Efficient one-pot three-component synthesis of 3,4-dihydro-12-phenyl-2H- benzo[b] xanthene-1,6,11(12H)-trione derivatives in ionic liquid

Article abstract of DOI:10.1007/s11164-012-0688-5

A series of 3,4-dihydro-12-phenyl-2H-benzo[b]xanthene-1,6,11(12H)-trione derivatives have been synthesized in high yields in the presence of ionic liquid [bmim⁺]Br^-. The reaction work-up is simple and the ionic liquid can be easily separated from the product and reused.

Full text of DOI:10.1007/s11164-012-0688-5

Res Chem Intermed (2013) 39:1323–1333
DOI 10.1007/s11164-012-0688-5
Efficient one-pot three-component synthesis of 3,4-
dihydro-12-phenyl-2H-benzo[b] xanthene-1,6,11
(12H)-trione derivatives in ionic liquid
•
Baixiang Du Gan Cai Bo Zhao Xiangxue Meng
•
•
•
•
Xiangshan Wang Yuling Li
Received: 5 March 2012 / Accepted: 8 June 2012 / Published online: 29 June 2012
Ó Springer Science+Business Media B.V. 2012
Abstract A series of 3,4-dihydro-12-phenyl-2H-benzo[b]xanthene-1,6,11(12H)-
trione derivatives have been synthesized in high yields in the presence of ionic
liquid [bmim?]Br-. The reaction work-up is simple and the ionic liquid can be
easily separated from the product and reused.
Keywords MCRs Á Benzo[b]xanthene Á Synthesis Á Ionic liquid
Introduction
In current day research, multicomponent reactions (MCRs) have proven to be one of
the most efficient tools to construct highly complex molecules and introduce
molecular diversity from simple building blocks via one-pot reaction [1, 2]. This
synthetic strategy has been widely used in organic, combinatorial, and medicinal
chemistry.
Xanthenes and benzoxanthenes are an important structural motif in biologically
relevant compounds and pharmaceuticals, which possess antiviral, anti-inflamma-
tory, anticancer, and antibacterial activities [3–6]. These are being utilized as
antagonists for drug-resistant leukemia lines [7] and in photodynamic therapy [8].
In addition, these heterocyclic molecules have been widely used as dyes [9],
pH-sensitive fluorescent materials for visualization of biomolecules [10]. The
1,4-naphthoquinone structure is also common in natural products associated with
anti-inflammatory, antifungal, antiviral, and antitumor activities [11–14]. Therefore,
the synthesis of benzoxanthenes with a 1,4-naphthoquinone structure is of great
importance to organic chemists.
B. Du Á G. Cai Á B. Zhao Á X. Meng Á X. Wang Á Y. Li (&)
Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, School of
Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou 221116, China
e-mail: ylli19722@163.com
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B. Du et al.
Some methods are available for the synthesis of benzoxanthenes with a 1,4-
naphthoquinone structure. Chen et al. developed a rapid and efficient method to
synthesize a series of benzoxanthenes with a 1,4-naphthoquinone structure by the
reaction of aldehydes and 2-hydroxynaphthalene-1,4-dione in mixed solvent of
acetic acid and ethylene glycol under microwave irradiation [15]. Bazgir reported
similar results catalyzed by p-toluenesulfonic acid (p-TSA) [16]. Bazgir et al.
synthesized dibenzo[a,i]xanthene-diones with a 1,4-naphthoquinone structure via
cyclo-condensation reaction of 2-hydroxynaphthalene-1,4-dione, aromatic alde-
hydes, and dimedone in aqueous media in the presence of p-TSA [17]. Wu
developed a simple and facile synthesis of 14-aryl-14H-dibenzo[a,i]xanthene-8,13-
dione derivatives by the one-pot condensation of 2-naphthol, aldehydes, and
2-hydroxy-1,4-naphthoquinone under solvent-free conditions in the presence of the
heterogeneous catalyst silica chloride [18]. Wu prepared 12-aryl-12H-benzo[i][1,3]-
dioxolo[4,5-b]xanthene-6,11-diones by condensing a variety of aldehydes with
3,4-methylenedioxyphenol and 2-hydroxy-1,4-naphthoquinone in the presence of a
catalytic amount of HClO4–SiO2 or silica sulfuric acid under solvent-free conditions
[19, 20]. However, these methods suffer from disadvantages such as the use of
organic solvents, long reaction times, requirement of complicated catalysts, and
harsh reaction conditions. The development of a synthetic protocol that is devoid of
the above-mentioned problems and yet environmentally benign, simple, and
efficient for the synthesis of benzoxanthenes with a 1,4-naphthoquinone structure is
in great demand.
