Br?nsted acidic ionic liquid as an efficient and reusable catalyst for synthesis of 14-aryl-or 14-alkyl-14 H-dibenzo[a,j]xanthenes under solvent-free conditions

Article abstract of DOI:10.1055/s-0029-1219399

A mild and efficient method has been developed for the preparation of 14-aryl-or 14-alkyl-14H-dibenzo[a,j]xanthenes from one-pot condensation of aldehydes with 2-naphthol using catalytic amount of Br?nsted acidic ionic liquid ([TEBSA][HSO) under thermal s

Full text of DOI:10.1055/s-0029-1219399

LETTER
741
Brønsted Acidic Ionic Liquid as an Efficient and Reusable Catalyst for
Synthesis of 14-Aryl- or 14-Alkyl-14H-dibenzo[a,j]xanthenes under
Solvent-Free Conditions
S
ynthesis of 14
H
-D
b
ibenzo[a,j]x
d
anthenes un
o
S
olvent-F
l
re
e
Conditio
R
ns . Hajipour,*a,b Yosof Ghayeb,b Nafisehsadat Sheikhan,b Arnold E. Ruohoa
a
Department of Pharmacology, University of Wisconsin, Medical School, 1300 University Avenue, Madison 53706-1532, WI, USA
Pharmaceutical Research Laboratory, College of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran
Fax +98(311)3912350; E-mail: haji@cc.iut.ac.ir
b
Received 8 June 2009
ful characteristics of solid acids and mineral liquid acids,
and are designed to replace customary mineral liquid ac-
ids like sulfuric acid and hydrochloric acid in chemical
procedures.27,28 N-(4-Sulfonic acid) butyl triethyl ammo-
Abstract: A mild and efficient method has been developed for the
preparation of 14-aryl- or 14-alkyl-14H-dibenzo[a,j]xanthenes
from one-pot condensation of aldehydes with 2-naphthol using cat-
alytic amount of Brønsted acidic ionic liquid ([TEBSA][HSO4]) un-
der thermal solvent-free conditions. Excellent yields, short reaction nium hydrogen sulfate ([TEBSA][HSO4]) has been syn-
times, easy workup and reusability of the catalyst as well as solvent-
thesized and applied as an effective and reusable catalyst
for estrification of various alcohols by different acids29
free conditions are advantages of this procedure.
and nitration of aromatic compounds.30
Keywords: [TEBSA][HSO4], Brønsted acidic ionic liquid, xan-
thenes, solvent-free, one-pot
In continuation of our investigations on the development
of new synthetic methodologies,31,32 we herein report a
new, convenient, mild and efficient procedure for the syn-
Xanthene derivatives due to large number of biological
thesis of 14-aryl- or 14-alkyl-14H-dibenzo[a,j]xanthenes
and pharmacological properties like antibacterial,1
from one-pot condensation of various aldehydes with 2-
antiviral2 and anti-inflammatory3 have received a great
naphthol in the presence of [TEBSA][HSO4] as an effec-
deal of attention. These compounds have also been used
tive and recoverable catalyst under solvent-free condi-
as dyes,4,5 in laser technology,6 in fluorescent materials
tions (Scheme 1).
