi, Gifu
502–8585, Japan: and b Faculty of Pharmacy, Meijo University;
150 Yagotoyama, Tempaku-ku, Nagoya 468–8503, Japan.
Received November 30, 2005; accepted January 16, 2006
Polymer-supported dicyanoketene acetal (poly-DCKA-1),
synthesized by copolymerization of a DCKA bearing a 4-vinyl-
benzyl group with ethyleneglycol dimethacrylate, was found to
be an excellent recyclable catalyst for the three-component
Mannich-type reaction of aldehydes, aromatic amines, and TMS
enolate of ethyl isobutyrate in water as the sole solvent.
Key words polymer; p-acid catalyst; aqueous media; Mannich-type re-
action; recycle
Organic reactions in water have recently been recognized
The catalytic activities of poly-DCKA-1 and the new
as useful tool for the synthesis of compounds because water DCKAs (DCKA-1, DCKA-2, and poly-DCKA-2) synthe-
is a cheap, safe, and benign solvent to the environment.1—4) sized were investigated in the two-component Mannich-type
Development of insoluble reagents with high efficiency in reaction using benzylidene aniline (1) and TMS-enolate (2),
synthetic reactions5–9) has recently attracted much attention prepared from ethyl isobutyrate, in water and acetonitrile
for their convenience of manipulation and recycling from the (CH3CN) as a solvent at room temperature. A mixture of
viewpoint of green chemistry.10,11) In this context, polymeric imine (1) (1.0 eq), TMS-enolate (2) (1.5 eq), and a catalyst
modification of reagents, especially of reaction promoters (0.2 eq) in a solvent was stirred for 24 h. Results including
and catalysts effective in organic reactions in water, is a the data of dicyanoketene ethyleneacetal (DCKEA) as a stan-
promising methodology.12—16) In our study on the develop- dard catalyst are summarized in Table 1. Poly-DCKA-1
ment of dicyanoketene acetals (DCKAs) as novel p-acid cat- showed high activity, providing a b-aminoester (3) not only
alysts,17—21) we have reported that a certain polymer-sup- in CH3CN (85% yield), but also in water (84% yield), al-
ported DCKA (poly-DCKA-1), prepared by copolymeriza- though the simple DCKA-1 gave 3 in poor to moderate
tion of a DCKA carrying a styrene functionality with ethyl- yields. However, while appreciable catalytic activity was ob-
eneglycol dimethacrylate (EGDMA), effectively catalyzes served for DCKA-2, poly-DCKA-2 was almost completely
the reactions of acetals, monothioacetalization,22,23) cyana- inactive in water.
tion,23,24) and Mukaiyama aldol reaction with silicone nucle-
Three-component Mannich-type reaction of benzaldehyde,
ophiles,23,24) and Mannich-type reaction of imines with sili- aniline, and 2 was carried out for assay of catalytic activity of
cone enolates in acetonitrile.25) The polymer was found also the DCKAs. The results are summarized in Table 2,45) which
to catalyze hydrolysis of acetals and silyl ethers in an aque-
ous system.26,27)
Table 1. Mannich-Type Reaction of Benzylidene Aniline with a Silyl Enol
Two-component Mannich-type reaction of aldimines with
silyl enolates and three-component reactions using aldehy-
des, amines, and silyl enolates are useful tools for synthesis
of b-aminocarbonyl compounds.28) Many Lewis acidic,29—34)
Brønsted acidic,35—38) combined Lewis–Brønsted acidic,39)
and Lewis basic catalysts40,41) working on the reactions effi-
Ether Catalyzed by DCKAs
Entry
Catalyst
Solvent
Yield (%)
1
2
3
4
5
6
7
8
9
None
DCKEA
DCKEA
DCKA-1
DCKA-1
DCKA-2
DCKA-2
Poly-DCKA-1
Poly-DCKA-1
Poly-DCKA-2
Poly-DCKA-2
Water
Water
CH3CN
Water
CH3CN
Water
CH3CN
Water
CH3CN
Water
14
35
28
64
34
45
5
84
85
7
10
11
CH3CN
30
Chart 1. Monomeric and Polymer-Supported DCKAs
∗ To whom correspondence should be addressed. e-mail: masakiy@ccmfs.meijo-u.ac.jp
© 2006 Pharmaceutical Society of Japan

592
Vol. 54, No. 4
Table 2. Three-Component Mannich-Type Reaction Catalyzed by DCKAs
Acknowledgment This work was supported in part by a
Grant in Aid from the Japan Society for the Promotion of
Science.
