Solvent-free catalytic preparation of 2,6-dibenzylidenecycloalkanones using 2-hydroxyethylammonium acetate ionic liquid as catalyst

Article abstract of DOI:10.1007/s00706-013-1082-8

Various 2,6-dibenzylidenecycloalkanones were readily prepared in a condensation reaction catalyzed by 2-hydroxyethylammonium acetate ionic liquid under solvent-free conditions in excellent yields. The major advantages of the present method are high yields, short reaction times, lack of solvent, simplicity of performance, and low cost. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-013-1082-8

Monatsh Chem (2014) 145:337–340
DOI 10.1007/s00706-013-1082-8
ORIGINAL PAPER
Solvent-free catalytic preparation of 2,6-dibenzylidenecyclo-
alkanones using 2-hydroxyethylammonium acetate ionic liquid
as catalyst
•
•
•
Li Q. Kang Yue Q. Cai Hao Wang
Li H. Li
Received: 24 July 2013 / Accepted: 28 August 2013 / Published online: 16 October 2013
Ó Springer-Verlag Wien 2013
Abstract Various 2,6-dibenzylidenecycloalkanones were
readily prepared in a condensation reaction catalyzed by
2-hydroxyethylammonium acetate ionic liquid under sol-
vent-free conditions in excellent yields. The major
advantages of the present method are high yields, short
reaction times, lack of solvent, simplicity of performance,
and low cost.
However, many reactions suffer from longer reaction times
and tedious purification procedures. Thus, there is a need
for the development of an alternative route for the pro-
duction of 2,6-dibenzylidenecycloalkanone derivatives.
Microwave-assisted synthesis [7], heterogeneous catalysis
[8, 9], and metal salt catalysis [10] have been reported; and
processes using ionic liquids as a reaction medium have
attracted a great deal of attention probably owing to their
unique characteristics [11–15].
Keywords Solvent-free Á Ionic liquid Á
Condensation reaction Á Green chemistry
Recently, we demonstrated the synthesis of 2,6-dibenzy-
lidenecycloalkanones catalyzed by amino-functionalized
ionic liquid [16]. Despite these considerable advances,
notable limitations remain for which improved methods will
have an immediate impact in the chemistry community. In
continued efforts to explore the applications of ionic liquids
as catalysts, we prepared 2-hydroxyethylammonium acetate
(2-HEAA) and found it to be effective in the condensation
reaction between various aromatic aldehydes and cyclo-
alkanones. To the best of our knowledge, there was no report
of the synthesis of 2,6-dibenzylidenecycloalkanones cata-
lyzed by2-HEAA under solvent-free conditions (Scheme 1).
Introduction
2,6-Dibenzylidenecycloalkanone derivatives are interme-
diates of various pharmaceuticals, agrochemicals, and
perfumes [1]. The typical methods for the preparation of
2,6-dibenzylidenecycloalkanones generally involve the
cross-aldol condensation of cycloalkanone with aldehydes
in the presence of strong acids or bases [2], which often
induce side reactions and lead to the corresponding pro-
ducts in low yields. In recent years many catalysts have
been applied to this kind of condensation, such as KF-
Al2O3 [3], FeCl3 [4], Yb(OTf)3 [5], and Cu(OTf)2 [6].
Results and discussion
Firstly, to investigate the optimized conditions, the reaction
of benzaldehyde and cyclohexanone was chosen as the
model reaction. The best result was achieved by carrying
out the reaction in the presence of 10 mol% of 2-HEAA
with 2:1 mol ratios of benzaldehyde and cyclohexanone at
80 °C for 1 h under solvent-free conditions (Table 1, entry
1). The product was obtained by simple recrystallization
from ethanol.
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-013-1082-8) contains supplementary
material, which is available to authorized users.
L. Q. Kang (&) Á H. Wang Á L. H. Li
School of Chemical and Environmental Engineering,
Shanghai Institute of Technology, Shanghai 200235, China
e-mail: klq@sit.edu.cn
Y. Q. Cai
School of Chemistry and Molecular Engineering, East China
University of Science and Technology, Shanghai 200237, China
Secondly, to establish the generality and scope of
2-HEAA as a catalyst for this synthesis, various aldehydes
123