Ionic liquids (IL) have attracted extensive interest as benign reaction media in
organic synthesis in recent years because of their unique properties of non-volatility,
nonflammability, recyclability, and ability to dissolve a wide range of materials.
As a result of their green credentials and potential to enhance reaction rates and
selectivity, ionic liquids have found increasing applications to organic synthesis
[21, 22].
In continuation of our studies in developing environmentally benign methodol-
ogies for synthesis of heterocyclic compounds, [23–25] here we report on the
synthesis of a series of 3,4-dihydro-12-phenyl-2H-benzo[b]xanthene-1,6,11(12H)-
trione derivatives by the reactions of aromatic aldehyde, 2-hydroxy-1,4-naphtho-
quinone, and cyclic 1,3-dicarbonyl compounds in ionic liquid [bmim?][Br-] at
90 °C (Scheme 1), and [bmim?][Br-] is used here as an efficient catalyst as well as
solvent, which can be recycled and reused. To the best of our knowledge, this
O
O
O
Ar
O
O
O
O
OH
+
R
R
+
IL
90 oC
Ar CHO
R
R
O
R = H or CH3
4
1
2
3
Scheme 1 The synthesis of compound 4
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Efficient one-pot three-component synthesis
1325
Table 1 Optimization of the
Entry
T/ °C
Medium
Time/h
Yielda/%
reaction conditions for synthesis
of 4a
1
60
80
100
70
rt
Acetone
24
24
24
24
24
7
20
35
36
24
0
2
EtOH
3
DMF
4
CH3CN
5
[bmim]Br
[bmim]Br
[bmim]Br
[bmim]Br
[bmim]Br
[bmim]Br
[emim]Br
[pmim]Br
[emim]BF4
[bmim]BF4
[pmim]BF4
[bmim]PF6
6
70
90
110
90
90
90
90
90
90
90
90
65
80
80
86
85
65
62
60
80
66
73
7
7
8
7
9
9
10
11
9
11
Reaction condition: 5 mL
12
of ionic liquid, 1 mmol of
9
13
9
4-chlorobenzaldehyde,
1 mmol of 2-hydroxy-1,4-
14
15
16
9
naphthoquinone, 1 mmol of 5,5-
dimethyl-1,3-cyclohexanedione
9
9
a
Isolated yields
methodology has not been reported in the literature. The ionic liquid not only makes
the synthetic process clean, and safe but also affords the products in high yield.
Results and discussion
In the initial studies, we investigated the condensation reaction of 4-chlorobenz-
aldehyde, 2-hydroxy-1,4-naphthoquinone, and 5,5-dimethyl-1,3-cyclohexanedione
in traditional solvents (acetone, EtOH, DMF, and CH3CN). The results are listed in
Table 1. In these cases, Product 4a was formed in low yields (Table 1, entries 1–4)
even after 24 h whereas the same reaction in the presence of ionic liquid
[bmim?][Br-] as an environmentally friendly medium provided 65 % of 4a in only
7 h at 70 °C (Table 1, entry 6).
To further optimize the reaction conditions, we investigated the effect of
temperature and reaction time on reaction rate as well as on yields of products. It
showed that no product could be detected at room temperature (Table 1, entry 5)
even after 24 h. The yield of product 4a was improved and the reaction time was
shortened as the temperature was increased from 70 to 110 °C. The yield plateaued
when the temperature was further increased to 110 °C (Table 1, entries 6–8). So, the
most suitable reaction temperature is 90 °C. The effect of reaction time on yields of
product 4a was also investigated. The reactions were performed in ionic liquid
[bmim?][Br-] for 7, 9, or 11 h at 90 °C (Table 1, entries 7, 9, 10), leading to 4a in
80, 86, and 85 % yield, respectively. Thus, the optimal reaction time is 9 h.
