Yb(OTf)3 catalyzed condensation reaction of β-naphthol and aldehyde in ionic liquids: a green synthesis of aryl-14H-dibenzo[a,j]xanthenes

Article abstract of DOI:10.1016/j.tetlet.2008.03.124

A facile, efficient and green synthesis of aryl-14H-dibenzo[a,j]xanthenes has been developed by one-pot condensation of β-naphthol and substituted benzaldehydes in the presence of ytterbium triflates in ionic liquids.

Full text of DOI:10.1016/j.tetlet.2008.03.124

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3391–3394
Yb(OTf) catalyzed condensation reaction of b-naphthol
3
and aldehyde in ionic liquids: a green synthesis
of aryl-14H-dibenzo[a, j]xanthenes
*
Weike Su , Dong Yang, Can Jin, Bo Zhang
College of Pharmaceutical Sciences, Zhejiang University of Technology, Zhejiang Key Laboratory of Pharmaceutical Engineering,
Hangzhou 310014, PR China
Received 21 November 2007; revised 20 March 2008; accepted 25 March 2008
Available online 28 March 2008
Abstract
A facile, efficient and green synthesis of aryl-14H-dibenzo[a, j]xanthenes has been developed by one-pot condensation of b-naphthol
and substituted benzaldehydes in the presence of ytterbium triflates in ionic liquids.
Ó 2008 Elsevier Ltd. All rights reserved.
The synthesis of xanthenes, especially benzoxanthenes,
has been of considerable interest to chemists because their
oxygen heterocycles may contribute to potential antibacte-
reactions have been improved by the condensation of
b-naphthol with aldehydes in the presence of a catalyst,
1
0
11
12
16
such as p-TSA,
sulfamic acid,
AcOH/H SO ,
2 4
1
2
3
13,14
15
rial, antiviral, and anti-inflammatory activities. Further-
iodine,
K CoW O ꢀ3H O,
cyanuric chloride,
5
12 40
2
4
17
more, these compounds can be used as dyes, in laser
LiBr.
However, searching another environmentally
5
technology, and pH-sensitive fluorescent materials for
friendly catalyst and green solvents is still highly desirable.
The use of lanthanide triflates has given many advanta-
ges in organic synthesis. Lanthanide triflates are mild and
selective catalysts, which have been used widely in C–C
and C–X bond-forming reactions, including Friedel–
6
the visualization of biomolecular assemblies (Fig. 1).
For the synthesis of benzoxanthenes, various methods
have been reported including the reaction of b-naphthol
7
8
with formamide, 2-naphthol-1-methanol, and carbon
9
18
19
20
monoxide. However, these methods have drawbacks such
Crafts,
Baylis–Hilman,
aromatic nitration,
and
2
1
as poor yields, prolonged reaction time, using of toxic
organic solvents, excess reagents/catalysts, and harsh
reaction conditions. Due to these disadvantages, several
Diels–Alder reactions. In contrast to classical Lewis
acids, which often are required in stoichiometric quantities,
lanthanide triflates readily promote a range of reactions in
catalytic quantities. Furthermore, lanthanide triflates can
be recovered and reused without the loss of activity.
Ionic liquids (ILs) are liquid salts at low temperature
R
(<100 °C), which represent a new class of solvents. They
offer the probability of organic reactions with easy iso-
lation and recovery of catalysts. Moreover, Ionic liquids
have no vapor pressure, which facilitates product separa-
O
Fig. 1. Benzoxanthenes.
22
tion by distillation.
Recently, our group has reported the wide use of metal
2
3
*
triflates as excellent catalysts in organic synthesis. As a
result of our ongoing interest in green chemistry and Lewis
Corresponding author.
E-mail address: suweike@zjut.edu.cn (W. Su).
