BF3·SiO2: an efficient alternative for the synthesis of 14-aryl or alkyl-14H-dibenzo[a,j]xanthenes

Article abstract of DOI:10.1016/j.tetlet.2008.08.101

Silica-supported boron trifluoride (BF₃·SiO₂) is an efficient, readily available, and reusable catalyst for the synthesis of 14-aryl or alkyl-14H-dibenzo[a,j]xanthenes by condensation of 2-naphthol and aldehydes. This reaction under

Full text of DOI:10.1016/j.tetlet.2008.08.101

Tetrahedron Letters 49 (2008) 6454–6456
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Tetrahedron Letters
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BF3ÁSiO2: an efficient alternative for the synthesis
of 14-aryl or alkyl-14H-dibenzo[a,j]xanthenes
b
a
Bi Bi Fatemeh Mirjalili a, , Abdolhamid Bamoniri , Ali Akbari
*
a Department of Chemistry, College of Science, Yazd University, Yazd, PO Box 89195-741, Islamic Republic of Iran
b Department of Chemistry, College of Science, University of Kashan, Kashan, Islamic Republic of Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Silica-supported boron trifluoride (BF3ÁSiO2) is an efficient, readily available, and reusable catalyst for the
synthesis of 14-aryl or alkyl-14H-dibenzo[a,j]xanthenes by condensation of 2-naphthol and aldehydes.
This reaction under heating or sonication conditions is very simple, affording good to excellent yields
of products.
Received 20 July 2008
Revised 19 August 2008
Accepted 27 August 2008
Available online 31 August 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
BF3ÁSiO2
Dibenzoxanthene
Ultrasound
2-Naphthol
Aldehyde
The synthesis of benzoxanthenes with therapeutic and pharma-
cological properties such as antibacterial,1 anti-inflammatory,2 and
antiviral3 is currently of great interest. Furthermore, these hetero-
cyclic compounds are used as sensitizers in photodynamic ther-
apy,4 as leuco-dyes in laser technology,5 as antagonists of the
paralyzing action of zoxazolamine,6 and in fluorescent materials
for visualization of biomolecules.7 The reported protocol for the
synthesis of 14-aryl or alkyl-14H-dibenzo[a,j]xanthene involves
the mixing of 2-naphthol with aldehydes in the presence of a cat-
alyst. This procedure is catalyzed with silica sulfuric acid,8,9 Dow-
BF3ÁSiO2 under normal heating or sonication conditions. Herein,
we report that BF3ÁSiO2 is an efficient and reusable catalyst for
the synthesis of 14-aryl or alkyl-14H-dibenzo[a,j]xanthene deriva-
tives, and is comparable with some other applied catalysts (Table
1). The reaction of 4-methylbenzaldehyde (1 mmol) with 2-naph-
thol (2 mmol) was investigated for optimization of the reaction
conditions (Table 1). Reaction at different temperatures and
various molar ratios of substrates in the presence of BF3ÁSiO2
revealed that the best conditions were solvent-free at 60 °C and a
ratio of aldehyde (mmol): 2-naphthol (mmol): 37% BF3ÁSiO2 (g)
of 1:2:0.08. However, the reaction conducted with 1-naphthol
instead of 2-naphthol did not afford any product.
15
ex-50W,10 NH4H2PO4,11 I2,12,13 sulfamic acid,14 HClO4–SiO2, PW
acid,16 cyanuric chloride,17 Yb(OTf)3,18 and alum.19
Homogeneous acidic catalysts such as H2SO4, HCl, and BF3 are
commonly used for organic synthesis. However, the above-men-
tioned catalysts have several disadvantages because they are cor-
rosive, toxic or volatile, and generate large amounts of waste.
The feasibility of the ultrasonic-assisted synthesis of 14-(4-
methylphenyl)-dibenzo[a,j]xanthene in the presence of 37%
BF3ÁSiO2 was also demonstrated (Table 1). The results obtained
show that reflux in chloroform under sonication conditions
reduced the reaction time to 6 min.
The reusability of the BF3ÁSiO2 catalyst was also examined. After
each run, the product was filtered, the solvent was evaporated, and
the catalyst residue was washed with CHCl3 and reused. Treatment
with CHCl3 removes tars more efficiently from the catalyst surface
(Table 1, entries 15 and 16). The catalyst was reusable, although a
gradual decline in activity was observed.