for visualization of biomolecules7 and in photodynamic
therapy.8 Thus, the synthesis of xanthene derivatives (es-
R
pecially benzoxanthenes) is very important. Different pro-
cedures have been reported for the preparation of
OH
15 mol% IL
RCHO
+
xanthene derivatives such as the reaction of aryloxymag-
nesium halides with triethylorthoformate,9 trapping of
benzynes by phenols10 and the reaction of 2-naphthol with
2-naphthol-1-methanol,11 formamide,12 carbon monox-
ide.13 In addition, 14H-dibenzo[a,j]xanthenes have been
synthesized by the one-pot condensation of 2-naphthol
with aldehydes in the presence of various catalysts such as
Yb(OTf)3,14 NH4H2PO4–SiO2,15 sulfamic acid,16 Am-
berlyst-15,17 HClO4–SiO2,18 I2,19 cyanuric chloride,20
120 °C, solvent-free
O
3
1
2
–
IL = Et3N+CH2(CH2)2CH2SO3HHSO4
R = Ph, aryl and alkyl
Scheme 1
Initially to optimize the amount of ionic liquid, the reac-
tion of 2-naphthol (1 mmol) and 3-nitrobenzaldehyde (1
mmol) was performed under solvent-free conditions at
120 °C in the presence of different quantities of [TEBSA]
[HSO4] (Table 1). As shown in Table 1, the yield of prod-
21
BF3·SiO2 and alum.22 However, some of these proce-
dures have disadvantages including long reaction times,
the use of toxic and volatile catalysts and solvents, excess
reagents, special apparatus and harsh reaction conditions.
Accordingly, the development of new and green methods
for convenient preparation of dibenzoxanthenes is very at-
tractive.
Table 1 Effect of Temperature and Different Amounts of [TEBSA]
[HSO4] on the Reaction of 2-Naphthol with 3-Nitrobenzaldehyde
Entry
[TEBSA][HSO4] Temp
Time
(min)
Yield of 3f
(mmol)
(°C)
120
120
120
120
120
100
(%)a
In recent years, ionic liquids have been widely used in
many reactions as catalyst or dual catalyst–solvent23,24 be-
cause of their specific properties like undetectable vapor
pressure, wide liquid range, reusability and high thermal
stability.25,26 Brønsted acidic ionic liquids consist of help-
1
2
3
4
5
6
0.2
5
5
85
91
84
75
60
83
0.15
0.1
5
0.05
0.025
0.15
5
SYNLETT 2010, No. 5, pp 0741–0744
1
6.
3
.2
0
1
0
5
Advanced online publication: 17.02.2010
DOI: 10.1055/s-0029-1219399; Art ID: S06309ST
10
© Georg Thieme Verlag Stuttgart · New York
a Isolated yields.

742
A. R. Hajipour et al.
LETTER
uct 3f in the presence of 0.15 mmol of [TEBSA][HSO4] yield (Table 2, entry 4). Also, aliphatic aldehydes were
gave the best yields. (Table 1, entries 1–5). Therefore 15 employed and the corresponding xanthenes were obtained
mol% of ionic liquid was chosen as the best quantities of in good yields with longer reaction times (Table 2, entries
[TEBSA][HSO4]. This reaction was also carried out at 13–16). When pyridine-2-carbaldehyde and pyridine-3-
100 °C, but the reaction time was longer and the yield of carbaldehyde were used, the yields of the products were
product 3f was lower (Table 1, entry 6).
moderate (Table 2, entries 17 and 18).
Thus, we employed 15 mol% of ionic liquid for one-pot The reusability of the [TEBSA][HSO4] was also investi-
synthesis of 14-aryl- or 14-alkyl-14H-dibenzo[a,j]xan- gated. After each run, water was added to the reaction
thenes from various aldehydes and 2-naphthol under sol- mixture and the product was filtered and the ionic liquid
vent-free conditions at 120 °C (Table 2). Aldehydes in the aqueous phase was extracted with CH2Cl2 three
reacted with 2-naphthol to produce the corresponding 14- times. Then the water was evaporated and the catalyst was
aryl- or 14-alkyl-14H-dibenzo[a,j]xanthenes in high to dried at 65 °C under reduced pressure for two hours and
excellent yields and very short reaction times. It was ob- reused in the reaction of 3-nitrobenzaldehyde and 2-naph-
served that aromatic aldehydes with electron-withdrawing thol under solvent-free conditions at 120 °C (Table 3, en-
substituents were converted to the corresponding xan- tries 1–5). The results demonstrate that the catalyst can be
thenes in higher yields and shorter reaction times than employed five times, although the activity of the catalyst
those with electron-donating substituents. It should be gradually decreased. This shows that Brønsted acidic ion-
mentioned that sterically hindered benzaldehyde like 2,6- ic liquid ([TEBSA][HSO4]) is an effective and recyclable
dichlorobenzaldehyde was converted to 14-(2,6-dichlo- catalyst for the synthesis of 14-aryl- or 14-alkyl-14H-
rophenyl)-14H-dibenzo[a,j]xanthene in a reasonably high dibenzo[a,j]xanthenes.
