A rapid and efficient method for the synthesis of 14H-dibenzo[7α.j] xanthenes, aryl-5H-dibenzo [b.i]xanthene-5,7,12,14-(13H)-tetraone and 1,8-dioxo-octahydroxanthenes by acidic ionic liquid

Article abstract of DOI:10.1016/j.cclet.2010.02.014

Various xanthenes have been synthesized by the condensation of β-naphthol, 2-hydroxynaphthalene-1,4-dione or dimedone with various aldehydes in the presence of trifluoroacetic acid as catalyst in 1,1,3,3-N,N,N',N'-tetramethylguanidinium trifluoroacetate (

Full text of DOI:10.1016/j.cclet.2010.02.014

Available online at www.sciencedirect.com
Chinese Chemical Letters 21 (2010) 761–764
www.elsevier.com/locate/cclet
A rapid and efficient method for the synthesis of 14H-dibenzo[a.j]
xanthenes, aryl-5H-dibenzo [b.i]xanthene-5,7,12,14-(13H)-tetraone
and 1,8-dioxo-octahydroxanthenes by acidic ionic liquid
Abbas Rahmati
Department of Chemistry, University of Isfahan, P.O. Box 81746-7344, Isfahan, Iran
Received 21 September 2009
Abstract
Various xanthenes have been synthesized by the condensation of b-naphthol, 2-hydroxynaphthalene-1,4-dione or dimedone with
various aldehydes in the presence of trifluoroacetic acid as catalyst in 1,1,3,3-N,N,N0,N0-tetramethylguanidinium trifluoroacetate
(TMGT) ionic liquid within 1 h at 75 8C.
# 2010 Abbas Rahmati. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Ionic liquid; 14H-Dibenzo[a.j]xanthenes; b-Naphthol; 2-Hydroxynaphthalene-1,4-dione; Dimedone
The development of simple method to synthesize worthful organic compounds from readily available compounds is
one of the major tasks in organic synthesis [1]. Xanthene’s heterocycles and derivatives are interest because they are an
important class of natural compounds such as Bikaverin and Guayin [2] which exhibiting a wide spectrum of
pharmaceutical and biological properties such as antiviral [3], antibacterial [4], antiinflamatory [5], u-opiat agonist [6],
antitomor [7], neuropharmacological [8], CNS stimulating [9] and applied in photodynamic therapy [10]. As a result,
numerous procedures for their synthesis have been reported [2,11–13].
The classical synthesis of aryl-14H-dibenzoxanthenes, involves the condensation of b-naphthol with aldehydes in the
presence of an acid catalyst. For this reason in menthion reaction different acidic catalysts such as sulfamic acid, p-
toluene sulfonic acid, amberelyst-15, wet cyanuric chloride; H2SO4, H3PO4 or HClO4, NaHSO4, Fe(HSO4)3; LiBr, alum,
hetropolyacides, Silicasulfuricacid, BF3.SiO2, Dowex-50W, SiO2/HClO4, iodine and SelectfluorTM have been used[14–
30]. In addition, expediting the synthesis using microwave irradiation in the presence of sulfamic acid and LiBr, requires
special instrumentation. Also aryl-5H-dibenzo[b.i]xanthene-5,7,12,14-(13H)-tetraone and 1,8-dioxo-octahydrox-
anthenes were prepared by reaction of 2-hydroxynaphthalene-1,4-dione and dimedone or 1,3-cyclohexanedione with
various aldehydes in acidic media, respectively [31,32]. However, most of these reactions require long reaction times,
high temperature, and use of toxic solvents. Also by-products are produced in this reaction.
During recent years, ionic liquids have attracted interests as environmentally friendly reagents due to their
favorable characteristics such as solvophobic properties and catalytic activities [33,34]. This property of ionic liquids
is very efficient for multi-component reactions (MCRs).
E-mail address: a.rahmati@sci.ui.ac.ir.
1001-8417/$ – see front matter # 2010 Abbas Rahmati. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.02.014

