Heterogeneous organic base-catalyzed reactions enhanced by acid supports

Article abstract of DOI:10.1021/ja0704333

Amorphous silica-alumina-supported amines (SA-NR2) were found to be excellent heterogeneous catalysts for a variety of carbon-carbon bond-forming reactions, such as cyano-O-ethoxycarbonylation, Michael reaction, and nitro-aldol reaction. These reactions were hard to proceed either with amines alone or on the SA alone. Solid-state ¹³C MAS NMR analysis revealed the acid-base interaction of the H⁺ site and amine group on the SA-NR2 surface, which makes an acid-base dual activation mechanism possible for carbon-carbon bond-forming reactions. Copyright

Full text of DOI:10.1021/ja0704333

Published on Web 07/13/2007
Heterogeneous Organic Base-Catalyzed Reactions Enhanced by Acid
Supports
Ken Motokura, Mizuki Tada, and Yasuhiro Iwasawa*
Department of Chemistry, Graduate School of Science, The UniVersity of Tokyo, Hongo, Bunkyo-ku,
Tokyo 113-0033, Japan
Received January 20, 2007; E-mail: iwasawa@chem.s.u-tokyo.ac.jp
Development of multifunctional catalytic materials plays a pivotal
role for achievement of highly efficient organic synthesis. Much
attention has been paid to double catalytic activation of electrophiles
and nucleophiles by acid and base functions, respectively.1 How-
ever, most of these bifunctional catalyst systems are homogeneous
ones, and recover and reuse of both acid and base catalysts are in-
dustrially problematic. In addition, a limited number of acid and
base species can be used in the bifunctional systems because many
types of homogeneous acids and bases neutralized readily in the
same reactor. Immobilization of incompatible catalysts on separate
solid supports has recently overcome these restrictions and realized
one-pot acid-base reaction sequences,2 and a few examples have
also been reported for dual activation of electrophiles and nucleo-
philes by acid and base functions on the same solid surface in a
single reaction.
The immobilization of both acid and base on a solid surface is
one of the most effective procedures for the design of the
bifunctional catalyst. The combinations of acids, such as hydrogen-
bonding ureas, sulfonic acids, and surface silanol groups, and
organic bases have been investigated;3 however, satisfactory
catalytic activity has not been achieved due to the random
positioning of these two functions and/or weak acidity. As an
alterative, our strategy for the design of an acid-base bifunctional
catalyst surface focuses on the utilization of a strong Brønsted acid
site derived from inorganic support surfaces. A major support
previously reported for amine reagents is weak acid silica,4 and
there is no research for strong heterogeneous acids, such as
amorphous silica-alumina (SA) and zeolites, as supports for basic
amine immobilization. Herein, we present novel SA-supported
organic amines (SA-NR2) as nanostructured heterogeneous catalysts.
The promising adjacent position of acid and base sites on the SA-
NR2 realized high catalytic activity for a variety of organic
transformations, such as cyano-ethoxycarbonylation, Michael reac-
tion, and nitro-aldol reactions.
The SA-supported 3-(diethylamino)propyl functional group (SA-
NEt2) was immobilized by treatment of amorphous silica-alumina
(Nikki Chemical Co., SiO2, 66.5; Al2O3, 25.1%, 380 m2/g) with a
toluene solution of 3-(diethylamino)propyltrimethoxysilane (DAPS)
under reflux for 24 h. Then the solid was filtered and washed with
dichloromethane, followed by drying under vacuum. The elemental
analysis determined that the C/N ratio of the SA-NEt2 was 7.7,
and the amount of the amine group was 1.4 molecules/nm2. The
presence of the intact 3-(diethylamino)propyl group was indicated
by the solid-state 13C MAS NMR spectra (Supporting Information,
SI). Solid-state 29Si MAS NMR revealed that immobilized Si atoms
exhibited chemical shifts due to the formation of Si-O bonds with
the SA surface (SI). A SA-supported aminopropyl functional group
(SA-NH2) and other solid-supported amines (support-NR2) were
also synthesized and characterized by similar procedures. The
elemental analysis of the SA-NH2 showed 1.7 NH2 per nm2 on the
SA surface.
One-pot catalytic cyanation-O-protection with a robust protecting
because
group has been investigated as a novel synthetic pathway5
of the instability of cyanohydrins and highly toxicity of traditional
cyanide sources, such as Me3SiCN and HCN. Cyano-ethoxycar-
bonylation of benzaldehyde (1) with ethyl cyanoformate (2) was
carried out using various heterogeneous and homogeneous acid and/
or base catalysts, as shown in Table 1. Remarkably, the SA-NEt2
was found to be an excellent catalyst for the reaction of 2 with 1,
affording 3 in a 95% yield (entry 1), while the reaction scarcely
proceeded using either triethylamine (entry 8) or SA (entry 9) as a
catalyst. The SA-NEt2 catalyst also showed a higher catalytic
activity than the mixture of triethylamine and SA (entry 7). The
catalytic activity decreased by decreasing Al content in the SA
support (entry 2). The activities of a SiO2- and Al2O3-supported
amine catalyst were lower than that of the SA-NEt2 (entries 3 and
4). It is noted that this is the first report of the cyano-ethoxycar-
bonylation reaction using heterogeneous catalyst.
Michael reaction of nitrile to R,â-unsaturated ketone using SA-
supported amine catalysts was also investigated (eq 1). The SA-
