Metal organic frameworks as solid acid catalysts for acetalization of aldehydes with methanol

Article abstract of DOI:10.1002/adsc.201000537

Room temperature acetalization of aldehydes with methanol has been carried out using metal organic frameworks (MOFs) as solid heterogeneous catalysts. Of the MOFs tested, a copper-containing MOF [Cu₃(BTC)₂] (BTC=1,3,5-benzenetricarboxylate) showed better catalytic activity than an iron-containing MOF [Fe(BTC)] and an aluminium containing MOF [Al ₂(BDC)₃] (BDC=1,4-benzenedicarboxylate). The protocol was validated for a series of aromatic and aliphatic aldehydes and used to protect various aldehydes into commercially important acetals in good yields without the need of water removal. In addition, the reusability and heterogeneity of this catalytic system was demonstrated. The structural stability of MOF was further studied by characterization with powder X-ray diffraction, Brunauer-Emmett- Teller surface area measurements and Fourier-transformed infrared spectroscopic analysis of a deactivated catalyst used to convert a large amount of benzaldehyde. The performance of copper MOF as acetalization catalyst compares favourably with those of other conventional homogeneous and heterogeneous catalysts such as zinc chloride, zeolite and clay. Copyright

Full text of DOI:10.1002/adsc.201000537

FULL PAPERS
DOI: 10.1002/adsc.201000537
Metal Organic Frameworks as Solid Acid Catalysts for
Acetalization of Aldehydes with Methanol
a
a
a,
Amarajothi Dhakshinamoorthy, Mercedes Alvaro, and Hermenegildo Garcia *
a
Instituto Universitario de Tecnologꢀa Quꢀmica CSIC-UPV and Departamento de Quꢀmica, Universidad Politꢁcnica de
Valencia, Av. De los Naranjos s/n, 46022 Valencia, Spain
Fax : (+34)-9-6387-7809; phone: (+34)-9-638-7807; e-mail: hgarcia@qim.upv.es
Received: July 8, 2010; Revised: September 24, 2010; Published online: November 17, 2010
Abstract: Room temperature acetalization of alde- tural stability of MOF was further studied by charac-
hydes with methanol has been carried out using terization with powder X-ray diffraction, Brunauer–
metal organic frameworks (MOFs) as solid heteroge- Emmett–Teller surface area measurements and Four-
neous catalysts. Of the MOFs tested, a copper-con- ier-transformed infrared spectroscopic analysis of a
taining MOF [Cu ACHTUNGTRNENUG( BTC) ] (BTC=1,3,5-benzenetri- deactivated catalyst used to convert a large amount
3 2
carboxylate) showed better catalytic activity than an of benzaldehyde. The performance of copper MOF
iron-containing MOF [Fe(BTC)] and an aluminium as acetalization catalyst compares favourably with
containing MOF [Al (BDC) ] (BDC=1,4-benzenedi- those of other conventional homogeneous and heter-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
2
3
carboxylate). The protocol was validated for a series ogeneous catalysts such as zinc chloride, zeolite and
of aromatic and aliphatic aldehydes and used to pro- clay.
tect various aldehydes into commercially important
acetals in good yields without the need of water re- Keywords: acetalization; copper MOFs; green
moval. In addition, the reusability and heterogeneity chemistry; metal organic frameworks; solid Lewis
of this catalytic system was demonstrated. The struc- acids
Introduction
coordination site in each copper metal. Precedents in
the literature based on the product distribution ob-
Metal organic frameworks (MOFs) have emerged as served for the rearrangement of cyclic acetal of 2-bro-
[
1–4]
[5]
a hot topic in heterogeneous catalysis.
zeolites, the large surface area and open porosity of behave as a soft Lewis acid catalyst Also, more re-
MOFs allows the access of substrates to the active cently, we have shown that Cu (BTC) is a suitable
Similarly to mopropiophenone have shown that Cu3 ACHTUNGERTUNNNG( BTC) can
2
AHCTUNGTRENNUNG
3
2
sites present inside the crystal structure. One of the heterogeneous catalyst for oxidation of benzylic com-
[
7]
advantages of MOFs compared to zeolites is the large pounds using tert-butyl hydroperoxide and N-meth-
[
8]
diversity of transition metals and organic linkers that ylation of amines using dimethyl carbonate. Consid-
[
1]
can be used for the synthesis of MOFs. In those ering that the use of MOFs as heterogeneous cata-
[
8–11]
cases in which not all the coordination positions lyst
is an area of much current interest it is still
around the metal nodes are compromised by the necessary to expand the reaction types that can be
structure, the metal ions can interact with organic catalyzed by MOFs trying to delineate the advantages
substrates and this can promote Lewis acid-catalyzed and limitations of these materials as catalysts, particu-
[
5]
or redox reactions. This is the case with Cu
(
A
H
U
G
R
N
N
(BTC)
larly versus other common solid catalysts such as zeo-
BTC=1,3,5-benzenetricarboxylic acid) whose struc- lite and clays.
ture is constituted by clusters of two copper ions coor- Formation of dimethyl acetals in the homogeneous
3
2
dinated with four carboxylate groups of organic link- phase is frequently carried out by using trimethyl or-
ers defining a paddle wheel building unit that acts as thoformate as the reagent due to the incompatibility
structural node held in place by the tripodal BTC of methanol with the Lewis acid catalyst, thus, for in-
[
6]
linkers. The micropore system of Cu ACHTUNGRTNEUNG( BTC) defines stance formation of dimethyl acetals using trimethyl
3 2
[
6]
nano cages of about 2.5 nm with windows of 0.8 nm.