Moreover, different ionic liquids were further studied as shown in Table 1 (entries
11–16). It was found that the ionic liquids with anion Br- afforded 4a in higher
yields than those with anion BF4- or PF6- (Table 1, entries 9, 14, 16). Additionally,
123

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B. Du et al.
for ionic liquids with anion Br-, the effect of the cation was also investigated, and
the ionic liquid with cation bmim? afforded 4a in the highest yields (Table 1,
entries 9, 11, 12) among all the cations, which implied that both cation and anion in
ionic liquids have effects on the reaction. On the basis of the above results, we can
conclude that [bmim]Br was the best ionic liquid for this reaction. The amount of
ionic liquid and ratio of reactants had no obvious effect on the reaction, and the
results are provided in Table 2.
After optimizing the reaction conditions, a variety of aromatic aldehydes were
employed under similar circumstances to evaluate the substrate scope of this
reaction. The results are summarized in Table 3. Data from Table 3 demonstrate
that aromatic aldehydes carrying both electron-withdrawing and electron-releasing
substituents were converted to their corresponding benzo[b]xanthene-1,6,11(12H)-
trione derivatives in good yields under the optimal conditions described above. All
1
the products were characterized by their melting points, H NMR, IR, and HRMS.
The IR spectra of compounds 4a–q showed intense bands in the region
1
1,616–1,698 cm-1 due to carbonyl stretching. The H NMR spectra which were
recorded in DMSO-d6 support the proposed structure of the compounds. The CH
1
proton (C12) appeared as a single at d 4.83–5.32 ppm in H NMR spectral data of
compounds 4a–q. The CH3 (C3) protons appeared as a single at d 0.94–1.10 ppm
1
and CH2 (C2 and C4) protons showed double at d 2.10–2.79 ppm in H NMR
spectral data of compounds 4a–l. The CH2 (C2, C3, and C4) protons appeared
1
multiplet at d 1.78–2.84 ppm in H NMR spectral data of compounds 4m–q.
We have not established an exact mechanism for the formation of 4, however, a
reasonable possibility is shown in Scheme 2. Firstly, Knoevenagel condensation
between aromatic aldehyde 1 and cyclic 1,3-dicarbonyl compounds 3 would give
intermediate 5. Then, Michael addition of 5 to 2-hydroxy-1,4-naphthoquinone 2
would furnish intermediate 6. By keto-enol tautomerization, 6 is in rapid
equilibrium with 7. Finally, the product 4 would be produced by an intramolecular
cyclization and dehydration.
Under the reaction conditions described above, various aromatic aldehydes were
reacted with 2-hydroxy-1,4-naphthoquinone and cyclic 1,3-dicarbonyl compounds
smoothly in ionic liquid media to give 4 in high yields (Table 3). The work-up of
the reaction involves only a filtration and simple washing step with water, then
recrystallizing with DMF.
Table 2 Synthesis of 4a in ionic liquid [bmim]Br with different conditions
Entry
Ionic liquids
Reactant ratioa
Volume of [bmim]Br (mL)
Yieldb (%)
1
2
3
4
5
a
[bmim]Br
[bmim]Br
[bmim]Br
[bmim]Br
[bmim]Br
1/1.1/1.1
1.1/1/1.1
1.1/1.1/1
1/1/1
5
5
86
86
86
85
86
5
2.5
10
1/1/1
Mol ratio of 4-chlorobenzaldehyde to 2-hydroxy-1,4-naphthoquinone and 5,5-dimethyl-1,3-cyclohex-
anedione at 90 °C
b
Isolated yields
123

Efficient one-pot three-component synthesis
1327
O
O
HO
Ar
O
O
O
O
O
O
R
R
2
R
R
R
Ar C H
+
CHAr
R
O
O
O
O
1
3
5
6
Ar
O
O
O
O
O
Ar
H
O
O
O
Ar
O
R
R
-H2O
R
R
R
R
O
OH
O
O
HO
4
7
Scheme 2 Mechanism of the reaction
Table 3 Synthesis of 4 in ionic liquid [bmim?][Br-]
Entry
Ar
R
Product
Time/h
Yieldsa/%
1
4-ClC6H4
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
4a
4b
4c
4d
4e
4f
9
8
86
85
86
88
83
84
85
82
86
87
80
80
85
86
88
89
83
2
3-FC6H4
3
3-ClC6H4
9
4
3,4-OCH2OC6H3
3,4-(CH3)2C6H3
2-BrC6H4
8
5
9
6
8
7
2-ClC6H4
4g
4h
4i
10
9
8
4-FC6H4
9
3-OHC6H4
2,3-Cl2C6H3
3-NO2C6H4
4-NO2C6H4
3,4-OCH2OC6H3
4-FC6H4
9
10
11
12
13
14
15
16
17
4j
9
4k
4l
8
9
4m
4n
4o
4p
4q
8
H
9
3-OHC6H4
4-ClC6H4
H
8
H
9
2-CH3OC6H4
H
10
Reaction condition: 5 mL of ionic liquid, 1 mmol of aromatic aldehyde, 1 mmol of 2-hydroxy-
1,4-naphthoquinone, 1 mmol of 5,5-dimethyl-1,3-cyclohexanedione(entries 1–12) or 1,3-cyclohexane-
dione(entries 13–17), 90 °C
a
Isolated yields
Finally, the recovery and reuse of the ionic liquid [bmim?][Br-] were studied by
using the preparation of 4a as a model. Because of the poor solubility of the
products in ionic liquids, they were easily separated by simple filtration, and the
123

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B. Du et al.
