The use of anhydrous CeCl3 as a recyclable and selective catalyst for the acetalization of aldehydes and ketones

Article abstract of DOI:10.1590/S0103-50532010000200026

An efficient, clean, chemoselective and solvent-free method for the synthesis of ketone and aldehyde dimethyl acetals was developed using trimethyl orthoformate and commercially available anhydrous CeCl₃ as a recyclable catalyst. The method is general and affords the protected carbonyl compounds in good yields and under mild conditions, including aryl and alkyl ketones and activated aldehydes. The catalyst could be utilised directly for 3 cycles, without significant loss of activity.

Full text of DOI:10.1590/S0103-50532010000200026

J. Braz. Chem. Soc., Vol. 21, No. 2, 371-374, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
The Use of Anhydrous CeCl3 as a Recyclable and Selective Catalyst for the
Acetalization of Aldehydes and Ketones
Claudio C. Silveira,*,a Samuel R. Mendes,a Francieli I. Ziembowicz,a
Eder J. Lenardãob and Gelson Perinb
aDepartamento de Química, Universidade Federal de Santa Maria,
CP 5001, 97105-970 Santa Maria-RS, Brazil
bInstituto de Química e Geociências, LASOL, Universidade Federal de Pelotas,
CP 354, 96010-900 Pelotas-RS, Brazil
Um método eficiente, limpo, quimiosseletivo e sem a utilização de solventes para a síntese
de dimetil acetais de aldeídos e cetonas foi desenvolvido usando ortoformiato de trimetila e
CeCl3 anidro como catalisador. O método é geral e, sob condições reacionais brandas, fornece
compostos carbonílicos protegidos em bons rendimentos, incluindo aril e alquil cetonas e aldeídos.
O catalisador pode ser reutilizado diretamente, três vezes, sem perda significativa da atividade.
An efficient, clean, chemoselective and solvent-free method for the synthesis of ketone and
aldehyde dimethyl acetals was developed using trimethyl orthoformate and commercially available
anhydrous CeCl3 as a recyclable catalyst. The method is general and affords the protected carbonyl
compounds in good yields and under mild conditions, including aryl and alkyl ketones and activated
aldehydes. The catalyst could be utilised directly for 3 cycles, without significant loss of activity.
Keywords: cerium(III) chloride, acetals, trimethyl orthoformate, aldehydes, ketones
Introduction
have some drawbacks, such as the use of toxic, strong and
corrosive acids, non-recyclable catalysts, volatile organic
solvents (VOCs) and, in some cases, non-commercially
available catalysts. A greener, atom efficient approach to
acetals is the use of trialkyl orthoesters instead of alcohols,
because they provide both alkoxy groups while scavenging
the water produced in the reaction.3,4,9,10,13,14
In view of our interest in the development of new,
cleaner methods for classical reactions22 and new
applications of cerium(III) in organic synthesis,23 we
decide to study the reaction of carbonyl compounds 1
with trimethyl orthoformate to obtain dimethyl acetals 2
(Tables 1 and 2).24
Acetalization of aldehydes and ketones is the most
frequently used strategy for protection of carbonyl
groups against nucleophilic reagents.1 Besides being very
useful derivatives in total synthesis, acetals can be easily
transformed into several utile functional groups.2 Because
of the versatility and usefulness of acetals in organic
synthesis, several methods for the protection3-20 and the
selective, mild deprotection21 of aldehydes and ketones
have been described. The classical procedure for protection
involves the Lewis3-15 or protic acid-catalyzed16-20 reaction
of a carbonyl compound with a large excess of an alcohol
in the presence of a water scavenger.Among the employed
Lewis acids are metal triflates,3-8 lanthanoid chlorides,9,10
Results and Discussion
SnCl4,11 FeCl3,12 LiBF4,13 ZnCl2 and pyridinium ions15
14
while HCl,16 p-TsOH,17 HBF4,18 2,6-pyridinedicarboxylic
acid19 and silica-supported HClO420 have been used as protic
acids. Despite the advocated advantages of several recently
described methods for the acetalization reaction, they
Initially, we chose benzaldehyde 1a (2.0 mmol) and
trimethyl orthoformate (2.2 mmol) as standard starting
materials to establish the best conditions for the reaction
under solvent-free media. We examined the temperature,
25
amount of anhydrous CeCl3 and the reaction time
(Table 1).
*e-mail: silveira@quimica.ufsm.br

