[HSO4] catalyzed efficient and green synthesis of 1,8-dioxo-octahydroxanthenes

Article abstract of DOI:10.1016/j.molcata.2012.11.002

A simple and efficient procedure for synthesis of 1,8-dioxo- octahydroxanthenes by one-pot condensation of aromatic aldehydes with 5,5-dimethyl-1,3-cyclohexanedione under solvent-free conditions using ionic liquid [Et₃NH][HSO₄] as catalyst is described. The procedure offers several advantages including cleaner reaction profiles, use of easily available, cheap, recyclable and environmentally benign nature of catalyst, high yields, and simple experimental and work-up procedures.

Full text of DOI:10.1016/j.molcata.2012.11.002

Journal of Molecular Catalysis A: Chemical 367 (2013) 99–102
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
[Et3NH][HSO4] catalyzed efficient and green synthesis of
1,8-dioxo-octahydroxanthenes
Zhongqiang Zhou∗, Xiaocui Deng
Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, Hubei Province, College of Chemistry and Materials Science,
South-Central University for Nationalities, Wuhan 430074, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 May 2012
Received in revised form 28 October 2012
Accepted 1 November 2012
Available online 9 November 2012
A simple and efficient procedure for synthesis of 1,8-dioxo-octahydroxanthenes by one-pot condensation
of aromatic aldehydes with 5,5-dimethyl-1,3-cyclohexanedione under solvent-free conditions using ionic
liquid [Et3NH][HSO4] as catalyst is described. The procedure offers several advantages including cleaner
reaction profiles, use of easily available, cheap, recyclable and environmentally benign nature of catalyst,
high yields, and simple experimental and work-up procedures.
© 2012 Elsevier B.V. All rights reserved.
Keywords:
1,8-Dioxo-octahydroxanthenes
[Et3NH][HSO4]
Solvent-free
Aromatic aldehydes
5,5-Dimethyl-1,3-cyclohexanedione
1. Introduction
[Hbim]BF4 [29] as catalysts. Rahmati reported that the synthesis
of xanthenedione derivatives could be proceeded in ionic liquid
Xanthenes are an important family of organic compounds
because they have wide range of biological and pharmaceutical
properties such as anti-inflammatory [1], anti-depressants and
antimalarial agents [2]. Furthermore, these compounds have been
used as dyes [3], and pH-sensitive fluorescent materials for the
visualization of biomolecular assemblies [4].
Many synthetic methods for preparing xanthenediones have
been reported by the condensation of aromatic aldehydes
and 5,5-dimethyl-1,3-cyclohexanedione in the presence of
[1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane
bis(tetrafluoroborate) [5], montmorillonite K10 [6], p-
dodecylbenzenesulphonic acid [7], alumina-sulfuric acid [8],
trimethylsilyl chloride [9], NaHSO4–SiO2 [10], ZnO–acetyl chloride
[11], PMA–SiO2 [12], NBS [13], Amberlyst-15 [14], Dowex-50W
[15], PPA–SiO2 [16], ZrOCl2·8H2O [17], trichloroisocyanuric acid
[18], silica sulfuric acid [19], heteropolyacid supported MCM-
41 [20], silica bonded N-propyl sulfamic acid [21], nanosized
MCM-41-SO3H [22], [Bmim][HSO4] [23,24], [Hmim]TFA [25],
[TMPSA]HSO4 [26], [DDPA][HSO4] [27], [Et3N-SO3H]Cl [28] and
tetramethylguanidinium trifluoroacetate catalyzed by trifluoroac-
etate acid [30]. Fan et al. and Ma et al. reported that the synthesis
of xanthenedione derivatives could be proceeded in ionic liquid
[bmim]BF4 catalyzed by FeCl3·6H2O [31], InCl3·4H2O [32], and
NaHSO4 [33], respectively. Each of these methods have their own
advantages but also suffer from one or more disadvantages such as
prolonged reaction time, low yields, use of hazardous or expensive
catalysts, use of organic solvents, tedious work-up processes, the
requirement of special apparatus, and difficulty in recovery and
reusability of the catalysts. Thus, the search for the new readily
available and green catalysts is still being actively pursued.