100
80
60
40
20
0
Fig. 1 Reusability of ionic
liquid [bmim?][Br-]
86
85
83
83
1
2
3
4
Reaction cycle number
filtrate could be recovered easily by drying at 80 °C in vacuum for several hours.
As shown in Fig. 1, the reaction medium can be recycled at least four times without
significant decrease of the yields, ranging from 86 to 83 %.
Experimental
General
Melting points were determined in open capillaries without further correction. IR
1
spectra were recorded on a Tensor 27 spectrometer in KBr. H NMR spectra were
obtained from solution in DMSO-d6 with Me4Si as an internal standard using a Bruker-
400 spectrometer. HRMS data were obtained using a MicroTOF-QII instrument.
General procedure for preparation of 4
A dry 50-mL flask was charged with aromatic aldehyde 1 (1 mmol), 2-hydroxy-
1,4-naphthoquinone 2 (1 mmol), cyclic 1,3-dicarbonyl compounds 3 (1 mmol), and
ionic liquid [bmim?][Br-] (5 mL). The mixture was stirred at 90 °C for 8–10 h to
complete the reaction (monitored by TLC), then cooled to room temperature. The
solid residue was filtered off, and the ionic liquid in filtrate was then recovered by
evaporation for several hours at 90 °C in vacuum. The crude products were further
purified by recrystallization from DMF and water to give 4.
Characterization data
3,4-dihydro-3,3-dimethyl-12-(4-chlorophenyl)-2H-benzo[b]xanthene-1,6,11(12H)-
trione 4a
Yellow solid; mp: 286–287 °C (lit [17]. 282–284 °C); IR (KBr): m 2,963, 2,938,
1
1,681, 1,664, 1,617 cm-1; H NMR (DMSO-d6, 400 MHz): d 0.95 (s, 3H, CH3),
1.07 (s, 3H, CH3), 2.10 (d, 1H, J = 16.0 Hz, CH2), 2.32 (d, 1H, J = 16.0 Hz, CH2),
123

Efficient one-pot three-component synthesis
1329
2.65 (d, 1H, J = 17.6 Hz, CH2), 2.70 (d, 1H, J = 17.6 Hz, CH2), 5.31 (s, 1H, CH),
7.20–7.43 (m, 4H, ArH), 7.82–8.06 (m, 4H, ArH); HRMS calcd for C25H19ClO4
(M ? Na)?: requires 441.0864, found: 441.0896.
3,4-dihydro-3,3-dimethyl-12-(3-fluorophenyl)-2H-benzo[b]xanthene-1,6,11(12H)-
trione 4b
1
Brown solid; mp: 201–202 °C; IR (KBr): m 2,954, 2,935, 1,663, 1,619 cm-1; H
NMR (DMSO-d6, 400 MHz): d 0.96 (s, 3H, CH3), 1.08 (s, 3H, CH3), 2.16 (d, 1H,
J = 16.0 Hz, CH2), 2.31 (d, 1H, J = 16.0 Hz, CH2), 2.65 (d, 1H, J = 17.6 Hz,
CH2), 2.75 (d, 1H, J = 17.6 Hz, CH2), 4.93 (s, 1H, CH), 6.97–7.01 (m, 1H, ArH),
7.13–7.20 (m, 2H, ArH), 7.30 (d, 1H, J = 7.6 Hz, ArH), 7.84–7.92 (m, 3H, ArH),
8.05–8.07 (m, 1H, ArH); HRMS calcd for C25H19FO4 (M ? H)?: requires
403.1340, found: 403.1349.
