1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) an efficient homogeneous catalyst for aldol condensation reactions. Study of the catalyst recovery and reusability using CO2

Article abstract of DOI:10.1016/j.tetlet.2010.11.032

In this work it was shown that TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene), a cheap and commercially available guanidine base, efficiently catalyzes aldol condensation reactions yielding interesting products for pharmacological and fragrance industries. This methodology works under solvent-less conditions and affords with very good conversions the corresponding products. Moreover, a simple and effective separation protocol using the CO₂ fixation was employed. The catalyst could be recovered and re-used for three consecutive runs without significant loss of activity.

Full text of DOI:10.1016/j.tetlet.2010.11.032

Tetrahedron Letters 52 (2011) 385–387
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) an efficient homogeneous catalyst
for aldol condensation reactions. Study of the catalyst recovery
and reusability using CO2
Iuliana Cota a, Francisco Medina a, , Jesús E. Sueiras a, Didier Tichit b
⇑
a Departament d’Enginyeria Química, Universidad Rovira i Virgili, Campus Sescelades, Avda. Paisos Catalans, 26, 43007 Tarragona, Spain
b Institut Charles Gerhardt, UMR 5253 CNRS/ENSCM/UM2/UM1, Montpellier, 8 rue de l’Ecole Normale, 34296 Montpellier Cedex 5, France
a r t i c l e i n f o
a b s t r a c t
Article history:
In this work it was shown that TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene), a cheap and commercially avail-
able guanidine base, efficiently catalyzes aldol condensation reactions yielding interesting products for
pharmacological and fragrance industries. This methodology works under solvent-less conditions and
affords with very good conversions the corresponding products. Moreover, a simple and effective sepa-
ration protocol using the CO2 fixation was employed. The catalyst could be recovered and re-used for
three consecutive runs without significant loss of activity.
Received 31 August 2010
Revised 4 November 2010
Accepted 8 November 2010
Available online 4 December 2010
Keywords:
TBD
Ó 2010 Elsevier Ltd. All rights reserved.
Aldol condensations
Base catalysis
CO2 fixation
1. Introduction
substituted ureas,11 5- and 6-enolexo aldolisation of acyclic ketoal-
dehydes,12 intramolecular aldolization of acyclic ketoaldehydes13
It is widely acknowledged that there is an increasing interest for
more environmental friendly processes in the chemical industry.
The key to the development of environmentally sustainable pro-
cesses is the substitution of old technologies by cleaner catalytic
alternatives. In this way, it is an exciting challenge to find new basic
catalysts able to perform, with high activity and selectivity, conden-
sation reactions for the synthesis of pharmaceutical and fine chem-
icals. Industrially, these reactions are carried out in homogeneous
phase with KOH or NaOH as catalysts.1,2 However, with this kind
of catalysts numerous disadvantages arise: loss of catalyst due to
the separation difficulties at the end of the reaction, corrosion prob-
lems in the equipment used, as well as generation of large amounts
of residual effluents that must be subsequently treated to minimize
their environmental impact. Consequently, new technological solu-
tions have to be developed in order to overcome the referred disad-
vantages and to generate new and more sustainable processes.
On the other hand, TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene) is
a strong bicyclic guanidine base with a pKa = 24.97.3 It has been
shown to promote various reactions4 including the Horner–
Wadsworth–Emmons reactions,5 nitroaldol (Henry) reaction,6
secondary amine alkylation,7 carboxylation of propylene glycol
with CO2,8 Michael reactions,9,10 synthesis of symmetrically N,N0-
etc. In these reactions TBD shows good activity and selectivity,
however, due to its homogeneous character serious disadvantages
in terms of product separation arise.
The objective of this study is to test the catalytic properties of
TBD for aldol condensation reactions between several ketones
and aldehydes to obtain valuable products in fine chemistry. More-
over a simple and efficient separation method of the catalysts,
using the CO2 fixation, is employed. This methodology affords a
clean and easy separation of the catalyst from the reaction media
and can be regarded as an efficient separation method to be
applied in organic chemistry.
2. Results and discussion
TBD is a strong guanidine base widely utilized as an acid scav-
enger and base catalyst.4
In order to determine the catalytic properties of TBD we used
aldol condensation between several aldehydes and ketones as
model reactions, yielding interesting products for the pharmaco-
logical and fragrance industries. The results are summarized in
Table 1.
An important precursor for the synthesis of vitamin A is the
pseudoionone, which is synthesized by condensation reaction
between citral and acetone. Commercial citral is a mixture of
two isomers due to the cis–trans isomerism at the C@C bond close
⇑
Corresponding author. Tel.: +34 944559787; fax: +34 977559621.
E-mail address: francesc.medina@urv.cat (F. Medina).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.11.032

