A facile and efficient method for synthesis of xanthone derivatives catalyzed by HBF4/SiO2 under solvent-free conditions

Article abstract of DOI:10.1007/s00706-009-0204-9

HBF₄/SiO₂ was used as an efficient, green, and inexpensive catalytic system for synthesis of 12-aryl or 12-alkyl-8,9,10,12- tetrahydro-11H-benzo[a]xanthen-11-one derivatives via a one-pot three-component reaction of aldehydes, 2-naph

Full text of DOI:10.1007/s00706-009-0204-9

Monatsh Chem (2009) 140:1481–1483
DOI 10.1007/s00706-009-0204-9
ORIGINAL PAPER
A facile and efficient method for synthesis of xanthone derivatives
catalyzed by HBF4/SiO2 under solvent-free conditions
•
Zhan-Hui Zhang Hong-Juan Wang
•
•
Xiao-Qian Ren Yan-Yan Zhang
Received: 12 February 2009 / Accepted: 11 October 2009 / Published online: 12 November 2009
Ó Springer-Verlag 2009
Abstract HBF4/SiO2 was used as an efficient, green, and
inexpensive catalytic system for synthesis of 12-aryl or
12-alkyl-8,9,10,12-tetrahydro-11H-benzo[a]xanthen-11-one
derivatives via a one-pot three-component reaction of
aldehydes, 2-naphthol, and cyclic 1,3-dicarbonyl com-
pounds. The reactions proceeded rapidly at 80 °C under
solvent-free conditions and the desired products were
obtained in good to excellent yields.
Xanthenes are an important class of compounds with
remarkable biological and medicinal properties, for
example antibacterial, antiviral, and anti-inflammatory
activity [6–9]. Furthermore, they are used as dyes, pH-
sensitive fluorescent materials, and in laser technologies
[10–12]. Among this class of molecules, xanthone is a
prominent structural motif found in numerous natural
products and synthetic compounds with important biolog-
ical activity [13–17]. Recently, methodology for synthesis
of 12-aryl- or 12-alkyl-8,9,10,12-tetrahydro-11H-benzo[a]
xanthen-11-one derivatives by condensation of aldehydes,
2-naphthol, and cyclic 1,3-dicarbonyl compounds in the
presence of NaHSO4ꢀSiO2 in 1,2-dichloroethane under
reflux has been described [18]. However, this procedure
also is limited in scope, because of relatively long reaction
times and the use of a harmful volatile organic solvent. As
a consequence, the development of an environmentally
benign practical procedure for accessing these xanthones
remains an elusive goal.
Keywords Multicomponent reaction ꢀ Aldehydes ꢀ
Heterogeneous catalyst ꢀ HBF4/SiO2 ꢀ
Solvent-free conditions
Introduction
With increasing environmental concerns, the development
of clean synthetic procedures has become crucial and
demanding research. In this sense, heterogeneous organic
reactions have many advantages, for example ease of
handling, separation, and recycling, low corrosion, and
environmentally safe disposal [1]. Multi-component reac-
tions enable the creation of complicated molecules using
only one process in a very fast, efficient, and raw materials
and time-saving manner [2]. In addition, solvent-free
conditions make synthesis simpler, save energy, and pre-
vent solvent waste, hazards, and toxicity [3–5]. It therefore
remains a challenge to develop multi-component reactions
with a suitable heterogeneous catalysts and the use of
solvent-free conditions.
The use of silica-supported HBF4 (HBF4/SiO2) as a
heterogeneous catalytic system to promote various trans-
formations is well documented in the literature [19–24]. In
particular, HBF4/SiO2 has been found to catalyze effi-
ciently thia-Michael additions to a,b-unsaturated carbonyl
compounds [25], Mannich-type reactions [26], and the
synthesis of 1,5-benzodiazepines [27] and 14-aryl-14H-
dibenzo[a,j]xanthene derivatives [28]. Considering these
topics and our ongoing project on developing several cat-
alytic systems for organic reactions [29–39], we now report
a highly efficient procedure for preparation of 12-aryl-
or 12-alkyl-8,9,10,12-tetrahydro-11H-benzo[a]xanthen-11-
one derivatives via a one-pot three-component reaction of
aldehydes, 2-naphthol, and cyclic 1,3-dicarbonyl com-
pounds in the presence of HBF4/SiO2 under solvent-free
conditions (Scheme 1).
Z.-H. Zhang (&) ꢀ H.-J. Wang ꢀ X.-Q. Ren ꢀ Y.-Y. Zhang
The College of Chemistry and Material Science,
Hebei Normal University, 050016 Shijiazhuang, China
e-mail: zhanhui@126.com
123