3,4-dihydro-3,3-dimethyl-12-(3-chlorophenyl)-2H-benzo[b]xanthene-1,6,11(12H)-
trione 4c
Brown solid; mp: 206–208 °C; IR (KBr): m 2,959, 2,927, 1,681, 1,616, 1,619 cm-1
;
1H NMR (DMSO-d6, 400 MHz): d 0.94 (s, 3H, CH3), 1.07 (s, 3H, CH3), 2.16 (d,
1H, J = 16.0 Hz, CH2), 2.31 (d, 1H, J = 16.0 Hz, CH2), 2.63 (d, 1H, J = 17.6 Hz,
CH2), 2.73 (d, 1H, J = 17.6 Hz, CH2), 4.87 (s, 1H, CH), 7.20–7.28 (m, 3H, ArH),
7.36 (s, 1H, ArH), 7.81–8.04 (m, 4H, ArH); HRMS calcd for C25H19ClO4
(M ? H)?: requires 419.1045, found: 419.1069.
3,4-dihydro-3,3-dimethyl-12-(3,4-methylenedioxyphenyl)-2H-benzo[b]xanthene-
1,6,11(12H)-trione 4d
Yellow solid; mp: 241–243 °C; IR (KBr): m 2,959, 2,935, 1,664, 1,618 cm-1
;
1HNMR(DMSO-d6, 400 MHz): d 0.97 (s, 3H, CH3), 1.07 (s, 3H, CH3), 2.19 (d, 1H,
J = 16.0 Hz, CH2), 2.31 (d, 1H, J = 16.0 Hz, CH2), 2.63 (d, 1H, J = 16.8 Hz,
CH2), 2.71 (d, 1H, J = 16.8 Hz, CH2), 4.83 (s, 1H, CH), 5.94 (d, 2H, J = 7.2 Hz.
CH2), 6.77–6.86 (m, 3H, ArH), 7.84–7.86 (m, 2H, ArH), 7.91–7.94 (m, 1H, ArH),
8.04–8.06 (m, 1H, ArH); HRMS calcd for C26H20O6(M ? Na)?: requires 451.1152,
found: 451.1159.
3,4-dihydro-3,3-dimethyl-12-(3,4-dimethylphenyl)-2H-benzo[b]xanthene-
1,6,11(12H)-trione 4e
1
Yellow solid; mp: 232–233 °C; IR (KBr): m 2,959, 1,681, 1,666, 1,618 cm-1; H
NMR (DMSO-d6, 400 MHz): d 0.96 (s, 3H, CH3),1.07 (s, 3H, CH3), 2.10 (s, 3H,
CH3), 2.14–2.17 (m, 4H, CH3 ? CH2), 2.30 (d, 1H, J = 16.0 Hz, CH2), 2.65 (d,
1H, J = 16.8 Hz, CH2), 2.67 (d, 1H, J = 16.8 Hz, CH2), 4.83 (s, 1H, CH),
6.99–7.08 (m, 3H, ArH), 7.83–7.92 (m, 3H, ArH), 8.04–8.06 (m, 1H, ArH); HRMS
calcd for C27H24O4 (M ? H)?: requires 413.1753, found: 413.1733.
123

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B. Du et al.
3,4-dihydro-3,3-dimethyl-12-(2-bromophenyl)-2H-benzo[b]xanthene-1,6,11(12H)-
trione 4f
Pale yellow solid; mp: 275–277 °C; IR (KBr): m 2,958, 2,931, 1,698, 1,661 cm-1
;
1HNMR(DMSO-d6, 400 MHz): d 0.99 (s, 3H, CH3), 1.10 (s, 3H, CH3), 2.12 (d, 1H,
J = 16.0 Hz, CH2), 2.33 (d, 1H, J = 16.0 Hz, CH2), 2.74 (d, 1H, J = 17.6 Hz,
CH2), 2.79 (d, 1H, J = 17.6 Hz, CH2), 5.07 (s, 1H, CH), 7.04–7.09 (m, 1H, ArH),
7.24–7.32(m, 2H, ArH), 7.90 (d, 1H, J = 8.0 Hz, ArH), 7.68–7.22 (m, 1H, ArH),
7.86–7.90 (m, 1H, ArH), 7.98–8.03 (m, 2H, ArH); HRMS calcd for C25H19BrO4
(M ? H)?: requires 463.0540, found: 463.0536.