Table 2 One-Pot Synthesis of 14-Aryl- or 14-Alkyl-14H-dibenzo[a,j]xanthenes in the Presence of Brønsted Acidic Ionic Liquid at 120 °C
under Solvent-Free Conditionsa
Entry
Aldehyde R
Product
Time (min)
Yield (%)b
Mp (°C)
Found
Reportedref.
184–18521
214–21621
289–29021
–
1
2
Ph
3a
3b
3c
3d
3e
3f
8
5
86
92
91
78
89
91
93
90
89
83
79
84
75
83
78
80
70
68
184–186
216–217
282–284
258–260
284–286
210–212
303–306
309–311
244–246
174–176
201–203
228–230
142–144
150–152
153–155
172–174
235–237
198–200
2-ClC6H4
4-ClC6H4
2,6-Cl2C6H3
4-BrC6H4
3-O2NC6H4
4-O2NC6H4
4-NCC6H4
4-MeOCOC6H4
3-MeOC6H4
4-MeOC6H4
4-MeC6H4
i-Pr
3
5
4
5
5
5
297–29821
210–21121
311–31221
291–29214
–
6
5
7
3g
3h
3i
5
8
5
9
5
10
11
12
13
14
15
16
17
18
3j
17
15
10
50
20
45
40
15
50
–
3k
3l
203–20521
227–22921
155–15721
150–15221
152–15421
178–18015
240–24214
200–20233
3m
3n
3o
3p
3q
3r
Et
n-Pr
Bn
2-pyridyl
3-pyridyl
a Ratio aldehyde/2-naphthol/IL = 1:2:0.15
b Yields refer to isolated products and all synthesized xanthene derivatives were characterized by spectral data (IR, 1H NMR and 13C NMR) and
melting points and comparison with authentic samples.
Synlett 2010, No. 5, 741–744 © Thieme Stuttgart · New York

LETTER
Synthesis of 14H-dibenzo[a,j]xanthenes under Solvent-Free Conditions
743
Table 3 Reusability of [TEBSA][HSO4] in the Preparation of
14-(3-Nitrophenyl)-14H-dibenzo[a,j]xanthene
(14) Su, W.; Yang, D.; Jin, C.; Zhang, B. Tetrahedron Lett. 2008,
49, 3391.
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Narsimha Reddy, P.; Sreenivasulu, N. Tetrahedron Lett.
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(17) Ko, S.; Yao, C.-F. Tetrahedron Lett. 2006, 47, 8827.
(18) Bigdeli, M. A.; Heravi, M. M.; Mahdavinia, G. H. J. Mol.
Catal. A: Chem. 2007, 275, 25.
Entry
Time (min)
Yield (%)a
1
5
5
8
8
8
91
91
88
85
81
2
3
4
(19) Pasha, M. A.; Jayashankara, V. P. Bioorg. Med. Chem. Lett.
2007, 17, 621.
5
(20) Bigdeli, M. A.; Heravi, M. M.; Mahdavinia, G. H. Catal.
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(21) Mirjalili, B. B. F.; Bamoniri, A.; Akbari, A. Tetrahedron
Lett. 2008, 49, 6454.
a Isolated yields.
(22) Dabiri, M.; Baghbanzadeh, M.; Shakouri Nikcheh, M.;
Arzroomchilar, E. Bioorg. Med. Chem. Lett. 2008, 18, 436.
(23) Sahoo, S.; Joseph, T.; Halligudi, S. B. J. Mol. Catal. A:
Chem. 2006, 244, 179.