20
Silica-supported boron trifluoride, BF3ÁSiO2, is a bench-top cata-
lyst which is easy to handle and enables better accessibility of
the reactants to the active sites. BF3ÁSiO2 is a solid superacid and
has surface species such as Al–OBF2 and Si–OBF2, and the ion pairs,
Al–OBF3ÀH+ or Si–OBF3ÀH+.21
In continuation of our investigations on the applications of solid
acids in organic synthesis,22 we investigated the synthesis of
14-aryl and alkyl-14H-dibenzo[a,j] xanthenes in the presence of
The applicability of the present method to a large scale process
was examined with 50 mmol of 2-naphthol and 25 mmol of
4-methylbenzaldehyde under thermal conditions, which gave
14-(4-methylphenyl)-dibenzo[a,j]xanthene in 90% yield.
* Corresponding author. Tel.: +98 351 8211674; fax: +98 351 8210644.
E-mail address: fmirjalili@yazduni.ac.ir (B. B. F. Mirjalili).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.101

B. B. F. Mirjalili et al. / Tetrahedron Letters 49 (2008) 6454–6456
6455
Table 1
Acid-catalyzed synthesis of 14-(4-methylphenyl)-dibenzo[a,j]xanthene via reaction of 2-naphthol (2 mmol) and 4-methylbenzaldehyde (1 mmol)
OH
Catalyst
H3C
H3C
CHO
O
+
Entry
Catalyst (g)
Solvent
Conditions
Power (kHz)
Time (h)
Yielda (%)
Reference
1
2
3
4
5
6
7
8
9
37% BF3ÁSiO2 (0.10)
37% BF3ÁSiO2 (0.10)
37% BF3ÁSiO2 (0.10)
37% BF3ÁSiO2 (0.10)
37% BF3ÁSiO2 (0.10)
37% BF3ÁSiO2 (0.10)
37% BF3ÁSiO2 (0.10)
37% BF3ÁSiO2 (0.10)
37% BF3ÁSiO2 (0.10)
25% BF3ÁSiO2 (0.10)
50% BF3ÁSiO2 (0.10)
37% BF3ÁSiO2 (0.04)
37% BF3ÁSiO2 (0.06)
37% BF3ÁSiO2 (0.08)
Chloroform
Ethanol
Solvent-free
Chloroform
Ethanol
rt
rt
rt
Reflux
Reflux
30 °C
60 °C
60 °C
60 °C
60 °C
60 °C
60 °C
60 °C
60 °C
60 °C
60 °C
Sonication/reflux
Sonication/reflux
Sonication/reflux
Sonication/25-35 °C
Sonication/reflux
Sonication/reflux
60 °C
80 °C
100 °C
Ultrasound/40 °C
90 °C
90 °C
125 °C
Reflux
125 °C
100 °C
110 °C
100 °C
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
20
20
15
20
20
20
—
24
24
24
24
24
3
3
1
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
6 min
4 min
7 min
15 min
15 min
6 min
0.25
45 min
2
0
0
0
—
—
—
—
—
—
—
—
—
38
42
42
96
95
94
74
95
42
73
94
90
87
90
67
62
40
0
91
94
86
86
88
93
88
92
92
92
91
91
88
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Chloroform
Chloroform
Chloroform
Chloroform
Ethanol
Chloroform
Solvent-free
Solvent-free
Solvent-free
Water
Solvent-free
Solvent-free
Solvent-free
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
—
—
—
—
—
—
—
—
—
—
—
—
8,9
10
11
12
13
14
15
15
16
17
19
37% BF3ÁSiO2 (0.08) 2nd run
37% BF3ÁSiO2 (0.08) 3rd run
37% BF3ÁSiO2 (0.08)
37% BF3ÁSiO2 (0.08)
37% BF3ÁSiO2 (0.08)
37% BF3ÁSiO2 (0.08)
37% BF3ÁSiO2 (0.08)
37% BF3ÁSiO2 (0.09)
37% BF3ÁSiO2 (0.09)
Silica sulfuric acid
Dowex-50 W
NH4H2PO4/SiO2
I2
I2
Sulfamic acid
HClO4–SiO2
—
—
—
—
—
—
—
—
—
—
40 min
0.4
3
11
9
8 min
1.5
35 min
3
1,2-Dichloroethane
Solvent-free
Solvent-free
Solvent-free
Water
HClO4–SiO2
PW acid
Cyanuric chloride
Alum
a
Isolated yield.
