Polyvinylpolypyrrolidone-supported boron trifluoride: A mild and efficient catalyst for the synthesis of 1,8-dioxooctahydroxanthenes and 1,8-dioxodecahydroacridines

Article abstract of DOI:10.1007/s00706-014-1206-9

Polyvinylpolypyrrolidone-supported boron trifluoride has been studied for the synthesis of 1,8-dioxooctahydroxanthenes and 1,8-dioxodecahydroacridines. The reaction proceeded via condensation of: (1) aromatic aldehydes (1 eq.) and 5,5-dimethyl-1,3-cyclohe

Full text of DOI:10.1007/s00706-014-1206-9

Monatsh Chem
DOI 10.1007/s00706-014-1206-9
ORIGINAL PAPER
Polyvinylpolypyrrolidone-supported boron trifluoride: a mild
and efficient catalyst for the synthesis of 1,8-
dioxooctahydroxanthenes and 1,8-dioxodecahydroacridines
•
Masoud Mokhtary Seyed Abdollah Mirfarjood Langroudi
Received: 13 July 2013 / Accepted: 17 March 2014
Ó Springer-Verlag Wien 2014
Abstract Polyvinylpolypyrrolidone-supported boron tri-
fluoride has been studied for the synthesis of 1,8-
dioxooctahydroxanthenes and 1,8-dioxodecahydroacridines.
The reaction proceeded via condensation of: (1) aromatic
aldehydes (1 eq.) and 5,5-dimethyl-1,3-cyclohexanedione
(2 eq.) in acetonitrile at room temperature, (2) aromatic
Introduction
The cancer cell cytotoxicity of xanthene derivatives has
been documented [1]. Xanthenes have pharmacological
properties such as antibacterial, antiviral, and anti-inflam-
matory activities [2–4]. They are also present or used in
dyes [5], antagonists for the paralyzing action of zoxazo-
lamine [6], pH-sensitive fluorescent materials for
visualization of biomolecules [7], and laser technologies
[8]. 1,8-Dioxodecahydroacridines with in-built 1,4-dihy-
dropyridine nucleii have shown very high lasing
efficiencies [9], and hence can act as photoinitiators [10].
One of the commonly used methods reported for the syn-
thesis of xanthene derivatives involves the condensation of
aldehydes with 5,5-dimethyl-1,3-cyclohexanedione. This
reaction can be carried out in the presence of diammonium
hydrogen phosphate [11], InCl3Á4H2O [12], FeCl3Á6H2O/
[Hmim]BF4 [13], NaHSO4ÁSiO2 or silica chloride [14],
silica sulfuric acid [15], amberlyst-15 [16], Fe3?–mont-
morillonite [17] and SiO2-R-SO3H [18]. In addition, the
condensation of aldehydes, 5,5-dimethyl-1,3-cyclohexane-
dione and different anilines for the synthesis of acridine
derivatives can also be carried out in the presence of dif-
ferent catalysts such as FSG-Hf(Npf2)4 [19], CTAB [20],
ZnO/CH3COCl [21], proline [22] and ionic liquid [23, 24].
However, some of these methods suffer from at least
one of the following disadvantages: strongly acidic wastes,
high cost and toxicity of the reagent, tedious work-up
procedures, unsatisfactory yields, harsh conditions, and
nonrecyclable reagents. Therefore, it seems that a major
task of current research is to replace both homogeneous
and less efficient and traditional heterogeneous acid
catalysis procedures with more acceptable methods based
on improved, stable, and recoverable catalysts. Substantial
investigations have been done to introduce novel supported
aldehydes
(1 eq.),
5,5-dimethyl-1,3-cyclohexanedione
(2 eq.), and aromatic amines (1 eq.) in acetonitrile at 80 °C
in the presence of polyvinylpolypyrrolidone-supported boron
trifluoride. This procedure cleanly converted a variety of aryl
aldehydes with different substituent groups at ortho, meta, or
para positions to the corresponding products. Convenience
and efficiency, an easy work-up procedure, high yield, and
simple preparation of the catalyst are some advantages of this
method. In addition, the polyvinylpolypyrrolidone-supported
boron trifluoride complex is a high loaded Lewis acid, which
is stable, easy to handle, and retains effective activity after
several months of storage.
Keywords Polyvinylpolypyrrolidone Á Boron trifluoride Á
Aldehydes Á 5,5-Dimethyl-1,3-cyclohexanedione Á
1,8-Dioxooctahydroxanthenes Á
1,8-Dioxodecahydroacridines
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-014-1206-9) contains supplementary
material, which is available to authorized users.
M. Mokhtary (&) Á S. A. Mirfarjood Langroudi
Department of Chemistry, Rasht Branch, Islamic Azad
University, P.O. Box 41635-3516, Rasht, Iran
e-mail: mmokhtary@iaurasht.ac.ir
123

