High surface area MgO as a highly effective heterogeneous base catalyst for michael addition and knoevenagel condensation reactions

Article abstract of DOI:10.1055/s-2005-918467

Magnesium oxide (MgO), obtained using a novel but simple procedure, was systematically investigated as a heterogeneous base catalyst for reactions taking place in the liquid phase, specifically the Michael addition and the Knoevenagel condensation. The ac

Full text of DOI:10.1055/s-2005-918467

3468
PAPER
High Surface Area MgO as a Highly Effective Heterogeneous Base Catalyst for
Michael Addition and Knoevenagel Condensation Reactions
High
Surface
A
re
h
a
MgO
a
s
a
u
H
ighlyEffec
n
tive
H
eterog
l
eneous
i
Base Catalys
X
t
u, Jonathan K. Bartley, Dan I. Enache, David W. Knight, Graham J. Hutchings*
Cardiff University, School of Chemistry, Main Building, Park Place, Cardiff, CF10 3AT, UK
Fax +44(29)20874075; E-mail: hutch@cf.ac.uk
Received 22 September 2005
In contrast, MgO is inexpensive and easily obtained. This
Abstract: Magnesium oxide (MgO), obtained using a novel but
simple procedure, was systematically investigated as a heteroge-
neous base catalyst for reactions taking place in the liquid phase,
specifically the Michael addition and the Knoevenagel condensa-
attracted us to explore the possibility of preparing more
active versions, which could find applications in large-
scale manufacture. It is a mild base and has the lowest sol-
tion. The activity of MgO was studied in detail, together with the ef- ubility among the alkaline earth oxides and so can poten-
fects of solvent and substrate on the catalytic activity for each type
tially be reused as it will not be lost due to leaching into
of reaction. A key finding is that the formation of enols affected the
the reaction mixture. However, the applications of MgO
activity of MgO. The experimental results show that the activity of
as a basic catalyst in liquid reactions have been very lim-
MgO did not change when it was reused and it is an excellent heter-
ited because MgO showed low activity in the reactions
ogeneous catalyst for the reactions studied.
tested.26 We have found that MgO with a high surface area
Key words: Michael addition, Knoevenagel condensation, solvent
can be produced, and in this study, we have systematically
effect, enol effect, basic catalysis
investigated MgO as a solid base catalyst for Michael ad-
ditions and Knoevenagel condensations, reactions which
are commonly used in the manufacture of fine chemicals.
In recent years, there has been increasing emphasis on the
The particular versions of the Michael addition studied
design and use of environmentally friendly solid acid and
were the addition of active methylene compounds, alco-
base catalysts to reduce the amount of toxic waste and by-
hols, and thiols to a,b-unsaturated carbonyl compounds, a
useful strategy for the construction of carbon–carbon
bonds (Scheme 1). The mechanism for such Michael ad-
ditions involves the formation of an anion from the active
methylene compound, conjugate addition of this to the
a,b-unsaturated carbonyl compound, and finally product
protonation.2 The Knoevenagel condensation (Scheme 2)
of active methylene compounds and aldehydes is one of
the most popular methods of synthesizing functionalized
alkenes. Basic catalysts can generate significant amounts
of carbanions from active methylene compounds, which
can then attack a carbonyl group to give the condensation
product.27
products arising from chemical processes prompted by
stringent environment protection laws.1 In contrast to the
extensive studies involving heterogeneous acid catalysts,
fewer efforts have been made to develop heterogeneous
base catalysts.2,3 Several solid bases have been reported as
being effective in this respect: (1) zeolites such as alkali
ion-exchanged zeolites4,5 and sodium metal clusters in ze-
olites;6 (2) supported alkali metal ions including alkaline
oxides supported on microporous7 and mesoporous sol-
ids,8 alkali metals supported on alumina (Na/NaOH/g-
Al2O3);9 (3) clay minerals, for example sepiolites10 and
hydrotalcites (HDT);11–13 (4) non-oxide bases including
phosphates14–17 and nitrides;18,19 (5) single-component
catalysts such as alkaline earth solids;20,21 and (6) mixed
metal oxides, for example magnesium–lanthanum mixed
oxide.22
Base-catalyzed Michael additions and Knoevenagel con-
densations have been extensively studied in homogeneous
systems,28,29 but very few studies have employed hetero-
Amongst these solid bases, hydrotalcite (HDT) or hydro-
talcite-like compounds have recently been studied the
most. The basic properties of HDT can be modified by re-
hydration or ion exchange, which improves the activity of
these catalysts.1,23–25 For example, HDT can be modified
by anion exchange with KF to obtain HDT-F.24 However,
this process is complex, costly, and requires experienced
people to operate it. As the cost of fabricating a catalyst
can be a critical factor in its industrial applications, few
commercial materials have been synthesized in this way.