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I. Cota et al. / Tetrahedron Letters 52 (2011) 385–387
Table 1
Condensation reactions catalyzed by TBDa
Entry
1c
Substrate
Ketone
Main products
Time (h)
2
Conversion (%)
99
Selectivityb (%)
O
O
O
O
76
O
O
O
2c
6
99
99
90
78
O
O
O
3d
0.5
H
H
O
O
H
4e
6
97
84
H
O
a
b
c
Reaction conditions: ratio ketone/substrate 4.4; T = 60 °C; TBD = 0.5 g (3.4 mmol).
Selectivity toward the main products.
Reaction carried out in the presence of 9.84 mol % TBD.
Reaction carried out in the presence of 11.34 mol % TBD.
Reaction carried out in the presence of 33.73 mol % TBD, ratio ketone/substrate 4.
d
e
to the aldehyde group.14 The two isomers of citral (entry 1) are
converted into the corresponding pseudoionones in only 2 h with
a conversion of 99% and selectivity of 76% using 9.84 mol % of
TBD. No traces of diacetone alcohol derived from the self-conden-
sation of acetone were found but other secondary products coming
from the self condensation of citral and oligomers derived from cit-
ral are detected in the reaction mixture.
When MEK (methyl ethyl ketone) is used instead of acetone, a
mixture of cis–trans isomers of n-methyl and isomethyl pseudoio-
nones are obtained as reaction products.15 After 6 h of reaction cit-
ral is coupled with MEK (entry 2) with a conversion of 99% and a
selectivity of 90%. The reaction was carried out in the presence of
9.84 mol % of TBD. No b-hydroxyl ketones were detected under
the reaction conditions, however, traces of other condensation
products coming from the self-condensation of the reagents and
oligomers derived from citral were detected.
Figure 1. Consecutive run experiments in benzaldehyde acetone condensation
reaction.
In the condensation reaction of benzaldehyde and acetone in
0.5 h of reaction a conversion of 99% is achieved with a selectivity
of 78% toward benzylidenacetone (entry 3), using 11.34 mol % TBD.
The decrease in selectivity is due to the formation of dibenzylide-
nacetone as the secondary product.
Since in our reaction system water is formed, we considered
applying the CO2 fixation as a separating method for the catalyst.
In a typical experiment, at the end of the reaction CO2 was bubbled
in the reaction mixture. Within a few minutes a white precipitate
was formed, which was easily separated from the reaction mixture
by filtration. The precipitate was heated up to 130 °C under inert
atmosphere to eliminate the CO2. Applying this protocol the cata-
lyst recovery was around 99%. After lowering the temperature to
60 °C a new charge of reagents was introduced and a second run
was performed.
The results obtained for the consecutive run experiments using
the condensation between benzaldehyde and acetone as model
reactions are presented in Figure 1. The catalysts were recycled
for three consecutive runs and in all runs a very good conversion
was obtained.
The condensation reaction between benzaldehyde and n-hepta-
nal leads to the formation of jasminaldehyde, a product widely
used in perfumery. In the synthesis of jasminaldehyde (entry 4)
the use of 33.73 mol % TBD led to a conversion of 97% obtained
in 6 h of reaction, with selectivity around 84%. The undesired prod-
uct comes from the self condensation of n-heptanal to 2-n-pentyl-
2-nonenal, secondary reaction which can be inhibited to some ex-
tent by a slow addition of n-heptanal during the reaction.
The main disadvantage of using TBD as the catalyst, is its solu-
bility in the reaction mixture. In a previous study done by Pereira
et al.16, the fixation of carbon dioxide by guanidines in the pres-
ence of catalytic amounts of water was reported. The authors spec-
ulated that three products could be expected from the reaction of
TBD with CO2: two tautomers presenting carbamic groups and
bicarbonate. The compounds formed from the fixation of CO2 with
TBD can release CO2 by heating up to 135 °C under inert atmo-
sphere and the TBD is recovered.
3. Conclusion
In conclusion, it was found that TBD, a cheap and commercially
available guanidine base, efficiently catalyzes aldol condensation

I. Cota et al. / Tetrahedron Letters 52 (2011) 385–387
387
reactions yielding interesting products for pharmacological and
Acknowledgments
fragrance industries. This methodology works under solvent-less
conditions and affords in very good yields the corresponding prod-
ucts. Moreover, a simple and efficient separation protocol using the
CO2 fixation was employed. The catalyst can be recovered and
re-used for three consecutive runs without significant loss of
activity.
This work was funded by MICINN project CTQ2009-12520-C-
0302. F.M. also acknowledges support form Catalan Government
through the ICREA Academia awards.
References and notes
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The reactions were performed in liquid phase using a 100 ml
batch reactor equipped with a magnetic stirrer and a condenser
system under argon atmosphere in order to avoid contamination
with CO2. To a stirred solution of substrate and ketone (ratio
ketone/substrate = 4.4) the catalyst (TBD) was added and the flask
was maintained at 60 °C using a water bath. Samples were taken
at regular time periods and analyzed by gas chromatography (GC)
using
0.32 mm ꢀ 0.25
a
FID detector and an AG Ultra
2
column (15 m ꢀ
lm). Tetradecane was used as the internal stan-
dard. All the reagents and TBD were purchased from Sigma–Al-
drich and used without further purification. CO2 (P99.995%)
was provided by Carburos Metalicos. In order to separate the cat-
alyst from the reaction media, at the end of the reaction CO2 was
bubbled at atmospheric pressure (ꢁ10 ml minꢂ1) at room temper-
ature under magnetic stirring for 30 min. A white precipitate is
formed which can be easily separated from the reaction media
by filtration. The TBD is recovered by heating the precipitate to
130 °C under argon atmosphere.
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