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.124

3392
W. Su et al. / Tetrahedron Letters 49 (2008) 3391–3394
Table 2
R
Reaction of b-naphthol (2 mmol) with 4-chloro-benzaldehyde (1 mmol) in
the presence of various catalysts (0.01 mmol) in [BPy]BF
3
4
a
OH
+
O
Entry Catalyst
Temperature ( °C) Time (h)
Yields (%)
M(OTf)n
ILs, 110
2
R
CHO
OH OH
3
4
º
C
b
1
2
3
4
5
6
7
8
9
AlCl
3
125
110
110
110
110
110
110
110
110
10
5
5
5
5
5
5
5
5
0
95
93, 92
60
80
0
0
0
0
0
1
2
Yb(OTf)
Yb(OTf)
3
4
c
3
ꢀxH
2
O
R
ILs = [BPy]BF or [BmIm]PF
Bi(OTf)
Zn(OTf)
Sr(OTf)2
Sc(OTf)
Y(OTf)
La(OTf)
3
4
6
2
Scheme 1. Reactions of aromatic aldehydes with b-naphthol in ILs.
35
75
25
10
30
17
30
55
3
3
3
acid catalyzed organic reactions, we wish to report a novel
catalyst for the preparation of benzoxanthenes by the con-
densation reaction of aromatic aldehydes with b-naphthol
in ILs system. To the best of our knowledge, metal triflates
have not been used in the synthesis of aryl-14H-
dibenzo[a,j]xanthene (Scheme 1).
a
b
c
Yield of isolated product based on 4-chloro-benzaldehyde.
mmol of anhydrous AlCl was used.
Yb(OTf) /[BPy]BF was recovered and reused.
1
3
3
4
With these results in hand, we turned our attention to
In our initial research, the condensation reaction of 2-
naphthol (2 mmol) with 4-chlorobenzaldehyde (1 mmol)
was carried out in different solvents in the presence of
Yb(OTf)3. Comparing with other organic solvents,
the scope of the aromatic aldehydes in the reaction. The
results are summarized in Table 3.
Most substituted benzaldehydes reacted with b-naph-
thol completely and afforded the corresponding products
(3) in high yields. Since electron-donating group can stabi-
lize the carbocation formed in the reaction, the reaction is
mild and the yield is high. In contrast, aldehydes with
electron-withdrawing group were more reactive and the
[
BPy]BF and [BmIm]PF were the most effective reaction
4 6
media (Table 1, entries 1 and 2). It was confirmed that 3
was the only product in the presence of Yb(OTf)3.
Simultaneously, the reaction of 4-chlorobenzaldehyde
with b-naphthol was also performed in the presence of
different catalysts (0.01 equiv) such as AlCl , Zn(OTf) ,
3
2
Bi(OTf) , Yb(OTf) , Yb(OTf) ꢀxH O, Sc(OTf) , Y(OTf) ,
Table 3
3
3
3
2
3
3
La(OTf) , Sr(OTf) in [BPy]BF (Table 2). Data showed
3
Yb(OTf) Catalyzed synthesis of 14-substitued-14H-dibenzo[a,j]xanthenes
in [BPy]BF
3
2
4
2
4
4
that AlCl did not catalyze the reaction, but Yb(OTf)
3
3
and Yb(OTf) ꢀxH O were the most effective catalysts in
3
2
R
OH
+
the terms of yields of the only product 3 (95%, 93%, respec-
Yb(OTf)3
2
RCHO
tively). Unexpectedly, when Sr(OTf) , Sc(OTf) , Y(OTf)
3
2
3
ILs, 110 C
º
or La(OTf) was used to promote the reaction at 110 °C
O
3
3
1
2
for 5 h in [BPy]BF , 4 was also formed (Table 2, entries
4
c
a
6
–9) due to the uncompleted cyclization. However,
Entry Aldehyde
(R)
Time Catalyst Product ILs
Yield
(%)
Zn(OTf) and Bi(OTf) only gave the desired product 3
(h)
(mol %)
2
3
in moderate yields, and none of 4 was detected.