762
A. Rahmati / Chinese Chemical Letters 21 (2010) 761–764
Scheme 1. Synthesis of xanthenes.
During the course of our studies on the development of new routs for the synthesis of organic compounds using ionic
liquids and our interest to trifluoroacetic acid (TFA) based ionic liquids [35,36], we wish to introduce a rapid and easy
procedure for the synthesis of 14H-dibenzo[a.j]xanthenes, aryl-5H-dibenzo[b.i]xanthene-5,7,12,14-(13H)-tetraone and
1,8-dioxo-octahydroxanthenes by the condensation of b-naphthol 2, 2-hydroxynaphthalene-1,4-dione 4 and dimedone 6
with various aldehydes 1 in the presence of the acidic ionic liquid under classical heating conditions at 75 8C (Scheme 1).
Initially, in order to examine the best ionic liquid, different ionic liquids such as tetramethylguanidinium
triflouroacetate (TMGT), tetramethylguanidinium acetate (TMGA), tetrabutylammonium bromide (TBAB),
tetrabutylammonium chloride (TBAC), methylimidazolium triflouroacetate (MIT), 1-butyl-3-methylimidazolium
bromide ([bmim]Br) and 1-butyl-3-methylimidazolium hexaflouroposphate ([bmim]PF6) in this condensation
reaction were applied. Although good yields were previously reported using TBAB [37], it was found that no
satisfactory results were obtained with the studied ionic liquids alone. On the contrary, the use of 0.1 mmol TFA with
ionic liquids TMGT and MIT gave acceptable results [38]. The use of only 0.1 mmol TFA with out ionic liquids yield
of reaction was 80%.
As indicated in Table 1, it was also found that the efficiency of the reaction is mainly affected by the amount of
catalyst and temperature. The best results were obtained in the presence of 0.2 mmol TFA and 0.3 g of ionic liquid at
75 8C. It is interesting to note, however, the yield of the reaction was not significantly affected by increasing the
amount of TFA. Also, in the absence of catalyst, the reaction yield was 0% even at 130 8C after 24 h, while increased to
80% in the absence of ionic liquid when just TFA was used through the reaction. Although satisfactory result was
obtained with TFA alone, because of the difficulties and dangers associated with the evaporation of TFA at the studied
temperature, the presence of a typical ionic liquid as a retentive solvent, that keeps the TFA in vessel and prevents its
evaporation [39], seems to be mandatory.
After optimization of reaction, to further explore the scope and limitations of this reaction, we extended the reaction
of b-naphthol with various alkyl and aryl aldehydes carrying either electron-releasing or electron-withdrawing
substituents. Also, we replaced the 2-hydroxynaphthalene-1,4-dione 4 and 5,5-dimethyl-1,3-cyclohexanedione 6
instead of 2-naphthol 2 in various conditions. The results showed that the reaction proceeds very efficiently in all cases.
The reaction temperature for 3f and 3h was 100 8C.
Acidic strength of ionic liquid in pure form before and after heating in the absence of reactants was also
investigated. It was found out that the acidic strength was not significantly affected by temperature up to 110 8C, while
decreased gradually from 110 to 130 8C where 70% reduction occurred after 20 h.
Comparison of the time, temperature, and yield of our method for the synthesis of 14-(4-methylphenyl)-14H-
dibenzo[a.j]xanthenes with the literature are indicated in Table 2. This compound was obtained with high yield from
80 to 92%. However, reaction times and temperature in this work have been reduced considerably relative to the I2,
SelectfluorTM, p-toluene sulfonic acid, sulfamic acid and Yb(OTf)3-ionic liquid.

