One-pot green procedure for synthesis of tetrahydrobenzo[a]xanthene-11-one catalyzed by Bronsted ionic liquids under solvent-free conditions

Article abstract of DOI:10.1002/cjoc.201180240

An efficient one-pot condensation of β-naphthol, aldehydes and cyclic 1,3-dicarbonyl compound has been achieved with ionic liquids as catalyst, thus a variety of 8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives were prepared in good yields. The pres

Full text of DOI:10.1002/cjoc.201180240

FULL PAPER
One-pot Green Procedure for Synthesis of Tetrahydrobenzo[a]-
xanthene-11-one Catalyzed by Brønsted Ionic Liquids under
Solvent-free Conditions
Zakeri, Masoumeha
Heravi, Majid M.*,a
Saeedi, Minaa
Karimi, Nargesa
Oskooie, Hossein A.a
Tavakoli-Hoseini, Niloofarb
a Department of Chemistry, School of Sciences, Alzahra University, Vanak, Tehran, Iran
b Department of Chemistry, School of Sciences, Islamic Azad University, Khorasan Branch, Mashhad, Iran
An efficient one-pot condensation of β-naphthol, aldehydes and cyclic 1,3-dicarbonyl compound has been
achieved with ionic liquids as catalyst, thus a variety of 8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives
were prepared in good yields. The present approach offers several advantages such as shorter reaction times, good
yields and mild reaction conditions.
Keywords ionic liquids, benzoxanthene, multicomponent reactions, solvent-free
Introduction
can be avoided.
Imidazolium and pyridinium-based ionic liquids
have been thoroughly studied over the past two decades
and still receive considerable attention.12 For example;
pyridinium ionic liquids were recently used as catalysts
in Morita-Baylis-Hillman reactions13 or for asymmetric
reductions of ketones.14
Xanthenes and benzoxanthenes have attracted con-
siderable interest because they possess various biologi-
cal activities such as anti-inflammatory,15 antiviral,16
and antibacterial.17 Some of them have been used as
antagonists for paralyzing the action of zoxazolamine18
and in photodynamic therapy.19 Moreover, these com-
pounds can be used as dyes,20 pH-sensitive fluorescent
materials for the visualization of biomolecular assem-
blies21 and in laser technologies.22 Therefore, the syn-
thesis of xanthene derivatives is of great importance.
Previously tetrahydrobenzo[a]xanthenes have been
synthesized under reflux in 4— 5 h in dichloromethane
or 1,2-dichloroethane in the presence of acid catalysts
such as BF3•Et2O,23 silica supported NaHSO4,24
Design of solvent free reactions and use of ionic liq-
uids1 in organic synthesis, particularly those based on
imidazolium cation,2 have experienced an impetus in
recent years. Some of their unique physical and chemi-
cal properties such as thermal stability, negligible va-
pour pressure, recyclability, ability to dissolve a wide
range of organic and inorganic compounds, increasing
reaction rate, selectivity and tendency to immobilize
starting materials and catalyst make them an attractive
substitute to various volatile and hazardous organic sol-
vents.3 There are many reports that acid/base-catalyzed
reactions in organic solvents can be smoothly carried
out in functionalized ionic liquids containing
acidic/basic counter-ions or cations in the absence of
any additional catalysts. For examples, sulfonic ionic
liquids as dual solvent catalysts in Fischer esterification,
alcohol dehydrodimerization, pinacol rearrangements,4
Friedel-Crafts alkylations5 and nitration of aromatic
compounds,6 carboxyl-functionalized ionic liquids for
acetalization7 and deoximation,8 guanidine-based ionic
liquids as bases in Henry reactions,9 amino-functional-
ized ionic liquid for microwave-assisted synthesis of
4H-pyrans,10 Bronsted ionic liquid with hydrogen sul-
fate counter-ion as the catalyst in the synthesis of cou-
marines,11 etc. The dual role of ionic liquids as solvents
and promoters will dramatically expand their potential
use in scale-up and clean production of significant
molecules. However, it is more desirable to conduct
those acid/base-catalyzed transformations in neutral
ionic liquids, therefore prolonged and complicated pro-
cedure for preparation of functionalized ionic liquids
Sr(OTf)2,25 TBAF,26 p-TSA,27 InCl3 and I2.29 These
synthetic methods afforded good yields however, have
limitations of long reaction time, harsh reaction condi-
tions and often expensive catalysts.