M. Mokhtary, S.A. Mirfarjood Langroudi
catalysts and chemical reagents. These include dispersing
catalysts on inorganic supports such as metal oxide, alu-
mina, silica, and zeolite. There are a number of advantages
in using polymer-supported catalysts over conventional
catalysis; the reactions can be performed under mild con-
ditions, and purification of the product is simplified
because of the use of an insoluble solid support. Polymer-
supported catalysts can also be recycled after use [25].
Polyvinylpyrrolidone displays a strong binding affinity
toward small molecules. Furthermore, its iodine complex,
povidon-iodine, is widely used as an anti-infective agent in
clinical treatments [26]. Recovery of boron trifluoride from
the reaction, however, results in the formation of large
amounts of waste, which on an industrial scale is environ-
mentally unacceptable. The use of a heterogeneous BF3
system would offer easier catalyst recovery and minimize
the production of waste currently formed during BF3
recovery. However, a suitable replacement support system
must also exhibit activities and selectivity comparable to the
existing homogenous route. In spite of boron trifluoride
etherate, polyvinylpolypyrrolidone-supported boron tri-
fluoride is non-corrosive and stable solid catalyst with
elevated Lewis acid properties. Following our interest in the
use of polyvinylpolypyrrolidone-supported boron trifluoride
(PVPP-BF3) for amidation of benzhydrol and tert-butyl
acetate with nitriles via Ritter reaction [27, 28], acylation of
alcohols, phenols and trimethylsilyl ethers [29], synthesis of
4-methylcoumarins via the Pechmann reaction [30],
chemoselective oxygenation of sulfides to sulfones [31], and
synthesis of 14-aryl-14H-dibenzo[a,j] xanthenes and
bis(naphthalen-2-yl-sulfane) derivatives [32], herein we
found that PVPP-BF3 could be used for the synthesis of 1,8-
dioxooctahydroxanthenes and 1,8-dioxodecahydroacridines
in excellent yields (Scheme 1).
of PVPP-BF3, which shows a strong broad absorption at
1,000–1,060 cm-1 for the B–F bonds and a moderate
absorption at 1,646 cm-1 corresponds to the imine group
on the backbone. A variety of 1,8-dioxooctahydro-
xanthenes were prepared from 5,5-dimethyl-1,3-
cyclohexanedione and aryl aldehydes (carrying both elec-
tron-withdrawing and electron-donating groups), in the
presence of PVPP-BF3 as a heterogeneous Lewis acid
catalyst; the product was of high purity, and we had
excellent yields (Table 1, 3a-k). Next, we have developed
this synthetic method for a one-pot efficient synthesis of
1,8-dioxodecahydroacridines by condensation of aromatic
aldehydes, 5,5-dimethyl-1,3-cyclohexanedione, and aro-
matic amines. In all cases, the corresponding 1,8-
dioxodecahydroacridines were obtained in excellent yields
in acetonitrile under reflux conditions (Table 2, 4a-k). It is
worth mentioning that the corresponding 1,8-dioxoocta-
hydroxanthenes and 1,8-dioxodecahydroacridines were
isolated by simple filtration of the catalyst followed by
crystallization from the crude filtrate. In addition, the
reactions worked well with almost all the aromatic
aldehydes with different substituent groups at ortho,
meta, or para positions. The effects of electrons and the
nature of substituent groups on the aromatic ring of the
aldehydes did not show the expected strong effects in
terms of yields under these reaction conditions. Inter-
estingly, this catalyst not only gave excellent yields of
the products, but also retained its activity after several
months of storage.
In a plausible mechanism, it is assumed that the reaction
may proceed initially through Lewis acid properties of the
PVPP-BF3 due to coordination with the carbonyl group to
facilitate the formation of intermediate 1 after activated
aldehyde via PVPP-BF3, dimedone attached to the car-
bonyl group. Then, removing H2O from
1 yields
intermediate 2. Next, the PVPP-BF3 catalyst again acti-
vates intermediate 2 to give a Michael acceptor. Afterward,
Michael addition of dimedone to intermediate 2 affords 3.
Intermediate 3 converts to 4 after tautomerisation. In the
next step, nucleophilic attack of amine at carbonyl group
creates intermediate 5. Then, intermediate 5 converts to 6
after tautomerisation. Finally, with intramolecular cycli-
zation and the removal of one water molecule, the acridine
derivatives 7 is generated (Scheme 2).
Results and discussion
Characterization of the Lewis acid sites presented on the
polymer was performed by recording the FT-IR spectrum
Scheme 1
To check the reusability of the catalyst, it was
employed in the synthesis of 3a four cycles under the
optimum conditions. The catalyst powder was recovered
by filtration and washed with dichloromethane, taking into
account the partial loss of catalyst during the recovery.
Afterward, the required amount of fresh dimedone and
123

