Molecular sieves in ionic liquids as an efficient and recyclable medium for the synthesis of imines

Article abstract of DOI:10.1055/s-2004-831328

A great variety of imines were efficiently isolated in high yields from the reaction of aldehydes and amines in ionic liquids. The ionic liquids could be recovered and reused for at least five cycles without loss in the yields being a useful alternative to dichloromethane or diethyl ether, which are the commonly used solvents for this reaction.

Full text of DOI:10.1055/s-2004-831328

LETTER
2135
Molecular Sieves in Ionic Liquids as an Efficient and Recyclable Medium for
the Synthesis of Imines
M
olecular Sieves
a
inIonic Li
r
quids los Kleber Z. Andrade,*a Sayuri Cristina S. Takada,a Luana Magalhães Alves,a Juliana Petrocchi Rodrigues,a
Paulo Anselmo Z. Suarez,*b Rodrigo Fleury Brandão,b Valério Cassiano D. Soaresb
a
Laboratório de Química Metodológica e Orgânica Sintética (LaQMOS), Instituto de Química, Universidade de Brasília, C.P. 4478,
70910-970, Brasília, DF, Brazil
Fax +55(61)2734149; E-mail: ckleber@unb.br
b
Laboratório de Processamento de Recursos Naturais (LAPREN), Instituto de Química, Universidade de Brasília, C.P. 4478, 70910-970,
Brasília, DF, Brazil
Received 6 May 2004
In this work we describe the use of molecular sieves in
Abstract: A great variety of imines were efficiently isolated in high
ionic liquids as an efficient and recyclable system for the
yields from the reaction of aldehydes and amines in ionic liquids.
synthesis of several imines.8 The ionic liquids used were
The ionic liquids could be recovered and reused for at least five cy-
prepared according to known procedures9 and are shown
cles without loss in the yields being a useful alternative to dichlo-
romethane or diethyl ether, which are the commonly used solvents in Figure 1. The choice for these compounds resides on
for this reaction.
the fact that they can be easily obtained and have been
used in a variety of organic reactions with very good
Key words: ionic liquids, imines, green chemistry
results,10 which are summarized in Table 1.
Imines or Schiff bases are important intermediates in or-
ganic synthesis.1 The formation of these compounds from
the reaction of aldehydes and primary amines is usually
carried out in ethereal or chlorinated organic solvents,
which are volatile, flammable and toxic. Thus, the search
for green reaction media to perform organic reactions is a
matter of much concern.2 In this respect, ionic liquids,
specially those obtained from quaternary ammonium
cations and weak coordinating anions, play an important
role.3
Figure 1 Employed ionic liquids
Aliphatic, aromatic and heteroaromatic aldehydes and
amines were investigated. The reactions were run at room
temperature and the crude imines were smoothly obtained
in excellent yields in all cases without the need for purifi-
cation. Slower reaction rates were obtained when
tryptamine was used probably due to its low solubility in
the ionic liquids (Table 1, entries 1, 7 and 8).
Among the known ionic liquids, those derived from di-
alkylimidazolium cations have received special attention
since their chemical and physical properties can be finely
tuned for a range of applications by varying the alkyl
chains or anions.3 Indeed, they are considered as environ-
mentally friendly substitutes for volatile organic solvents,
because of some important characteristics such as: low
vapor pressure, ability to act as catalysts, chemical and
thermal stability, nonflammability, high ionic conductivi-
ty and a wide electrochemical potential window.3 For
these reasons, ionic liquids have found increasing applica-
tions in organic synthesis recently.4
In order to compare the reaction rates in ionic liquids with
conventional solvents, some reactions were carried out in
CH2Cl2 (Table 2). We found out that the use of 4 Å mo-
lecular sieves as water scavenger had little effect in the
yields but lowered the reaction times in [bmim]PF6 as
compared to the reactions run in CH2Cl2 (compare entries
1, 5, 6, 8–10 and 13, Table 2). On the other hand, no effect
of this kind was observed in [bmim]BF4 (entries 4, 12,
Table 2), which might be due to the differences in solubil-
ity of water in these two ionic liquids3d and the formation
of different polarity regions.11
There are some recent reports of imines formation in ionic
liquids in the literature. However, in these studies the im-
ines were formed in situ and subsequently used without
being isolated, for example, in Diels–Alder5 and asym-
metric Mannich-type reactions6 as well as in three-com-
ponent coupling reactions.7 Thus, no systematic study has
been conducted so far towards the synthesis and isolation
of imines in ionic liquids.
The products were easily separated from the ionic liquids
by simple extraction with diethyl ether and were usually
obtained in high purity (>90% by 1H NMR) requiring no
purification for further uses. The remaining system con-
taining the ionic liquid and molecular sieves, was then
dried by heating under vacuum for 30 minutes.12
SYNLETT 2004, No. 12, pp 2135–2138
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0
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Advanced online publication: 01.09.2004
DOI: 10.1055/s-2004-831328; Art ID: S0404ST
© Georg Thieme Verlag Stuttgart · New York