In the as-synthesized material each copper atom has a been previously reported.
position bound to a solvent molecule. It is possible to methanol is desirable due to its availability.
desorb reversibly this solvent molecule leaving a free acid catalysts can be more tolerant to the use of
orthoformate as reagent with MOFs as catalyst has
[
12,13]
However, the use of
[
14]
Solid
3022
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 3022 – 3030

Metal Organic Frameworks as Solid Acid Catalysts for Acetalization of Aldehydes
and that their activity compares favourably with that
of acid zeolites and clays.
Formation of Dimethyl Acetals Catalyzed by MOFs
Initially benzaldehyde was selected as a model sub-
strate and its acetalization reaction by methanol as a
solvent and reagent in the presence of different cata-
Scheme 1.
methanol and in this way acetalization of various ali- lysts was screened with the aim to achieve the highest
phatic and aromatic aldehydes with methanol has conversion without compromising the product selec-
[
15]
been reported with Al-MCM-41
aluminosilicate
and mesoporous tivity. The results obtained for the transformation of
[16]
as heterogeneous catalysts under benzaldehyde with methanol to 1,1-dimethoxytoluene
mild reactions conditions at moderate to high temper- are shown in Table 1. The only product observed in
atures. On the other hand, faujasites have also been this reaction is the corresponding dimethyl acetal, ac-
reported as solid acid catalyst with triethyl orthofor- compained in some cases at longer times with a very
mate for the protection of aldehydes and are notably minor amount of benzoic acid (see footnote [b] in
[
17]
inefficient using methanol as solvent.
changed montmorillonites
Metal ex- Table 1). In particular we did not observe the pres-
have also been report- ence of the corresponding hemiacetal probably due to
ed for the protection of aldehydes and ketones with the unfavourable formation equilibrium. A blank con-
[
18,19]
[
20]
ethylene glycol and methanol. MoO /SiO2 and am- trol shows that when the reaction between benzalde-
monium triflate and other acids supported on silica
3
[
21]
hyde and methanol is performed in the absence of
have been reported for the protection of carbonyl
compounds using glycerol. On the other hand, solid
acids such as Filtrol-24, Amberlyst-15 have been used Table 1. Acetalization of benzaldehyde with methanol using
[a]
as heterogeneous catalysts for the acetalization of n- different catalysts.
[
22]
octanal with alcohols.
Polymeric acid materials
have been used as a recyclable catalyst for the acetali-
[
23]
zation of aldehydes with methanol.
[bmim]HSO4
[
24]
was used as an acidic ionic liquid catalyst for acetal-
ization and thioacetalization of carbonyl compounds
and their subsequent deprotection using glycerol at
room temperature. Due to their milder acid strength
and larger hydrophobicity MOFs could also be suita-
ble as Lewis acid catalysts for acetalization of carbon-
ylic compounds by alcohols. In the present work, we
[b]
Entry
Catalyst
–
Time [h]
Conversion [%]
1
2
3
4
5
6
7
8
9
28
2
24
8
21
63
88
Cu
Cu
Cu
Cu
Cu
Cu
ACHTUNGTRENNUNG( BTC)
3
2
2
2
2
2
2
A
H
U
G
R
N
U
G
3
[c]
A
H
U
G
R
N
U
G
3
3
report that Cu
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(BTC) exhibits high activity for the
[d]
[e]
[f]
3
2
A
H
U
G
R
N
U
G
8
75, 74, 71
3
selective acetalization of aldehydes by methanol at
room temperature (Scheme 1). Generally ketones do
not undergo acetalization under similar conditions.
[g]
A
H
U
G
R
N
U
G
48
110
2
24
24
66[ (2)
3
h]
A
H
U
G
R
N
U
G
61 (3)
3
Fe
Fe
A
T
N
T
E
N
N
49
71
66
Compared to other related MOFs such as Fe
and Al (BDC)
acid), the activity of Cu
A
T
N
T
E
N
G
A
T
N
T
E
N
N
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(BDC=1,4-benzenedicarboxylic 10
(BTC) was higher, a fact
Al
2
A
H
U
G
E
N
N
3
2
3
A
H
U
T
E
N
N
[a]
3
2
Reaction conditions: benzaldehyde (0.94 mmol), catalyst
50 mg) and methanol (3 mL), room temperature.
Determined by GC using nitrobenzene as internal stan-
dard. Values in parentheses correspond to the benzoic
acid.
that can reflect the relative Lewis acidity of the mate-
rial.