A. Rahmati / Chinese Chemical Letters 21 (2010) 761–764
763
Table 1
Optimization of one-pot synthesis of 14-(4-methylphenyl)-14H-dibenzo [a.j]xanthene under classical heating conditions in the presence of TMGT
(0.3 g).a.
Experimental number
TFA catalyst (mmol)
Time (h)
Temperature (8C)
Yield (%)
1
2
0.1
0.2
0.5
1
1
1
125
125
125
125
125
25
86
96
96
96
96
30
65
94
95
96
80
86
66
84
94
94
0
3
1
4
1
5
2
1
6
0.2
0.2
0.2
0.2
0.2
0.2b
0.5b
0.2
0.2
0.2
0.2
0
1
7
1
50
8
1
75
9
1
100
125
75
10
11
12
13
14
15
16
17
1
1
1
75
0.3
0.6
1
75
75
75
1.3
24
75
75
a
p-Methylbenzaldehyde(1mmol) and b-naphthol (2 mmol).
In the absence of ionic liquid.
b
Table 2
Comparison of TMGT/TFA-catalyzed method with different synthesis methods of 14-(4-methylphenyl)-14H-dibenzo[a.j]xanthenes.
Experimental number
Catalyst
Solvent
Time (h)a
Temperature (8C)
Yield (%) [Ref.]
1
2
3
4
5
6
7
LiBr
–
1.08
130
90
82 [22]
88 [29]
92 [30]
92 [15]
92 [14]
93 [40]
94
I2
–
3
Selectofor
P-TSA
NH2SO3H
Yb(OTf)3
CF3CO2H
–
11
3 (18)b
125
125
125
120
75
–
–
11
6
[BPy]BF4
TMGT/TFA
1
a
Solvent-free conditions.
b
Reflux conditions.
In conclusion, we have introduced an efficient, easy and clean approach for the synthesis of biologically active aryl-
14H-dibenzo[a.j]xanthenes, aryl-5H-dibenzo[b.i]xanthene-5,7,12,14-(13H)-tetraone and 1,8-dioxooctahydro-
xanthenes using TFA as a catalyst in ionic liquid media. Less waste and ease of product separation are all
among desirable factors in chemical industries which we have considered in our chemistry approach.
1. Experimental
To the 50 mL solution of 1,1,3,3-N,N,N0,N0-tetramethylguanidin (5.70 g, 50 mmol) in n-hexane, trifluoroacetic acid
(6.90 g, 60 mmol) was added in portions within 30 min. The obtained mixture was then stirred for 5 h at ambient
temperature. After completion of the reaction, the mixture was cooled at 0 8C for 8 h. A biphasic mixture was formed.
The product was obtained by decantation of the solvent followed by washing the remained residue with n-hexane to
remove organic impurities, and finally heating the product at 80 8C until complete evaporation of n-hexane residues.
12.58 g of acidic ionic liquid was obtained.
1.1. General procedure
A mixture of aldehyde (1 mmol), b-naphthol 2, 2-hydroxynaphthalene-1,4-dione 4 or 5,5-dimethyl-1,3-
cyclohexanedione 6 (2 mmol), and TMGT/TFA (0.32 g) was heated at 75 8C for reported time. The solid material