Ionic liquids have been turned to be a kind of promising alter-
native medium/catalysts for various chemical processes. Protic
ionic liquids are easily produced through the combination of a
Brønsted acid and Brønsted base [34]. Li reported that protic ionic
liquid [Et3NH][HSO4] has been used as catalyst and environmen-
tally benign solvent for the cracking reactions of dialkoxypropanes
[35]. Recently, [Et3NH][HSO4] catalyzed electrophilic substitution
reactions of indoles with various carbonyl compounds for the
one pot efficient synthesis of bis(indolyl)methanes has also been
reported [36]. Herein, we report a facile method for the synthesis
of 1,8-dioxo-octahydroxanthenes by the condensation of aromatic
aldehydes with 5,5-dimethyl-1,3-cyclohexanedione using easily
∗
Corresponding author. Tel.: +86 27 67842752; fax: +86 27 67842752.
E-mail address: zhou-zq@hotmail.com (Z. Zhou).
1381-1169/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2012.11.002

100
Z. Zhou, X. Deng / Journal of Molecular Catalysis A: Chemical 367 (2013) 99–102
O
R
O
the next run. All the products are known compounds and were char-
acterized by spectral data and comparison of their physical data
with literature data.
O
O
[Et3NH][HSO4]
+
2
100 ºC, solvent-free
R
H
O
3
O
1
2
2.4. General procedure for the synthesis of
1,8-dioxo-octahydroxanthenes under solvent conditions
Scheme 1. [Et3NH][HSO4] catalyzed synthesis of 1,8-dioxo-octahydroxanthenes.
A
mixture of aldehyde (1, 5 mmol), 5,5-dimethyl-1,3-
available, cheap, and reusable protic ionic liquid [Et3NH][HSO4] as
catalyst under solvent-free conditions (Scheme 1).
cyclohexanedione (2, 10 mmol) and [Et3NH][HSO4] (1 mmol)
in 5 mL of solvent was heated under reflux conditions for the
specified time given in Table 1. After completion of the reaction,
the organic solvent was evaporated, and the crude products were
purified by crystallization from 95% ethanol.
2. Experimental
2.1. Material and instruments
3. Results and discussion
FT-IR spectra were obtained on a Nexus 470 spectrophotometer.
1H NMR spectra were recorded on a Bruker Avance III 400 with TMS
as internal standard. Melting points were determined on a melting
point apparatus and are uncorrected.
In order to optimize the reaction conditions, firstly, we inves-
tigated the effect of different solvents on the reaction rate and
as well as yields of the products (Table 1). As a model reaction,
the reaction of benzaldehyde (5 mmol) with 5,5-dimethyl-1,3-
cyclohexanedione (10 mmol) catalyzed by [Et3NH][HSO4] (1 mmol,
20 mol% relative to reactants) in various solvents including ethanol,
benzene, chloroform, tetrahydrofurane, acetonitrile and water was
investigated under reflux condition. The results were summarized
in Table 1. In protic solvents such as ethanol, the reaction was very
slow and resulted in lower product yield. Conducting the reactions
in aprotic solvents such as benzene, chloroform, tetrahydrofurane
and acetonitrile improved both the reaction rates as well as prod-
uct yields. Water has been identified as an ideal solvent because
it is inexpensive, non-flammable, abundant and environmentally
benign. However, when the same reaction was carried out in water,
the expected product was obtained only in trace amount after 2 h.
Solvent-free conditions make procedures simpler, save energy,
and prevent solvent wastes, hazards, and toxicity. Furthermore,
we conducted the condensation of benzaldehyde (5 mmol) and
5,5-dimethyl-1,3-cyclohexanedione (10 mmol) with stirring under
solvent-free conditions. As shown in Table 1, the yields of the reac-
tion under solvent-free conditions were higher and the reaction
times were shorter than under solvent conditions.