(
[b]
[c]
Results and Discussion
Reaction was performed in the presence of pyridine
(
30 mg)
[
[
[
[
d]
e]
f]
Yield of first reuse.
Yield of second reuse.
Yield of third reuse.
In this study, we first present the results obtained on
acetalization of benzaldehyde with methanol cata-
lyzed by MOFs as solid heterogeneous catalysts with
various alcohols and, then, we show its general applic-
ability discussing the factors determining the reactivi-
ty of various aldehydes under the experimental condi-
tions studied. In addition, it will be shown that MOFs
can be used as heterogeneous and reusable catalysts
g]
Reaction conditions: benzaldehyde (9.4 mmol), Cu3
AHCTUNGTNERGUN( BTC) (50 mg) and methanol (3 mL), room tempera-
2
ture.
[h]
Reaction conditions: benzaldehyde (18.8 mmol), Cu3
AHCTUNGTREGUN(NN BTC) (250 mg) and methanol (5 mL), room tempera-
2
ture.
Adv. Synth. Catal. 2010, 352, 3022 – 3030
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Amarajothi Dhakshinamoorthy et al.
FULL PAPERS
catalyst formation of some 1,1-dimethoxytoluene
(
21%) occurs.
On the other hand, three commercially available
MOFs were tested to find the most active one for the
acetalization of aldehydes. It was found that Cu3
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(BTC) shows the best catalytic activity at room tem-
2
perature with very high selectivity. Thus, acetalization
of benzaldehyde was carried out in the presence of
Cu3 ACHTUNGTRENNUNG( BTC) as heterogeneous solid catalyst using
2
methanol and resulted in 88% conversion of benzal-
dehyde as shown in Figure 1.
Figure 1 compares the time-conversion plot in the
presence of Cu ACHTUNGTRENNUNG( BTC) and Fe AHCTNUTGRNEGNU
3 2
though Fe
ACHTUNGTRENNUNG
Figure 2. EPR spectrum of Cu ACHTUNGTENRUNG( BTC) .
3 2
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
ACHTUNGTRENNUNG
2
3
2
available for coordination with substrates and re-
agents and a recent study has shown that Cu (BTC)
behaves as a Lewis acid. Fe ACHUTGTNERNNUG( III) in Fe CAHTUNGTRENNUNG
A
H
U
G
R
N
U
trum recorded for Cu3
(BTC) has value of 2.16.
also a free coordination position around the Fe(III) With the aim of studying the stability and produc-
ion and hence it also can act as a solid Lewis acid. tivity of Cu (BTC) on the transformation of benzal-
ACHTUNGENTRNUNG( BTC) corresponding to a G
3
2
2
[
5]
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
3
2
Furthermore, Al ACHTUNGTRNENUG( BDC) exhibited a lower activity dehyde to 1,1-dimethoxytoluene, the reaction was car-
2 3
than the above MOFs. The results obtained with Fe- ried out in methanol with a large excess of benzalde-
(BTC) and Al (BDC) as heterogeneous catalysts are hyde with respect to Cu3(BTC) (see Table 1, entries 9
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
ACHTUNGTRENNUNG
2
3
2
also given in Table 1.
and 10). Turnover frequency (TOF) values estimated
To provide evidence in favour of the Lewis acid at 1 h reaction time for the experiments with 50 and
À1
nature of the active sites, a control experiment using 250 mg of Cu
A
H
U
G
R
N
U
G
3
2
Cu3
chiometric amount of pyridine with respect to the dehyde, the intrinsic activity of Cu ACHTUNGTRNEUNG( BTC) is about
3 2
ACHTUNGTRENNUNG( BTC) was performed in the presence of a stoi- showing that in these experiments with excess benzal-
2
Cu(II) ions present in the catalyst for the acetaliza- two times higher than when higher proportions of Cu3
tion of benzaldehyde with methanol as described in (BTC) catalysts are used. At 48 h reaction time, 66%
AHCTUNGTRENNUNG
2
Table 1. The conversion of benzaldehyde under these of 1,1-dimethoxytoluene was observed with very high
conditions was only 3% after 8 h and this dramatic selectivity. In another experiment with 18.8 mmol of
decrease in conversion is in agreement with the poi- benzaldehyde, the reaction was allowed to continue
soning of Cu ACHTUNGTRENNUNG( BTC) active sites by the strong interac- until the maximum consumption of benzaldehyde.
3 2
tion of pyridine with the Lewis acid sites. In addition, After 110 h, it was oberved that the conversion of
a quantitative EPR measurement indicates that in benzaldehyde had stopped and at this moment the
good agreement with the stoichiometry and structure catalyst was recovered from the reaction mixture,
of Cu ACHTUNGTRENNUNG( BTC) this material contains copper ions in washed with methanol, dried and analyzed by powder
3 2
the +2 oxidation state. Figure 2 shows the EPR spec- XRD, IR and BET surface area measurements. As it
can be seen from Figure 3, the characteristic IR
À1
stretching frequencies (1800–1500 cm ) of the fresh
material which correspond to the organic linkers
remain unaltered in the deactivated catalyst. In addi-
tion, the stretching frequencies corresponding to ben-
zaldehyde or to its acetal are also missing and there-
fore no evidence for the presence of adsorbed prod-
ucts was obtained. Similarly it was also noticed that in
powder XRD the pattern of the used catalyst coin-
cides in the peak positions and intensities with that of
the fresh material (see below the reusability tests).