764
A. Rahmati / Chinese Chemical Letters 21 (2010) 761–764
residues were then washed with water and filtered. For further purification, it was crystallized from ethanol to afford
1
pure product. All the products (except 3k) are known compounds, which were characterized by IR and H NMR
spectral data and their mp’s compared with literature reports.
14-(2,6-dichlorophenyl)-14H-dibenzo[a.j]xanthene (3K). White solid, mp: 286–287 8C; IR (KBr) (nmax/cmꢀ1):
1
3426, 1597, 1250 cmꢀ1; H NMR (CDCl3): d 7.05 (s, CH), 6.98–8.06 (m, 15H-arom); 13C NMR (CDCl3): d 36.34
(CH), 112.34, 117.74, 123.86, 123.89, 126.55, 128.43, 128.79, 129.83, 130.90, 131.80, 132.35, 137.94, 149.88; MS,
m/z (%): 428 (M + 2, 5), 426 (M+, 100), 279 (35), 251 (20), 216 (75), 189 (30), 151 (15), 121 (25), 39 (50).
The ionic liquid was separated from the products by washing, and then water was removed by vacuum evaporation.
However, for recovery of remained organic material in ionic liquid, these compounds were extracted by addition of n-
hexane (10 mL) to ionic liquid. The mixture was stirred for 2 h. Then it was cooled at 0 8C for 4 h. By decanted of the
mixture ionic liquid was obtained.
Acknowledgment
I gratefully acknowledge the financial support of the Research Council of the University of Isfahan.
References
[1] P. Laszlo, Organic Reactions: Simplicity and Logic, Wiley, New York, 1995.
[2] A. Bekaert, J. Andrieux, M. Plat, Tetrahedron Lett. 33 (1992) 2805.
[3] R.W. Lambert, J.A. Martin, J.H. Merrett, et al. PCT Int. Appl. (1997), WO9706178.
[4] T. Hideo, Chem. Abstr. 95 (1981) 80922b; Jpn. Tokkyo Koho J.P. 56005480, 1981.
[5] J.P. Poupelin, G.S. Ruf, O.F. Blanpin, et al. Eur. J. Med. Chem. 13 (1978) 67.
[6] R.H.B. Galt, M.J. Horbury, R.J. Pearce, et al. J. Med. Chem. 32 (1989) 2357.
[7] G.W. Rewcastle, G.J. Atwell, L. Zhuang, et al. J. Med. Chem. 34 (1991) 217.
[8] C. Kaiser, A.M. Pavloff, E. Garvey, et al. J. Med. Chem. 15 (1972) 665.
[9] J.W. Lewis, M.J. Readhead, J. Med. Chem. 13 (1970) 525.
[10] R.M. Ion, A. Planner, K. Wiktorowicz, et al. Acta Biochim. Pol. 45 (1998) 833.
[11] A. Jha, J. Beal, Tetrahedron Lett. 45 (2004) 8999.
[12] D.W. Knight, P.B. Little, J. Chem. Soc. Perkin Trans. 1 (2001) 1771.
[13] D.W. Knight, P.B. Little, Synlett (1998) 1141.
[14] B. Rajitha, B.S. Kumar, Y.T. Reddy, et al. Tetrahedron Lett. 46 (2005) 8691.
[15] A.R. Khosropour, M.M. Khodaei, H. Moghannian, Synlett (2005) 955.
[16] S. Ko, C.F. Yao, Tetrahedron Lett. 47 (2006) 8827.
[17] M.A. Bigdeli, M.M. Heravi, G.H. Mahdavinia, Catal. Commun. 8 (2007) 1595.
[18] R.J. Sarma, J.B. Baruah, Dyes Pigm 64 (2005) 91.
[19] A. Khoramabadi-Zad, Z. Kazemi, H. Amiri-Rudbari, J. Korean Chem. Soc. 46 (2002) 541.
[20] Z. Karimi-Jaberi, M.M. Hashemi, Monatsh. Chem. 139 (2008) 605.
[21] H.R. Shaterian, M. Ghashang, J. Braz. Chem. Soc. 19 (2008) 1053.
[22] A. Saini, S. Kumar, J.S. Sandhu, Synlett (2006) 1928.
[23] M. Dabiri, M. Baghbanzadeh, M. Shakouri, et al. Bioorg. Med. Chem. Lett. 18 (2008) 436.
[24] M.M. Amini, M. Seyyedhamzeh, A. Bazgir, Appl. Catal. A 323 (2007) 242.
[25] M. Seyyedhamzeh, P. Mirzaei, A. Bazgir, Dye Pigment 76 (2008) 836.
[26] B.B.F. Mirjalili, A. Bamoniri, A. Akbari, Tetrahedron Lett. 49 (2008) 6454.
[27] G. Imani-Shakibaei, P. Mirzaei, A. Bazgir, Appl. Catal. A 325 (2007) 188.
[28] M.A. Bigdeli, M.M. Heravi, G.H. Mahdavinia, J. Mol. Catal. A 275 (2007) 25.
[29] P.S. Kumar, B.S. Kumar, B. Rajitha, et al. Arkivoc xii (2006) 46.
[30] B. Das, B. Ravikanth, R. Ramu, et al. J. Mol. Catal. A 255 (2006) 74.
[31] A. Bazgir, Z. Noroozi Tisseh, P. Mirzaei, Tetrahedron Lett. 49 (2008) 5165.
[32] E.C. Horning, M.G. Horning, J. Org. Chem. 11 (1946) 95.
[33] N. Jain, A. Kumar, S. Chauhan, et al. Tetrahedron 61 (2005) 1015.
[34] T. Welton, Chem. Rev. 248 (2004) 2459.
[35] A. Shaabani, A. Rahmati, Catal. Lett. 100 (2005) 177.
[36] A. Shaabani, A. Rahmati, S. Naderi, Bioorg. Med. Chem. Lett. 15 (2005) 5553.
[37] S. Kantevari, M. Venu Chary, A.P. Rudra Das, et al. Catal. Commun. 9 (2008) 1575.
[38] G. Zhao, T. Jiang, H. Gao, et al. Green Chem. 6 (2004) 75.
[39] P. Wasserscheid, T. Welton, Ionic Liquids in Synthesis, Wiley-VCH, 2003.
[40] W. Su, D. Yang, C. Jin, et al. Tetrahedron Lett. 49 (2008) 3391.