During the course of our studies on the synthesis of
substituted xanthene compounds30 and our interest in
multicomponent reactions,31 this report deals with the
simple, mild and rapid synthesis of benzo[a]xanthen-11-
one derivatives in high yields using ionic liquid cata-
lysts under solvent-free conditions.
28
*
E-mail: mmh1331@yahoo.com; Tel.: 0098-912-1329147; Fax: 009821-8047861
Received January 14 2010; revised and accepted April 25, 2011.
Chin. J. Chem. 2011, 29, 1441— 1445
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Zakeri et al.
FULL PAPER
Experimental
Herein, we report an efficient and environmentally
benign protocol for the synthesis of 12-aryl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one derivatives by multi-
component condensation of β-naphthol, aldehydes and
cyclic 1,3-dicarbonyl compounds catalyzed by ionic
liquids and also under solvent-free neat conditions. The
products were obtained in high yields by a simple
work-up. The condensation of benzaldehyde (1.0 mmol),
β-naphthol (1.0 mmol), and 5,5-dimethylcyclohexane-
1,3-dione (1.2 mmol) was attempted in different ionic
liquids under heating (Scheme 2).
Materials and methods
Melting points were measured by using the capillary
tube method with an electro thermal 9200 apparatus.
GC-Mass analysis was performed on a GC-Mass model:
5973 network mass selective detector, GC 6890 egilent
Mass spectra were obtained with a Massens POEK-
TROMETER CH-7A VARIN MAT BREMEN spec-
trometer. IR spectra were recorded from KBr disk on
the FT-IR Bruker Tensor 27. All products were well
characterized by comparison with authentic samples by
TLC, spectral and physical data.
Scheme 2 Synthesis of tetrahydrobenzo[a]xanthene-11-one
derivatives
Synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xan-
then-11-one derivative: General procedure
O
OH
Ionic liquid
Aldehyde (1.0 mmol), β-naphthol (1.0 mmol), and
5,5-dimethyl-1,3-cyclohexanedione (1.2 mmol) were
mixed thoroughly and placed in a 10 mL round-bot-
tomed flask. Catalyst (10 mol%) was added to the
mixture and the mixture was heated in an oil bath main-
tained at 120 ℃ for appropriate time as given in Table
1. The reaction mixture was then cooled to room
temperature and quenched with water (5 mL). The solid
mass obtained was washed with H2O. The solid product
obtained was filtered and recrystallized from ethanol to
yield pure xanthen-11-one derivative. The acidic ionic
liquid is soluble in water and simply separated from the
products.
R1
R1
R-CHO
+
+
Solvent free
120 o
O
C
1
2
3
R1
O
R1
R
O
4
In order to study the generality of this procedure, a
series of aldehydes were applied. The results are shown
in Table 1. In all cases, aromatic aldehydes substituted
with either electron-donating or electron-withdrawing
groups underwent the reaction smoothly and gave the
products in good to excellent yields. It could also be
concluded that the aldehydes bearing halogen groups at
para position required shorter reaction time and gave
higher yields. Aliphatic aldehydes also gave the ex-
pected xanthene-11-one derivatives in moderate yields
with longer reaction time.
Preparation of ILs
For the present study, three Brønsted acidic ionic
liquids were prepared according to the literature proce-
dure.32,33 The obtained ionic liquids were used as cata-
lysts for synthesis of tetrahydrobenzo[a]xanthene-11-
one.
Results and discussion
Effect of different ionic liquids
In this article, three halogen-free Brønsted acidic
ionic liquids with different cations, 1-(4-sulfonic acid)
Experiments show that the catalytic performance of
1-(4-sulfonic acid) butyl-3-methylimidazolium hydro-
gen sulfate, 1-(4-sulfonic acid) butylpyridinium hydro-
butyl-3-methylimidazolium
hydrogen
sulfate,
1-(4-sulfonic acid) butylpyridinium hydrogen sulfate
and 1-methylimidazolium hydrogen sulfate (Scheme 1)
were synthesized and used as environmentally benign
catalysts for synthesis of benzo[a]-xanthen-11-one de-
rivatives under mild reaction conditions.
