Remarkable acceleration of cyanosilylation by the mesoporous Al-MCM-41 catalyst

Article abstract of DOI:10.1039/b718462j

The presence of the heterogeneous mesoporous Al-MCM-41 catalyst remarkably accelerated the cyanosilylation of various aldehydes and ketones with trialkylsilyl cyanide, giving the corresponding cyanohydrin silyl ethers in quantitative yields under mild reaction conditions. The Royal Society of Chemistry.

Full text of DOI:10.1039/b718462j

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Remarkable acceleration of cyanosilylation by the mesoporous
Al-MCM-41 catalystw
Katsuyuki Iwanami, Jun-Chul Choi, Baowang Lu, Toshiyasu Sakakura and
Hiroyuki Yasuda*
Received (in Cambridge, UK) 29th November 2007, Accepted 11th January 2008
First published as an Advance Article on the web 23rd January 2008
DOI: 10.1039/b718462j
The presence of the heterogeneous mesoporous Al-MCM-41
catalyst remarkably accelerated the cyanosilylation of various
aldehydes and ketones with trialkylsilyl cyanide, giving the
corresponding cyanohydrin silyl ethers in quantitative yields
under mild reaction conditions.
silylation with trimethylsilyl cyanide (TMSCN). Prior to the
reaction, the catalysts were pretreated in vacuo at 120 1C for
1 h. Fig. 1 shows the progress of the reactions with time. When
mesoporous aluminosilicate (Al-MCM-41, Si/Al = 20) was
used as the catalyst, the reaction rapidly proceeded even at
0 1C to quantitatively yield the desired cyanohydrin trimethyl-
silyl ether in 5 min (Fig. 1; Table 1, entry 1). In contrast,
aluminium-free mesoporous silica (MCM-41) and the pre-
pared amorphous SiO2–Al2O3 with the same Si/Al ratio as
Al-MCM-41 barely catalyzed the reaction (Fig. 1; Table 1,
entries 2 and 3). Furthermore, two types of commercially
available amorphous SiO2–Al2O3 (Si/Al = 5 and 2) were
inactive (Table 1, entries 4 and 5).15 These results indicate
that both the ordered mesoporous structure and the presence
of aluminium in silicates are indispensable for promoting the
reaction. It is remarkable that Al-MCM-41 is much more
active than amorphous SiO2–Al2O3 in acid-catalyzed reac-
tions. Note that the pseudo-first order rate constant of Al-
MCM-41 normalized to the surface area is about two thou-
sand times larger than that of SiO2–Al2O3 (Si/Al = 20).
Zeolite catalysts such as H-Y and H-ZSM-5 were ineffective
for the reaction (Table 1, entries 6 and 7), possibly due to their
small pore sizes. For comparison, Fig. 1 also includes the
result of Et3N, a good homogeneous catalyst for this
reaction.11a The catalytic activity per weight of Al-MCM-41
was about 600 times higher than that of Et3N (Table 1, entry
The development of efficient heterogeneous catalysts for the
production of fine and speciality chemicals has been a very
active area of research because heterogeneous catalysts have
the advantage in terms of catalyst separation, handling, and
recycling.1 Solid catalysts also allow the design of continuous
flow processes. Ordered mesoporous materials are very attrac-
tive as solid catalysts for fine chemicals synthesis often invol-
ving bulky reactants and products due to their large pore
openings and high surface areas.2 For instance, aluminium
substituted mesoporous silicas show acid catalysis for numer-
ous fine chemicals syntheses, including the aldol reaction,3
Friedel–Crafts reaction,4 Diels–Alder reaction,5 acetalization,6
and esterification.7 However, the acidic properties of meso-
porous aluminosilicates are close to that of conventional
amorphous silica–alumina and there are few examples of the
reactions in which mesoporous aluminosilicates exhibit much
higher catalytic activities than amorphous silica–alumina.8
Herein, we report the great advantage of Al-MCM-41 over
amorphous silica–alumina or zeolites as a catalyst for cyano-
silylation.
The cyanosilylation of carbonyl compounds with trialkylsi-
lyl cyanide is an important reaction in organic synthesis for
producing cyanohydrin derivatives, which can be transformed
into a variety of building blocks, including a-hydroxy acids,
a-hydroxy ketones, and b-amino alcohols.9 Lewis acids,10 Lewis
bases,11 N-heterocyclic carbenes,12 and organic or inorganic
salts13 homogeneously catalyze this reaction. Although several
heterogeneous catalysts have been reported,14 the catalytic
activities are lower than homogeneous catalysts. Moreover,
heterogeneous catalytic reactions suffer from substrate limita-
tions; the yields of the cyanohydrin products from aliphatic
aldehydes and ketones are unsatisfactory.
We initially used benzaldehyde as a model substrate to
investigate the effect of mesoporous catalysts on the cyano-
National Institute of Advanced Industrial Science and Technology
(AIST), Tsukuba Central 5, Tsukuba, Ibaraki 305-8565, Japan.