1
2
3
4
5
6
7
8
9
3-Cl–C H
5
5
5
5
5
5
3
3
3
7
6
6
1
1
1
1
1
1
1
1
1
1
1
1
3a
3b
3c
3d
3e
3f
3g
3h
3i
[BPy]BF4
87
89
90
91
88
90
89
91
92
89
93
95
6
4
4-Cl–C
6
H
4
[BPy]BF
[BPy]BF
[BPy]BF
[BPy]BF
[BPy]BF
[BPy]BF
[BPy]BF
[BPy]BF
[BPy]BF
[BPy]BF
[BPy]BF
4
4
4
4
4
4
4
4
4
4
4
3-Br–C
4-Br–C
6
H
H
4
6
4
3-F–C
4-F–C
6
H
H
4
Table 1
Solvent effect on the reaction of 2-naphthol (2 mmol) with 4-chlorobenz-
6
4
a
3-NO
4-NO
2
–C
–C
6
H
H
4
4
3
aldehyde (1 mmol)catalyzed by Yb(OTf) (0.01 mmol)
b
2
6
Entry
Solvent
Time (h)
Yield of 3 (%)
6 4
4-CN–C H
c
1
2
3
4
5
6
7
8
9
0
a
b
c
[BPy]BF
[BmIm]PF
[BPy]Br
[EPy]Br
[BmIm]Cl
4
5
5
95, 92
10
11
12
C
6
H
5
3j
3k
3l
6
93
55
0
0
0
60
60
15
0
6
4-Me–C H
4
10
10
10
10
10
10
10
10
6 4
4-MeO–C H
O
13
6
1
3m
[BPy]BF4
94
O
CH
3
CN
CHCl
ClCH
3
2
CH
2
Cl
CH
3
CH
2
OH
14
7
1
10
3n
[BPy]BF
[BmIm]PF
4
80
82
b
1
THF
N
6
a
b
c
Reactions carried out at 110 °C or refluxing.
Yield of isolated product based on 4-chloro-benzaldehyde.
BPy]BF was reused.
Yield of isolated product based on aldehydes.
Reaction carried out in [BmIm]PF
Mol based on aldehydes.
6 3
with 10 mol % of Yb(OTf) .
[
4

W. Su et al. / Tetrahedron Letters 49 (2008) 3391–3394
3393
reaction with b-naphthol was faster. Thus, the aromatic
aldehydes bearing both electron-donating and electron-
withdrawing groups are desirable substrates for this reac-
tion. When picolinaldehyde (2n) was used, the reaction
proceeded relatively slowly and the yield was lower than
others. It should be pointed out that hindered benzalde-
hydes such as 2,6-dimethoxy benzaldehyde did not react
with b-naphthol under the present reaction condition even
for 8 h. On the other hand, we found that phenol cannot
react with substituted benzaldehydes.
Yb(OTf) might be served as the Lewis-acid catalyst for
several stages.
3
In conclusion, ytterbium triflate is an efficient catalyst
for the preparation of aryl 14H-dibenzo[a,j]xanthene deriv-
atives by the condensation of b-naphthol with aromatic
aldehydes. This method may be used to synthesize some
useful ligands like Xantphos. Some studies are in progress
in our team. In the above reaction, Yb(OTf)3 showed
unique catalysis in contrast to other metal triflates, and
ionic liquids represented a unique class of new reaction
In addition, when the reaction was carried out in
media. Reactions using Yb(OTf) /ionic liquids as reaction
3
[
(
BPy]BF in the absence of Yb(OTf) , condensation adduct
4j) was the only product, 3j was not detected. However, 4j
media prevented uncontrolled by-products and were easy
to handle. The simple experimental procedure, short reac-
tion time, good product yields, mild reaction condition,
and green standard are the advantages of this method.
4
3
could be converted into 3j smoothly in quantitative yield in
Yb(OTf) /[BPy]BF system. But this conversion was diffi-
3
4
cult to proceed in conventional organic solvents such as
toluene, nitrobenzene, and nitromethane. at high tempera-
ture even in the presence of more (20 mol %) Yb(OTf)3
Yb(OTf) /ionic liquids may potentially be used as new type
catalyst and solvent for a wide range of synthetic reactions.
3
(
Scheme 2).
Acknowledgment
Based on the experimental results, a plausible mecha-
nism was proposed in Scheme 3. In this hypothesis,
We thank the National Natural Science Foundation of
China [20676123 and 20476098] for financial support.
OH OH
References and notes
OH
[
BPy]BF4
2
PhCHO
+
110
º
C
1. 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,
Ph
60%
1
26, 212377.
. Hideo, T. Jpn. Tokkyo. Koho. JP 56005480, 1981; Chem. Abstr. 1981,
5, 80922.
4j
2
9
OH OH
O
3. Poupelin, J. P.; Saint-Rut, G.; Foussard-Blanpin, O.; Narcisse, G.;
Yb(OTf)3
BPy]BF4
10
Uchida-Ernouf, G.; Lacroix, R. Eur. J. Med. Chem. 1978, 13, 67.