Also, it is very clear that the catalyst does not contain
additional phases and retains its structural integrity as
shown by the absence of any additional peaks. The
Figure 1. Time conversion plot for the acetalization of ben-
BET surface area of the fresh and used catalysts is
zaldehyde with (a) Cu ACHUTNGRENUNG( BTC) and (b) Fe ACHTUNGTRENNNUG
3 2
2
À1
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Adv. Synth. Catal. 2010, 352, 3022 – 3030

Metal Organic Frameworks as Solid Acid Catalysts for Acetalization of Aldehydes
Table 2. Comparison of Cu3
ACHTUNGTRENNUNG( BTC) with other homogeneous
2
and heterogeneous catalysts for the acetalization reaction of
[a]
aldehydes and ketones.
Entry Catalyst (wt)
Substrate
Time Yield
[
h]
[%]
1
2
Cu
120 mg)
Cu(NO ) ·3H O
120 mg)
A
T
N
T
E
N
N
(NO ) ·3H O
benzaldehyde 8
acetophenone 8
92
3
2
2
(
A
H
U
G
R
N
U
G
16
3
2
2
(
3
4
5
ZnCl (70 mg)
benzaldehyde 8
acetophenone 8
benzaldehyde 8, 24
48
8
86, 94
2
ZnCl (70 mg)
2
Cu
A
H
U
G
R
N
N
(BTC)
3
2
(
100 mg)
6
Cu (BTC)
A
H
U
G
R
N
N
acetophenone 24
9
3
2
(
100 mg)
Figure 3. FT-IR spectra of Cu3
reaction as reported in Table 1 (entry 7).
A
H
U
G
R
N
U
(BTC) (a) fresh and (b) after
7
8
Bentonite (100 mg) benzaldehyde 8
5
10
2
NaY zeolite
100 mg)
NaY zeolite
100 mg)
benzaldehyde 8
benzaldehyde 8
(
[b]
9
8
(
ited structural damage that increases the microporosi-
ty of the material due to the creation of some defects
[c]
1
1
0
1
USY 500 (100 mg) benzaldehyde 24
63
69
[c]
Beta-806 (100 mg) benzaldehyde 24
(
lack of organic ligand or metal nodes) and due to its
[
a]
Reaction conditions: substrate (1 mmol); methanol
(3 mL), room temperature.
b]
small degree it will go undetected in XRD, IR or any
other technique.
In order to understand the catalyst deactivation,
two control experiments were carried out. In the first
experiment, acetalization of benzaldehyde (1 mmol)
[
[
Activated at 2008C for 3 h before the reaction.
Calcined at 4008C.
c]
was performed with 100 mg of Cu ACHTUGNTENRNUG( BTC) in 3 mL of the same trend that was as observed with Cu ACHTUNGTRENNUNG( BTC)
3
2
3
2
methanol adding a stoichiometric amount of water to as catalyst. On the other hand, anhydrous zinc chlo-
benzaldehyde and after 24 h, 38% conversion of ride, one of the most used Lewis acids in organic
acetal was formed. In the other experiment, deacetali- chemistry, exhibited mild reactivity with benzalde-
zation of 1,1-dimethoxytoluene (1 mmol) was carried hyde and poor reactivity with acetophenone at room
out with 100 mg of Cu3
with stoichiometric amount of water and after 24 h, of the most recommended Lewis acid catalysts for
3% conversion of benzaldehyde was noticed. These acetalization reactions, its activity is lower than that
experiments clearly show the role of water in shifting of both copper nitrate and Cu (BTC) and a larger
ACHTUNGTRENNUNG( BTC) in 3 mL of methanol temperature. Therefore, although zinc chloride is one
2
4
AHCTUNGTRENNUNG
3
2
the equilibrium and controlling the product yield. amount of this metal chloride would be necessary to
However, the fact that in both experiments Cu3 achieve higher conversion. On the other hand, typical
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(BTC) was still active even in the presence of water solid acids like bentonite showed very poor activity
2
indicates that water is not a poison of the catalyst with benzaldehyde. Finally, NaY zeolite was also
active sites.
tested for the acetalization of benzaldehyde with
methanol. Both activated and unactivated NaY zeo-
lite catalysts exhibited mild reactivity with benzalde-
hyde and this may be due to the strong interaction of
zeolite active sites with methanol. On the other hand
when acid zeolites with strong Brønsted acid and
Comparison of Cu
Catalysts
ACHTUNGTRENNUNG( BTC) with Conventional Acid
3 2
In order to put into the context the catalytic activity Lewis acid sites are used as catalyst such USY 500
of Cu (BTC) and to understand the influence of mi- and beta-806, the formation of corresponding acetal
ACHTUNGTRENNUNG
3
2
croporosity in the activity of Cu ACHTUNGTRENUNG( BTC) , other homo- resulted in 63 and 69% yields, respectively, under the
3 2
geneous and heterogeneous catalysts were also tested present experimental conditions. These values are still
for acetalization of benzaldehyde and acetophenone much lower than the 94% reached with Cu (BTC) .