O
O
MgO
X
Y
R
X
R
+
Solvent (r.t.)
R'
R'
acceptor
donor
Y
Scheme 1
CN
R'
R
H
R
MgO
+
H2O
+
O
Solvent (r.t.)
SYNTHESIS 2005, No. 19, pp 3468–3476
x
x.
x
x
.
2
0
0
5
R'
H
CN
Advanced online publication: 14.11.2005
DOI: 10.1055/s-2005-918467; Art ID: C08805SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 2

PAPER
High Surface Area MgO as a Highly Effective Heterogeneous Base Catalyst
3469
geneous catalysts.1 To date the heterogeneous catalysts
studied have shown either low activity or have been pre-
pared in a complex way.23,30 To the best of our knowledge,
there are no reported studies systematically dealing with
the activity of MgO in such Michael additions, in particu-
lar, the catalyst preparation method, reaction conditions,
and most importantly, the interaction between MgO and
the substrate. In homogeneous base-catalyzed systems,
the reaction rate increases with the pKa value (acid value)
of the substrate and the basic strength of the catalyst. In
the heterogeneous base-catalyzed system, there have been
no studies which systematically investigate the relation-
ship between the acid value of the substrate and the activ-
ity of MgO. This will be critical for preparing a successful
solid basic catalyst.
Figure 1 The effect of calcination temperature on the activity of
MgO for the Michael addition between chalcone and diethyl malon-
ate.
In this paper we investigate a high area form of MgO as a
catalyst for a number of different Michael additions and
Knoevenagel condensations and it was found to be very
active and reusable. It was also found that the activity of
MgO, to a large extent, depended upon the solvent and the
structure of the substrate. The effect of substrate acidity in
the heterogeneous system with MgO is different from ho-
mogeneous base-catalyzed systems. This discovery may
be very helpful for future studies of other metal oxide cat-
alysts. Finally, we propose mechanisms for these reac-
tions involving MgO catalysis.
Michael Addition Reaction
Figure 1 presents the variation of the conversion of chal-
cone and diethyl malonate after a reaction time of 30 min-
utes as a function of the calcination temperature.
Calcination of the catalyst below 400 °C, leads to a very
low conversion. A calcination temperature of 400–500 °C
gave maximum conversion. When the catalyst was cal-
cined above 500 °C, the activity of MgO decreased and
continued to decrease as the calcination temperature in-
creased. The results are consistent with changes in the sur-
face area of the catalyst, which varies with calcination
temperature (Figure 1), the maximum surface area was
obtained after calcining the samples at 400–500 °C.
Figure 2 The powder X-ray diffraction patterns of MgO calcined at
different temperatures.
The activity of the catalyst was obtained for a number of
different donor species (Table 2). The results show that
the Michael additions were not affected by the pKa value
of the nucleophile. Theoretically, the lower the pKa value
of the donor, the easier to abstract the proton and, there-
fore, form the carbanion and perhaps the Michael adduct.
Several structurally diverse nucleophiles such as malono-
nitrile (Table 2, entry 6, pKa 11.1), ethyl cyanoacetate
(Table 2, entry 7, pKa 13.1), and diethyl malonate
(Table 2, entry 8, pKa 16.4) underwent clean and remark-
ably fast Michael additions to chalcone by this procedure
(Scheme 1). However, 2,4-pentanedione (Table 2, entry
2, pKa 13.3) and ethyl acetoacetate (Table 2, entry 4,
pKa 14.3), which are more acidic than diethyl malonate
did not undergo fast Michael addition. In the case of 2,4-
pentanedione, no conversion was obtained after the reac-
tion time was extended to 36 hours. This low activity can
be ascribed to the formation of a cis-enol 2b (Scheme 4).