References and Notes
1) Li C.-J., Chan T.-H., “Organic Reactions on Aqueous Media,” John
Wiley & Sons, New York, 1997.
2) Grieco P. A. (ed.), “Organic Synthesis in Water,” Blackie Academic
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Entry
Catalyst
Solvent
Yield (%)
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Rev., 102, 3215—3892 (2002).
1
2
3
4
5
6
7
8
DCKA-1
DCKA-1
DCKA-2
DCKA-2
Poly-DCKA-1
Poly-DCKA-1
Poly-DCKA-2
Poly-DCKA-2
Water
CH3CN
Water
CH3CN
Water
CH3CN
Water
51
29
73
Trace
91
51
12
35
CH3CN
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Table 3. Three-Component Mannich-Type Reaction Using Various Alde-
hydes Catalyzed by Poly-DCKA-1 in Water
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Entry
RCHO
RꢀNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
Yield (%)
1
2
3
4
5
6
7
8
9
p-MeO–C6H4–CHO
p-NO2–C6H4–CHO
p-Cl–C6H4–CHO
2-Furyl-CHO
PhCH2CHO
PhCH2CH2CHO
(E)-PhCHCHCHO
PhCHO
70
41
70
64
35
52
64
84
75
p-MeO–C6H4–NH2
o-MeO–C6H4–NH2
PhCHO
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DCKA-1 as a Catalyst in Water
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Two-component system
Three-component system
Cycle
Yield (%)
1st
84
2nd
85
3rd
80
1st
91
2nd
90
3rd
88
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shows the remarkable efficiency of poly-DCKA-1 in water
among the DCKAs examined.
Table 3 demonstrates the generality of the catalytic func-
tion of poly-DCKA-1 in the aqueous three-component Man-
nich-type reaction of 2, aniline, and anisidines, and various
aldehydes including aliphatic ones, which produce unstable
imines.45)
Poly-DCKA-1 could be used repeatedly without apprecia-
ble loss of catalytic activity in the three-component Mannich-
type reaction as well as the two-component reaction after a
simple operation to recover the catalyst46) (Table 4).
In conclusion, the novel recyclable solid catalyst poly-
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39) Hamada T., Manabe K., Kobayashi S., J. Am. Chem. Soc., 126, 7768—
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DCKA-1, which contains neither proton nor metal, was 40) Takahashi E., Fujisawa H., Mukaiyama T., Chem. Lett., 33, 936—937
(2004).
found highly effective in the Mannich-type reaction in water.

April 2006
593
41) Miura K., Tamaki K., Nakagawa T., Hosomi A., Angew. Chem. Int.
Ed., 39, 1958—1960 (2000).
42) Middleton W. J., Engelhardt V. A., J. Am. Chem. Soc., 80, 2788—2795
(1958).
43) DCKA-1 was obtained in 79% yield from TCNE and 2-benzyl-
propane-1,3-diol, which was synthesized from diethyl malonate by
benzylation followed by reduction with LiAlH4. DCKA-2 and DCKA-
4 were synthesized in 68% and 81% yield, respectively, by benzylation
and p-vinylbenzylation of DCKA-3 bearing a primary hydroxyl group
which was prepared from TCNE and 2-methyl-2-hydroxymethyl-
propane-1,3-diol.
molar amount of EGDMA in toluene for 2 h in the presence of AIBN
(0.05 eq). Poly-DCKA-2 thus obtained was found to contain 2.06
mmol/g of the DCKA unit by elemental analysis.
45) An appreciable decrease in the yield of the desired 3 was observed
when a mixture of all the reagents including the catalyst (DCKA-1)
and water was stirred at once, although the reason for the phenomenon
was not obvious. Thus reaction conditions so that an aldehyde and an
amine were treated in water for 30 min at room temperature to make
the corresponding imine before addition of the catalyst and 2 were
adopted in the three-component Mannich-type reaction.
46) The catalyst was recovered by filtration, followed by washing succes-
sively with water and ethyl acetate and drying in vacuo at room tem-
perature for 4 h, and then reused.
44) A new polymer-supported DCKA (poly-DCKA-2) was synthesized as
a colorless powder by refluxing mono-DCKA-3 with an equivalent