Synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones catalyzed by biodegradable ionic liquid

Article abstract of DOI:10.1007/s11164-012-0709-4

A biodegradable acyclic SO₃H-functionalized ionic liquid has been used as a novel catalyst for the synthesis of 12-aryl-8,9,10,12- tetrahydrobenzo[a]xanthene-11-ones via one-pot multi-component condensation of β-naphthol, aromatic aldehydes, an

Full text of DOI:10.1007/s11164-012-0709-4

Res Chem Intermed (2013) 39:1745–1751
DOI 10.1007/s11164-012-0709-4
Synthesis of 12-aryl-8,9,10,
12-tetrahydrobenzo[a]xanthene-11-ones
catalyzed by biodegradable ionic liquid
•
Dong Fang Jin-ming Yang Yan-fang Cao
•
Received: 17 May 2012 / Accepted: 26 June 2012 / Published online: 13 July 2012
Ó Springer Science+Business Media B.V. 2012
Abstract A biodegradable acyclic SO3H-functionalized ionic liquid has been used as
a novel catalyst for the synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-
ones via one-pot multi-component condensation of b-naphthol, aromatic aldehydes, and
cyclic 1,3-dicarbonyl compounds, under solvent-free conditions, to afford good to
excellent yields ranging from 85 to 93 % within 30–60 min. After the reaction the
products could be simply separated from the reaction mixture and the catalyst could be
recycled and reused several times without noticeable reduction of catalytic activity.
Keywords Xanthene Á Synthesis Á Biodegradable ionic liquid Á Solvent-free Á
Multi-component reaction
Introduction
Xanthenes and benzoxanthenes are important heterocyclic compounds because of
their wide range of biological and pharmaceutical properties, for example antiviral
and anti-inflammatory activity, and their efficacy in photodynamic therapy [1, 2].
Furthermore, some of these compounds have been used as dyes [3], as pH-sensitive
fluorescent materials for visualization of bimolecules [4], and in laser technology
[5]. Thus, their versatility has made xanthenes prime synthetic candidates thus
accentuating the need to develop synthetic routes to xanthenes and benzoxanthenes.
Reported methods for synthesis of tetrahydrobenzo[a]xanthene-11-ones involve
three-component condensation of dimedone with an aromatic aldehyde and
2-naphthol in the presence of Lewis acids, Brønsted acids, or other organic
D. Fang (&) Á J. Yang Á Y. Cao
Department of Pharmaceutical Engineering, Yancheng Normal University,
50 Kai Fang Da Dao Yancheng, Jiangsu 224002, People’s Republic of China
e-mail: fangdong106@sina.com
123

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D. Fang et al.
compounds as catalysts [6–17]. However, the search for the new readily available
and green catalysts is still being actively pursued.
With increasing public concern over degradation of the environment and over
future resources, it became obvious that the solvents used in organic synthesis were
high on the list of environmental pollutants. An important approach is to develop
new processes involving the solvent-free conditions. In recent years, ionic liquids
have attracted increasing attention because of their particular properties, for
example negligible vapor pressure, wide liquid range, and high thermal stability,
making them a greener alternative to volatile organic solvents. In addition, Brønsted
acidic task-specific ionic liquids (TSILs) have a dual role (solvent and catalyst) in
multi-component reactions [18, 19], affording higher yields and selectivity than
traditional acid catalysts. Very recently, Luo and co-workers [20] used a magnetic
nanoparticle-supported dual acidic ionic liquid to catalyze the one-pot synthesis of
benzoxanthenes. In fact, use of Brønsted acidic TSILs as catalysts is a topic with
ongoing activity, and the development and investigation of TSILs for multi-
component reactions is, currently, extremely important.
In our previous work, novel, efficient, and eco-friendly SO3H-functional
halogen-free acidic TSILs were designed and their catalytic activity in multi-
component reactions was investigated [21–23]. In continuation of our work in
studying TSIL-catalyzed multi-component reactions, we now report here the
synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones in a biodegrad-
able acidic ionic liquid.
Results and discussion
The biodegradable ionic liquid [DDPA][HSO4], which combines a propane sulfonic
acid group with an acyclic dimethyldodecylammonium cation, was prepared in
accordance with our previous work. This catalyst is readily biodegradable; it can be
biodegraded in the activated sludge process [21].
Initially in this study, b-naphthol, benzaldehyde, and dimedone were selected as
model reactants to compare the catalytic performance of the TSILs. As shown in
Table 1, almost no xanthenes could be detected in the absence of ionic liquids (entry
1), which indicated that the catalyst was necessary for this multi-component
condensation reaction. All the prepared ionic liquids proved very active, generally
leading to 65–93 % yield of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones
in the presence of 3 % TSILs (entries 4, 7–9). In addition, the ionic liquid
[DDPA][HSO4] is biodegradable, which makes this procedure efficient and
environmentally benign. Hence, [DDPA][HSO4] should be the best catalyst for
this condensation among these catalysts; the optimized reaction conditions are listed
in Table 1 (entry 4).
Subsequently, the performance of [DDPA][HSO4], after recycling, in the same
model condensation reaction was investigated for economic and environmental
reasons. After the reaction, the catalyst could be extracted from the mixture with
water, washed with ethyl acetate, dried under vacuum, and reused in a subsequent
123

Synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones
1747
Table 1 Synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones in the presence of different
catalysts
Entry
Catalyst
Molar ratio (mol%)a
Time (min)
Yield (%)b
1
2
–
–
1
2
3
4
5
3
3
3
3
180
60
60
60
60
60
60
60
60
60
–
80
86
91
91
92
90
90
65
79
[DDPA][HSO4]
[DDPA][HSO4]
[DDPA][HSO4]
[DDPA][HSO4]
[DDPA][HSO4]
[MIMPSA][HSO4]
[PyPSA][HSO4]
[BMIM][HSO4]
p-Toluenesulfonic acid
3
4
5
6
7
8
9
10
1 mmol benzaldehyde, 1 mmol b-naphthol, 1.2 mmol dimedone
a
Molar ratio of catalyst to benzaldehyde
b
Isolated yields
reaction. The catalyst can be reused at least six times without appreciable decrease
in yield, which ranged from 91 to 88 % (Table 2), or reaction rate.
Multi-component condensation of other substituted benzaldehydes, b-naphthol,
and cyclic 1,3-dicarbonyl compounds under solvent-free conditions in the presence
of [DDPA][HSO4] was then accomplished under the above optimized reaction
conditions; the results are presented in Table 3.
As is apparent from Table 3, the procedure enabled effective preparation of the
required products, 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones 4. All
aromatic aldehydes with either electron-withdrawing or electron-donating groups,
for example nitro, or methoxy groups, gave reasonable to good yields ranging from
85 to 93 % within 30–60 min. Both dimedone and 1,3-cyclohexanedione gave good
results. However, aromatic aldehydes with electron-withdrawing groups are less
active than those with electron-donating groups. The benzoxanthenes were
characterized by the use of 1H NMR spectral data and comparison of their physical
properties with literature values.
Table 2 Reuse of the ionic
liquid [DDPA][HSO4]
Entry
Run
Isolated
yield (%)
1
2
3
4
5
6
7
Fresh
91
91
90
91
89
89
88
1
2
3
4
5
6
1 mmol benzaldehyde, 1 mmol
b-naphthol, 1.2 mmol
dimedone, 0.03 mmol catalyst,
90 °C, 60 min
123

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D. Fang et al.
Table 3 Synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones catalyzed by [DDPA]
[HSO4]
Entry
R1
R2
Time (min)
mp (°C) [Ref.]
Yield (%)a
1
C6H5
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
60
60
45
30
60
60
60
45
30
60
60
60
45
60
60
60
148–150 [8]
173–175 [17]
178–180 [8]
178–180 [8]
184–186 [17]
220–222 [8]
222–224 [8]
166–167 [8]
176–178 [8]
175–176 [8]
202–204 [8]
185–187 [20]
202–204 [20]
228–230 [20]
201–203 [20]
179–181 [20]
91
92
90
91
89
87
85
91
93
86
85
87
85
90
88
85
2
m-ClC6H4
p-ClC6H4
3
4
2,4-ClC6H3
p-BrC6H4
p-HOC6H4
o-NO2C6H4
m-NO2C6H4
p-NO2C6H4
p-CH3C6H4
p-CH3OC6H4
C6H5
5
6
7
8
9
10
11
12
13
14
15
16
p-ClC6H4
H
m-NO2C6H4
p-CH3C6H4
p-CH3OC6H4
H
H
H
1 mmol benzaldehyde, 1 mmol b-naphthol, 1.2 mmol cyclic 1,3-dicarbonyl compounds, 0.03 mmol
catalyst, 90 °C
a
Isolated yields
The results obtained with b-naphthol, benzaldehyde, and dimedone under the
optimized conditions were compared with those obtained by use of other catalysts
reported in recent years for this reaction, the data listed in Table 4 show that the
biodegradable ionic liquid [DDPA][HSO4] was relatively a good catalyst for
synthesis of tetrahydrobenzo[a]xanthene-11-ones.
Table 4 Comparison of our results with those for previously reported methods
Entry
Catalyst
Reaction conditions
Time
Yield (%) [Ref.]
1
InCl3
Neat/120 °C
CH2Cl2/reflux
CH2Cl2/80 °C
H2O/80 °C
[bmim]BF4/80 °C
Neat/80 °C
30 min
4 h
84 [8]
2
NaHSO4ÁSiO2
Sr(OTf)2
87 [9]
3
5 h
85 [10]
88 [12]
90 [13]
90 [14]
93 [15]
85 [16]
89 [17]
89 [20]
91 (This work)
4
Proline triflate
p-Toluenesulfonic acid
Caro’s acid–SiO2
TCT
2.5 h
3 h
5
6
30 min
30 min
2 h
7
Neat/80 °C
8
CAN
DCM-EtOH/us/26 °C
Neat/110 °C
Neat/90 °C
9
Trityl chloride
AIL@MNP
[DDPA][HSO4]
50 min
45 min
60 min
10
11
Neat/90 °C
123

Synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones
1749
Conclusions
In summary, it was demonstrated that a readily available, economical, task-specific
ionic liquid could be used as a recyclable catalyst for the condensation of
benzaldehydes, b-naphthol, and cyclic 1,3-dicarbonyl compounds in the synthesis of
12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones under solvent-free condi-
tions. The merit of this methodology is that it is simple, highly efficient, and
environmentally benign.
Experimental
Melting points were determined on an X-6 melting point apparatus with microscope.
1H NMR spectra were recorded on a Bruker DRX300 (300 or 500 MHz)
spectrometer and 13C NMR spectra on Bruker DRX300 (75.5 MHz) spectrometer.
Mass spectra were obtained with an automated Finnigan Trace Ultra-Trace DSQ
GC/MS spectrometer. All chemicals (AR grade) were commercially available and
used directly without further purification.
Synthesis of SO3H-functional acidic ionic liquid [DDPA][HSO4]
The biodegradable SO3H-functionalized ionic liquid [DDPA][HSO4] was synthe-
sized in accordance with our previous methods [21]. The pyridine, imidazole-based
SO3H-functionalized ionic liquids used for comparison were obtained in accordance
with reported methods [24, 25]. Structural analysis of TSILs was performed by use
1
of H NMR, 13C NMR, and MS data (Scheme 1).
Selected spectral data for SO3H-functionalized [DDPA][HSO4]:
3-(N,N-dimethyldodecylammonium)propanesulfonic acid hydrogen sulfate
1
[DDPA][HSO4]. H NMR (300 MHz, D2O): d0.53 (t, 3H, J = 6.62 Hz, –CH3),
0.95–1.02 (m, 18H, –(CH2)9–), 1.42 (m, 2H, –C–CH2–C–N), 1.83–1.87 (m, 2H, –C–
CH2–C–SO3), 2.60 (t, 2H, J = 6.91 Hz, –CH2–SO3), 2.77 (s, 6H, N–CH3), 2.98 (t,
J = 7.95 Hz, 2H, –C–CH2–N), 3.14 (t, J = 8.25 Hz, 2H, –CH2–C–C–SO3). Ansl.
Calcd. For CHNOS: C, 47.09; H, 9.07; N, 3.23; Found: C, 46.82; H, 9.08; N, 3.09.
MS (m/z): 432.18 (M? - 1).
C12H25
CH3
O
O
O
H2SO4
S
H2O
+
C12H25
N
N
SO3H HSO4
CH3
CH3
CH3
[DDPA][HSO4]
Scheme 1 Synthesis and structure of the acidic functional ionic liquid [DDPA][HSO4]
123

1750
D. Fang et al.
R1-CHO
2
R1
O
OH
[DDPA][HSO4]
90 °C
+
R2
R2
O
O
O
1
R2
4
R2
3
Scheme 2 Synthesis of tetrahydrobenzo[a]xanthene-11-ones catalyzed by [DDPA][HSO4]
General procedure for synthesis of 12-aryl-8,9,10,12-
tetrahydrobenzo[a]xanthene-11-ones
In a typical experiment, [DDPA][HSO4] (0.3 mmol) was added, with stirring, to b-
naphthol (1 mmol) 1, aldehyde (1 mmol) 2, and a cyclic 1,3-dicarbonyl compound
(1.2 mmol) 3 in a round-bottomed flask. The mixture was then stirred for a specific
time at 90 °C (Scheme 2). On completion (monitored by TLC), 5 mL water was
added and the precipitated crude product was collected by filtration and
recrystallized from ethanol (95 %) to afford pure 12-aryl-8,9,10,12-tetra-
hydrobenzo[a]xanthene-11-one 4. The ionic liquid contained in the filtrate was
then washed with ethyl acetate and used for subsequent cycles after drying under
vacuum. The products were identified by IR and 1H NMR, and comparison of their
physical data (m.p.) with those reported in the literature.
Selected data for benzoxanthene:
9,9-dimethyl-12-phenyl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-one (product
1
4a, C25H22O2). White solid; m.p. 148–150 °C; H NMR (300 MHz, CDCl3): d
0.92 (s, 3H, CH3), 0.95 (s, 3H, CH3), 2.26 (d, J = 16.2 Hz, 1H, CH2), 2.33 (d,
J = 16.2 Hz, 1H, CH2), 2.52 (s, 2H, CH2), 5.62 (s, 1H, CH), 6.81–7.70 (m, 11H,
Ar-H).
Acknowledgments We express our sincere thanks to the Ministry of Science and Technology of the
P.R. China (11C26213201395), Jiangsu Provincial Department of Education (JHB2011-52), and the Key
Laboratory of Organic Synthesis of Jiangsu Province (KJS1112) for financial assistance.
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