Synthesis of 14-substituted-14H-dibenzo[a,j] xanthenes and 1,8-dioxo-octahydroxanthenes using silica chloride (SiO2-Cl) under solvent-free conditions

Article abstract of DOI:10.1080/10426500903029456

A simple and efficient synthesis of 14-substituted-14H-dibenzo[a,j] xanthenes and 1,8-dioxo-octahydroxanthenes has been accomplished by the one-pot condensation of -naphthol or dimedone and aldehydes under solvent-free conditions in the presence of SiO2-C

Full text of DOI:10.1080/10426500903029456

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Synthesis of 14-Substituted-14H-
Dibenzo[a,j] Xanthenes and 1,8-
Dioxo-Octahydroxanthenes Using Silica
Chloride (SiO2-Cl) Under Solvent-Free
Conditions
Liqiang Wu a , Chunguang Yang a , Limin Yang a & Lijuan Yang a
a School of Pharmacy , Xinxiang Medical University , Xinxiang,
Henan, China
Published online: 23 Mar 2010.
To cite this article: Liqiang Wu , Chunguang Yang , Limin Yang & Lijuan Yang (2010) Synthesis of 14-
Substituted-14H-Dibenzo[a,j] Xanthenes and 1,8-Dioxo-Octahydroxanthenes Using Silica Chloride
(SiO2-Cl) Under Solvent-Free Conditions, Phosphorus, Sulfur, and Silicon and the Related Elements,
185:4, 903-909, DOI: 10.1080/10426500903029456
To link to this article: http://dx.doi.org/10.1080/10426500903029456
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Phosphorus, Sulfur, and Silicon, 185:903–909, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903029456
SYNTHESIS OF 14-SUBSTITUTED-14H-DIBENZO[a,j]
XANTHENES AND 1,8-DIOXO-OCTAHYDROXANTHENES
USING SILICA CHLORIDE (SiO2-Cl) UNDER
SOLVENT-FREE CONDITIONS
Liqiang Wu, Chunguang Yang, Limin Yang, and Lijuan Yang
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, China
A simple and efficient synthesis of 14-substituted-14H-dibenzo[a,j]xanthenes and 1,8-dioxo-
octahydroxanthenes has been accomplished by the one-pot condensation of β-naphthol
or dimedone and aldehydes under solvent-free conditions in the presence of SiO2-Cl as a
heterogeneous catalyst.
Keywords Dimedone; 1,8-dioxo-octahydroxanthenes; β-naphthol; silica chloride; solvent-
free; 14-substituted-14H-dibenzo[a,j]xanthenes
INTRODUCTION
The synthesis of 14-substituted-14H-dibenzo[a,j]xanthenes has been considered of
great interest to organic chemists owing to their wide range of biological and therapeutic
properties such as antiviral,1 antibacterial,2 and anti-inflammatory activities,3 as well as
in photodynamic therapy4 and for antagonism of the paralyzing action of zoxazolamine.5
Furthermore, due to their useful spectroscopic properties, they are used as dyes,6 in laser
technologies,7 and in fluorescent materials for visualization of biomolecules.8 The most
common methods for the synthesis of 14-substituted-14H-dibenzo[a,j]xanthenes are the re-
action of β-naphthol with aldehydes or acetals in the presence of a catalyst, such as p-TSA,9
sulfamic acid,10 AcOH-H2SO4,11 cyanuric chloride,12 I2,13 HClO4-SiO2,14 Yb(OTf)3,15
BF3-SiO2,16 LiBr,17 Al(HSO4)3,18 Dowex-50W,19 NaHSO4-SiO2,20 ceric sulfate,21 ionic
liquid,22 K5CoW12O40 3H2O,23 NH4H2PO4/SiO2,24 or cellulose sulfuric acid.25
However, most of these procedures have significant drawbacks such as long reaction
times,10,20 low yields,17,19 harsh reaction conditions,10,18,20 difficult workup,24 and use of
environmentally toxic or expensive reagents or media.11,15,19,21–23 Thus, there is still a
need for a simple and general procedure for the one-pot synthesis of 14-substituted-14H-
dibenzo[a,j]xanthenes.
Homogeneous acidic catalysts such as H2SO4, HCl, and BF3 are commonly used
for organic synthesis. However, the above-mentioned catalysts have several disadvantages
Received 25 January 2009; accepted 8 May 2009.
We are pleased to acknowledge the financial support from Xinxiang Medical University (No. 04GXLP05).
Address correspondence to Liqiang Wu, School of Pharmacy, Xinxiang Medical University, Xinxiang,
Henan 453003, China. E-mail: wliq1974@sohu.com
903