2.2. Preparation of [Et3NH][HSO4]
Sulfuric acid (19.6 g, 0.2 mol) 98% solution in water was dropped
into the triethylamine (20.2 g, 0.2 mol) under stirring at 60 ◦C in 1 h
[35]. After the addition, the reaction mixture was stirred for an addi-
tional period of 1 h at 70 ◦C to ensure the reaction had proceeded
to completion. Then the trace of water was removed by heating
the residue at 80 ◦C in high vacuum until the weight of the residue
remained constant.
2.3. General procedure for the synthesis of
1,8-dioxo-octahydroxanthenes under solvent-free conditions
To a mixture of aldehyde (1, 5 mmol) and 5,5-dimethyl-
1,3-cyclohexanedione (2, 10 mmol), [Et3NH][HSO4] (1 mmol) was
added and the mixture was heated on an oil bath at 100 ◦C with good
stirring. During the reaction process, the mixture spontaneously
solidified up. The progress of the reaction was monitored by thin
layer chromatography (ethyl acetate/hexane = 1/3). After comple-
tion of the reaction, the obtained solid was recrystallized from 95%
ethanol to afford the desired compound in pure form. The mother
liquor (consisting of 95% ethanol, ionic liquid [Et3NH][HSO4], and
some other residual reactants or byproducts) was further vacu-
umed to dryness and the resulting catalyst was reused directly for
To optimize the reaction temperature, the mixture was heated at
different temperatures ranging from 20 to 110 ◦C. The yield of prod-
uct 3 was increased when the reaction was raised from 20 to100 ◦C.
However, no increase in the yield of product 3 was observed
when the reaction temperature was raised from 100 to 110 ◦C.
Table 1
Effect of different reaction conditions on [Et3NH][HSO4] catalyzed synthesis of 1,8-dioxo-octahydroxanthenes.a
Entry
Solvent
Temperature ( ◦C)
Catalyst (mol%)
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
THF
CH3CN
CHCl3
C6H6
Ethanol
Ethanol
H2O
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
20
40
60
80
80
90
100
110
100
100
100
20
20
20
20
20
–
20
20
20
20
20
–
20
20
20
5
10
30
120
120
120
120
120
20 h
120
120
120
120
30
15 h
20
20
20
20
70
88
88
86
54
0 [13]
Trace
45
48
77
84
41 [24]
91
94
94
90
91
93
20
20
a
Reaction condition: benzaldehyde (5 mmol), 5,5-dimethyl-1,3-cyclohexanedione (10 mmol).
Isolated yield.
b

Z. Zhou, X. Deng / Journal of Molecular Catalysis A: Chemical 367 (2013) 99–102
101
Table 2
[Et3NH][HSO4] catalyzed synthesis of 1,8-dioxo-octahydroxanthenes.a
Entry
Aldehyde
Time (min)
Yieldb (%)
Melting point ( ◦C)
Found
Reported
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Benzaldehyde
4-Tolualdehyde
20
25
25
20
20
40
45
30
30
30
40
30
20
20
70
94
96
94
90
97
94
87
86
87
77
82
92
83
84
83
205–206
207–208
248–250
225–226
225–227
183–184
240–241
170–171
224–227
237–238
247–248
226–228
203–205
250–251
178–180
203–204 [24]
208–209 [33]
242–244 [24]
225–227 [24]
226–227 [17]
177–180 [18]
240–241 [24]
170–172 [24]
226–228 [33]
230–232 [24]
248–251 [17]
225–227 [18]
202–205 [18]
248–250 [33]
177–178 [13]
4-Methoxybenzaldehyde
2-Chlorobenzaldehyde
4-Fluorobenzaldehyde
3-Methoxybenzaldehyde
4-Bromobenzaldehyde
3-Nitrobenzaldehyde
4-Hydroxy-3-methoxybenzaldehyde
4-Chlorobenzaldehyde
2,4-Dichlorobenzaldehyde
4-Nitrobenzaldehyde
2-Hydroxybenzaldehyde
4-Hydroxybenzaldehyde
Cinnamaldehyde
a
Reaction condition: aromatic aldehyde (5 mmol), 5,5-dimethyl-1,3-cyclohexanedione (10 mmol), [Et3NH][HSO4] (1 mmol) at 100 ◦C under solvent-free conditions.