2136
C. K. Z. Andrade et al.
LETTER
Table 1 Experimental Conditions and Results of the Reactions between Aldehydes and Amines in Ionic Liquids13,14
Entry
1
Aldehyde
Amine
Ionic liquid
[bmim]BF4
Time (min)
300
Yield (%)
89
2
[bmim]BF4
30
95
3
4
[bmim]PF6
[bmim]PF6
15
15
98
96
5
6
[bmim]PF6
[bmim]PF6
150
120
93
90
7
8
[bmim]BF4
[bmim]BF4
240
300
90
95
9
10
11
[bmim]BF4
[bmim]PF6
[bmim]PF6
180
180
20
90
94
95
12
13
[bmim]PF6
[bmim]PF6
20
91
88
120
14
15
[bmim]PF6
[bmim]PF6
120
50
85
89
Synlett 2004, No. 12, 2135–2138 © Thieme Stuttgart · New York

LETTER
Molecular Sieves in Ionic Liquids
2137
Table 1 Experimental Conditions and Results of the Reactions between Aldehydes and Amines in Ionic Liquids13,14 (continued)
Entry
16
Aldehyde
Amine
Ionic liquid
[bmim]PF6
Time (min)
15
Yield (%)
95
a Reactions carried out without molecular sieves.
The reaction of benzylamine and piperonal was used to and amines in ionic liquids in the presence of molecular
evaluate the possibility of recycling this system. In this sieves. These reaction media proved to be useful alterna-
sense, after the reaction end the product was extracted tives to organic solvents in this reaction due to the sim-
with Et2O and a new charge of reagents was added. The plicity of the reaction and workup procedures combined
results are shown in Table 3. As depicted in Table 3, it is with the possibility of its easy recovery and reuse.
evident that the system still retains high conversion after
repeating the recycling procedure up to 4 times.
Acknowledgment
It is important to note that no residual ionic liquid in the
The authors thank the Instituto de Química, Universidade de
ether layer or any organic product in the ionic liquids was
Brasília, FINATEC and FUNPE-UnB for financial support, and
FINEP-CT INFRA nº 0970/01. R.F.B., P.A.Z.S. and L.M.A. thank
detected by 1H NMR analysis.
CNPq for research fellowships.
In summary, imines could be efficiently prepared and iso-
lated under mild conditions by the reaction of aldehydes
Table 2 Effect of the Use of Molecular Sieves in the Synthesis of Imines in Different Solvents
Entry
1
Aldehyde
Amine
4 Å MS
Yes
Solvent
Time (min)
15
Yield (%)
98
[bmim]PF6
2
3
4
5
6
No
[bmim]PF6
[bmim]BF4
[bmim]BF4
CH2Cl2
45
15
96
95
93
91
88
Yes
No
10
Yes
Yes
45
[bmim]PF6
120
7
8
9
No
[bmim]PF6
CH2Cl2
330
180
15
91
83
96
Yes
Yes
[bmim]PF6
10
11
12
13
No
[bmim]PF6
[bmim]BF4
[bmim]BF4
CH2Cl2
25
80
80
30
97
89
91
94
Yes
No
Yes
Synlett 2004, No. 12, 2135–2138 © Thieme Stuttgart · New York

2138
C. K. Z. Andrade et al.
LETTER
Table 3 Recovery and Reuse of the Ionic Liquid Phase Containing Molecular Sieves in the Synthesis of Imines
Entry
Cycle
Time (min)
Yield (%)
1
2
3
4
5
1
2
3
4
5
15
15
15
15
15
98
98
96
96
96
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Synlett 2004, No. 12, 2135–2138 © Thieme Stuttgart · New York