338
L. Q. Kang et al.
Scheme 1
Ar CHO
1
O
O
2-HEAA
n=0, 1
Ar
Ar
+
( )
( )
n
n
2
3
O
H3N
2-HEAA
OH
O
Table 1 Preparation of 2,6-dibenzylidenecycloalkanones catalyzed by
2-HEAA (Scheme 1)
Table 2 Comparison of results using 2-HEAA with other catalysts
for synthesis of 2,6-dibenzylidenecycloalkanones
Entry Ar
n
t/h Producta Yieldb/ m.p. (lit. m.p.)/°C
Entry
Catalyst
t/h
Isolated yield/%
%
1
2
3
4
5
6
7
2-HEAA
1
4
93
92
78
76
76
–
1
C6H5
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
2
1
1
1
1
1
1
2
1
1
1
1
1
2
3a
3b
3c
3d
3e
3f
93
90
85
86
91
93
91
88
90
82
82
89
89
85
85
88
82
117.1–117.3 (117–118)
[5]
[aemim][BF4]
[bmim][OH]
[bmim][HSO4]
[bsmim][CF3SO3]
Ethanolamine
Acetic acid
2
p-CH3C6H4
p-CH3OC6H4
p-(CH3)2NC6H4
p-ClC6H4
164.3–164.5 (164–165)
[5]
10
5
3
161.5–163.8 (161–163)
[5]
5
4
250.8–251.7 (250–252)
[5]
10
10
–
5
146.7–147.9 (148–149)
[5]
Reaction conditions: benzaldehyde (4.0 mmol), cyclohexanone
(2.0 mmol), catalyst (0.2 mmol), 80 °C, solvent-free conditions,
monitored by TLC
6
p-FC6H4
152.7–152.9 (156–158)
[17]
7
m-NO2C6H4
o-ClC6H4
3g
3h
3i
185.6–185.9 (188–189)
[5]
8
102.5–102.7 (102–104)
[18]
para position of benzaldehyde underwent the conversion
smoothly and gave the products in good to excellent yields
(Table 1, entries 5, 6). An electron-withdrawing nitro
substituent at the meta position of benzaldehyde also gave
good product yield (Table 1, entry 7). However, the pre-
sence of a chlorine group in the ortho and para position of
benzaldehyde did not significantly improve the yield of the
product probably owing to steric effects (Table 1, entry 9).
Electron-rich groups such as para-methoxy decrease the
product yield (Table 1, entry 5). It is noteworthy that self-
condensations of cycloalkanones and aldehydes as side reac-
tions were not observed. 2,6-Dibenzylidenecycloalkanones
were generated, without formation of 2-benzylidenecycloal-
kanones,regardlessofthemoleratioofaldehydeandketonein
the reaction being 1:1 or 2:1.
9
2,4-Cl2C6H3
3,4-OCH2OC6H3
161.3–162.2 (163–164)
[5]
10
11
12
13
14
15
16
17
a
3j
182.5–182.8 (182–183)
[9]
3-CH3O-4-
HOC6H3
3k
3l
171.8–172.2 (172–174)
[5]
C6H5
187.5–187.9 (188–189)
[5]
p-ClC6H4
p-HOC6H4
p-CH3OC6H4
m-BrC6H4
3m
3n
3o
3p
3q
224.4–255.2 (224–225)
[5]
288.5–288.8 (288–290)
[19]
212.7–213.3 (211–212)
[5]
212.8–213.4 (210–212)
[20]
3-CH3O-4-
HOC6H3
172.1–172.4 (172–174)
[1]
Lastly, for comparison, ionic liquids including [aemim]
[BF4], [bmim][OH], [bmim][HSO4], and [bsmim][CF3SO3]
were examined under the same catalytic conditions for the
synthesis of 2,6-dibenzylidenecycloalkanones (Table 2,
entries 1–5). From Table 2 it can be seen that 2-HEAA
appears to promote the reaction more effectively than a
number of other ionic liquids, particularly in terms of the
time and yields required to complete the reaction and
operation. On the other hand, ethanolamine or acetic acid
corresponded to worse activities in the reaction of
Products were characterized by 1H NMR, IR, and by comparison of their
physical properties with those reported in the literature
b
Yield of isolated product
1 and cycloalkanones 2 were reacted following the
optimized method to prepare a series of 2,6-dibenzylide-
necycloalkanones. In this work, 2-HEAA was used
successfully as a new and suitable catalyst. Aromatic
aldehydes containing electron-withdrawing groups at the
123