Isolated yield.
b
Therefore, 100 ◦C was chosen as the reaction temperature for all
further reactions.
Finally, the efficiency of [Et3NH][HSO4] was compared with
that of other ionic liquids reported earlier in the synthesis of 1,8-
dioxo-octahydroxanthenes by one-pot condensation of aromatic
aldehydes with 5,5-dimethyl-1,3-cyclohexanedione. The data sum-
marized in Table 4 show the promising feature of this method in
terms of reaction rate and the yield of product compared with those
reported in the literature. Additionally, the present catalyst seems
to be more beneficial from the economical and accessibility point
of view.
To determine the optimum concentration of catalyst, we have
investigated the model reaction at 5, 10, 20 and 30 mol% of
[Et3NH][HSO4] at 100 ◦C under solvent-free conditions. The product
was obtained in 90, 91, 94 and 93% yield, respectively. This indi-
cates that 20 mol% of [Et3NH][HSO4] is sufficient for the best result.
Subsequently, therefore, all reactions were carried out at 100 ◦C
in the presence of 20 mol% of [Et3NH][HSO4] under solvent-free
conditions.
A
plausible mechanism for the synthesis of 1,8-dioxo-
Using these optimized reaction conditions, the scope and effi-
ciency of this approach was explored for the synthesis of a wide
variety of 1,8-dioxo-octahydroxanthenes and the obtained results
are summarized in Table 2. It can be observed from Table 2 that
several functionalities present in the aryl aldehydes such as halo-
gen, methoxy and nitro group were tolerated. In all the cases the
corresponding benzoxanthenes were obtained in good to excellent
yield after 20–70 min. Thus, the aromatic aldehydes bearing both
electron-donating and electron-withdrawing groups are desirable
substrates for this reaction.
octahydroxanthenes catalyzed by [Et3NH][HSO4] is shown in
Scheme 2. We propose that one molecule of 5,5-dimethyl-1,
3-cyclohexanedione was firstly condensed with an activated
aldehyde [I] to afford intermediate [II]. Then another molecule
of 5,5-dimethyl-1,3-cyclohexanedione reacted with [II] via
Michael addition reaction to give the intermediate [III]. Finally,
O
R
H
Subsequently, the reusability of [Et3NH][HSO4] was examined
by using benzaldehyde as a model substrate under solvent-free
conditions. After completion of the reaction, the obtained solid
was recrystallized from 95% ethanol to afford the desired com-
pound in pure form. The mother liquor (consisting of 95% ethanol,
[Et3NH][HSO4], and some other residual reactants or byproducts)
was vacuumed to remove solvent and the resulting catalyst was
directly used in subsequent runs without further treatment. As can
be seen from Table 3, the ionic liquid [Et3NH][HSO4] can be recycled
at least six times without any loss of catalytic activity.
[Et3NH][HSO4]
OH
OH
R
O
O
OH
-H
R
H
(I)
OH
OH
O
R
O
O
O
O
O
R
H
O
-H2O
-H
+H
R
OH
OH2
O
O
R
O
(II)
Table 3
Recycling of the [Et3NH][HSO4] catalyst.a
O
O
R
O
O
R
O
Run
Time (min)
Yieldb (%)
+H
1
2
3
4
5
6
7
20
20
20
20
20
20
20
94
94
94
94
95
95
96
O
H
O
OH
O
OH
OH
(III)
O
R
O
O
O
R
O
H
-H2O
-H
O
a
OH2
Reaction
condition:
benzaldehyde
(5 mmol),
5,5-dimethyl-1,3-
cyclohexanedione (10 mmol), [Et3NH][HSO4] (1 mmol) at 100 ◦C under solvent-free
conditions.