AHCTUNGTRENNUNG
3
2
with methanol under identical conditions. Specifically, Due to the high hydrophilicity of zeolites, particularly
the amount of the catalyst used in Table 2 was adjust- faujasites, it is well documented that alcohols and
ed to have a similar population of acid sites as in Cu3 other polar solvents are poor media for liquid phase
ACHTUNGTRENNUNG( BTC) . The results are given in Table 2. Copper ni- reactions catalyzed by zeolite, since the solvent
2
[17]
trate showed high conversion for benzaldehyde but strongly competes with substrates for adsorption. In
this was considerably much lower for acetophenone, this regard, hydrocarbons and apolar compounds are
Adv. Synth. Catal. 2010, 352, 3022 – 3030
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asc.wiley-vch.de
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Amarajothi Dhakshinamoorthy et al.
FULL PAPERS
in general most suited as solvents in the case of zeo- would easily fit inside the reaction cavity, diffusing
lites. In contrast, as it can be seen in Table 1, the use fast through the micropore system. As the size of the
of methanol as solvent can be tolerated by Cu
A
H
U
G
R
N
N
(BTC)
reaction products increases, fitting of the product
and MOFs in general. These studies clearly shown inside the reaction cavity is more difficult and the in-
that Cu (BTC) is the superior catalyst for this reac- tracrystalline diffusion will be slower, these two fac-
3
2
ACHTUNGTRENNUNG
3
2
tion in terms of high yield of the acetal and very high tors resulting in a decrease of the catalyst activity. To
selectivity with respect to other conventional homoge- support this explanation, we performed analogous ex-
neous and heterogeneous catalysts when the reaction periments using copper nitrate as homogeneous cata-
is performed at room temperature.
lyst. It was observed that at 7 h reaction time the con-
For the sake of comparison, copper nitrate trihy- versions of benzaldehyde in ethanol and 1-propanol
drate was used as homogeneous catalyst with a similar in the presence of copper nitrate were 47 and 55%,
copper content as that of Cu3
as Lewis acid sites for this reaction. The TOF values times higher than those obtained using Cu ACHTUNGTRENNUNG( BTC)
3 2
ACHTUNGTRENNUNG( BTC) to probe Cu(II) respectively. These conversion values are two to five
2
calculated at 1 h reaction time for acetalization of (Figure 4). Thus, in contrast to the previous case of di-
benzaldehyde using copper nitrate or Cu
A
H
U
G
R
N
N
(BTC) were methyl acetal formation in which the catalytic activi-
3
2
À1
1.8 and 1.5 h , respectively. These data indicate that ties of Cu
A
H
U
G
R
N
N
(BTC) and copper nitrate are similar, for
3
2
the activity of Cu(II) as Lewis acid in the homogene- longer alcohols, particularly 1-propanol, the homoge-
ous phase is not diminished when Cu(II) ions are neous catalyst not constrained by diffiusion limita-
forming part of the MOF structure, due to the availa- tions is much more active than the microporous Cu3
bility of one free coordination position around these
copper ions.
ACHTUNGTNRENUNG( BTC) .
2
After establishing the reaction conditions and the
most suitable catalysts, we were also interested in Heterogeneity and Reusability Tests
studying the effect of the alcohol on the reactivity of
benzaldehyde. Hence, we have selected also ethanol To verify that the observed catalysis of Cu ACHTUNGNRTEUNG( BTC) is
3 2
and 1-propanol and treated them with benzaldehyde heterogeneous and not due to some leached copper
using Cu (BTC) as solid catalysts and compared the species present in the liquid phase, the reaction was
ACHTUNGTRENNUNG
3
2
results with those achieved with methanol. A clear carried out under the optimized conditions described
tendency was observed and the initial reaction rate in Table 1 and the Cu (BTC) solid catalyst was fil-
AHCTUNGTRENNUNG
3
2
and final conversion decreased significantly along tered from the reaction mixture at about 50% forma-
with the chain length of the alcohol as shown in tion of 1,1-dimethoxytoluene. After filtering off the
Figure 4. Cu3
ACHTUNGTNERNUNG( BTC) catalyst, the solution in the absence of
2
Assuming that in the case of Cu ACHTUNGTERNN(UNG BTC) acetaliza- solid was again stirred. After 24 h, the product forma-
3
2
tion takes place predominantly in the micropore tion was slightly increased to 63% (see Figure 5). This
system of Cu (BTC) , the most likely explanation to increase (13%) in the percentage of product in the
ACHTUNGTRENNUNG
3
2
rationalize the lower reactivity of the alcohols as the absence of Cu ACHTGNUTRNEUNG( BTC) has to be due, at least in part,
3 2
chain length increases is the influence of steric factors to the uncatalyzed acetal formation observed in the
and operation of shape selectivity. Thus, small acetals blank experiment (Table 1, entry 1). To provide fur-
ther data to clarify this issue, the reaction mixture
Figure 4. Reaction between benzaldehyde with (a) metha-
nol, (b) ethanol and (c) 1-propanol catalyzed by Cu3(BTC) .