Polyvinylpolypyrrolidone-supported boron trifluoride
Table 1 Synthesis of 1,8-dioxooctahydroxanthenes via condensation of aryl aldehydes and 5,5-dimethyl-1,3-cyclohexanedione using PVPP-BF3
Entry
Aldehyde
Prod.
Time/h
Yield/%a
M.p./°C
Found
M.p./°C
References [23, 33]
1
C6H5CHO
3a
3b
3c
3d
3e
3f
4
94
98
98
97
96
92
96
98
95
95
96
200–202
240–242
230–232
226–228
184–186
246–248
190–192
218–220
244–246
166–168
226–228
199–201
242–244
229–231
224–226
186–187
246–248
192–194
216–218
243–245
164–166
224–226
2
4-BrC6H4CHO
4-ClC6H4CHO
2-ClC6H4CHO
3-ClC6H4CHO
4-HOC6H4CHO
3-BrC6H4CHO
4-CH3C6H4CHO
4-CH3OC6H4CHO
3-NO2C6H4CHO
4-NO2C6H4CHO
3.5
3.5
4.5
4
3
4
5
6
4
7
3g
3h
3i
4
8
4
9
4
10
11
3j
3
3k
3
All entries were carried out using 5,5-dimethyl-1,3-cyclohexanedione (2 mmol), benzaldehyde (1 mmol), and 0.1 g PVPP-BF3 at room
temperature.
a
All yields refer to isolated products
Table 2 Synthesis of 1,8-dioxodecahydroacridines via condensation of aryl aldehydes, 5,5-dimethyl-1,3-cyclohexanedione, and aromatic
amines using PVPP-BF3
Entry
Aldehyde
Amine
Prod.
Time/h
Yield/%b
M.p./°C
Found
M.p./°C
References [20, 34]
1
C6H5CHO
C6H5NH2
4a
4b
4c
4d
4e
4f
3.5
3
92
98
96
98
94
96
94
90
97
96
95
252–254
245–246
273–275
222–224
274–276
279–281
262–263
293–295
270–272
280–282
284–285
254–256
243–245
274–275
220–222
272–274
281–282
260–262
292–294
269–271
281–283
283–284
2
4-ClC6H4CHO
3,4-Cl2C6H4CHO
4-CH3OC6H4CHO
3-NO2C6H4CHO
4-NO2C6H4CHO
C6H5CHO
C6H5NH2
3
C6H5NH2
2.5
3.5
3
4
C6H5NH2
5
C6H5NH2
6
C6H5NH2
3
7
4-CH3C6H4NH2
4-CH3C6H4NH2
4-CH3C6H4NH2
4-CH3C6H4NH2
4-CH3C6H4NH2
4g
4h
4i
4
8
4-CH3OC6H4CHO
4-ClC6H4CHO
4-CH3OC6H4CHO
3-NO2C6H4CHO
4
9
3.5
4
10
11
4j
4k
3
All entries were carried out using 5,5-dimethyl-1,3-cyclohexanedione (2 mmol), benzaldehyde (1 mmol), aromatic amine (1 mmol), and 0.1 g
PVPP-BF3 under reflux conditions.
a
All yields refer to isolated products
123

