An effective bismuth trichloride-catalyzed synthesis of 1,8-dioxo-octahydroxanthenes

Article abstract of DOI:10.1080/10426500701724530

Bismuth trichloride has been found to be an efficient catalyst for the synthesis of 1,8-dioxo-octahydroxanthenes from aromatic aldehydes and 5,5-dimethyl-1,3-cyclohexanedione under solvent-free conditions in high yields. Copyright Taylor & Francis Group,

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Phosphorus, Sulfur, and Silicon
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An Effective Bismuth
Trichloride-Catalyzed
Synthesis of 1,8-Dioxo-
Octahydroxanthenes
Jian-Jiong Li a , Xu-Ye Tao a & Zhan-Hui Zhang a
a The College of Chemistry & Material Science ,
Hebei Normal University , Shijiazhuang, China
Published online: 24 Jun 2008.
To cite this article: Jian-Jiong Li , Xu-Ye Tao & Zhan-Hui Zhang (2008) An Effective
Bismuth Trichloride-Catalyzed Synthesis of 1,8-Dioxo-Octahydroxanthenes,
Phosphorus, Sulfur, and Silicon and the Related Elements, 183:7, 1672-1678, DOI:
10.1080/10426500701724530
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Phosphorus, Sulfur, and Silicon, 183:1672–1678, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701724530
An Effective Bismuth Trichloride-Catalyzed Synthesis
of 1,8-Dioxo-Octahydroxanthenes
Jian-Jiong Li, Xu-Ye Tao, and Zhan-Hui Zhang
The College of Chemistry & Material Science, Hebei Normal University,
Shijiazhuang, China
Bismuth trichloride has been found to be an efficient catalyst for the synthesis
of 1,8-dioxo-octahydroxanthenes from aromatic aldehydes and 5,5-dimethyl-1,3-
cyclohexanedione under solvent-free conditions in high yields.
Keywords Aldehyde; bismuth trichloride; solvent-free; xanthene
INTRODUCTION
Heterocycles play an important role in the design and discovery of new
physiological/pharmacologically active compounds.1 Chemically, 1,8-
dioxo-octahydroxanthenes are heterocyclic compounds with the xan-
thene framework. Xanthene derivatives are very useful and important
organic compounds widely used as dye,2 in laser technologies,3 and fluo-
rescent materials for visualization of biomolecules.4 Furthermore, these
compounds have shown promising activities such as antibacterial, an-
tiviral and anti-inflammatory activities.5 They are also valuable syn-
thons because of the inherent reactivity of the inbuit pyran ring.6
Thus, the synthesis of these heterocyclic compounds is inter-
esting for both organic synthesis and medicinal chemistry. Many
methods are disclosed for the synthesis of xanthenes.7 Recently, the
condensation of aldehydes with 1,3-cyclohexanedione or 5,5-dimethyl-
1,3-cyclohexanedione to the corresponding xanthenes has attracted
much attention, which was conducted in the presence of strong protonic
acids,5 Lewis acids such as InCl3·4H2O,8 FeCl3·8H2O,9 NaHSO4,10
Received 30 July 2007; accepted 5 August 2007.
The authors thank the Science Foundation from Hebei Normal University
(L20061314), the Nature Science Foundation of Hebei Province (B2005000151) and the
Natural Science Foundation of Hebei Education Department (2006318) for financial sup-
port of this work.
Address correspondenceto Zhan-Hui Zhang, The College of Chemistry & Material Sci-
ence, Hebei Normal University, Shijiazhuang 050016, China. E-mail: zhanhui@126.com
1672

Bismuth Trichloride-Catalyzed Synthesis of Xanthenes
1673
and heterogeneous catalysts like Dowex-50W,11 NaHSO4·SiO2,12
silica
TiO2/SO2−
sulfuric,13
polyaniline-p-toluenesulfonate,14
PPA-SiO2,15
,
16 and Amberlyst-15.17 Other catalysts, such as trimethylsi-
4
lyl chloride,18 p-dodecylbenzenesulfonic acid,19,20 trienthylbenzy-
lammonium chloride,21 and NH2SO3/SDS22 have also been used for
this transformation. It has also reported that the above condensation
process could proceed in ionic liquid23 or ethylene glycol.24−25 However,
some of these methodologies have not been entirely satisfactory,
with disadvantage such as low yields, prolonged reaction time, harsh
reaction conditions, and requirement of excess of catalysts, special
apparatus. Consequently, there is still need to develop a more efficient,
simple, milder and high yielding protocol for the synthesis of xanthene
derivatives.
In recent years, bismuth compounds have been used as catalysts
in organic synthesis because these compounds are relatively non-
toxic, easy to handle, low cost, and good stability.26 Among these, bis-
muth (III) trichloride has gain special attention because this com-
pound not only is commercially available and inexpensive, but also
of high stability. Bismuth (III) trichloride has been reported to be
an efficient reagent for many important organic transformations, in-
cluding intramolecular hetero-Diels-Alder reactions,27 selective hy-
droarylation of styrenes with electron-rich arenas,28 propargylic sub-
stitution reaction,29 C-alkylation of pyrroles with electron-deficient
olefins,30 Pechmann condensation,31 chemoselective deprotection of N-
Boc group in amino acids and peptides,32 regioselective ring opening of
epoxides33−34 and aziridines,35 direct deoxygenative allylation of sub-
stituted benzylic alcohols with allyltrimethylsilane,36 the synthesis of
quinolines,37 4-substituted coumarins,38 α-amino phosphonates.39 In
continuation of our previous work on the applications of cheap and
ecofriendly materials as catalysts for development of new synthetic
methodologies,40 in this paper, we would like to report a mild and high
yielding solvent-free method to prepare 1,8-dioxo-octahydroxanthene
derivatives using a catalytic amount of BiCl3 (Scheme 1).
O
Ar
O
O
O
BiCl3 (10 mol%)
ArCHO +2
neat conditions, 80 oC
O
1
2
3
SCHEME 1