gen
sulfate
could
be
much
better
than
1-methylimidazolium hydrogen sulfate, under the same
reaction conditions. Poor results were observed using
1-methylimidazolium hydrogen sulfate as catalyst due
to its weak acidity. It should be noted that the reaction
rate is dependent upon the ionic liquid chosen and in
this reaction, 1-methylimidazolium hydrogen sulfate,
gives lower rate enhancement (Entries 3, Table 2) than
1-(4-sulfonic acid) butyl-3-methylimidazolium and
1-(4-sulfonic acid) butylpyridinium as catalysts. Proba-
bly, this is due to the lower acidity of methylimidazo-
lium hydrogen sulfate counter-anion. These results sug-
gest that the performance of these ionic liquids is de-
pendent upon the character of the side chain of the
cation and the N-heterocyclic ring.
Scheme 1 Structures of three Brønsted acidic ionic liquids
CH3
SO3H
N
N
N
H
HSO4
HSO4
[HMIM][HSO4]-
CH3
N
SO3H
N
HSO4
[(CH2)4SO3HMIM][HSO4]-
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Chin. J. Chem. 2011, 29, 1441— 1445

One-pot Synthesis of Tetrahydrobenzo[a]xanthene-11-one under Solvent-free Conditions
Table 1 Results of synthesis of tetrahydrobenzo[a]xanthene-11-one catalyzed by 1-(4-sulfonic acid) butyl-3-methylimidazolium under
different reaction times
m.p./℃
Entry
Aldehyde
Product
R1
Time/min
Yielda/%
Found
Lit.
O
4a
C6H4CHO
CH3
60
90
149—141
149—15034
O
O
O
4b
4c
4d
4e
4-CH3-C6H4CHO
4-OCH3-C6H4CHO
4-Cl-C6H4CHO
CH3
CH3
CH3
CH3
60
60
55
55
90
85
90
95
175—176
205—208
184—185
186—188
175—17634
208—20935
187—18835
186—18734
O
O
OCH3
O
O
Cl
O
4-Br-C6H4CHO
O
Br
O
4f
4g
4h
4-OH-C6H4CHO
2-Cl-C6H4CHO
3-NO2-C6H4CHO
CH3
CH3
CH3
65
75
95
85
75
75
223—226
179
223—22535
179—18035
168—17035
O
OH
O
O
Cl
O
168—172
O
NO2
Chin. J. Chem. 2011, 29, 1441— 1445
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Zakeri et al.
FULL PAPER
Continued
m.p./℃
Entry
Aldehyde
Product
R1
Time/min
Yielda/%
Found
Lit.
O
178—18035
O
4i
4-NO2-C6H4CHO
CH3
90
78
178—181
NO2
O
4j
CH3CH2CHO
CH3
CH3
120
120
75
70
164—166
170—173
Oily25
O
O
4k
CH3CH2CH2CHO
—
O
a Isolated yields.
Table 2 Preparation of 9,9-dimethyl-12-phenyl-8,9,10,12-tetra-
hydro-benzo[a]xanthen-11-one using different ionic liquids (10
mol%) under solvent-free conditions
3-methylimidazolium at 120 ℃.
Reusability of the 1-(4-sulfonic acid) butyl-3-methyl-
imidazolium as a catalyst
Entry
1
Ionic liquid
Time/min Yielda/%
One of the advantages of these ionic liquids is its
ability to be recyclable as catalyst. We were able to
separate catalyst from the reaction medium easily by
extraction with water. The catalyst was recovered by
evaporation of the water of the aqueous layer at 90 ℃
in a vacuum oven. Then, the catalyst was washed with
diethyl ether, dried at 50 ℃ under vacuum for 1 h, and
reused in subsequent runs.
1-(4-sulfonic acid) butyl-
3-methylimidazolium
60
90
1-(4-sulfonic acid) butyl-
pyridinium
2
3
60
60
86
70
1-methylimidazolium
a Isolated yields.
As it is shown in Table 3, after five times of reus-
ability, 1-(4-sulfonic acid) butyl-3-methylimidazolium
was still active enough to give the reasonable yields of
the products. This indicated that 1-(4-sulfonic acid) bu-
tyl-3-methylimidazolium was highly efficient and recy-
clable catalyst for synthesis of tetrahydrobenzo[a]-
xanthene-11-one.