The XRD pattern of the precursors did not change when
the calcination temperature was below 400 °C (Figure 2),
however, MgO was only observed when the calcination
temperature was higher than 400 °C. As the calcination
temperature was increased to 600 °C, MgO became more
crystalline resulting in a loss of surface area.
Results of the Michael addition reactions are presented in
Table 1. The conversion was calculated by the decrease in
the amount of the a,b-unsaturated carbonyl compound.
MgO was found to be an efficient and selective catalyst
for 1,4-addition to chalcone. MgO was found to be more
active compared with other catalysts reported in the liter-
ature such as HDT-F, HDT-t-BuO, HDT-OH, Ba(OH)2,
and xonotlite and it was prepared using a much simpler
procedure.
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C. Xu et al.
PAPER
Table 1 Michael Additions Catalyzed by MgO
Entry
1
Acceptor
Chalcone
Donor
Solvent
Toluene
Time (h)
Yield (%)
Diethyl malonate
2
2a
93
95
95
75
96
95
2b
48c
6d
8e
2
3
Chalcone
Ethyl cyanoacetate
Dimethyl malonate
p-Toluenethiol
Toluene
Toluene
0.5
–
88
e
Complex mixtures
2-Cyclohexen-1-one
1
93
90
1b
4
5
6
Methyl crotonate
Toluene
Toluene
MeCN
0.5
1
100
13
4-Phenyl-3-buten-2-one Malononitrile
Chalcone Malononitrile
1.5
2d
88
88
a HDT-F.24
b HDT-t-BuO.23
c Using t-BuOK on xonotlite as catalyst.30
d HDT-OH.31
e Ba(OH)2·1–1.5H2O.32
Table 2 Effect of the Donor Using Chalcone as the Acceptor
Entry
Donor
pKa in DMSO
10.3
Solvent
Time (h)a
0.5
Yield (%)a
1
2
3
4
5
6
7
8
p-Toluenethiol
Toluene
Toluene
DMSO
Toluene
Toluene
MeCN
17
2,4-Pentanedione
5,5-Dimethyl-1,3-cyclohexanedione (3a)
Ethyl acetoacetate
Nitromethane
13.3
0.5 (36)
0.5 (21)
0.5 (21)
0.5
0 (0)
7 (90)
0 (7)
7
11.2
14.3
17.2
Malononitrile
11.1
0.5
80
Ethyl cyanoacetate
Diethyl malonate
13.1
Toluene
Toluene
0.5
88
16.4
0.5
69
a The number in parenthesis corresponds to the extended reaction time and the yield observed.
In general, 1,3-dicarbonyl compounds, which include b- form. In solution, such compounds enolize practically ex-
diketones and b-keto-esters, may exist in three tautomeric clusively to the cis-enolic form 1b, which is stabilized by
forms: the diketo form 1a, the cis-enolic form 1b, and the intramolecular hydrogen bonding.
trans-enolic form 1c (Scheme 3).33 Open-chain 1,3-dicar-
bonyl compounds are rarely observed in the trans-enolic
the new cis-enol 2b, which is stabilized by the intramolec-
When MgO was added to a solution of 2,4-pentanedione,
R
R'
C
R
C
R'
C
R
C
C
H
CH
O
O
C
R'
O
O
HO
CH
C
O
H2
1b
1a
1c
Scheme 3
Synthesis 2005, No. 19, 3468–3476 © Thieme Stuttgart · New York

PAPER
High Surface Area MgO as a Highly Effective Heterogeneous Base Catalyst
3471
R
CH
R'
R
C
R'
C
C
O
C
O
+
MgO
O
O
C
H2
Mg
O
Mg
Mg
O
O
2a
2b
Scheme 4
ular Mg–O bond, was presumably formed (Scheme 4).34
This cis-enol is so strongly adsorbed onto the catalyst sur-
face that the active site is blocked and the activity stops.
To confirm this, three reactions between diethyl malonate
and chalcone were conducted as shown in Figure 3. For
the reaction conducted without 2,4-pentanedione, the con-
version increased steadily with time. However, when 2,4-
pentanedione was added after running the reaction for ten
minutes, the conversion stopped. Finally, if 2,4-pen-
tanedione was added before the reaction began, the reac-
tion rate decreased dramatically.