1674
J.-J. Li et al.
TABLE I The Condensation Reaction of 4-Chlorobenzaldehyde and
5,5-Dimethyl-1,3-cyclohexanedione under Different Reaction
Conditions
Cl
Cl
CHO
O
O
O
O
O
+
2
+
O
Cl
1j
O
OH OH
2
4
3j
Entry BiCl3(mol%) Temperature (◦C) Time (h)
Yield (%)a
b
1
2
3
4
5
6
7
8
0
0
10
10
10
5
25
80
25
60
80
80
80
80
10
2
6
2
2
4
2
2
—
c
—
15
71
93
80
90
92
15
20
aIsolated yield; bcompound 4 was formed in 32% yield; and ccompound 4 was
formed in 90% yield.
RESULTS AND DISCUSSION
Initially, 4-chlorobenzaldehyde (1j) was selected as probe aldehyde to
optimize the reaction conditions, and the results are listed in Table I.
Obviously, the temperature and the amount of catalyst had important
effects on the reaction. The reaction in absence of catalyst afforded only
intermediate 4 as a lone product (Table I, entries 1 and 2). However,
the addition of a catalytic amount of BiCl3 resulted in the product 3j.
The result showed that BiCl3 had catalytic effect on the synthesis 3j.
With 10 mol% of catalyst, the yield of 3j increased from 15% to 93% as
◦
the temperature increased from 25◦C to 80 C (Table I, entries 3–5).
Similar changes in the yields with the catalyst amount at a constant
temperature were also observed. Therefore, it was reasonable to con-
clude that the best conditions were 10 mol% of BiCl3 at 80◦C, where the
maximum yield of 93% could be obtained within 2 h. Higher amounts
of the catalyst did not improve the results to a greater extent.
Having established the optimized experimental conditions, var-
ious aldehydes (1) were subjected to react with 5,5-dimethyl-1,3-
cyclohexanedione (2) in order to investigate the reaction scope and

Bismuth Trichloride-Catalyzed Synthesis of Xanthenes
1675
TABLE II BiCl3-Catalyzed Synthesis of
1,8-Dioxo-octahydroxanthene Derivatives at 80 ◦C
Entry
Aldehydes
Time (h) Yield (%)a Found M.P. (◦C) (Lit.)
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
PhCHO
4-MeC6H4CHO
3
4
5
5
6
6
6
4
2
2
6
3
6
2
4
4
4
9
90
86
88
90
75
78
80
85
90
93
80
91
82
85
85
88
91
75
200–202 (201–203)18
210–211 (210–212)8
224–226 (224–226)24
161–162 (160–162)18
182–183 (184–185)41
225–227( 226–228) 19
247–248 (246–249) 42
224–225 (224–226)19
226–227 (225–227)21
228–230 (230–232)18
225–227 (228–230)19
183–185 (182–184)20
253–254 (254–255)18
238–239 (240–242)18
145–146 (145–147)8
222–224 (223–224)42
162–164
4-MeOC6H4CHO
3-MeOC6H4CHO
3,4-(MeO)2C6H3CHO
3-MeO-4-OHC6H3CHO
4-OHC6H4CHO
3,4-(OCH2O)C6H3CHO
4-FC6H4CHO
4-ClC6H4CHO
2-ClC6H4CHO
3-ClC6H4CHO
2,4-Cl2C6H3CHO
4-BrC6H4CHO
3-NO2C6H4CHO
4-NO2C6H4CHO
Thiophene-2-carbaldehyde
Pyridine-2-carbaldehyde
203–204
aIsolated yield.
several representative results are summarized in Table II. As shown
in Table II, benzaldehyde, and other aromatic aldehydes contain-
ing electron-withdrawing groups (such as halide, nitro) or electron-
donating groups (such as methyl, methoxy, hydroxyl) were employed
and reacted well to give the corresponding 1,8-dioxo-octahydroxanthene
derivatives in good to excellent yields. Generally, ortho-substituted ben-
zaldehydes required longer reaction times due to the steric hindrance
(Table II, entries k and m). Thiophene-2-carbaldehyde (Table II, entry
q) was also a good partner and excellent yield was obtained, whereas re-
action of pyridine-2-carbaldehyde (Table II, entry r) afforded only 75%
yield and long reaction time was required. Structures of synthesized
1
compounds were assigned on the basis of their IR, H NMR, elemen-
tal analyses, and also by comparison with authentic samples.17 The
IR spectra of products 3a–3r showed two absorption bands at 1580–
1622 and 1640–1662 cm−1, corresponding to the stretching vibrations
of the conjugated system of bonds C C C O. The disappearance of
the band at 1705–1725 due to C O group of aldehydes confirmed the
formation of product. In addition, 3r showed the absence of a band at
3500–3000 cm−1 corresponding to a hydroxyl group, thus confirming
the ring closure. The appearance of a singlet at δ4.86 due to the CH