Effect of different reaction conditions using 1-(4-
sulfonic acid) butyl-3-methylimidazolium as catalyst
1-(4-sulfonic acid) butyl-3-methylimidazolium ex-
hibited the most excellent catalytic performance with
high yield under the same reaction conditions. Therefore,
we choose 1-(4-sulfonic acid) butyl-3-methylimidazo-
lium as the high effective catalyst to investigate further
the effect of reaction time and possibility of reusability
on this reaction. A test reaction using benzaldehyde,
2-naphthol and dimedone at 120 ℃ in the absence of
solvent and without any catalyst was performed in order
to establish the real effectiveness of the catalysts. It was
found that only 20% conversion to product was obtained
even after 3 h of heating. To optimize the catalyst load-
ing, 3 mol%, 5 mol% and 7 mol% was tested but the
yields were not good. A 10 mol% loading of
1-(4-sulfonic acid) butyl-3-methylimidazolium was suf-
ficient to push the reaction forward and higher amounts
of catalyst did not increase the yields significantly. The
best results were obtained when the reactions were car-
ried out with 10 mol% of 1-(4-sulfonic acid) butyl-
Table 3 Reusability of the 1-(4-sulfonic acid) butyl-3-methyl-
imidazolium for synthesis of 9,9-dimethyl-12-phenyl-8,9,10,12-
tetrahydro-benzo[a]xanthen-11-one
Time/min
Yielda/%
Entry
1
60
60
90
85
85
78
70
2
3
70
4
100
120
5
a Isolated yields.
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Chin. J. Chem. 2011, 29, 1441— 1445

One-pot Synthesis of Tetrahydrobenzo[a]xanthene-11-one under Solvent-free Conditions
Conclusion
Chem. 1978, 13, 67.
17 Lambert, R. W.; Martin, J. A.; Merrett, J. H.; Parkes, K. E.
B.; Thomas, G. J. WO 9706178, 1997.
18 Saint-Ruf, G.; De, A.; Hieu, H. T. Bull. Chim. Ther. 1972, 7,
83.
19 (a) Ion, R. M. Prog. Catal. 1997, 2, 55.
(b) Ion, R. M.; Frackowiak, D.; Planner, A.; Wiktorowicz,
K. Acta Biochim. Pol. 1998, 45, 833.
In summary, three Brønsted acidic ionic liquids were
successfully prepared and utilized as effective catalysts
for synthesis of tetrahydrobenzo[a]xanthene-11-one
under solvent-free conditions. The product was easily
separated with high yields. Catalysts were readily recy-
cled and reused to produce almost identical results. No
organic solvent was used, resulting in eco-friendly
process. The use of these new ionic liquids in this reac-
tion provides a better and practical alternative to the
existing procedures and provides great promise toward
further useful applications.
20 (a) Banerjee, A.; Mukherjee, A. K. Stain. Technol. 1981, 56,
83.
(b) Menchen, S. M.; Benson, S. C.; Lam, J. Y. L.; Zhen, W.;
Sun, D.; Rosenblum, B. B.; Khan, S. H.; Taing, M. US
6583168, 2003.
21 Knight, C. G.; Stephens, T. Biochem. J. 1989, 258, 683.
22 (a) Siirkecioglu, O.; Talini, N.; Akar, A. J. Chem. Res.,
Synop. 1995, 502.
Acknowledgment
The authors are grateful for the partial financial
support from Alzahra University research council via
special grant.
(b) Ahmad, M.; King, T. A.; Ko, D. K.; Cha, B. H.; Lee, J. J.
Phys. D: Appl. Phys. 2002, 35, 1473.
23 Mashraqui, S. H.; Patil, M. B.; Mistry, H. D.; Ghadigaonkar,
S.; Meetsma, A. Chem. Lett. 2004, 33, 1058.
24 Das, B.; Laxminarayana, K.; Krishnaiah, M.; Srinivas, Y.
Synlett 2007, 3107.
25 Li, J.; Tang, W.; Lu, L.; Weike, S. Tetrahedron Lett. 2008,
49, 7117.
26 Gao, S.; Tsai, C. H.; Yao, C. F. Synlett 2009, 949.
27 Khurana, J. M.; Magoo, D. Tetrahedron Lett. 2009, 50,
4777.