H3C
CH3
CH3
H3C
O
HO
O
O
3a
3b
Scheme 5
position of methyl crotonate is less positive. Since the
same MgO catalyst and reaction conditions were used for
these reactions, the proton-abstracting ability of MgO did
not change. Therefore, it can be proposed that proton ab-
straction is not the crucial step, hence, the lower electro-
philicity of the acceptor crotonate is probably the key
factor preventing reaction.
Table 3 Effect of the Donor with Methyl Crotonate as the Acceptora
Entry Donor
pKa in
DMSO
Time (h) Yield (%)
1
2
3
4
5
6
7
8
p-Toluenethiol
10.3
13.3
14.2
17.2
11.1
13.1
16.4
29
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
44
0
2,4-Pentanedione
Ethyl acetoacetate
Nitromethane
0
0
Malononitrile
0
Ethyl cyanoacetate
Dimethyl malonate
MeOH
0
Figure 3 The effect of 2,4-pentanedione on the Michael addition
between chalcone and diethyl malonate.
0
0
In contrast, cyclic 1,3-dicarbonyl compounds, e.g. 5,5-
dimethyl-1,3-cyclohexanedione 3a (Scheme 5), can only
exist as a trans-enol 3b (Scheme 5) and intramolecular
hydrogen bonding is not possible. When MgO is added to
a solution of 5,5-dimethyl-1,3-cyclohexanedione, the cis-
enol with an intramolecular Mg–O bond is therefore im-
possible. As predicted, it was found that the product of the
Michael addition with 5,5-dimethyl-1,3-cyclohexanedi-
one (Table 2, entry 3) can be obtained with high conver-
sion. The activity of nitromethane can be ascribed to the
nitro/aci-nitro tautomerism35 and low pKa value (Table 2,
entry 5).
a Reactions were performed in toluene (10 mL).
One of the most important parameters for the success of
the planned reaction is the selection of a suitable solvent
(Table 4). When chloroform or methanol was used as the
solvent, MgO was inactive but a high conversion could be
obtained using hexane as the solvent. Chloroform is an
aprotic and acidic solvent with high electrophilicity. It
tends to coordinate strongly with anions, and consequent-
ly the attack of an anion onto a,b-unsaturated carbonyl
compounds was blocked. Methanol is an acid and protic
solvent, which stabilizes both anions and cations. Hexane
is non-polar, essentially non-solvating, does not undergo
auto-ionization, and plays a minimal role in the reaction.
When methyl crotonate was used as the acceptor, high
conversion was obtained only with p-toluenethiol
(Table 3). Compared with chalcone, the charge at the b-
Synthesis 2005, No. 19, 3468–3476 © Thieme Stuttgart · New York

3472
C. Xu et al.
PAPER
Table 4 Solvent Effects on the Michael Additiona
Table 5 Reusability of MgO
Entry
Catalyst
S
BET (m2/g) Time (min) Yield (%)
Solvent
CHCl3
MeOH
EtOAc
MeCN
Toluene
Hexane
DMSO
pKa
Polarity
4.1
Time (h)
Yield (%)
1
2
3
4
5
MgO (1st use)
MgOa (2nd use)
MgOb (2nd use)
MgOc (2nd use)
MgOd (2nd use)
288
30
30
30
30
30
54
25
34
32
50
2
2
2
2
2
2
2
–
16
25
25
40
48
30
5.1
Trace
50
50
66
80
8
239
165
287
4.4
5.8
2.4
a MgO was washed with toluene (3 ×); MgO was separated from tol-
uene by centrifugation.
0
b MgO was washed with toluene before calcination.
c MgO was refluxed in toluene, filtered, washed with toluene, dried at
110 °C, and then refluxed in H2O before calcination.
d MgO was washed with toluene, then refluxed in H2O before calci-
nation.
7.2
a Reagents and conditions: chalcone, diethyl malonate, solvent (10
mL).
However, the solubility of the product in hexane is low,
which may enhance the reaction rate.
ly; however, neither influenced the overall yield of the
reaction. Considering that the content of water in common
solvents is less than 0.3%, for these reactions with MgO
as catalyst, solvents can be used directly without drying.