Scheme 2. Plausible mechanism for the synthesis of 1,8-dioxo-octahydroxanthenes
b
Isolated yield.
catalyzed by [Et3NH][HSO4].

102
Z. Zhou, X. Deng / Journal of Molecular Catalysis A: Chemical 367 (2013) 99–102
Table 4
Comparison of ionic liquids used as catalysts for the synthesis of 1,8-dioxo-octahydroxanthenes.a
Entry
Ionic liquid
Conditions
Time (min)
Yield (%)
Reference
1
2
3
4
5
6
7
8
[Bmim][HSO4]
[Bmim][HSO4]
[Hmim]TFA
[TMPSA]HSO4
[DDPA][HSO4]
[Et3N-SO3H]Cl
[Hbim]BF4
Solvent-free, 100 ◦
C
25
180
180
60
60
60
93
85
85
94
93
97
85
94
[23]
[24]
[25]
[26]
[27]
[28]
[29]
Present work
Solvent-free, 80 ◦
Solvent-free, 80 ◦
C
C
H2O, 100 ◦
H2O, 100 ◦
C
C
Solvent-free, 80 ◦
C
Ultrasonication, rt, MeOH
45
20
[Et3NH][HSO4]
Solvent-free, 100 ◦
C
a
Based on benzaldehyde.
cyclodehydration of the intermediate [III] gave the expected
products 1,8-dioxo-octahydroxanthenes.
[10] B. Dashttp, P. Thirupathi, K.R. Reddy, B. Ravikanth, L. Nagarapu, Catal. Commun.
8 (2007) 535–538.
[11] M.T. Maghsoodlou, S.M. Habibi-Khorassani, Z. Shahkarami, N. Maleki, M. Ros-
tamizadeh, Chin. Chem. Lett. 21 (2010) 686–689.
4. Conclusion
[12] P. Srihari, S.S. Mandal, J.S.S. Reddy, R.S. Rao, J.S. Yadav, Chin. Chem. Lett. 19
(2008) 771–774.
[13] G.H. Mahdavinia, J. Iran Chem. Res. 1 (2008) 11–17.
[14] B. Das, P. Thirupathi, I. Mahender, V.S. Reddy, Y.K. Rao, J. Mol. Catal. A: Chem.
247 (2006) 233–239.
[15] G.I. Shakibaei, P. Mirzaei, A. Bazgir, Appl. Catal. A: Gen. 325 (2007) 188–192.
[16] S. Kantevari, R. Bantu, L. Nagarapu, J. Mol. Catal. A: Chem. 269 (2007) 53–57.
[17] H. Lü, J. Li, Z. Zhang, Appl. Organometal. Chem. 23 (2009) 165–169.
[18] M.A. Bigdeli, F. Nemati, G.H. Mahdavinia, H. Doostmohammadi, Chin. Chem.
Lett. 20 (2009) 1275–1278.
[19] M. Seyyedhamzeh, P. Mirzaei, A. Bazgir, Dyes Pigments 76 (2008) 836–839.
[20] G. Karthikeyan, A. Pandurangan, J. Mol. Catal. A: Chem. 311 (2009) 36–45.
[21] F. Rashedian, D. Saberi, K. Niknam, J. Chin. Chem. Soc. 57 (2010) 998–1006.
[22] S. Rostamizadeh, A.M. Amani, G.H. Mahdavinia, G. Amiri, H. Sepehrian, Ultrason.
Sonochem. 17 (2010) 306–309.