Reaction conditions: Benzaldehyde (0.1 mL), alcohol
Figure 5. (a) Acetalization of benzaldehyde with Cu ACHTUNGTRENNUNG( BTC)
3 2
A
H
U
G
R
N
N
and (b) filtration of Cu ACHTUNGTNERUNG( BTC) at 50% conversion. Reaction
2
3 2
conditions: benzaldehyde (0.94 mmol), methanol (3 mL) and
Cu3(BTC) (50 mg).
(
3 mL), room temperature, Cu
A
H
U
G
R
N
N
(BTC) (100 mg).
ACHTUNGTRENNUNG
3
2
2
3026
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Adv. Synth. Catal. 2010, 352, 3022 – 3030

Metal Organic Frameworks as Solid Acid Catalysts for Acetalization of Aldehydes
Cu3 ACHTUNGTERNNUN(G BTC) as General Heterogeneous Catalyst for
2
the Room Temperature Formation of Dimethyl
Acetals
In order to expand the scope of this reaction, various
aromatic and aliphatic aldehydes as well as some ke-
tones were subjected to the present protocol using
Cu3 ACHTUNGTERNNUN(G BTC) as a sold acid catalyst. The results are
2
given in Table 3.
Benzaldehyde was converted to its dimethyl acetal
in very good yield with Cu3 ACHTUGNTERNN(UNG BTC) as heterogeneous
2
catalyst employing twice the amount of solid used for
the initial experiments shown in Table 1. Bromo- and
chloro-substituted benzaldehydes were also protected
Figure 6. Powder XRD pattern of (a) fresh and (b) three to their corresponding dimethyl acetal in good yields.
times used and (c) deactivated catalyst of Cu3
acetalization of benzaldehyde test [18.8 mmol of benzalde- due to poisioning of the catalyst by the formation of
hyde and 250 mg of Cu ACHTUNGTRNEU(GN BTC) ]. Reaction conditions: the
3 2
same as given in Table 1. The deactivated catalyst was ob-
tained from the productivity test by using a large excess of
benzaldehyde [18.8 mmol and 250 mg of Cu ACHTUNGNRTEUNG( BTC) ] and
leaving the system to evolve for over 110 h (Table 1,
entry 7).
ACHTUNGTRENNUNG
(BTC) for the In the case of p-tolualdehyde the low yield could be
2
the corresponding acid. On the other hand, even 4-
tert-butylbenzaldehyde gives high dimethyl acetal
yields at room temperature. 2-Fluorobenzaldehyde
showed better conversion than p-cyanobenzaldehyde
to give their corresponding dimethyl acetal deriva-
tives. Even long and rigid substrates such as 4-phenyl-
benzaldehyde exhibited very good reactivity towards
3 2
was analyzed by AES-ICP whereby the presence of the formation of dimethyl acetal product in high
.9 ppm of copper in the solution was measured. This yield. A disubstituted benzaldehyde was also subject-
5
Cu(II) leached may be also responsible for the slight ed to this protocol and we observed that the yield is
increment in the product formation after removal of moderate or probably very low due to the large kinet-
catalyst. The percentage of copper leaching detected ic diameter of the molecule that results in an unfav-
corresponds to 0.15% of the total copper present in ourable diffusion through the micropore system. Be-
the catalyst (15.7 mg) and is, therefore, negligible sides steric factors, in the case of p-hydroxybenzalde-
from the point of view of the change in the composi- hyde, 5-chlorosalicylaldehyde and 2-hydroxy-5-nitro-
tion of the Cu ACHTUNGTRENNUNG( BTC) solid. Hence it can be conclud- benzaldehyde, the lack of formation of the dimethyl
3 2
ed that the catalysis occurs both in the solid and acetal could also be due to the presence of free hy-
liquid phases with a relatively large prevalence of the droxy groups. Interestingly, the presence of double
solid catalyst and without significant alteration of the and triple bonds on the substrate that can typically
Cu3 ACHTUNGTRENNUNG( BTC) composition. We notice that the occur- react in the presence of Lewis acid catalysts does not
2
rence of some minor Cu(II) leaching could be in interfere in the acetalization reaction. Then, phenyla-
agreement with the previous observation of a surface cetaldehyde and furfuraldehyde were also subjected
area increase of the catalyst upon use.