1676
J.-J. Li et al.
proton in the 1H NMR spectrum of 3r further confirmed the formation
of product.
In summary, we have demonstrated that BiCl3 is an efficient catalyst
for the synthesis of 1,8-dioxo-octahydroxanthene derivatives by con-
densation of aldehydes with 5,5-dimethyl-1,3-cyclohexanedione. This
method is bestowed with several unique merits, such as high conver-
sions, simplicity in operation, solvent-free conditions, and use of low
cost and commercially available bismuth chloride as catalyst.
EXPERIMENTAL
Melting points were recorded on X-4 apparatus. IR spectra were ob-
tained using Shimadzu FTIR-8900 spectrometer. 1H NMR spectra were
recorded with a Bruker AV 300 or a Varain Mercury Plus 400 spectrom-
eter using TMS as internal standard. Elemental analyses were carried
out on Vario EL III CHNOS Elemental Analyzer.
Representative Procedure for the Synthesis
of 1,8-Ddioxo-octahydroxanthene Derivatives
Thiophene-2-carbaldehyde (0.112 g,
1 mmol), 5,5-dimethyl-1,3-
cyclohexanedione (0.280 g, 2 mmol) and BiCl3 (0.031 g, 0.1 mmol) were
added to a mortar. The mixture was ground by pestle and heated at 80◦C
for an appropriate time (monitored by TLC). After completion of the re-
action, mixture was cooled to room temperature, extracted with 3 × 10
ml dichloromethane. The organic layer was washed with water, dried
over MgSO4, and concentrated to obtained crude product. The crude
product was purified by silica gel column chromatography (40% ethyl
acetate in n-hexane as eluent) to furnish the pure 3,3,6,6-Tetramethyl-
9-thiophen-2-yl-1,8-dioxo-octahydroxanthene (0.323g, 91%) as white
solid.
3,3,6,6-Tetramethyl-9-(4-bromophenyl)-1,8-dioxo-
octahydroxanthene (3n)
White solid; IR (KBr): 2933, 1661, 1586, 1362, 1274, 1200, 1138, 1047,
694 cm−1; 1H NMR (300 MHz, CDCl3): δ1.00 (s, 6H), 1.11 (s, 6H), 2.26
(s, 6H), 2.15–2.47 (m, 8H), 4.70 (s, 1H), 7.18 (d, J = 8.1 Hz, 2H), 7.30
(d, J = 8.1 Hz, 2H) ppm; Anal. calcd. for C23H25BrO3: C, 64.34; H, 5.87.
Found: C, 64.08; H, 5.98.
3,3,6,6-Tetramethyl-9-thiophen-2-yl-1,8-dioxo-
octahydroxanthene (3q)
White solid; IR (KBr): 2956, 2895, 2871, 1658, 1622, 1371, 1359, 1199
1
cm−1; H NMR (300 MHz, CDCl3): δ1.05 (s, 6H), 1.11 (s, 6H), 2.26 (s,

Bismuth Trichloride-Catalyzed Synthesis of Xanthenes
1677
4H), 2.45 (s, 4H), 5.15 (s, 1H), 6.82 (dd, J = 5.1, 3.6 Hz, 1H), 6.96 (d,
J = 3.6 Hz, 1H), 7.02 (dd, J = 5.1, 0.9 Hz, 1H) ppm; Anal. calcd. for
C21H24O3S: C, 70.75; H, 6.79; Found: C, 70.90; H, 6.62.
3,3,6,6-Tetramethyl-9-pyridin-2-yl-1,8-dioxo-
octahydroxanthene (3r)
White solid; IR (KBr): 2958, 2930, 2874, 1681, 1657, 1623, 1199 cm−1
;
1H NMR (400 MHz, CDCl3): δ1.00 (s, 6H), 1.09 (S, 6H), 2.15 (d, J = 16
Hz, 2H), 2.23 (d, J = 16 Hz, 2H), 2.44 (d, J = 17.6 Hz, 2H), 2.52 (d, J =
17.6 Hz, 2H), 4.86 (s, 1H), 6.94-7.00 (m ,1H), 7.45-7.61 (m 2H), 8.37 (d,
J = 4.4 Hz, 1H); Anal. calcd. for C22H25NO3: C, 75.19; H, 7.17; N, 3.99;
Found: C, 75.45; H, 7.32; N, 3.78.
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