In conclusion, we have reported a facile, convenient and
solvent-free method for the preparation of 14-aryl- or 14-
alkyl-14H-dibenzo[a,j]xanthenes from coupling of vari-
ous aromatic and aliphatic aldehydes with 2-naphthol in
the presence of N-(4-sulfonic acid) butyl triethyl ammoni-
um hydrogen sulfate ([TEBSA][HSO4]) as an efficient
catalyst. Employing a relatively nontoxic (halogen-free)
and reusable Brønsted acidic ionic liquid as an effective
catalyst, high catalytic efficiency, short reaction time,
high yields, straightforward workup and environmentally
benign method are benefits of this method.
(24) Forbes, D. C.; Weaver, K. J. J. Mol. Catal. A: Chem. 2004,
214, 129.
(25) Welton, T. Chem. Rev. 1999, 99, 2071.
(26) Wasserscheid, P.; Keim, W. Angew. Chem. Int. Ed. 2000, 39,
3773.
(27) Wilkes, J. S. J. Mol. Catal. A: Chem. 2004, 214, 11.
(28) Cole, A. C.; Jensen, J. L.; Ntai, I.; Tran, K. L. T.; Weaver,
K. J.; Forbes, D. C.; Davis, J. H. Jr. J. Am. Chem. Soc. 2002,
124, 5962.
(29) Gui, J.; Cong, X.; Liu, D.; Zhang, X.; Hu, Z.; Sun, Z. Catal.
Commun. 2004, 5, 473.
(30) Fang, D.; Shi, Q.-R.; Cheng, J.; Gong, K.; Liu, Z.-L. Appl.
Acknowledgment
We gratefully acknowledge the financial support received for this
project from the Isfahan University of Technology (IUT), IR Iran
(A.R.H.), and Grants GM 033138, MH 065503, NS 033650
(A.E.R.) from the National Institutes of Health. Further financial
support from the Center of Excellency in Sensor and Green Chemi-
stry Research (IUT) is gratefully acknowledged.
Catal. A: Gen. 2008, 345, 158.
(31) Hajipour, A. R.; Zarei, A.; Khazdooz, L.; Mirjalili, B. B. F.;
Sheikhan, N.; Zahmatkesh, S.; Ruoho, A. E. Synthesis 2005,
3644.
(32) Hajipour, A. R.; Mirjalili, B. B. F.; Zarei, A.; Khazdooz, L.;
Ruoho, A. E. Tetrahedron Lett. 2004, 45, 6607.
(33) Zarei, A.; Hajipour, A. R.; Khazdooz, L. Dyes Pigments
2010, 85, 133.
(34) All reagents were purchased from Merck and Aldrich and
used without further purification. All yields refer to isolated
products after purification. [TEBSA][HSO4] was
synthesized according to reported procedure.29 Products
were characterized by spectroscopy data (IR, 1H NMR,
13C NMR spectra) and melting point. 1H NMR (300, 400 and
500 MHz) and 13C NMR (75, 100 and 125 MHz) spectra
were run in DMSO-d6 and CDCl3 solvents relative to TMS
(d = 0.00 ppm). IR spectra were recorded on a Shimadzu 435
IR spectrophotometer and performed using KBr pellets. All
melting points were taken on a Gallenkamp melting
apparatus and are uncorrected.
References and Notes
(1) Hideo, T. Jpn. Tokkyo Koho, JP 56005480, 1981; Chem.
Abstr. 1981, 95, 80922b.
(2) Lambert, R. W.; Martin, J. A.; Merrett, J. H.; Parkes,
K. E. B.; Thomas, G. J. PCT Int. Appl., WO 9706178, 1997;
Chem. Abstr. 1997, 126, 212377y.
(3) Poupelin, J. P.; Saint-Rut, G.; Foussard-Blanpin, O.;
Narcisse, G.; Uchida-Ernouf, G.; Lacroix, R. Eur. J. Med.