E-mail: h.yasuda@aist.go.jp; Fax: +81 29 861 4580;
Tel: +81 29 861 4559
w Electronic supplementary information (ESI) available: Experimental
and characterization details. See DOI: 10.1039/b718462j
Fig. 1 Time course of cyanosilylation. Reaction conditions: benzal-
dehyde (1 mmol), TMSCN (5 mmol), catalyst (5 mg), CH2Cl2 (10 mL),
0 1C.
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Table 1 Cyanosilylation of benzaldehyde with TMSCN by various
catalystsa
The Al-MCM-41 catalyzed cyanosilylation smoothly pro-
ceeded using a slight excess (1.2 equiv.) of TMSCN at room
temperature (Table 2, entry 1). After the run, the catalyst was
thoroughly removed by filtration, and a new reaction was
performed by adding benzaldehyde and TMSCN to the re-
sulting filtrate. However, an increase in the yield was not
observed, which indicates that Al-MCM-41 works as a hetero-
geneous catalyst. In addition, the recovered catalyst could be
reused without a significant loss in the yield (Table 2, entry 2).
The Al-MCM-41 catalyzed cyanosilylation was applicable to a
wide range of carbonyl compounds. Aromatic aldehydes sub-
stituted with an electron-donating group or an electron-with-
drawing group and aliphatic aldehydes were uniformly
transformed into the corresponding cyanohydrin trimethylsilyl
ether in quantitative yields and an extremely short reaction
time (1 min) (Table 2, entries 3–11). Excellent yields for the
desired adducts were obtained for sterically hindered alde-
hydes such as mesitaldehyde and pivalaldehyde (Table 2,
entries 4 and 11). The Al-MCM-41 catalyst was also effective
for the cyanosilylation of aromatic, aliphatic, and alicyclic
ketones to yield the corresponding cyanohydrin silyl ether
quantitatively, but a slightly longer reaction time was neces-
sary (Table 2, entries 12–15). It is noteworthy that benzylace-
tone, a less reactive aliphatic ketone,14b,14c completely afforded
the desired product in 5 min. Furthermore, we have found that
the Al-MCM-41 catalyst is effective for the cyanosilylation
with a bulky silyl cyanide like tert-butyldimethylsilyl cyanide
(TBSCN) (Table 3). Although the reaction with TBSCN was
slower compared to the reaction with TMSCN, the corre-
sponding cyanohydrin TBS ethers were given in high yields.
Finally, we performed the continuous cyanosilylation of
benzaldehyde with TMSCN using a fixed-bed flow reactor in
order to demonstrate the merit of Al-MCM-41 as a hetero-
geneous catalyst. The desired cyanohydrin trimethylsilyl ether
was constantly produced with yields larger than 98% for at
least 24 h (Fig. 2). No significant changes in the structure of
Al-MCM-41 were detected by XRD before and after the
reaction, whereas the surface area and the pore volume had
slightly decreased after the reaction. The total productivity of
the experiment was equivalent to 120 gram per day per
gram-catalyst.
Entry Catalystb
Solvent Time/min Yieldc (%) kd/minÀ1
1
2
3
4
5
6
7
8
9
Al-MCM-41
MCM-41
SiO2–Al2O3 (20) CH2Cl2 60
SiO2–Al2O3 (5) CH2Cl2 60
SiO2–Al2O3 (2) CH2Cl2 60
CH2Cl2
CH2Cl2 60
5
100
0
1
2
4
1.6
—
1.3 Â 10À4
1.7 Â 10À4
1.7 Â 10À3
6.7 Â 10À4
—
H-Y
H-ZSM-5
g-Al2O3
CH2Cl2 60
CH2Cl2 60
CH2Cl2 60
CH2Cl2 60
Toluene 15
4
0
10
14
100
30
3
1.5 Â 10À3
2.7 Â 10À3
4.9 Â 10À1
5.0 Â 10À2
2.3 Â 10À3
5.0 Â 10À4
Et3Ne
10
11
12
13
a
Al-MCM-41
Al-MCM-41
Al-MCM-41
Al-MCM-41
DMF
CH3CN 15
THF 15
15
1
Reaction conditions: benzaldehyde (1 mmol), TMSCN (5 mmol),
b
catalyst (5 mg), solvent (10 mL), 0 1C. Figures in parentheses are the
molar ratio of Si/Al. Each yield was determined by GC using
c
d
phenanthrene as an internal standard. Pseudo-first order rate con-
e
stant. Et3N (5 mg) corresponds to 5 mol%.