Ethyl acetate, acetonitrile, and toluene are aprotic and ba-
sic solvents that tend to coordinate strongly with cations.
This should result in the basicity of the solid base increas-
ing. In the case of toluene, high conversions can be ob-
tained and although the highest conversion was obtained
with hexane, toluene was selected as the solvent for the
Michael additions because of the toxicity of hexane.
In addition, the volume of the solvent used in the reaction
affected the activity of MgO. For the Michael additions
between chalcone and diethyl malonate it was found that
with toluene as the solvent a higher concentration of reac-
tants resulted in a higher conversion (1 mL per mmol of
reactant, 93% conversion, 2 h; 5 mL per mmol of reactant,
66% conversion, 2 h), which may point to the reaction rate
being influenced by the reactant concentration.
We also attempted to reuse the catalyst by a variety of
methods (Table 5). Direct reuse of the catalyst (Table 5,
entry 2) led to a greater than 50% decrease in activity
while treatment of the catalyst prior to reuse also resulted
in lower conversions (Table 5, entry 3,4). This phenome-
non probably arose because the reactant and product were
not completely desorbed from MgO and therefore, the ac-
tive sites were blocked. However, we found that by wash-
ing MgO with toluene and then refluxing in water before
calcinations, the catalyst could be recovered and reactivat-
ed (Table 5, entry 5). The activity and surface area for the
freshly prepared and the reused catalyst are almost the
same. It should be noted that the catalytic activity also de-
creased when the calcined catalyst was allowed to stand in
air for a few hours before use, but such a loss of activity
was not observed when the catalyst was stored in a desic-
cator over molecular sieves for one month.
Figure 4 The effect of H2O on the reaction between chalcone and
malononitrile.
Both NMR spectroscopy and MS showed that D2O did not
undergo proton exchange with malononitrile, but did with
the reactant chalcone and product. Therefore, it can be de-
duced that the Michael addition is an irreversible process,
otherwise some of the malononitrile protons would have
exchanged with the deuterium from D2O.
Knoevenagel Condensation
In order to study the effect of water in the solvent, three
reactions were carried out. One reaction was carried out in
an anhydrous solvent (MeCN) and the other two in a sol-
vent containing 2% water and 2% heavy water. Figure 4
shows the effect the presence of both water and heavy wa-
ter had on the reaction causing the rate to decrease initial-
Knoevenagel condensations involving aromatic carbonyl
compounds with (a) malononitrile and (b) ethyl cyanoace-
tate (Scheme 2) as the active methylene compound were
carried out at room temperature with MgO as catalyst and
the results are reported in Table 6. The aromatic alde-
hydes readily condensed with malononitrile, while with
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PAPER
High Surface Area MgO as a Highly Effective Heterogeneous Base Catalyst
3473
Table 6 Knoevenagel Condensation of Aldehydes with Ethyl Cyanoacetate and Malononitrile
Entry
1
R
R¢
Solvent
DMF
Time (min)
Conversion (%)
Selectivity (%)
Phenyl
CN
5
94
100
30
100
2
3
Phenyl
CO2Et
CN
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
30
30
30
60
60
30
30
60
60
97
100
99.9
99
100
100
100
100
100
100
100
100
100
2-Furyl
4
2-Furyl
CO2Et
CN
5
2-Methyl-butyl
2-Methyl-butyl
Butyl
6
CO2Et
CN
80
7
88
8
Butyl
CO2Et
CN
76
9
c-C5H10
97
10
11
12
c-C5H10
CO2Et
CN
23
Cinnamyl
Cinnamyl
CO2Et
60
50
57
ethyl cyanoacetate the reaction was slightly slower. This tion rate. It should also be noted that the Knoevenagel
may be attributed to the fact that abstraction of a proton condensation product was formed with almost 100% se-
from the active methylene group of ethyl cyanoacetate lectivity in the presence of MgO, but in only 66% selec-
was relatively more difficult due to its lower acidity. As tivity in the absence of MgO (Table 9, entry 2).