3,4-dihydro-3,3-dimethyl-12-(2-chlorophenyl)-2H-benzo[b]xanthene-1,6,11(12H)-
trione 4g
Yellow solid; mp: 276–277 °C; IR (KBr): m 2,989, 2,943, 1,698, 1,660 cm-1;1H
NMR (DMSO-d6, 400 MHz): d 0.99 (s, 3H, CH3), 1.10 (s, 3H, CH3), 2.13 (d, 1H,
J = 16.4 Hz, CH2), 2.33 (d, 1H, J = 16.4 Hz, CH2), 2.73 (d, 1H, J = 16.8 Hz,
CH2), 2.75 (d, 1H, J = 16.8 Hz, CH2), 5.07 (s, 1H, CH), 7.13–7.18 (m, 1H, ArH),
7.20–7.24 (m, 1H, ArH), 7.29–7.36 (m, 2H, ArH), 7.68–7.72 (m, 1H, ArH),
7.86–7.90(m, 1H, ArH), 7.97–8.03 (m, 2H, ArH); HRMS calcd for C25H19ClO4
(M ? H)?: requires 419.1045, found: 419.1023.
3,4-dihydro-3,3-dimethyl-12-(4-fluorophenyl)-2H-benzo[b]xanthene-1,6,11(12H)-
trione 4h
Yellow solid; mp: 227–229 °C; IR (KBr): m 2,956, 1,682, 1,662, 1,618 cm-1
;
1HNMR (DMSO-d6, 400 MHz): d 0.95 (s, 3H, CH3), 1.07(s, 3H, CH3), 2.17 (d,
1H, J = 16.4 Hz, CH2), 2.31 (d, 1H, J = 16.4 Hz, CH2), 2.65 (d, 1H,
J = 18.0 Hz, CH2), 2.71 (d, 1H, J = 18.0 Hz, CH2), 4.91(s, 1H, CH),
7.85–7.92 (m, 3H, ArH); 7.07 (t, 2H, J = 8.8 Hz, ArH), 7.35–7.81 (m, 2H,
ArH), 8.04–8.06 (m, 1H, ArH); HRMS calcd for C25H19FO4 (M ? Na)?: requires
425.1165, found: 425.1188.
3,4-dihydro-3,3-dimethyl-12-(3-hydroxyphenyl)-2H-benzo[b]xanthene-
1,6,11(12H)-trione 4i
1
Yellow solid; mp: 200–202 °C; IR (KBr): m 2,955, 2,936, 1,661, 1,616 cm-1; H
NMR (DMSO-d6, 400 MHz): d 0.98 (s, 3H, CH3), 1.08 (s, 3H, CH3), 2.18 (d, 1H,
J = 16.4 Hz, CH2), 2.32 (d, 1H, J = 16.4 Hz, CH2), 2.66 (d, 1H, J = 17.6 Hz,
CH2), 2.71 (d, 1H, J = 18.0 Hz, CH2), 4.83 (s, 1H, CH), 6.52–6.54 (m, 1H, ArH),
6.71 (d, 1H, J = 7.6 Hz, ArH), 6.75 (s, 1H, ArH), 7.02 (t, 1H, J = 8.0 Hz, ArH),
7.84–7.94 (m, 3H, ArH), 8.04–8.07 (m, 1H, ArH), 9.32 (s, 1H, OH); HRMS calcd
for C25H20O5 (M ? H)?: requires 401.1389, found: 401.1387.