904
L. WU ET AL.
because they are corrosive, toxic, or volatile, and generate large amounts of waste. Silica
chloride (SiO2-Cl), which was easily prepared from silica gel and thionyl chloride, is a
good solid acid in terms of convenience, cheapness, easy production, and insolubility in
all organic solvents. Due to its insolubility in organic solvents, excellent in situ proton
generation, and acceptance of different nucleophiles, SiO2-Cl can be used for different pur-
poses in organic chemistry, such as SiO2-Cl–catalyzed protection of carbonyl compounds,26
acetylation of alcohols,27 synthesis of 2-aminothiazoles,28 and as a starting material for the
preparation of other silica bonded reagents.29 In this article, we report a simple, efficient,
and environmentally benign synthesis of 14-substituted-14H-dibenzo[a,j]xanthenes. Dur-
ing our study, we also observed the formation of 1,8-dioxo-octahydroxanthenes in excellent
yields by a one-pot condensation of dimedone and aldehydes under solvent-free conditions
in the presence of SiO2-Cl (see Scheme 1).
R
OH
SiO2-Cl
neat, 110oC
2
RCHO
+
O
3
2
1
O
O
R
O
SiO2-Cl
neat, 110oC
RCHO
+
2
O
O
5
6
4
Scheme 1
RESULTS AND DISCUSSION
We started to study this reaction by examining the amount of catalyst for the reaction
involving β-naphthol (2 mmol) with benzaldehyde (1 mmol) to afford the product 14-
phenyl-14H-dibenzo[a,j]xanthene under solvent-free conditions at 110◦C. The best result
was obtained with 250 mg/mmol SiO2-Cl. Higher amounts of catalyst did not improve the
result to any great extent (see Table I).
To optimize the temperature of the reaction and compare the efficiency of the solvent-
free vs. solution conditions, a model reaction was examined in several solvents, including
Table I The amount of catalyst of optimization of reaction con-
ditions of 14-phenyl-14H-dibenzo[a,j]xanthenes
Entry
SiO2-Cl (mg/mmol)
Yield (%)
1
2
3
4
5
6
7
100
150
200
250
300
350
400
58
72
84
93
91
93
91

SYNTHESIS OF 14-SUBSTITUTED-14H-DIBENZO[a,j]XANTHENES
905
Table II Solvent and temperature of optimization of reaction conditions
of 14-phenyl-14H-dibenzo[a,j]xanthenes
Entry
Solvent
CH2Cl2
CH3CN
THF
DMF
DMSO
Benzene
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Temp. (◦C)
Yield (%)
1
2
3
4
5
6
7
8
9
Reflux
Reflux
Reflux
110
110
Reflux
90
100
110
120
130
47
86
36
56
52
22
72
88
93
91
92
91
10
11
12
140
CH2Cl2, MeCN, THF, benzene, DMF, DMSO, and solvent-free conditions. Thus, a mixture
of β-naphthol (2 mmol), benzaldehyde (1 mmol), and SiO2-Cl (0.25 g) in the appropriate
solvent (10mL) or solvent-free was stirred for 3 h. As is shown in Table II, acetonitrile
as a solvent under reflux and thermal solvent-free at 110◦C showed the best results, but
solvent-free conditions eliminate the use of solvents, especially toxic acetonitrile.
A range of 14-substituted-14H-dibenzo[a,j]xanthenes was synthesized by the reaction
of β-naphthol (1, 2 mmol) with aldehyde (2, 1 mmol). The reaction proceeded at 110◦C
within 4 h in excellent yields after the addition of the acid catalyst SiO2-Cl (see Table III).
In these experiments, the catalyst was isolated by filtration and could be run up to three
recycles with no significant loss of activity (Table III, entry 1). In addition, we noticed also
Table III Preparation of 14-substituted-14H-dibenzo[a,j]xanthenes catalyzed by SiO2-Cla
Entry
R
Products
Time (h)
Yield (%)
Mp (◦C)
Found Reported[ref.]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3
3.5
3.5
3.5
3
3
3
3
3
3
4
4
4
4
4
4
4
93 (78, 67)
181–182
225–226
204–205
256–257
285–286
213–214
295–296
303–304
208–209
288–289
250–251
186–187
>300
183–185 [21]
224–227 [21]
202–204 [21]]
258–259 [12]
286–289 [21]
212–214 [21]
297–298 [22a]
306–308 [21]
210–211 [21]
290–291 [21]
252–254 [21]
188–189 [22a]
4-(CH3)C6H4
4-(MeO)C6H4
2-(MeO)C6H4
4-(Cl)C6H4
2-(Cl)C6H4
4-(Br)C6H4
4-(NO2)C6H4
3-(NO2)C6H4
2-(NO2)C6H4
2, 4-(Cl)2C6H4
3, 5-(MeO)2C6H4
4-(I)C6H4
88
89
86
96
92
94
93
94
89
87
85
90
83
85
82
80
Naphth-1-yl
Pyrid-4-yl
Et
200–201
227–228
146–147
156–157
202–204 [21]
229–230 [22a]
148–151 [21]
155–157 [12]
i-Pr
aAll of the isolated products are known compounds, and their spectral and physical data have been reported in
the literature.12,21,22a

