An efficient green synthesis of xanthenedione derivatives promoted by acidic ionic liquid

Article abstract of DOI:10.1002/hc.20486

Xanthenedione derivatives were prepared through the condensation reaction of aromatic aldehydes with 5,5-dimethyl-1,3-cyclohexanedione promoted by acidic ionic liquid. The reaction time was 20-40 min with the yields between 82.3% and 95.3%. It was shown t

Full text of DOI:10.1002/hc.20486

Heteroatom Chemistry
Volume 19, Number 6, 2008
An Efficient Green Synthesis of Xanthenedione
Derivatives Promoted by Acidic Ionic Liquid
Jing-Jun Ma, Chun Wang, Qiu-Hua Wu, Ran-Xiao Tang,
Hai-Yan Liu, and Qing Li
College of Sciences, Agricultural University of Hebei, Baoding 071001, People’s Republic of China
Received 23 April 2007; revised 10 February 2008, 7 March 2008
of organic cation, inorganic anion, and alkyl chain
ABSTRACT: Xanthenedione derivatives were pre-
attached to the organic cation. These structural vari-
pared through the condensation reaction of aromatic
ations offer flexibility to the chemist to devise the
aldehydes with 5,5-dimethyl-1,3-cyclohexanedione
most idealized solvent and catalyst, catering for the
promoted by acidic ionic liquid. The reaction time
needs of a particular process [2].
was 20–40 min with the yields between 82.3% and
Xanthenedione derivatives have attracted con-
95.3%. It was shown that the proposed method
siderable attention owing to their unique biological
was fast, high efficient, and environmentally be-
activity, and they were valuable intermediates be-
ꢀ
C
nign.
2008 Wiley Periodicals, Inc. Heteroatom Chem
cause of the inherent activity of the inbuilt pyran
ring [3]. The conventional synthetic methods of xan-
thenedione derivatives were carried out in organic
solvent [4]. As an improvement, the condensation re-
action of aromatic aldehydes with 5,5-dimethyl-1,3-
cyclohexanedione was proceeded in water for 6 h,
using NH2SO3H and SDS as catalyst [5]. Microwave
irradiation has also been used to promote the con-
densation reaction [6]. Very recently, Fan et al. re-
ported that the synthesis of xanthenedione deriva-
tives could be proceeded in ionic liquid [bmim]BF4
catalyzed by Lewis acid InCl3 [7] and FeCl3·6H2O
[8], respectively, the reaction time was between 4
and 10 h. However, some of these methods have not
been entirely satisfactory, associating with disadvan-
tages such as longer reaction time, using volatile and
toxic organic solvent, using catalyst that cannot be
recycled, and so on.
19:609–611, 2008; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20486
INTRODUCTION
Room temperature ionic liquids (RTILs) have re-
ceived increasingly attention as potential “greener”
alternatives to volatile organic solvent, and they have
been investigated extensively as a solvent or cata-
lyst for many important organic reactions because
of their special properties such as their negligible
vapor pressure, tunable polarity, high thermal sta-
bility, good solvating ability, ease of recyclability,
and their potential to enhance reaction rates and
selectivity [1]. They have also been referred as “de-
signer solvents,” as their properties can be altered
by the fine-tuning of parameters such as the choice
In continuing our endeavor in green synthesis
and using ionic liquids as a recyclable, eco-friendly
reaction medium to enhance rates and selectivity
[9], herein, we report a condensation reaction of
cyclohexanedione derivatives with aromatic aldehy-
des (Scheme 1), which could efficiently proceed in
task-specific acidic ionic liquid without any other
Correspondence to: Chun Wang; e-mail: wangc69@yahoo.com.
cn.
Contract grant sponsor: Natural Science Foundation of Agri-
cultural University of Hebei.
Contract grant numbers: 2004-20 and 2005-18.
2008 Wiley Periodicals, Inc.
c
ꢀ
609