NEt2 possessed high catalytic activity and selectivity in the addition
reaction of ethyl cyanoacetate (4) to methyl vinyl ketone (5), giving
90% yield of 2-cyano-5-oxo-2-(3-oxobutyl)hexanoic acid ethyl ester
(6). Notably, the reaction using a mixture of triethylamine and SA
afforded lower yield of 6 compared to the SA-NEt2 catalyst, and
both triethylamine and SA showed no catalytic activity. In general,
the conjugate addition of nitrile compounds to R,â-unsaturated
ketones needs strong base or transition metal catalysts,6 which faced
difficulties for handling due to moisture sensitivity, deactivation
by air containing carbon dioxide, and high toxicity. The use of the
simple and stable alkyl amine as a heterogeneous catalyst meets
the environmentally friendly organic synthesis.
The nitro-aldol reaction of 1 with nitromethane using various
catalysts was examined, as shown in Table 2. The SA-NH2 catalyst
gave the highest yield of â-nitrostyrene (entry 1) and also showed
a higher catalytic activity than the mixture of a primary amine and
SA (entry 4). The reaction did not proceed using SA-NEt2 (entry
2).7 In the SA-NH2-catalyzed reaction, the TON value based on
the amine group reached up to 330, which is significantly higher
than that for a previously reported MCM-41-supported amine
catalyst (TON ) 37).4b
After these reactions, both SA-NEt2 and SA-NH2 catalysts were
separated from the reaction mixture easily and were able to be
reused with retention of high catalytic activity and selectivity (SI).
The acid-base interaction between the Brønsted acid site on the
SA surface and amine group was confirmed by the solid-state 13C
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J. AM. CHEM. SOC. 2007, 129, 9540-9541
10.1021/ja0704333 CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Cyano-Ethoxycarbonylation on Various Catalystsa
to the neighbor of the acid site by silane-coupling reaction, and
the acid-base interaction decreases.
Among the solvents examined in the Michael reaction using SA-
NEt2, nonpolar solvents, such as toluene and diethyl ether, were
good solvents, whereas polar solvents DMF and DMSO gave poor
results with respect to conversion of the enone (SI). Interestingly,
this solvent effect of the SA-NEt2-catalyzed reaction shows a sharp
contrast to that using MgO as a typical solid base catalyst (SI),
and it is suggested that the Brønsted acid site on the SA surface,
which is deactivated by electron-donating solvents, plays a crucial
role in the catalysis of the SA-NR2. On the basis of these results,
a proposed reaction mechanism involves the dual activation of donor
and acceptor substrates at the amine base site and the neighboring
Brønsted acid site on the SA surface, respectively (Scheme 1C).
Initial rate kinetics of triethylamine-catalyzed cyanation of 1 with
2 indicates first-order dependence on the concentration of 1 and
zero-order dependence on 2, and the rate-determining step is the
carbon-carbon bond-forming step. On the other hand, the initial
rate in the SA-NR2-catalyzed reaction is zero-order dependence on
both 1 and 2. Activation of 1 by the acid site accelerated the
carbon-carbon bond-forming step, and another step in the catalytic
cycle became the new rate-determining step.
In summary, the use of acidic silica-alumina as a support for
basic amine catalyst enables coexistence of strong acid and base
sites on the solid surface with suitable distance. This SA-NR2
catalyst possessed high catalytic activities for various carbon-
carbon bond-forming reactions. The advanced solid-state NMR
analyses revealed that the basic amine groups were immobilized
at the neighboring position of the surface acid site without strong
acid-base interaction. This concept, a novel design method of
acid-base bifunctional solid surface, can be applied to creation of
new heterogeneous catalysts for efficient organic synthesis.
entry
catalyst
yield (%)
entry
catalyst
yield (%)
1
SA-NEt2
95
57
17
16
3
6
7
8
9
10
SA-NH2
Et3N + SA
Et3N + p-TsOH‚H2O
<1
70
<1
1
2b
3
SA(L)-NEt2
SiO2-NEt2
Al2O3-NEt2
USY-NEt2
4
5
Et3N
SA
<1
a See SI for the reaction rate and detailed reaction conditions. b SA having
low Al content (SA(L), SiO2, 82.5; Al2O3, 12.6%) was used as a support.
Table 2. Nitro-Aldol Reaction on Various Catalystsa
entry
catalyst
yield (%)
entry
catalyst
yield (%)
1
2
3
4
SA-NH2
SA-NEt2
SiO2-NH2
n-C6H13NH2 + SA
99
<1
37
5
n-C6H13NH2
+p-TsOH‚H2O
n-C6H13NH2
<1
6
7
13
<1
12
SA
a See SI for the reaction rate and detailed reaction conditions.
Figure 1. (A) 13C NMR spectra of DAPS in CDCl3. (B-D) Solid-state
13C MAS NMR spectra of (B) the SA-NEt2, (C) the SA treated with a
toluene solution of DAPS (room temp, 5 min), and (D) triethylamine
adsorbed on SA. O: signal assignable to the terminal carbon of amine.
Supporting Information Available: Details of experimental
procedures and characterizations. This material is available free of
charge via the Internet at http://pubs.acs.org.
Scheme 1
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site, the solid SA was separated from the toluene solution of DAPS
before heat treatment in the SA-NEt2 catalyst preparation, and then
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shift of the terminal carbon of amine was also observed (∼8.0 ppm,
Figure 1C). The immobilization process is proposed, as shown in
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