can be seen from Table 6, all reactions proceeded selec-
Of the seven substrates tested, only malononitrile and eth-
tively to the dehydrated products without any side reac-
yl cyanoacetate resulted in high conversion (Table 10)
tions. The rate of reaction is high and was generally equal
while the other substrates gave rise to no Knoevenagel
or better than those reported in the literature (Table 7).
condensation product. The formation of enol forms can
An attempt was made to check the reusability of the cata- explain the lack of reactivity of 2,4-pentanedione and eth-
lyst in the following manner. The reaction was performed yl acetoacetate, whereas the activity of nitromethane can
as usual for 30 minutes, then the stirring was stopped, and be ascribed to nitro/aci-nitro tautomerism35 and its low
the reaction mixture was placed in a centrifuge for ten pKa value.
minutes. After the supernatant was separated from the cat-
The effect of the donor on the reaction may be used to de-
alyst, DMF was added and the mixture stirred, centri-
termine the reaction mechanism. Scheme 6 has been pro-
fuged, and separated a second time. Fresh reactants and
posed by Moison20 as the mechanism for the Knoevenagel
solvent were added to the residual catalyst and the reac-
condensation. The mechanism for the Michael addition
tion was performed under identical conditions as before.
(Scheme 7) is based on the generally accepted route. Both
As can be seen in Table 8, the activity and selectivity of
of the intermediates (Schemes 6 and 7) can be confirmed
the catalyst was found to be almost the same. The washing
by the effect the formed enols had on the reaction. The
and relocation may result in some loss of catalyst, which
formation of the intermediate requires interaction be-
probably explains why the conversion using the recovered
tween acid sites (Mg2+) and acceptor, the conjugated basic
MgO was slightly lower than in the case of fresh MgO.
sites and anion formed from methylene compounds. The
Methanol is a good solvent for the reaction between ben- formation of cis-enols between the open-chain 1,3-dicar-
zaldehyde and malononitrile (Table 9, entry 1). However, bonyl compounds and the Mg2+ active site prevents the at-
there was no reaction using ethyl cyanoacetate in methan- tack of the acceptor on the Mg2+ active site, and thus
ol; in contrast, DMF was found to be a good solvent with formation of the intermediate.
a high yield obtained after a reaction time of only 30 min-
utes.
A simple method for the preparation of MgO, a catalyst
that exhibits a high activity for base-catalyzed reactions,
Again, the volume of solvent used affected the activity of is described. The experimental results show that an opti-
MgO. The concentration of the substrate was varied in mal calcination temperature in the range 400–500 °C
both toluene (0.8 mL per mmol of reactant, 17% conver- gives poorly crystalline, high surface area MgO that can
sion, 30 min; 5 mL per mmol of reactant, 0% conversion, be regenerated by washing, and then reused. The catalytic
30 min) and DMF; from these results we can conclude the activity of such MgO for both Michael additions and
higher the concentration of substrate the higher the reac- Knoevenagel condensations was found to compare favorably
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3474
C. Xu et al.
PAPER
Table 7 Comparison of MgO with Different Heterogeneous Catalysts for the Knoevenagel Condensation between Benzaldehyde and
Malononitrile
Catalyst
Catalyst amount
Reaction conditions
Time (min)
Conversion (%)
Yield (%)
94
MgO (this work)
0.05 g
r.t., 2 mmol, MeOH (1.5 mL)
5
30
94
100
MgOa,20
4 g
r.t., 10 mmol
5
60
HDTb,36
5 wt%
5 wt%
0.05 g
0.05 g
0.05 g
0.035 g
50 wt%
0.1 g
60 °C
54
62
MgOb,36
60 °C
60
NiAlHTcb,37
HDT-OH25
HDT-t-Bu23
HDT-F24
Zeolite38
Resin39
60 °C, 1 mmol
30
97
100
99
r.t., 2 mmol, toluene (10 mL)
r.t., 2 mmol, DMF (10 mL)
r.t., 1 mmol, DMF (5 mL)
r.t., 1:1.3, MeCN
60
10
15
100
78
720
300
150
4
r.t., 10 mmol, benzene (5 mL)
r.t., 20 mmol, MeCN (15 mL)
r.t., 1.5 mmol/2 mmol
100 °C, 10 mmol
92
40
KF/Al2O3
0.78 g
80
FAP/BTEAC/waterb,41 1.25 g
98
b,42
ZnCl2
0.136 g
0.25 g
1.5 g
10
91
Aminosilica43
AlPO4/Al2O3
r.t., 20 mmol, solvent (25 mL)
r.t., 10 mmol
240
15
99
b,44
80
17
Na2Ca2P2O7
0.04 g
0.1 g
r.t., 1.5 mmol, MeOH (1.6 mL)
r.t., 10 mmol
7
94
Xenotliteb,30
1440
81
a Commercially available MgO.
b Reaction carried out in the absence of solvent.