In summary, we developed
a simple, efficient and eco-
friendly procedure for synthesis of 1,8-dioxo-octahydroxanthenes
by one-pot condensation of aromatic aldehydes with 5,5-dimethyl-
1,3-cyclohexanedione under solvent-free conditions using ionic
liquid [Et3NH][HSO4] as catalyst. The procedure offers several
advantages including cleaner reaction profiles, use of easily avail-
able, cheap, recyclable and environmentally benign nature of
catalyst, high yields, and simple experimental and work-up pro-
cedures.
[23] J. Ma, C. Wang, Q. Wu, R. Tang, H. Liu, Q. Li, Heteroatom. Chem. 19 (2008)
609–611.
[24] K. Niknam, M. Damya, J. Chin. Chem. Soc. 56 (2009) 659–665.
[25] M. Dabirir, M. Baghbanzadeh, E. Arzroomchilar, Catal. Commun. 9 (2008)
939–942.
[26] D. Fang, K. Gong, Z. Liu, Catal. Lett. 127 (2009) 291–295.
[27] D. Fang, J. Yang, Z. Liu, J. Heterocyclic Chem. 48 (2011) 468–472.
[28] A. Zare, A.R. Moosavi-Zare, M. Merajoddin, M.A. Zolfigol, T. Hekmat-Zadeh, A.
Hasaninejad, A. Khazaei, M. Mokhlesi, V. Khakyzadeh, F. Derakhshan-Panah,
M.H. Beyzavi, E. Rostami, A. Arghoon, R. Roohandeh, J. Mol. Liq. 167 (2012)
69–77.
Acknowledgements
We thank the Natural Science Foundation of Hubei Province
(grant No. 2007ABA291) for financial support.
References
[29] K. Venkatesan, S.S. Pujari, R.J. Lahoti, K.V. Srinivasan, Ultrason. Sonochem. 15
(2008) 548–553.
[30] A. Rahmati, Chin. Chem. Lett. 21 (2010) 761–764.
[31] X. Fan, Y. Li, X. Zhang, X. Hu, J. Wang, Chin. J. Org. Chem. 25 (2005) 1482–1486.
[32] X. Fan, X. Hu, X. Zhang, J. Wang, Can. J. Chem. 83 (2005) 16–20.
[33] J. Ma, J. Li, R. Tang, X. Zhou, Q. Wu, C. Wang, M. Zhang, Q. Li, Chin. J. Org. Chem.
27 (2007) 640–642.
[1] J.P. Poupelin, G. Saint-Rut, O. Fussard-Blanpin, G. Narcisse, G. Uchida-Ernouf, R.
Lakroix, Eur. J. Med. Chem. 13 (1978) 67–71.
[2] K. Chibale, M. Visser, D.V. Schalkwyk, P.J. Smith, A. Saravanamuthu, A.H. Fair-
lamb, Tetrahedron 59 (2003) 2289–2296.
[3] A. Banerjee, A.K. Mukherjee, Stain. Technol. 56 (1981) 83–85.
[4] C.G. Knight, T. Stephens, J. Biochem. 258 (1989) 683–687.
[5] M.R.P. Heravi, J. Iran Chem. Soc. 6 (2009) 483–488.
[34] T.L. Greaves, C.J. Drummond, Chem. Rev. 108 (2008) 206–237.
[35] C. Wang, L. Guo, H. Li, Y. Wang, J. Weng, L. Wu, Green Chem. 8 (2006) 603–607.
[36] A. Rajendran, D. Raghupathy, M. Priyadarshini, Int. J. Chem. Tech. Res. 3 (2011)
298–302.
[6] M. Dabiri, S.C. Azimi, A. Bazgir, Chem. Pap. 62 (2008) 522–526.
[7] T. Jin, J. Zhang, J. Xiao, A. Wang, T. Li, Synlett (2004) 0866–0870.
[8] A. Pramanik, S. Bhar, Catal. Commun. 20 (2012) 17–24.
[9] S. Kantevari, R. Bantu, L. Nagarapu, ARKIVOC 2006 Part (xvi) (2006) 136–148.