906
L. WU ET AL.
that the reaction was able to tolerate various aldehydes, including aromatic and aliphatic
derivatives.
This new synthetic strategy resulted in a remarkable improvement in synthetic effi-
ciency, and more importantly, it enhanced the utilization efficiency of the modified silica
chloride, and decreased the production of chemical waste without using a highly toxic
reagent for the synthesis of 14-substituted-14H-dibenzo[a,j]xanthenes. The Si-Cl bond
is labile and can give rise to Lewis acid centers on silica (Scheme 2). The Cl is easily
displaced selectively by the acetyl oxygen of aldehyde by a nucleophilic substitution re-
action, generating a cationic center on the carbonyl carbon, which is easily attacked by
the nucleophile β-naphthol to form intermediate X. Interception of this intermediate by
β-naphthol produces Y, which subsequently cyclizes to the corresponding 14-substituted-
14H-dibenzo[a,j]xanthenes.
R
H
SiO2-O-C
HO
OH
-HCl
R
H
+
Cl
SiO2-O-C
SiO2-Cl + RCHO
X
OH
R
R
+
-H2O
O
OH OH
Y
Scheme 2
In order to assess the capability of the present method with respect to the reported
methods for the preparation of 14-substituted-14H-dibenzo[a,j]xanthenes from β-naphthol
and aldehydes, the synthesis of compound 3a was compared with the reported methods. It
is clear from Table IV that the present method has high yields, moderate reaction times,
simple procedure, and uses inexpensive and environmentally benign catalysts.
Encouraged by these results, we were delighted to observe that the present protocol
could safely be extended to the condensation reaction involving dimedone 4 and aldehyde
5. 1,8-Dioxo-octahydroxanthenes were obtained in excellent yields (see Table V).
CONCLUSION
In conclusion, we have developed a simple and highly efficient practical method for
synthesis of 14-substituted-14H-dibenzo[a,j]xanthenes and 1,8-dioxo-octahydroxanthenes
using SiO2-Cl under solvent-free conditions. The notable features of this method are sim-
ple experimental procedure and excellent yields (80–96%), which make it a useful and
attractive process for the synthesis of 14-substituted-14H-dibenzo[a,j]xanthenes and 1,8-
dioxo-octahydroxanthenes. We believe that this methodology will be a valuable addition to
the existing methods.