610 Ma et al.
drogen sulfate counteranion. According to the lit-
O
Ar
O
O
O
erature, the Hammett function (H ) of [bmim]HSO4
0
[bmim] HSO4
H3C
H3C
CH3
CH3
and [bmim]H2PO4 was 0.73 and 2.55, respectively
[10]. The catalytic performances of [emim]HSO4,
[bmim]HSO4, and [hmim]HSO4 were similar, indi-
cating the low impact of the cation of the ionic liq-
uids on the catalytic activity. [bmim]HSO4 was cho-
sen for the further study in this work.
2
ArCHO +
O
CH3
CH3
2
3
1
SCHEME 1
Effects of reaction temperature on the yields of
the products were studied by performing the con-
densation reaction at room temperature, 80◦C, and
100◦C, respectively (entries 3, 8, 9). The results show
that the higher reaction temperature, the more effi-
ciently the reaction could proceed.
catalyst. The reaction time in this method was con-
siderably reduced compared with those in the docu-
mented methods [5,7,8].
A variety of substituted aromatic aldehydes were
subjected to the condensation reaction to study the
substituted effects on their reactivity. The results are
summarized in Table 2. For most of the substrates,
the reaction could be completed in 20–40 min
with high yields, with the substrates having either
electron-donating groups or electron-withdrawing
groups. However, when the aromatic aldehydes
had a bigger ortho-position substituent, such as
2-nitrobenzaldehyde and 2,4-dinitrobenzaldehyde,
the reaction could not take place owing to the stere-
oeffect. 9-Anthraldehyde and acetophenone either
could not react with 2 under the above conditions.
The reusability and recycling of [bmim]HSO4
was also investigated. For the condensation reaction
of 4-chlorobenzaldehyde and 5,5-dimethylcyclo-
hexanedione, the product was separated by directly
filtering from the reaction mixture. The extract was
dried under vacuum at 90◦C for 2 h to eliminate
any water. The recycled [bmim]HSO4 was reused
for subsequent reactions. The catalytic activity of
[bmim]HSO4 did not show any significant decrease
even after five runs.
RESULTS AND DISCUSSION
In our initial research, 4-chlorobenzaldehyde was
selected as a representative reactant to optimize
the reaction conditions. As shown in Table 1,
the reaction could proceed efficiently in acidic
ionic liquids [hmim]HSO4, [emim]HSO4, and
[bmim]HSO4 (entries 1–3). However, only moderate
yield of 3b (3,3,6,6-tetramethyl-9-(4-chlorobenzyl)-
1,8-dioxo-1,2,3,4,5,6,7,8-octahydro-xanthene) could
be obtained when [bmim]H2PO4 was employed
(entry 4). Attempts to perform the reaction in
[bmim]Br, [bmim]BF4, and [bmim]PF6 (entries 5–7)
were failed, even at prolonged reaction time. These
results suggested that the used ionic liquids play the
dual role of acidic catalyst and solvent. Moreover,
the catalytic activity of the ionic liquids was depen-
dent heavily upon the Bro¨nsted acidity of the coun-
teranion. The catalytic performance of the ionic liq-
uids with hydrogen sulfate counteranion was much
better than that of the other employed ionic liq-
uids under the same reaction conditions. Probably,
this was due to the high Bro¨nsted acidity of hy-
TABLE 2 Synthesis of Xanthenedione Derivatives in Acidic
Ionic Liquid [bmim]HSO4
TABLE 1 Condensation Reactions of 4-Cholorobenzenalde-
hyde and 5,5-Dimethyl-1,3-cyclo-hexane Dione in Different
Ionic Liquidsa
Entry
Ar
Time (min)
Yield (%)
3a
3b
3c
3d
3e
3f
3g
3h
3i
4-(CH3)2NC6H4
4-ClC6H4
2-ClC6H4
35
20
20
25
20
30
25
25
20
40
30
25
88
95
94
94
95
93
93
90
89
83
90
92
Entry
RTILs
T (◦C)
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
9
[Hmim]HSO4
[Emim]HSO4
[Bmim]HSO4
[Bmim]H2PO4
[Bmim]Br
[Bmim]BF4
[Bmim]PF6
80
80
80
80
80
80
80
r.t.
100
30
30
30
30
60
60
60
30
30
85
83
86
4-HOC6H4
4-CH3OC6H4
3,4-(OCH2O)C6H3
C6H5
46
Trace
Trace
Trace
27
4-BrC6H4
4-CH3C6H4-
3-NO2C6H4
C6H5CH=CH
4-HO-3-CH3OC6H3
3j
3k
3l
[Bmim]HSO4
[Bmim]HSO4
95
aReaction conditions: 1 mmol 4-chlorobenzaldehyde, 2 mmol 5,5-
dimethyl-1,3-cyclo-hexanedione, 1 mL ionic liquid.
bIsolated yields.
N
H
3m
30
82
Heteroatom Chemistry DOI 10.1002/hc