123

Efficient one-pot three-component synthesis
1331
3,4-dihydro-3,3-dimethyl-12-(2,3-dichlorophenyl)-2H-benzo[b]xanthene-
1,6,11(12H)-trione 4j
1
Yellow solid; mp: 224–226 °C; IR (KBr): m 2,956, 1,668, 1,620 cm-1; HNMR
(DMSO-d6, 400 MHz): d 0.94 (s, 3H, CH3), 1.08 (s, 3H, CH3), 2.12 (d, 1H,
J = 16.0 Hz, CH2), 2.31 (d, 1H, J = 16.0 Hz, CH2), 2.65 (d, 1H, J = 17.6 Hz,
CH2), 2.71 (d, 1H, J = 17.6 Hz, CH2), 5.32 (s, 1H, CH), 7.23 (t, 1H, J = 8.0 Hz,
ArH); 7.32 (dd, 1H, J1 = 8.0 Hz, J2 = 1.6 Hz, ArH), 7.43 (dd, 1H, J1 = 8.0 Hz,
J2 = 2.0 Hz, ArH), 7.83–7.91 (m, 3H, ArH), 8.05 (d, 1H, J = 8.8 Hz, ArH); HRMS
calcd for C25H18O4Cl2 (M ? H)?: requires 453.0655, found: 453.0659.
3,4-dihydro-3,3-dimethyl-12-(3-nitrophenyl)-2H-benzo[b]xanthene-1,6,11(12H)-
trione 4k
1
Brown solid; mp: 194–196 °C; IR (KBr): m 2,958, 2,923, 1,668, 1,620 cm-1; H
NMR (DMSO-d6, 400 MHz): d 0.96 (s, 3H, CH3), 1.09 (s, 3H, CH3), 2.25 (d, 1H,
J = 16.0 Hz, CH2), 2.34 (d, 1H, J = 16.0 Hz, CH2), 2.70 (d, 1H, J = 17.6 Hz,
CH2), 2.75 (d, 1H, J = 18.0 Hz, CH2), 5.04 (s, 1H, CH), 7.55–7.59 (m, 1H, ArH),
7.83–7.85(m, 3H, ArH), 8.03–8.07 (m, 3H, ArH), 8.14–8.18 (m, 1H, ArH); HRMS
calcd for C25H19O6N(M ? Na)?: requires 452.1105, found: 452.1111.
3,4-dihydro-3,3-dimethyl-12-(4-nitrophenyl)-2H-benzo[b]xanthene-1,6,11(12H)-
trione 4l
1
Yellow solid; mp: 234–236 °C; IR (KBr): m 2,961, 2,870, 1,661, 1,617 cm-1; H
NMR (DMSO-d6, 400 MHz): d 0.95 (s, 3H, CH3), 1.08 (s, 3H, CH3), 2.17 (d, 1H,
J = 16.0 Hz, CH2), 2.33 (d, 1H, J = 16.0 Hz, CH2), 2.71 (t, 2H, J = 18.4 Hz,
CH2), 5.03 (s, 1H, CH), 7.66 (d, 2H, J = 8.4 Hz, ArH), 7.85–7.89 (m, 3H, ArH),
8.06–8.13 (m, 3H, ArH); HRMS calcd for C25H19O6N(M ? H)?: requires
430.1285, found:430.1258.
3,4-dihydro-12-(3,4-methylenedioxyphenyl)-2H-benzo[b]xanthene-1,6,11(12H)-
trione 4m
Yellow solid; mp: 206-208 °C; IR (KBr): m 2,951, 2,885, 1,656, 1,616 cm-1;1H
NMR (DMSO-d6, 400 MHz): d 1.92–2.00 (m, 2H, CH2), 2.33–2.37(m, 2H, CH2),
2.73–2.81 (m, 2H, CH2), 4.85 (s, 1H, CH), 5.94 (s, 2H, CH2), 6.77–6.87 (m, 3H,
ArH), 7.86–7.93 (m, 3H, ArH), 8.04–8.06 (m, 1H, ArH); HRMS calcd for C24H16O6
(M ? H)?: requires 423.0839, found: 423.0823.
3,4-dihydro-12-(4-fluorophenyl)-2H-benzo[b]xanthene-1,6,11(12H)-trione 4n
1
Brown solid; mp: 242-244 °C; IR(KBr): m 2,920, 2,850, 1,667, 1,618 cm-1; H
NMR (DMSO-d6, 400 MHz): 1H NMR (DMSO-d6, 400 MHz): d 1.91–2.01 (m, 2H,
CH2), 2.29–2.37 (m, 2H, CH2), 2.73–2.81 (m, 2H, CH2), 4.92 (s, 1H, CH), 7.06 (d,
2H, J = 8.8 Hz, ArH), 7.36 (dd, 2H, J1 = 5.6 Hz, J2 = 2.8 Hz, ArH), 7.83–7.91
123

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B. Du et al.