[
4
. Banerjee, A.; Mukherjee, A. K. Stain Technol. 1981, 56, 83.
1
º
C
Ph
Ph
5. (a) Sirkeeioglu, O.; Talinli, N.; Akar, A. J. Chem. Res., Synop. 1995,
502; (b) Ahmad, M.; King, T. A.; Ko, D. K.; Cha, B. H.; Lee, J. J.
Phys. D: Appl. Phys. 2002, 35, 1473.
3
j quantitative
6
. Knight, C. G.; Stephens, T. Biochem. J. 1989, 258, 683.
7. Papini, P.; Cimmarusti, R. Gazz. Chim. Ital. 1947, 77, 142.
. Sen, R. N.; Sarkar, N. J. Am. Chem. Soc. 1925, 47, 1079.
OH OH
O
Yb(OTf)3
toluene
8
9. Ota, K.; Kito, T. Bull. Chem. Soc. Jpn. 1976, 49, 1167.
10. Khosropour, A. R.; Khodaei, M. M.; Moghannian, H. Synlett 2005,
110
º
C
Ph
trace
Ph
3j
955.
1
1. Rajitha, B.; Kumar, B. S.; Reddy, Y. T.; Reddy, P.; Sreenivasulu, N.
Scheme 2. Conversion of 4j to 3j in Yb(OTf)3/ILs system.
Tetrahedron Lett. 2005, 46, 8691.
YbL3
OH OH
OH
O
O
YbL3
1
+
Ph
H
OH
OH
1
Ph
Ph
OH
YbL3
Ph
4
j
L = OTf
YbL3
YbL3
OH
O
O
H
Ph
Ph
3
j
Scheme 3. Reaction mechanism of b-naphthol with benzaldehye.

3394
W. Su et al. / Tetrahedron Letters 49 (2008) 3391–3394
1
1
2. Sarma, R. J.; Baruah, J. B. Dyes Pigments 2005, 64, 91.
3. Das, B.; Ravikanth, B.; Ramu, R.; Laxminarayana, K.; Rao, B. V. J.
Mol. Catal. A: Chem. 2006, 255, 74.
Recovering the catalytic system; general procedure: After completion
of the extraction, the underlayer (ionic layer) Yb(OTf)3ꢀxH2O/
4
[BPy]BF was washed with 10 mL of ether again, then the ionic liquid
1
1
1
4. Pasha, M. A.; Jayashankara, V. P. Bioorg. Med. Chem. Lett. 2007, 17,
was dried at 100 °C under 50 mmHg for 30 min. Then the recovered
catalytic system could be reused in the next experiment. Spectral data
for selected products:
621.
5. Nagarapu, L.; Kantevari, S.; Mahankhali, V. C.; Apuri, S. Catal.
Commun. 2007, 8, 1173.
6. Bigdeli, M. A.; Heravi, M. M.; Mahdavinia, G. H. Catal. Commun.
3-Chloro-phenyl-14H-dibenzo[a,j]xanthenes ð3aÞ. White crystals; mp
1
210–211 °C; yield: 87%. H NMR (400 MHz, CDCl
3
): d = 8.32 (d,
2007, 8, 1595.
J = 8.4 Hz, 2H), 7.80–7.83 (m, 4H), 7.59 (t, J = 7.6 Hz, 2H), 7.40–
1
1
1
2
7. Saini, A.; Kumar, S.; Sandhu, J. S. Synlett 2006, 1928.
8. Kawada, A.; Mitamura, S.; Kobayashi, S. Chem. Commun. 1996, 183.
9. Balan, D.; Adolfsson, H. J. Org. Chem. 2001, 66, 6498.
0. Waller, F. J. A.; Barrett, G. M.; Braddock, D. C.; Ramprasad, D.
Chem. Commun. 1997, 613.
7.49 (m, 6H), 7.07 (t, J = 8.0 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H), 6.45
(s, 1H). MS (EI): m/z (%) = 394 (6, M +2), 392 (17, M ), 281 (100).