1482
Z.-H. Zhang et al.
Scheme 1
O
R1
O
OH
HBF4/SiO2
R1
R1
R1
Solvent-free, 80 oC
+
+ RCHO
O
R
O
1
2
3
4
Results and discussion
In order to check the recyclability of the catalyst after
completion of the reaction, the reaction mixture was dissolved
in ethyl acetate and the catalyst was recovered after filtration.
The recovered catalyst was reused again for the synthesis of
4m. The reaction was found to proceed smoothly and afforded
comparable yields of 93, 92, 92, and 90%, confirming the
recyclability and reusability of the catalyst in this reaction.
In conclusion, we have introduced a new catalyst system
for synthesis of various xanthone derivatives via one-pot
three-component reaction of aldehydes, 2-naphthol, and
cyclic 1,3-dicarbonyl compounds. Advantages of our pro-
cedure include simplicity of operation, high yields of
products, short reaction time, solvent-free conditions, and
the use of an inexpensive and readily available catalyst.
We started our study by examining the reaction of
4-chlorobenzaldehyde (2m), 2-naphthol (1), and 5,5-
dimethyl-1,3-cyclohexanedione. After initial screening of
amounts of HBF4/SiO2, solvents, and reaction tempera-
tures, we found that use of 10 mol% HBF4/SiO2 at 80 °C
under solvent-free conditions produced 12-(4-chloro-
phenyl)-9,9-dimethyl-8,9,10,12-tetrahydro-11H-benzo[a]
xanthen-11-one (4m), after 1 h, in 95% yield. Notably, the
desired product could not be obtained under similar reac-
tion conditions, even after a long time (2 h) in the absence
of the catalyst. This method is superior to available
methods with regard to yield and reaction time [18].
To explore the scope and limitations of the procedure, a
number of aldehydes were examined under the optimized
conditions. As shown in Table 1, aromatic aldehydes
substituted with an electron-withdrawing group or an
electron-donating group were transformed into the corre-
sponding xanthones in good to excellent yields. Moreover,
it was observed that aliphatic aldehydes were viable sub-
strates, although long reaction times were required for
slightly lower yields. The products obtained were charac-
Experimental
Melting points were determined on an X-4 apparatus. IR
spectra were obtained using a Shimadzu FTIR-8900 spec-
1
trometer. H NMR spectra were recorded with a Varian
Mercury Plus 400 spectrometer using TMS as internal
standard. Elemental analysis was performed on a Vario EL
III CHNOS elemental analyzer and the results obtained
agreed favorably with calculated values.
1
terized by IR and H NMR spectroscopy; the results were
in agreement with those published in the literature [18, 41].
Table 1 Preparation of
xanthone derivatives in the
presence of HBF4/SiO2
Compound
R
R1
Time (min)
Yield (%)a
mp (°C)
4a
4b
4c
4d
4e
4f
Ph
H
65
70
70
60
60
60
60
90
90
65
70
70
60
65
55
90
92
90
89
92
93
94
92
85
83
91
90
89
95
94
92
84
189–190 [18]
180–182 [40]
193–194 [40]
209–210 [40]
206–208 [40]
235–236 [40]
234–235 [40]
Oil [18]
4-MeO-C6H4
3-MeO-4-HO-C6H4
3-Cl-C6H4
4-Cl-C6H4
3-NO2-C6H4
4-NO2-C6H4
CH3CH2
H
H
H
H
H
4g
4h
4i
H
H
C6H11
H
186–187
4j
Ph
Me
Me
Me
Me
Me
Me
Me
150–151 [40]
175–176 [41]
208–209 [18]
187–188 [18]
150–152 [18]
174–175 [40]
Oil [18]
4k
4l
4-Me-C6H4
4-MeO-C6H4
4-Cl-C6H4
4-HO-C6H4
4-NO2-C6H4
CH3CH2
4m
4n
4o
4p
a
Yields refer to isolated
products
123

A facile and efficient method for the synthesis of xanthone derivatives
1483
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Representative procedure for the synthesis of xanthones
A mixture of 281 mg 2m (2 mmol), 288 mg 1 (2 mmol),
350 mg 5,5-dimethyl-1,3-cyclohexanedione (2.5 mmol),
and 0.4 g HBF4/SiO2 (0.2 mmol) was heated at 80 °C for
the appropriate time according to Table 1. After comple-
tion of reaction, as indicated by TLC, the mixture was
washed with ethyl acetate and filtered to recover the cat-
alyst. The organic filtrate was separated and concentrated
under reduced pressure. The crude product was recrystal-
lized from EtOH to afford 737 mg 4m (95%).
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White solid; m.p.: 186–187 °C; IR (KBr): vꢀ ¼ 2;931;
2,860, 2,848, 1,643, 1,618, 1,595, 1,514, 1,391, 1,256,
1,234, 1,188, 1,134, 993, 949, 833 cm-1
;
1H NMR
(400 MHz, CDCl3): d = 0.97–1.10 (m, 6H, cyclohexane),
1.26–1.81 (m, 5H, cyclohexane), 2.10–2.15 (m, 2H, CH2),
2.32–2.41 (m, 2H, CH2), 2.57–2.78 (m, 2H, CH2), 4.68 (d,
J = 4.0 Hz, 1H, CH), 7.24 (d, J = 8.8 Hz, 1H, Ar–H),
7.45 (d, J = 7.6 Hz, 1H, Ar–H), 7.56 (d, J = 7.6 Hz, 1H,
Ar–H), 7.71 (d, J = 8.8 Hz, 1H, Ar–H), 7.83 (d, J =
8.0 Hz, 1H, Ar–H), 8.12 (d, J = 8.0 Hz, 1H, Ar–H) ppm;
13C NMR (100 MHz, CDCl3): d = 20.2, 26.3, 28.0, 28.5,
31.2, 32.6, 37.2, 45.6, 113.4, 116.8, 119.0, 123.8, 124.8,
126.6, 127.8, 128.5, 131.5, 131.6, 149.2, 168.6, 197.8 ppm.
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Acknowledgments We are grateful for financial support from the
National Natural Science Foundation of China (20872025), the Nat-
ure Science Foundation of Hebei Province (B2008000149), the
Natural Science Foundation of Hebei Education Department
(2006318), and the Science Foundation of Hebei Normal University
(L20061314).
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296:42
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35. Mo L-P, Ma Z-C, Zhang Z-H (2005) Synth Commun 35:1997
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