An Efficient Green Synthesis of Xanthenedione Derivatives Promoted by Acidic Ionic Liquid 611
EXPERIMENTAL
greenness of procedure, and can avoid the use of
the hazardous organic solvents and toxic catalysts.
It provides a practical alternative to the existing pro-
cedures. The application studies of the task-specific
ionic liquids for other reactions are in progress.
Melting points were recorded on an electrothermal
apparatus and are uncorrected. 1H NMR (400 MHz)
and 13C NMR (100 MHz) spectra were determined
with a Brucker AVANCE 400 spectrometer (CDCl3),
using TMS as an internal standard. IR spectra (cm−1)
were measured with a BIO-RAD FTS3000 spectrom-
eter. RTILs employed in the work were prepared ac-
cording to the literature [11].
SUPPLEMENTARY INFORMATION
Analytical data of different compounds are available
as supplementary material from the author on re-
quest (wangc69@yahoo.com.cn).
General Procedure
In
1
a
typical procedure, aromatic aldehydes
REFERENCES
(1 mmol), 5,5-dimethyl-1,3-cyclohexanedione
(2 mmol) and [bmim]HSO4 (1 mL) were
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2
stirred at 100◦C for a certain period of time
to complete the reaction (monitored by TLC).
The products were separated by filtering and
washed with water. The obtained solid was re-
crystallized from 80% ethanol. Then, the de-
sired products 3,3,6,6-tetramethyl-9-aryl-1,8-dioxo-
1,2,3,4,5,6,7,8-octahydroxanthene 3a–m were ob-
tained. All the products were fully characterized by
IR, 1H NMR, and elemental analysis.
Spectral Data for Compound 3m: mp 256–257◦C.
1H NMR (CDCl3) δ: 0.92 (s, 6H), 1.11 (s, 6H),
2.13–2.26 (m, 4H), 2.47–2.57 (m, 4H), 5.12 (s, 1H),
7.03–7.41 (m, 5H), 8.16 (s, 1H); 13C NMR (CDCl3)
δ: 24.07, 27.94, 29.50, 32.49, 41.20, 51.24, 111.79,
115.03, 117.83, 118.97, 119.45, 121.48, 124.42,
126.15, 136.87, 162.37; IR (KBr): 3357.5, 3058.6,
2956.3, 2869.6, 1668.1, 1660.4, 1614.1, 1454.1,
1359.6, 1195.7, 1164.8, 1135.9, 734.8; Anal. Calcd.
for C25H27O3 N: C, 77.09; H, 6.99; N, 3.60. Found: C,
77.11; H, 6.95; N, 3.67.
CONCLUSIONS
The present synthetic method is a simple and effi-
cient green synthesis of 3,3,6,6-tetramethyl-9-aryl-
1,8-dioxo-1,2,3,4,5,6,7,8-octahydroxanthene deriva-
tives. The method offers marked improvements
with regard to operational simplicity, reaction time,
general applicability, high yields of products, and
Heteroatom Chemistry DOI 10.1002/hc