(m, 3H, ArH), 8.03–8.05 (m, 1H, ArH); HRMS calcd for C23H15FO4 (M ? Na)?:
requires 397.0847, found:397.0830.
3,4-dihydro-12-(3-hydroxyphenyl)-2H-benzo[b]xanthene-1,6,11(12H)-trione 4o
Brown solid; mp: 262-264 °C; IR (KBr): m 3,211, 2,933, 1,669, 1,610, 1,619 cm-1
;
1H NMR (DMSO-d6, 400 MHz): d 1.89–2.05 (m, 2H, CH2), 2.31–2.36(m, 2H,
CH2), 2.69–2.84 (m, 2H, CH2), 4.83 (s, 1H, CH), 6.51–6.54 (m, 1H, ArH),
6.69–6.73 (m, 2H, ArH), 7.02 (t, 1H, J = 8.0 Hz, ArH), 7.82–7.85 (m, 2H, ArH),
7.90–7.92 (m, 1H, ArH), 8.02–8.04 (m, 1H, ArH), 9.38 (s, 1H, OH); HRMS calcd
for C23H16O4 (M ? Na)?: requires 395.0895, found: 395.0897.
3,4-dihydro-12-(4-chlorophenyl)-2H-benzo[b]xanthene-1,6,11(12H)-trione 4p
Brown solid; mp: 210–212 °C; IR (KBr): m 2,939, 1,668, 1,621, 1,591, 1,488, 1,355,
1
1,198, 992, 932, 720 cm-1; H NMR (DMSO-d6, 400 MHz): d 1.86–1.93 (m, 1H,
CH2), 1.97–2.03 (m, 1H, CH2), 2.28–2.36 (m, 2H, CH2), 2.67–2.74 (m, 1H, CH2),
2.77–2.82 (m, 1H, CH2), 4.87 (s, 1H, CH), 7.28 (d, 2H, J = 8.4 Hz, ArH), 7.34 (d,
2H, J = 8.4 Hz, ArH), 7.81–7.83 (m, 2H, ArH), 7.86–7.89 (m, 1H, ArH), 8.01–8.03
(m, 1H, ArH); HRMS calcd for C23H15O4Cl(M ? Na)?: requires 413.0557, found:
413.0554.
3,4-dihydro-12-(2-methoxypheny)-2H-benzo[b]xanthene-1,6,11(12H)-trione 4q
1
Yellow solid; mp: 246-248 °C; IR (KBr): m 2,951, 2,833, 1,666, 1,619 cm-1; H
NMR (DMSO-d6, 400 MHz): d 1.78–1.88 (m, 1H, CH2), 1.96–2.00 (m, 1H, CH2),
2.25–2.32 (m, 2H, CH2), 2.69–2.75 (m, 2H, CH2), 3.69 (s, 3H, OCH3), 5.00 (s, 1H,
CH), 6.84–6.90 (m, 2H, ArH), 7.11–7.16 (m, 1H, ArH), 7.32 (dd, 1H, J1 = 7.6 Hz,
J2 = 2.0 Hz, ArH), 7.81–7.85 (m, 3H, ArH), 7.86–7.88 (m, 1H, ArH); HRMS calcd
for C24H18O5 (M ? Na)?: requires 409.1052, found: 409.1054.
Conclusion
In conclusion, an efficient, environmentally benign, atom-economical, and simple
methodology for the preparation of 3,4-dihydro-12-phenyl-2H-benzo[b]xanthene-
1,6,11(12H)-trione derivatives in a three-component reaction in ionic liquid is
reported. Prominent among the advantages of this method are operational
simplicity, mild reaction conditions, higher yields (80–89 %), and environmental
friendliness. Meanwhile, ionic liquid [bmim?][Br-] could be reused for several
rounds without apparent loss of activity.
Acknowledgments We are grateful to the National Natural Science Foundation of China (No.
21104064, 21172188), Natural Science Foundation of XuZhou Normal University (10XLR03) and
Priority Academic Program Development of Jiangsu Higher Education Institutions for financial support.
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1333
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