Table 2
The reaction of 2-naphthol (1 mmol) and various aldehydes (0.5 mmol) in the
presence of 37% BF3ÁSiO2 (0.08 g)
Entry
Ra
Yieldb (%)
Mp (°C)
ReportedRef.
O
60 °Cc
))))d
Found
OH
BF3.SiO2
method A or B
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
CH3CH2
(CH3)2CH
CH3CH2CH2
C6H5
88
82
89
96
97
93
96
88
94
97
95
93
94
91
92
94
85
85
88
95
98
91
95
88
90
96
91
94
95
93
89
91
150–152
155–157
152–154
184–185
297–298
203–205
209–211
258–259
227–229
289–290
214–216
311–312
210–211
198–197
190–191
214–215
150–15223
155–15717
152–15415
18524
R
O
+
H
R
R=alkyl or aryl
4-Br–C6H4
4-MeO–C6H4
3-Cl–C6H4
2-MeO–C6H4
4-Me–C6H4
4-Cl–C6H4
2-Cl–C6H4
4-O2N–C6H4
3-O2N–C6H4
3-H3C–C6H4
3-Br–C6H4
2-O2N–C6H4
29717
203–20517
210–21311
258–25917
227–22917
28924
Scheme 1.
214–21613
311–31213
21124
The current method is simple, efficient, and less time-consum-
ing for the synthesis of 14-aryl-14H-dibenzo [a,j] xanthene
derivatives.
2-Naphthol and various aldehydes were used as substrates for
the synthesis of 14-aryl-14H-dibenzo[a,j]xanthene derivatives un-
der normal heating or sonication conditions (Scheme 1 and Table
2).25
In conclusion, we have demonstrated a simple method for the
synthesis of 14-aryl or alkyl-14H-dibenzo[a,j]xanthenes using
37% BF3ÁSiO2 as a reusable, eco-friendly, inexpensive, and efficient
catalyst. Short reaction times, high yields, scale-up, and easy work-
up are the advantages of this protocol.
19812
190–19214
21412
a
All the products are known and were characterized by IR and 1H NMR and by
comparison of their physical properties with those reported in the literature.
b
Isolated yield.
c
The 2-naphthol (2 mmol) was stirred with aldehyde (1 mmol) in the presence of
0.08 g of freshly prepared 37% BF3ÁSiO2 under neat conditions at 60 °C.
d
The mixture of 2-naphthol (2 mmol) and aldehyde (1 mmol) was refluxed in
chloroform in the presence of 0.08 g of 37% BF3ÁSiO2 under sonication (20 kHz) for
6 min.

6456
B. B. F. Mirjalili et al. / Tetrahedron Letters 49 (2008) 6454–6456
16. Amini, M. M.; Seyyedhamzeh, M.; Bazgir, A. Appl. Catal. A: Gen. 2007, 323, 242.
Acknowledgment
17. Bigdeli, M. A.; Heravi, M. M.; Hossein Mahdavinia, G. Catal. Commun. 2007, 8,
1595.
Financial support for this work by the Research Council of Yazd
University is gratefully acknowledged.
18. Su, W.; Yang, D.; Jin, C.; Zhang, B. Tetrahedron Lett. 2008, 49, 3391.
19. Dabiri, M.; Baghbanzadeh, M.; Shakouri Nikcheh, M.; Arzroomchilar, E. Bioorg.
Med. Chem. Lett. 2008, 18, 436.
20. Sadeghi, B.; Mirjalili, B. F.; Hashemi, M. M. Tetrahedron Lett. 2008, 49,
2575.
References and notes
21. Klapotke, T. M.; Mc Monagle, F.; Spence, R. R.; Winfield, J. M. J. Fluorine Chem.
2006, 127, 1446.