SYNTHESIS OF 14-SUBSTITUTED-14H-DIBENZO[a,j]XANTHENES
Table IV Comparison of the effect of catalysts in synthesis of 3a
907
CHO
OH
cat.
2
+
neat,
O
Entry
Catalysis
Temp (◦C)
Time (h)
Yield (%)
Reference
1
2
3
4
5
6
7
8
9
Sulfamic acid (10 mol%)
BF3-SiO2 (80 mg/mmol)
I2 (20 mol%)
125
60
90
8
0.25
2.5
1
0.5
1.5
3.5
8
89
90
87
76
86
78
89
85
94
88
93
10
16
13
17
18
19
14
20
LiBr (15 mol%)
130
125
100
100
125
110
100
110
Al(HSO4)3 (50 mg/mmol)
Dowex-50W (400 mg/mmol)
HClO4-SiO2 (200 mg/mmol)
NaHSO4-SiO2 (10 mol%)
Cyanuric chloride (20 mol%)
Ceric sulfate (20 mol%)
SiO2-Cl (250 mg/mmol)
0.6
2
3
12
21
10
11
The research
EXPERIMENTAL
NMR spectra were determined on a Bruker AV-300 spectrometer at room temperature
using TMS as internal standard; coupling constants (J) were measured in Hz. Elemental
analyses were performed by a Vario-III elemental analyzer. Melting points were determined
on a XT-4 binocular microscope and were uncorrected. Commercially available reagents
were used throughout without further purification unless otherwise stated.
Preparation of SiO2-Cl
To an oven-dried (120◦C, vacuum) sample of silica gel (10 g) in a round-bottomed
flask (250 mL) equipped with a condenser and a drying tube, thionyl chloride (40 mL) was
added, and the mixture was refluxed for 48 h. The unreacted thionyl chloride was distilled
off. The resulting white-grayish powder was flame-dried and stored in a tightly capped
bottle.
Table V Preparation of 1,8-dioxo-octahydroxanthenes catalyzed by SiO2-Cla
Entry
R
Products
Time(h)
Yield(%)
Mp(◦C)
Found Reported[ref.]
1
2
3
4
5
6
Ph
6a
6b
6c
6d
6e
6f
3
3.5
3.5
4
3
4
89
87
86
87
91
89
201–203
220–221
242–243
243–245
225–226
242–244
204–205 [30]
217–218 [30]
245–247 [30]
224–226 [30]
228–230 [30]
4-(CH3)C6H4
4-(MeO)C6H4
2-(Cl)C6H4
4-(Cl)C6H4
4-(I)C6H4

908
L. WU ET AL.
Typical Procedure: Preparation of 14-Substituted-14H-dibenzo[a,j]
xanthenes and 1,8-Dioxo-octahydroxanthenes
To a mixture of β-naphthol or dimedone (2 mmol) and aldehyde (1 mmol), SiO2-Cl
(250 mg) was added. The mixture was stirred at 110◦C for an appropriate time (Table III).
After completion of the reaction (TLC), ethyl acetate (20 mL) was added, and the solid
catalyst was removed by filtration. The solvent was evaporated, and the crude product was
recrystallized from EtOH to afford the pure product 3 or 6. All products were characterized
by comparison of their physical data and 1H NMR/13C NMR data with those of authentic
samples. The spectral data of some new 14-substituted-14H-dibenzo[a,j]xanthenes and
1,8-dioxo-octahydroxanthenes are given below.
14-(4-Iodophenyl)-14H-dibenzo[a,j]xanthene (3m). White solid, mp
1
>300◦C. IR (KBr, cm−1): 3432, 3022, 2918, 1635, 1590, 1243, 833, 802. H NMR
(CDCl3, 300 MHz): δ = 6.60 (s, 1H, ArCH), 7.32–7.80 (s, 14H, ArH), 8.22 (d, J = 8.2
Hz, 2H, ArH). 13C NMR(CDCl3, 75 MHz): δ = 39.8, 116.5, 118.9, 123.2, 125.1, 126.7,
129.6, 129.8, 130.8, 131.6, 131.9, 133.4, 144.0, 150.1. Anal. calcd for C27H17IO: C 66.96,
H 3.54; found C 67.12, H 3.34.
9-(4-Iodophenyl)-3,3,6,6-tetramethyl-3,4,6,7-tetrahydro-2H-xanthene-
1,8(5H,9H)-dione (6f). White solid, mp 242–244◦C. IR (KBr, cm−1): 3446, 3022, 2923,
1650, 1592, 1355, 1262, 1211, 1150, 705. 1H NMR (CDCl3, 300 MHz): δ = 1.02 (s, 6H,
CH), 1.16 (s, 6H, CMe2), 2.22–2.36 (q, J = 16.2 Hz, 4H, CH2), 2.53 (s, 4H, CH2), 4.76 (s,
1H, CH), 7.18 (d, J = 8.2 Hz, 2H, ArH), 7.36 (d, J = 8.2 Hz, 2H, ArH). 13C NMR(CDCl3,
75 MHz): δ = 28.4, 29.6, 31.8, 33.2, 41.6, 51.7, 116.8, 120.4, 130.8, 131.4, 143.9, 164.3,
192.8. Anal. calcd for C23H25IO3: C 57.99, H 5.29; found C 58.14, H 5.20.
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