28 Nandi, G. C.; Samai, S.; Kumar, R.; Singh, M. S. Tetrahe-
dron 2009, 65, 7129.
29 Wang, R. Z.; Zhang, L. F.; Cui, Z. S. Synth. Commun. 2009,
39, 2101.
30 Oskooie, H. A.; Heravi, M. M.; Karimi, N.; Tahershamsi, L.
Synth. Commun. in press.
31 (a) Heravi, M. M.; Sadjadi, S.; Mokhtari Haj, N.; Oskooie,
H. A.; Hekmat Shoar, R.; Bamoharram, F. F. Tetrahedron
Lett. 2009, 50, 943.
References
1
(a) Wasserscheid, P.; Keim, W. Angew. Chem., Int. Ed.
2000, 39, 3772.
(b) Jain, N.; Kumar, A.; Chauhan, S.; Chauhan, S. M. S.
Tetrahedron 2005, 61, 1015.
2
3
4
(a) Gu, Y.; Shi, F.; Deng, Y. J. Org. Chem. 2004, 69, 391.
(b) Ranu, B. C.; Jana, R. J. Org. Chem. 2005, 70, 8621.
Leadbeater, N. E.; Torenius, H. M. J. Org. Chem. 2002, 67,
3145.
Cole, A. C.; Jensen, J. L.; Ntai, I.; Tran, K. L. T.; Weaver,
K. J.; Forbes, D. C.; Davis, Jr. J. H. J. Am. Chem. Soc. 2002,
124, 5962.
5
6
7
Qiao, K.; Yokoyama, C. Chem. Lett. 2004, 33, 472.
Qiao, K.; Yokoyama, C. Chem. Lett. 2004, 33, 808.
Li, D.; Shi, F.; Peng, J.; Guo, S.; Deng, Y. J. Org. Chem.
2004, 69, 3582.
8
9
Li, D.; Shi, F.; Peng, J.; Guo, S.; Deng, Y. Tetrahedron Lett.
2004, 45, 265.
Jiang, T.; Gao, H.; Han, B.; Zhao, G.; Chang, Y.; Wu, W.;
Gao, L.; Yang, G. Tetrahedron Lett. 2004, 45, 2699.
(b) Heravi, M. M.; Alimadadi Jani, B.; Derikvand, F.;
Bamoharram, F. F.; Oskooie, H. A. Catal. Commun. 2008,
10, 272.
(c) Heravi, M. M.; Baghernejad, B.; Oskooie, H. A.; Hek-
mat Shoar, R. Tetrahedron Lett. 2008, 49, 6101.
(d) Heravi, M. M.; Baghernejad, B.; Oskooie, H. A. Tetra-
hedron Lett. 2009, 50, 767.
10 Peng, Y.; Song, G. H. Catal. Commun. 2007, 8, 111.
11 Singh, V.; Kaur, S.; Sapehiyia, V.; Singh, J.; Kad, G. L.
Catal. Commun. 2005, 6, 57.
12 (a) Welton, T. Chem. Rev. 1999, 99, 2071.
(b) Binnemans, K. Chem. Rev. 2005, 105, 4148.
13 Zhao, S. H.; Zhang, H. R.; Feng, L. H.; Chen, Z. B. J. Mol.
Catal. A: Chem. 2006, 258.
14 Xiao, Y.; Malhotra, S. V. Tetrahedron: Asymmetry 2006, 17,
1062.
15 Hideo, T.; Teruomi, J. (Sankyo Co.) Jp 56005480, 1981.
16 Poupelin, J. P.; Saint-Ruf, G.; Foussard-Blanpin, O.; Mar-
cisse, G.; Uchida-Ernouf, G.; Lacroix, R. Eur. J. Med.
32 Wang, W.; Shao, L.; Cheng, W.; Yang, J.; He, M. Catal.
Commun. 2008, 9, 337.
33 Gui, J.; Cong, X.; Liu, D.; Zhang, X.; Hub, Z.; Sun, Z.
Catal. Commun. 2004, 5, 473.
34 Wang, R. Z.; Zhang, L. F.; Cui, Z. S. Synth. Commun. 2009,
39, 2101.
35 Nandi, G. C.; Samai, S.; Kumar, R. Tetrahedron 2009, 65,
7129.
(E1001147 Pan, B.)
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