1. Hideo, T. Jpn. Tokkyo Koho JP 56005480, 1981; Chem. Abstr. 1981, 95, 80922b.
2. Poupelin, J. P.; Saint- Rut, G.; Foussard-Blanpin, O.; Narcisse, G.; Uchida-Ernouf,
G.; Lacroix, R. Eur. J. Med. Chem. 1978, 13, 67.
3. 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, p212377y.
4. Ion, R. M.; Planner, A.; Wiktorowicz, K.; Frackowiak, D. Acta Biochim. Pol. 1998,
45, 833.
22. (a) Shirini, F.; Zolfigol, M. A.; Safari, A.; Mohammadpoor-Baltork, I.; Mirjalili, B.
F. Tetrahedron Lett. 2003, 44, 7463; (b) Hajipour, A. R.; Zarei, A.; Khazdooz, L.;
Mirjalili, B. F.; Sheikhan, N.; Zahmatkesh, A.; Ruoho, A. E. Synthesis 2005, 3644;
(c) Hajipour, A. R.; Mirjalili, B. F.; Zarei, A.; Khazdooz, L.; Ruoho, A. E.
Tetrahedron Lett. 2004, 45, 6607; (d) Zolfigol, M. A.; Mohammadpoor-Baltork, I.;
Mirjalili, B. F.; Bamoniri, A. Synlett 2003, 1877.
23. Khoramabadi-zad, A.; Akbari, S. A.; Shiri, A.; Veisi, H. J. Chem. Res. (S) 2005,
5277.
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 6,583,168, 2003; Chem. Abstr. 2003 139,
54287f.
6. Saint-Ruf, G.; De, A.; Hieu, H. T. Bull. Chim. Ther. 1972, 7, 83.
7. Bekaert, A.; Andrieux, J.; Plat, M. Tetrahedron Lett. 1992, 33, 2805.
8. Seyyedhamzeh, M.; Mirzaei, P.; Bazgir, A. Dyes Pigments 2008, 76, 836.
9. Shaterian, H. R.; Ghashang, M.; Hassankhani, A. Dyes Pigments 2008, 76, 564.
10. Imani Shakibaei, G.; Mirzaei, P.; Bazgir, A. Appl. Catal. A: Gen. 2007, 325, 188.
11. Mahdavinia, G. H., Rostamizadeh, S., Amani, A. M., Emdadi, Z. Ultrason.
Sonochem., in press.
12. Pasha, M. A.; Jayashankara, V. P. Bioorg. Med. Chem. Lett. 2007, 17, 621.
13. Das, B.; Ravikanth, B.; Ramu, R.; Laxminarayana, K.; Rao, B. V. J. Mol. Catal. A:
Chem. 2006, 255, 74.
14. Rajitha, B.; Sunil Kumar, B.; Thirupathi Reddy, Y.; Narsimha Reddy, P.;
Sreenivasulu, N. Tetrahedron Lett. 2005, 46, 8691.
24. Khosropour, A. R.; Khodaei, M.; Moghannian, H. Synlett 2005, 955.
25. General procedure for the synthesis of aryl or alkyl-14H-dibenzo[a,j]xanthenes,
method A: A mixture of 2-naphthol (2 mmol), aldehyde (1 mmol), and 37%
BF3ÁSiO2 (0.08 g) was heated at 60 °C. The progress of the reaction was
monitored by TLC. After completion of the reaction, the mixture was washed
with chloroform and filtered to recover the catalyst. The filtrate was
evaporated, and the crude product was recrystallized from iso-propanol,
and chloroform (80:20) to afford the pure 14-aryl or alkyl-14H-
dibenzo[a,j]xanthene derivatives in 82–97% yields.
Method B: In a two-necked flask, a mixture of 2-naphthol (2 mmol), aldehyde
(1 mmol), 37% BF3ÁSiO2 (0.08 g), and chloroform (10 ml) was irradiated in a
BANDELIN Sonopulse HD 3200 ultrasonic apparatus at reflux. After 6 min, the
mixture was filtered to recover the catalyst, and the filtrate was evaporated.
The residue was crystallized from iso-propanol and chloroform (80:20), and
the pure products were obtained in 85–98% yields.
15. Bigdeli, M. A.; Heravi, M. M.; Mahdavinia, G. H. J. Mol. Catal. A: Chem. 2007, 275,
25.