to this reaction and resulted in good yield of the cor-
The reusability of Cu (BTC) was further investi- responding acetal derivatives. With a view to study
AHCTUNGTRENNUNG
3
2
gated for the acetalization reaction of benzaldehyde the influence of the steric nature of the substrate on
with methanol under identical conditions as described the reactivity, 1-pyrenecarboxaldehyde was used as
in Table 1. After the required time, the reaction mix- model substrate and showed good yield towards the
ture was allowed to settle down and the supernatant dimethyl acetal. a,b-Unsaturated aldehyde also
liquid was decanted and the solid used for another showed good reactivity as other aromatic aldehydes.
consecutive run with fresh benzaldehyde without fur- Besides the reactivity of furfuraldehyde as heteroaro-
ther treatment. After three consecutive reuses, the matic aldehyde, we wanted to study the acetalization
catalyst did not show any changes in its crystallinity of 4-pyridylcarboxaldehyde. Unfortunately, this sub-
as determined by powder XRD. A comparison of the strate resulted in no conversion as the pyridine coor-
XRD patterns of the fresh and three times used Cu3 dinates with the catalytically active sites rather than
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(BTC) is provided in Figure 6. As it can be seen the carbonyl group and hence, the catalyst becomes
2
there, even though there is some copper leached into deactivated. Finally, n-heptanal also showed good re-
the solution during the reaction, the crystallinity of activity with very high selectivity towards the synthe-
the used Cu ACHTUNGTRENNUNG( BTC) samples after catalysis is main- sis of the commercially important dimethyl acetal of
3 2
tained except with some changes in the relative inten- heptanal that corresponds to the vegetable topnote in
[
25]
sity of some peaks.
fragrances and also in fine chemicals.
Adv. Synth. Catal. 2010, 352, 3022 – 3030
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3027

Amarajothi Dhakshinamoorthy et al.
FULL PAPERS
Table 3. Acetalization of various aldehydes with methanol
Table 3. (Continued)
[a]
using Cu ACHTUNGTRENNUNG( BTC) as heterogeneous solid acid catalysts.
3 2
[b]
Entry Aldehyde
Acetal
Yield [%]
86
[b]
Entry Aldehyde
1
Acetal
Yield [%]
1
3
4
[c]
94 (92)
85
1
81
76
2
3
4
1
5
83
30
16
17
18
–
75
9
5
6
7
73
86
52
19
80
[a]
Reaction conditions: aldehyde (1 mmol), methanol
3 mL), Cu (BTC) (100 mg), 24 h, room temperature.
Determined by GC using nitromethane as internal stan-
dard.
Yield of homogeneous reaction. Benzaldehyde (1 mmol),
copper nitrate trihydrate (120 mg) and methanol (3 mL),
room temperature, 8 h.
Attempts to prepare the dimethyl acetals of p-hydroxy-
benzaldehyde, 5-chlorosalicylaldehyde and 2-hydroxy-5-
nitrobenzaldehyde failed.
(
ACHTUNGTRENNUNG
3
2
[b]
[
[
c]
d]
8
82
57
72
The above results show that Cu CAHTUNGTRNEU(GN BTC) is a general
3 2
catalyst for the room temperature formation of di-
methyl acetals of aldehydes. Concerning ketone ace-
talization the situation is less clear. Thus, acetophe-
none was subjected to identical reaction conditions
and showed poor reactivity when compared to benzal-
dehyde. In contrast, cyclohexanone showed better re-
activity to give the corresponding dimethyl acetal in
good yields. Further reactions with cycloheptanone,
cyclooctanone, 2-octanone and a-tetralone resulted in
a low conversion to their corresponding dimethyl ace-
tals.
Finally, we also wanted to test the catalytic activity
and percentage selectivity in the reaction of benzalde-
hyde with glycerol. When the reaction was performed
in acetonitrile at room temperature with equimolar
amounts of benzaldehyde with glycerol, we observed
[
d]
9
1
0
1
1
1
2
88
60
25% conversion of benzaldehyde with 86% of (2-
phenyl-1,3-dioxolan-4-yl)methanol and 14% 2-phenyl-
3028
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ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 3022 – 3030

Metal Organic Frameworks as Solid Acid Catalysts for Acetalization of Aldehydes
1,3-dioxan-5-ol. The results with benzaldehyde and over ketones, a fact that is not surprising considering
glycerol are remarkable since the product distribution the difference in the reactivity of these two types of
towards the most desirable fragrance that is the five- carbonyl groups.
membered hydroxymethyl cyclic ethylene acetals is
6
.1 times higher than that of the thermodynamically
more stable, but less desirable, six-membered ring Conclusions
acetal. This ratio is similar to what has been reported
for the acetalization of benzaldehyde with glycerol We have described herein the use of Cu ACHTUNGTENRUNG( BTC) as a
3 2
using acid zeolites and it was attributed to the occur- convenient, efficient and reusable heterogeneous
[
23]
rence of the reaction in a confined space,
as it solid catalyst for formation of dimethyl acetals at
should be the case of Cu (BTC) . To provide a com- room temperature. Out of the three MOFs tested, Cu3
AHCTUNGTRENNUNG
3
2
parison, Scheme 2 also provides the ratio of five- vs.