9). The rate of cyanosilylation catalyzed by Al-MCM-41
greatly depended on the type of solvent, but the most suitable
solvent was CH2Cl2. Additionally, toluene was a good solvent,
but a slightly longer reaction time was required (Table 1, entry
10). On the other hand, the reaction in polar solvents such as
DMF16 and CH3CN was slow, and the reaction did not
proceed in THF (Table 1, entries 11–13). A similar trend has
been reported for the Sn-montmorillonite catalyzed
cyanosilylation.14a
Table
2 Cyanosilylation of various carbonyl compounds with
TMSCN catalyzed by Al-MCM-41a
Entry
Substrate
Time/min
Yieldb (%)
1
2d
3
4
5
6
7
8
9
PhCHO
PhCHO
1
1
1
1
1
1
1
1
1
1
1
5
60
5
100 (99)c
96
100
99
100
100
99
100
99
In summary, we have demonstrated that Al-MCM-41 is a
highly active heterogeneous catalyst for the cyanosilylation of
carbonyl compounds. Using a very small amount of Al-MCM-
41, various cyanohydrin silyl ethers are quantitatively and
4-MeC6H4CHO
2,4,6-Me3C6H2CHO
4-MeOC6H4CHO
4-BrC6H4CHO
4-CF3C6H4CHO
2-Naphthaldehyde
PhCH2CH2CHO
c-C6H11CHO
t-BuCHO
Acetophenone
Acetophenone
Benzylacetone
Cyclohexanone
Table
3
Cyanosilylation of various carbonyl compounds with
TBSCN catalyzed by Al-MCM-41a
10
11
12
13
14
15
a
100
94
90
99 (98)e
100 (99)e
100
5
Entry
Substrate
Time/min
Yieldb (%)
Reaction conditions: substrate (1 mmol), TMSCN (1.2 mmol), Al-
b
MCM-41 (5 mg), CH2Cl2 (2 mL), room temperature. Each yield was
1
2
3
a
PhCHO
PhCH2CH2CHO
Benzylacetone
10
30
120
97
83
97
determined by 1H NMR spectroscopy using 1,1,2,2-tetrachloroethane
c
as an internal standard. Isolated yield of the corresponding cyano-
hydrin formed by desilylating the cyanohydrin trimethylsilyl ether via
d
Reaction conditions: substrate (1 mmol), TBSCN (1.2 mmol),
Al-MCM-41 (5 mg), CH2Cl2 (2 mL), room temperature. (TBS =
e
acidic hydrolysis. Recovered catalyst was used. Isolated yield after
silica gel column chromatography.
b
t-BuMe2Si). Isolated yield after silica gel chromatography.
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Fig. 2 Cyanohydrin trimethylsilyl ether yield during a continuous
flow reaction. Reaction conditions: benzaldehyde (6.7 wt%) and
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15 The catalytic activity of amorphous SiO2–Al2O3 (Si/Al = 5 and 2)
greatly depended on the temperature of the pretreatment. When
the catalysts were pretreated in vacuo at 300 1C for 3 h, the pseudo-
first order rate constant increased from 1.7 Â 10À4 (in vacuo at
120 1C for 1 h) to 8.0 Â 10À3 minÀ1 for SiO2–Al2O3 (Si/Al = 5) and
from 1.7 Â 10À3 to 7.6 Â 10À3 minÀ1 for SiO2–Al2O3 (Si/Al = 2).
On the other hand, the influence of the pretreatment on the
catalytic activity of Al-MCM-41, MCM-41, amorphous SiO2–
Al2O3 (Si/Al = 20), and zeolites (H-Y and H-ZSM-5) was small.
16 Recentry, Olah et al. reported that DMF itself highly promotes the
cyanosilylation of aldehydes with TMSCN at room temperature
(G. K. S. Prakash, H. Vaghoo, C. Panja, V. Surampudi,
R. Kultyshev, T. Mathew and G. A. Olah, Proc. Natl. Acad. Sci.
U. S. A., 2007, 104, 3026). In our examination, when benzaldehyde
(1 mmol) was treated with TMSCN (5 mmol) in DMF (10 mL) at
0 1C without the Al-MCM-41 catalyst, the desired product was
obtained in 12% yield in 15 min.
quickly obtained from a wide range of aldehydes and ketones
under mild reaction conditions. This report clearly exhibits the
promising abilities of mesoporous aluminosilicates as catalysts
in organic synthesis, especially for fine chemicals synthesis.
The active sites over the Al-MCM-41 catalyst are presently
unclear, but the effective combination of both the activation of
carbonyl compounds by the acid sites arising from H/Al-
MCM-41 and the activation of trialkylsilyl cyanide by the
base sites possibly based on Na/Al-MCM-41 may be respon-
sible for the excellent catalytic activity. Further studies to
elucidate the acceleration mechanism of the Al-MCM-41
catalyst for cyanation are currently under way.
This research was financially supported by the Project of
‘‘Development of Microspace and Nanospace Reaction En-
vironment Technology for Functional Materials’’ of New
Energy and Industrial Technology Development Organization
(NEDO), Japan.
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¨
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1004 | Chem. Commun., 2008, 1002–1004