Chem. 1978, 13, 67.
(4) Banerjee, A.; Mukherjee, A. K. Stain Technol. 1981, 56, 83.
(5) Menchen, S. M.; Benson, S. C.; Lam, J. Y. L.; Zhen, W.;
Sun, D.; Rosenblum, B. B.; Khan, S. H.; Taing, M. U. S.
Patent, US 6583168, 2003; Chem. Abstr. 2003, 139, 54287f.
(6) Sirkecioglu, O.; Talinli, N.; Akar, A. J. Chem. Res., Synop.
1995, 502.
Preparations of Brønsted Acidic Ionic Liquid {N-(4-
Sulfonic Acid) Butyl Triethyl Ammonium Hydrogen
Sulfate ([TEBSA][HSO4])}: 1,4-Butane sultone (10 mmol,
1.0 mL), triethylamine (10 mmol, 1.4 mL) and MeCN (5
mL) were charged into a 100-mL round-bottom flask. Then,
the mixture was refluxed for 10 h. The white solid zwitterion
was filtered and washed with EtOAc to remove nonionic
residues and dried in vacuum (2 g, 85% yield). Then, a
stoichiometric amount of concentrated sulfuric acid (96%,
0.5 mL) was added dropwise to zwitterions and the mixture
was stirred for 6 h at 80 °C to produce the Brønsted acidic
ionic liquid. 1H NMR (400 MHz, DMSO-d6): d = 1.16 (br s,
9 H), 1.59–1.73 (m, 4 H), 2.53 (t, J = 7.6 Hz, 2 H), 3.09–3.25
(m, 8 H), 6.46 (s, 2 H). 13C NMR (100 MHz, DMSO-d6):
d = 7.60, 20.27, 22.23, 50.67, 52.48, 56.15.
(7) Bekaert, A.; Andrieux, J.; Plat, M. Tetrahedron Lett. 1992,
33, 2805.
(8) Ion, R. M.; Frackowiak, D.; Planner, A.; Wiktorowicz, K.
Acta Biochim. Pol. 1998, 45, 833.
(9) Casiraghi, G.; Casnati, G.; Cornia, M. Tetrahedron Lett.
1973, 679.
(10) Knight, D. W.; Little, P. B. J. Chem. Soc., Perkin Trans. 1
2001, 1771.
(11) Sen, R. N.; Sarkar, N. N. J. Am. Chem. Soc. 1925, 47, 1079.
(12) Papini, P.; Cimmarusti, R. Gazz. Chim. Ital. 1947, 77, 142.
(13) Ota, K.; Kito, T. Bull. Chem. Soc. Jpn. 1976, 49, 1167.
Synlett 2010, No. 5, 741–744 © Thieme Stuttgart · New York

744
A. R. Hajipour et al.
LETTER
167.05. IR (KBr): 3060, 2998, 2950, 1709, 1621, 1607,
1591, 1515, 1459, 1433, 1402, 1287, 1251, 1241, 1190, 1116
cm–1. HRMS: m/z [M + H+] calcd for C29H20O3: 417.1412;
found: 417.1561.
General Procedure for the Preparation of 14-Aryl- or 14-
Alkyl-14H-dibenzo[a,j]xanthenes: A mixture of aldehyde
(1 mmol), 2-naphthol (2 mmol) and [TEBSA][HSO4] (0.15
mmol) was stirred at 120 °C in an oil bath. The completion
of the reaction was monitored with TLC (EtOAc–cyclo-
hexane, 1:3). After the appropriate time (as shown in
Table 2), the mixture was cooled to r.t. and H2O (10 mL) was
added and the product was filtered and then recrystallized
from EtOAc. The products were characterized by spectral
data (IR, 1H NMR and 13C NMR) and comparison of their
physical data with the literature data. The spectral data of
some synthesized compounds are given below.