Solvent-free catalytic preparation
339
Scheme 2
[H3NCH2CH2OH][CH3COO]
O
O
H
H
R
H
(
)
n
O
H2O
R
R
(
)
n
[HOCH2CH2NH3][CH3COO]
O
H
R
H
H
O
(
)
n
H2O
R
benzaldehyde and cyclohexanone compared with 2-HEAA,
suggesting the advantageous role of the ionic liquid
2-HEAA as the catalyst over other organic molecules
(Table 2, entries 1, 6, and 7).
liquids, 2-HEAA has the advantages such as low cost,
simplicity of synthesis, and negligible toxicity [23], and it
is consistent with the principles of green chemistry.
Our hypothesis for the high conversion with excellent
yields of 2,6-dibenzylidenecycloalkanones when the ionic
catalyst 2-HEAA is applied is based on the effect of its
special structure, containing the functional group –N?H3
and –OH. The –N?H3 group makes the ionic liquid
capable of bonding with the carbonyl oxygen of alde-
hydes, thereby increasing the reactivity of the parent
carbonyl compounds. The group –OH prompts the
cyclohexanone a-H to leave. Many current studies have
established that hydrogen bonding can occur between the
reactant and the cationic or anionic components of ionic
liquids [21, 22]. Based on this, the following mechanism
for the condensation reaction catalyzed by ionic liquid
2-HEAA was postulated (Scheme 2). From this mecha-
nism, a general influence of electron-withdrawing and
electron-donating groups on the feasibility of the reaction
is supposed. Electron-withdrawing groups such as halo
substituents at the para position of the aromatic aldehydes
increase the electrophilic strength of the carbonyl group
and subsequently increase the yield of the reaction. On the
other hand, electron-rich groups such as para-methoxy
decrease the product yield.
Experimental
Melting points were measured on a WRS-IB digital melting
point instrument. IR spectra were measured on an AVA-
TAR 360 FT-IR spectrophotometer in KBr pellets. 1H NMR
were recorded on AVANCE 500 MHz or Bruker AM-400
spectrometer with TMS as an internal standard. Ethanol-
amine was obtained from Aldrich at 0.99 purity by mass,
whereas acetic acid was at 0.996 purity by mass. The ionic
liquid 2-HEAA was synthesized and purified according to
Ref. [24]. Ionic liquids 1-aminoethyl-3-methylimidazolium
fluoroborate ([aemim][BF4]) [25], 1-butyl-3-methylimida-
zolium hydroxide ([bmim][OH]) [26], 1-butyl-3-
methylimidazolium hydrogen sulfate ([bmim][HSO4]) [27],
and 1-sulfobutyl-3-methylimidazolium trifluoromethane-
sulfonate ([bsmim][CF3SO3]) [28] were synthesized and
purified according to the cited procedures.
General procedure for the preparation
of 2,6-dibenzylidenecycloalkanones
In conclusion, we have developed an efficient and clean
approach to the synthesis of 2,6-dibenzylidenecycloalk-
anones by using 2-HEAA ionic liquid as catalyst. This
method offers some advantages in terms of low reaction
times, high yields, solvent-free conditions, and simplicity
of performance. Moreover, compared with other ionic
Cycloalkanone (2 mmol), aromatic aldehyde (4 mmol),
and 2-HEAA ionic liquid (0.2 mmol) were added in a
Pyrex beaker (50 cm3). The mixture was stirred at 80 °C
for a certain period of time to complete the reaction
(monitored by TLC). After cooling, the product was re-
crystallized with ethanol and afforded the crystalline
123

340
L. Q. Kang et al.
1
products 3a–3q. All compounds were characterized by H
NMR, IR, and physical data.
12. Zhang XY, Fan XS, Wang JJ (2004) J Chin Chem Soc 51:1339
13. Zhao G, Jiang T, Gao H, Han B, Huang J, Sun D (2004) Green
Chem 6:75
14. Hou RS, Wang HM, Chang YW (2006) J Chin Chem Soc 53:431
15. Wan Y, Chen XM, Pang LL, Ma R, Yue CH, Yuan R, Lin W, Yin
W, Bo RC, Wu H (2010) Synth Commun 40:2320
16. Kang LQ, Song GH, Wang JY, Wei BG (2008) J Chin Chem Soc
55:1125
Acknowledgments We are grateful to the Science and Technology
Foundation of Shanghai Institute of Technology (No. KJ 2010-08) for
financial support.
17. Sabitha G, Reddy GS, Kiran K, Reddy KB, Yadav JS (2004)
Synthesis 45:263
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