+
+
4-Cyano-phenyl-14H-dibenzo[a,j]xanthenes (3i).White crystals; mp
1
291–292 °C; yield: 91%. H NMR (400 MHz, CDCl
3
): d = 8.27(d,
J = 8.8 Hz, 2H), 7.85 (t, J = 8.8 Hz, 4H), 7.58–7.64 (m, 4H), 7.43–
1
3
2
2
2
1. Kobayashi, S.; Ishitani, H. J. Am. Chem. Soc. 1994, 116, 4083.
2. Welton, T. Chem. Rev. 1999, 99, 8.
3. (a) Su, W.; Li, J.; Zheng, Z.; Shen, Y. Tetrahedron Lett. 2005, 46,
7.51 (m, 6H); 6.55 (s, 1H). C NMR (100 MHz, CDCl3): d = 155.1,
147.8, 135.1, 133.9, 131.9, 130.9, 129.2, 128.1, 126.3, 124.3, 123.8,
+
123.2, 121.1, 117.2, 116.8, 48.9. MS (EI): m/z (%) = 383 (21, M ), 281
6037; (b) Su, W.; Jin, C. Org. Lett. 2007, 9, 993; (c) Su, W.; Hong, Z.;
(100).
Shan, W.; Zhang, X. Eur. J. Org. Chem. 2006, 2723; (d) Chen, J.; Wu,
H.; Zheng, Z.; Jin, C.; Zhang, X.; Su, W. Tetrahedron Lett. 2006, 47,
5-Benzo[d][1,3]dioxole-14H-dibenzo[a,j]xanthenes ð3mÞ White crys-
1
tals; mp 313–315 °C; yield: 94%. H NMR (400 MHz, CDCl
3
):
5383; (e) Yu, C.; Dai, X.; Su, W. Synlett 2007, 646; (f) Su, W.; Chen,
d = 8.37 (d, J = 8.8 Hz, 2H), 7.78–7.84 (m, 4H), 7.59 (t, J = 7.6 Hz,
J.; Wu, H.; Jin, C. J. Org. Chem. 2007, 72, 4524.
4. Preparation of aryl-14H-dibenzo[a,j]xanthenes; general procedure: To
2H), 7.40–7.48(m, 4H), 7.10 (d, J = 7.6 Hz, 1H), 6.87 (s, 1H), 6.61 (d,
1
3
2
J = 8.8 Hz, 1H), 6.42 (s, 1H), 5.74 (s, 2H). C NMR (100 MHz,
CDCl ): d = 148.7, 147.8, 145.9, 139.0, 131.3, 131.1, 128.8, 126.8,
a mixture of aromatic aldehyde (1 mmol) and b-naphthol (2 mmol) in
3
[
BPy]BF
The reaction mixture was stirred at 110 °C for the given time (Table
). After completion (by TLC), the reaction mixture was cooled to
4
(2 mL), ytterbium triflate (0.01 mmol, 6.2 mg) was added.
124.2, 122.6, 121.2, 118.0, 117.3, 108.8, 107.7, 100.8, 58.4, 37.6. MS
(EI): m/z (%) = 402 (29, M ), 281 (100).
+
2
2-Pyridyl-14H-dibenzo[a,j]xanthenes ð3nÞ. White crystals; mp 240–
1
room temperature, then ether (10 mL) was added to the mixture and
stirred for 20 min. The above extraction was repeated, and the upper
ether layers were combined and washed with brine. After dryness and
condensation, the product was purified by column chromatography
or TLC over silica gel (hexane/AcOEt = 1:1). The products could be
242 °C; yield: 80%. H NMR (400 MHz, CDCl
3
): d = 8.67 (2H, d,
J = 8.4 Hz), 8.52 (d, J = 4.8 Hz, 1H), 7.80 (d, J = 7.2 Hz, 4H), 7.57 (t,
J = 8.0 Hz, 2H), 7.47 (d, J = 8.8 Hz, 2H), 7.40 (t, J = 7.6 Hz, 2H),
7.33 (t, J = 7.2 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 6.90 (t, J = 7.2 Hz,
1
3
3
1H), 6.74 (s, 1H). C NMR (100 MHz, CDCl ): d = 164.6, 148.2,
1
easily identified by the singlet peak (about 6.4–6.6 ppm) in H NMR
spectra.
147.7, 137.1, 131.9, 130.9, 129.2, 128.4, 126.9, 124.3, 123.8, 123.2,
+
121.2, 117.9, 116.0, 41.9. MS (EI): m/z (%) = 359 (22, M ), 281 (100).