372
The Use of Anhydrous CeCl3 as a Recyclable and Selective Catalyst
J. Braz. Chem. Soc.
Table 1. Acetalizationa of benzaldehyde using CeCl3
O
CH3O OCH3
CH(OCH3)3
CeCl3, Ar
H
H
2a
1a
Entry
CeCl3 / (mol%)b
Solvent
Temperature / °C
time / h
Yield / (%)
1
10
10
10
10
5
-
r.t.
0
6
1
83
85
70
22
95
77
87
50
45
75
65
2
-
3
-
-20
-78
0
3
4
-
5
5
-
1
6
1
-
0
6
7
2
-
0
6
8
10
10
10
10
CH3NO2
CH3CN
CH3OH
CH3OH
r.t.
r.t.
r.t.
0
10
24
6
9
10
11
5
aReaction conditions: trimethyl orthoformate (2.2 mmol); benzaldehyde 1a (2.0 mmol) and solvent (2 mL) when mentioned. bAnhydrous cerium (III) chloride.25
It was found that using 10 mol% of dry CeCl3 the
acetal 2a was obtained in 83% yield after stirring at
room temperature for 6 h (Table 1, entry 1). The reaction
time was reduced to 1 h when the mixture was stirred
at 0 °C, affording the same result (Table 1, entry 2). By
stirring at lower temperatures, such as -20 and -78 °C,
the product was obtained only in modest yields (entries
3 and 4). The effect of the amount of the catalyst was
also evaluated. When 5 mol% of CeCl3 was used, 2a was
obtained in excellent yield (95%) after stirring at 0 °C for
1 h (Table 1, entry 5). The use of lower amounts of CeCl3
did not presented satisfactory results (entries 6 and 7). We
also tested the effect of the solvent in the reaction, such
as CH3CN, CH3NO2 and CH3OH (entries 8-11). When
CH3OH (2 mL) was used, 2a was obtained in 75% yield
after stirring for 6 h at room temperature (entry 10) and
in 65% yield after 5 h at 0 °C (entry 11). The lower yields
observed in these cases are probably due to the reduction
of the catalytic activity of CeCl3 in view of a competition
between the heteroatom of the solvent and the carbonyl
group of the aldehyde for the cerium metal centre.3
Since the best conditions were established, the protocol
was extended to other aromatic and aliphatic aldehydes and
ketones (Table 2).
under reflux. Besides, a longer reaction time (8-10 h) was
required to obtain satisfactory yields from ketones. The
chemoselectivity of the reaction was also investigated.
Thus, when an equimolar mixture of benzaldehyde 1a,
cyclohexanone 1h and trimethylorthoformate was subjected
to acetalization reaction in presence of CeCl3, only the acetal
of benzaldehyde 2a was isolated after stirring for 4 h, while
the cyclohexanone was completely recovered, along with a
small amount of 1a. This result shows the high selectivity
of our method. In addition, citral 1g, which is a mixture of
trans- and cis-3,7-dimethylocta-2,6-dienal (Z:E = 40:60),
was selectively converted to the respective dimethyl acetal
in 78% yield after 4 h without any isomerization of the
double bonds (Z:E = 40:60; entry 7). To extend the scope
of CeCl3-catalyzed acetalization of carbonyl compounds
we sought to explore the use of triethyl orthoformate for
the synthesis of diethyl acetals, under the same conditions
employed to methyl acetals. In this way, the reaction was
performed with benzaldehyde and cyclohexanone, and the
corresponding diethyl acetals were obtained in 93 and 86%
isolated yield, respectively.
It was observed that the CeCl3 can be successfully
reused up to 2 times without any treatment, with good
results. Thus, for example, after the completion of the
acetalization of benzaldehyde 1a (in 10.0 mmol scale),
the crude product 2a was simply separated by decantation
from the insoluble catalyst and a small amount of CeCl3
(0.05 mmol; 0.5 mol % each time) was added each time
before repeating the reaction. Under these conditions, 2a
was obtained with similar yield (2 runs, 93 and 94% yield
The dimethyl acetals 2 were obtained in good to
excellent yields under solvent-free conditions after stirring
at 0 °C for 1-4 h in all but three tested examples. In the case
of solid p-chlorobenzaldehyde (entry 4) and the less reactive
ketones acetophenone and heptan-2-one (entries 11 and
12), it was necessary the use of methanol (2 mL) as solvent

Vol. 21, No. 2, 2010
Silveira et al.
373
Table 2. Acetalization of aldehydes and ketones using CeCl3
Conclusions
HC(OMe)3
O
MeO OMe
R'
CeCl3 (5 mol%)
In summary, anhydrous CeCl3 has proved to be an
R
R
R'
Ar, 0 ºC
effective, robust and recyclable catalyst for the acetalization
of aryl and alkyl carbonyl compounds. The method is
simple, clean and general and the catalyst can be reused
directly for 2 times without loss of activity. For almost
all the examples studied, this new, green methodology
eliminates completely the necessity of using organic
solvents in the reaction.
2a-l
1a-l
Entry
1
Substrate 1
Product 2a
time / h
1
Yield/ (%)b
95
CHO
2a
2b
2c
2d
1a
CHO
2
3
4
2
3
90
88
CH3O
1b
Acknowledgments
O
CHO
This project is funded by MCT/CNPq, CAPES and
FAPERGS.
1c
CHO
2.5
95c
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Cl
1d
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3, respectively.

374
The Use of Anhydrous CeCl3 as a Recyclable and Selective Catalyst
J. Braz. Chem. Soc.
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Received: July 3, 2009
Web Release Date: November 26, 2009