R'
CN
H
R
HC
H
C
H
R'
O
C
X
H
HC
R
C
O
–
+
O2
Mg2
Y
Scheme 6 Knoevenagel condensation
H
–
+
with previous studies using more complicated and expen-
sive catalysts. Indeed, the simplicity of its preparation and
the ease of reactivation after use may offer sufficient com-
pensation to make MgO the base catalyst of choice even
O2
Mg2
Scheme 7 Michael addition
if slightly better yields can be obtained with alternative
catalysts. It was found that the activity of MgO did not in-
crease with the acidity of the substrate, in contrast to many
homogeneous systems.
Table 8 Knoevenagel Condensation between Benzaldehyde and
Ethyl Cyanoacetate with Fresh MgO and Reused MgO
Catalyst
Time (min) Conversion (%) Selectivity (%)
MgO (1st use)
MgO (2nd use)
30
30
94
90
100
100
The catalysts used in this study were obtained by calcination of the
precursors (MgCO3)4Mg(OH)2, or rehydrated Mg(OH)2 at 450 °C
for 2 h. The heating ramp used in all cases was 10 °C/min. MS were
carried on a Perkin-Elmer Turbomass GC-MS.
Synthesis 2005, No. 19, 3468–3476 © Thieme Stuttgart · New York

PAPER
High Surface Area MgO as a Highly Effective Heterogeneous Base Catalyst
3475
Table 9 The Effect of the Solvent on the Knoevenagel Condensation Reaction
Entry
R
R¢
Solvent
Catalyst amount (g)
Time (min)
Conversion (%)
Selectivity (%)
1
2
Ph
Ph
CN
MeOH (1.6 mL)
DMF (1.6 mL)
DMF (5 mL)
0.05
0.05
30
30
100
94
100
100
CO2Et
0.05
0
30
30
77
30
100
66
DMF (10 mL)
0.05
30
69
100
100
Toluene (1.6 mL)
0.05
0.2
30
30
17
60
Toluene (10 mL)
MeOH (1.6 mL)
0.05
0.05
30
30
0
0
(5) Barthomeuf, D.; Coudurier, G.; Vedrine, J. C. Mater. Chem.
Phys. 1988, 18, 553.
Table 10 The Effect of the Donor on the Knoevenagel Condensa-
tion with Benzaldehyde
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Entry
Donor
pKa in
DMSO
Time (h) Conversion/
%
1
2
3
4
5
6
2,4-Pentanedione
Ethyl acetoacetate
Nitromethane
13.3
14.2
17.2
11.1
13.1
16.4
0.5
0.5
0.5
0.5
0.5
0.5
0
0
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0
Malononitrile
100
97
0
Ethyl cyanoacetate
Dimethyl malonate
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173, 315.
The reactions were carried out in a standard round-bottom glass
flask equipped with a vertical condenser at r.t. under vigorous stir-
ring. Reactions were performed with acceptor (2 mmol), donor (2
mmol), and catalyst (0.2 g), in toluene (2 mL) or MeCN (5 mL) at
r.t. for the specified time.
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Knoevenagel Condensation
Reactions were performed with acceptor (2 mmol) and donor (2
mmol) using MgO (0.05 g) in DMF (2 mL) or MeOH (5 mL) at r.t.
for the specified time. Samples were taken periodically and injected
off-line into a GC equipped with a DB-5 capillary column and an
FID detector. Product yields and purities were determined by a
combination of GC analysis and 1H NMR spectroscopy. The prod-
ucts were identified by MS and by 1H NMR spectroscopy.
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Acknowledgment
The authors wish to thank EPSRC and Johnson-Matthey Plc. for
funding this study.
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