ACHTUNGTNERNU(GN BTC) showed better catalytic activity. With this cat-
2
six-membered rings obtained for the reaction of ben- alyst, formation of dimethyl acetal occurs in higher
zaldehyde with glycerol using copper nitrate as homo- yields compared to other diethyl and dipropyl acetals
geneous catalyst. As it can be seen in Scheme 2, the that we consider to be a reflection of relative diffu-
most interesting five-membered ring is formed with a sion coefficients inside the MOF. The catalytically
significantly lower selectivity using the homogeneous active sites for this reaction are the metal ions acting
copper nitrate than with Cu CAHTUNGTRNEU(GN BTC) . In addition, the as Lewis acids as demonstrated by the poisoning
3 2
reaction mixture is complicated by the presence of effect of bases and by comparison with the activity of
other undesirable by-products. copper nitrate in the homogeneous phase. The pres-
To understand the competitive selectivity of alde- ent protocol has the following advantages: (i) the use
hyde versus ketone acetalization, the reaction was of cheap, easy to handle and commercially available
performed between benzaldehyde and acetophenone catalysts, (ii) mild reaction conditions, (iii) high selec-
using Cu ACHTUNGTRENNUNG( BTC) as heterogeneous catalyst in the tivity and yields and (iv) excellent chemoselectivity.
3 2
presence of methanol. After the required reaction Compared to zeolites and clays, Cu ACHTUNGTRNENUG( BTC) gives
3 2
time, the sample was analyzed by GC and we noticed higher activity for dimethyl acetal formation by meth-
that the ratio of the dimethyl acetals of benzaldehy- anol.
de:acetophenone was 97:3 (Scheme 3). This experi-
ment clearly indicates that the present protocol is
highly selective for the acetalization of aldehydes Experimental Section
General Procedures
All reagents, starting materials and MOFs were obtained
commercially from Aldrich and used without any further pu-
rification unless otherwise noted. Methanol (HPLC grade),
ethanol and 1-propanol used in this work were commercial
samples used as received. The specified water contents of
these alcohols were around 0.02, 4 and 0.2% respectively.
Copper nitrate trihydrate was received from Fluka. Cu3
AHCTUNGTNERN(GU BTC) was characterized by IR, EPR and XRD. The per-
2
centage conversion, purity and relative yields of the final
products were determined using a Hewlett Packard 5890
series II gas chromatograph with FID detector and high
purity helium as carrier gas. The products were identified by
GC-MS using a Hewlett Packard 6890 series spectrometer.
Scheme 2. Reaction of benzaldehyde with glycerol using Cu3
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(BTC) as catalyst in acetonitrile. Reaction conditions: ben-
2
zaldehyde (1 mmol), glycerol (1 mmol), Cu3 ACHTUNGTERNNNU(G BTC) (100 mg)
2
or copper nitrate trihydrate (120 mg), room temperature,
acetonitrile (3 mL), 24 h.
Powder XRD patterns of fresh and reused Cu3
2
ACHTUNGTNERUNNG( BTC) were
recorded in a Philips X’Pert diffractometer using the CuKa
À1
radiation at a scan rate of 0.28 min .
Typical Procedure for Acetalization of Aldehydes
with Methanol
A 50-mL round-bottomed flask was charged with 50 or
1
00 mg of catalyst in 5 mL of methanol and substrate
Scheme 3. Competitive reaction of benzaldehyde and aceto-
(1 mmol). The reaction mixture was stirred for the required
time at room temperature. After the required reaction time,
the reaction mixture was filtered. The mass balances of the
recovered reaction mixture accounted for more than 95% of
the initial substrate as confirmed by GC using nitrobenzene
pheneone with Cu ACHTUNGTRENNUNG( BTC) in the presence of methanol. Re-
3 2
action conditions: benzaldehyde (1 mmol), acetophenone
1 mmol), Cu (BTC) (100 mg), methanol (3 mL), 24 h,
(
ACHTUNGTRENNUNG
3
2
room temperature.
Adv. Synth. Catal. 2010, 352, 3022 – 3030
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3029

Amarajothi Dhakshinamoorthy et al.
FULL PAPERS
as internal standard. The products were analyzed by GC
and characterized by GC-MS. The yields of the product
were determined using nitrobenzene as internal standard
considering the response factors unity. A similar procedure
was followed for the other heterogeneous or homogeneous
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3 2 2
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[9] A. Dhakshinamoorthy, M. Alvaro, H. Garcia, Chem.
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T
U
N
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E
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N
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Eur. J. 2010, 16, 8530.
2
to thermal dehydration at 4008C for 2 h before their use.
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[
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ACHTUNGTNRENUNG( BTC) was tested for the acetaliza-
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tion, the solid catalyst was allowed to settle completely and
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with methanol.
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Project [MACADEMIA (FP7/2007-2012) under grant ac-
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3030
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ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 3022 – 3030