Compound 3j: 1H NMR (300 MHz, CDCl3): d = 3.59 (s, 3
H), 6.42 (s, 1 H), 6.48 (d, J = 8.2 Hz, 1 H), 7.04 (t, J = 8.4
Hz, 2 H), 7.13 (d, J = 7.5 Hz, 1 H), 7.37 (t, J = 7.2 Hz, 2 H),
7.44 (d, J = 9.0 Hz, 2 H), 7.55 (t, J = 7.6 Hz, 2 H), 7.71–7.82
(m, 4 H), 8.36 (d, J = 8.7 Hz, 2 H). 13C NMR (75 MHz,
CDCl3): d = 38.17, 55.23, 111.19, 115.16, 117.40, 118.23,
121.00, 122.94, 124.45, 127.00, 128.99, 129.07, 129.50,
131.27, 131.68, 145.01, 148.96, 159.97. IR (KBr): 3070,
3015, 2961, 2934, 2899, 1603, 1593, 1581, 1514, 1486,
1457, 1431, 1401, 1271, 1252, 1241 cm–1.
Compound 3d: 1H NMR (400 MHz, DMSO-d6): d = 7.03 (s,
1 H), 7.11–7.21 (m, 2 H), 7.39–7.47 (m, 4 H), 7.55 (t, J = 8.0
Hz, 2 H), 7.65–7.69 (m, 1 H), 7.95 (t, J = 10.0 Hz, 4 H), 8.48
(d, J = 8.0 Hz, 2 H). 13C NMR (125 MHz, CDCl3): d = 36.79,
112.77, 118.16, 124.26, 126.33, 126.95, 128.81, 129.19,
130.23, 131.34, 132.79, 138.40, 150.31. IR (KBr): 3057,
1622, 1598, 1515, 1463, 1429, 1404, 1353, 1252 cm–1.
HRMS: m/z [M + H+] calcd for C27H16Cl2O: 427.0578;
found: 426.8718.
Compound 3l: 1H NMR (500 MHz, CDCl3): d = 2.18 (s, 3
H), 6.51 (s, 1 H), 7.00 (d, J = 8.0 Hz, 2 H), 7.44–7.48 (m, 4
H), 7.53 (d, J = 8.9 Hz, 2 H), 7.63 (t, J = 8.3 Hz, 2 H), 7.83
(d, J = 8.9 Hz, 2 H), 7.87 (d, J = 8.0 Hz, 2 H), 8.45 (d, J = 8.5
Hz, 2 H). IR (KBr): 3070, 3020, 2902, 1620, 1591, 1509,
1458, 1431, 1401, 1247 cm–1.
Compound 3m: 1H NMR (500 MHz, CDCl3): d = 0.88 (d,
J = 6.9 Hz, 6 H), 2.31–2.35 (m, 1 H), 5.50 (d, J = 3.8 Hz, 1
H), 7.47 (d, J = 8.8 Hz, 2 H), 7.50 (d, J = 7.1 Hz, 2 H), 7.65
(t, J = 7.0 Hz, 2 H), 7.83 (d, J = 8.8 Hz, 2 H), 7.92 (d, J = 8.1
Hz, 2 H), 8.35 (d, J = 8.5 Hz, 2 H). IR (KBr): 3068, 2959,
2925, 2876, 1631, 1620, 1590, 1516, 1457, 1434, 1398,
1251, 1237 cm–1.
Compound 3i: 1H NMR (500 MHz, CDCl3): d = 3.82 (s, 3
H), 6.56 (s, 1 H), 7.47 (dt, J = 0.9, 7.9 Hz, 2 H), 7.55 (d, J =
8.9 Hz, 2 H), 7.61–7.67 (m, 4 H), 7.83–7.89 (m, 6 H), 8.38
(d, J = 8.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3): d = 38.54,
52.36, 116.88, 118.45, 122.86, 124.82, 127.37, 128.74,
129.33, 129.65, 130.32, 131.48, 131.73, 149.12, 150.42,
Synlett 2010, No. 5, 741–744 © Thieme Stuttgart · New York

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