M. Mokhtary, S.A. Mirfarjood Langroudi
Scheme 2
BF3-PVPP
PVPP-BF3
O
Dimedone
O
Ar
OH
Acridine
7
Ar
H
O
O
Ar
H
-H2O
O
1
-H2O
H
Ar
O
O
Ar
O
NH
O
O
PVPP-BF3
6
R
Ar
O
O
O
Ar
O
2
O
O
Dimedone
O
N
3
R
RNH2
5
Ar
O
OH HO
4
Table 3 Comparison of our results with previously reported data for the synthesis of 3a
Entry
Catalyst
Reaction conditions
Time/h
Yield/%
Reference
1
2
3
4
5
6
7
8
SiO2-R-SO3H
Neat/80 °C
CH3CN/reflux
CH3CN/reflux
EtOH/100 °C
CH3CN/reflux
CH3CN/reflux
80 °C
4.5
5
75
86
92
94
90
93
92
94
[18]
ZnO/CH3COCl
[21]
Amberlyst-15
5
[16]
Fe3?–montmorillonite
NaHSO4ÁSiO2
Silica chloride
6
[17]
6.5
6
[14]
[14]
FeCl3Á6H2O/[Hmim]BF4
PVPP-BF3
6
[13]
CH3CN/RT
4
This work
benzaldehyde were added according to the amount of
catalyst. The results showed that the catalyst can be
reused four consecutive times. To improve the catalytic
activity of the catalyst after three cycles, it is best to
separate the polyvinylpolypyrrolidone by filtration and
treat it as follows: carefully rinse the dichloromethane;
dry the product, and then treat with boron trifluoride
etherate again to prepare fresh polyvinylpolypyrrolidone
immobilized boron trifluoride catalyst. The polymer sup-
port can be used several times for the immobilization of
boron trifluoride.
In order to examine the efficiency of the present method
for the synthesis of 1,8-dioxooctahydroxanthenes and 1,8-
dioxodecahydroacridines, compounds 3a and 4a were
compared with some of those reported in the literature
(Tables 3, 4). As one can see, our results show a very good
comparability with previously reported data when all terms
including yields, reaction times, and reaction conditions are
taken into account.
In summary, we have developed a simple and
efficient method for the synthesis of 1,8-dioxooctahy-
droxanthenes and 1,8-dioxodecahydroacridines using a
123

Polyvinylpolypyrrolidone-supported boron trifluoride
Table 4 Comparison of our
results with previously reported
data for the synthesis of 4a
Entry
Catalyst
Reaction conditions
Time/h
Yield/%
Reference
1
2
3
4
5
6
7
Bronsted acid (IL)
FSG-Hf(Npf2)4
Amberlyst-15
Proline
H2O/reflux
4
85
49
81
83
80
86
92
[34]
EtOH:H2O/reflux
CH3CN/reflux
EtOH(aq)/65 °C
H2O/reflux
6
[19]
5
[16]
5
[22]
CTAB
1.5
5
[20]
[Hmim]TFA
PVPP-BF3
80 °C
CH3CN/reflux
[24]
3.5
This work
Synthesis of 1,8-dioxodecahydroacridines: general
procedure
polyvinylpolypyrrolidone-supported boron trifluoride
complex as a high-loaded of Lewis acid, which is stable,
easy to prepare and handle, and retains effective activity
after several months of storage. In addition, this method
is suitable both for preparative and industrial usage
because of its low cost, biocompatibility, and the recy-
clability of the polyvinylpolypyrrolidone as a safe
polymer support.
A
mixture
of
5,5-dimethyl-1,3-cyclohexanedione
(2 mmol), aromatic aldehyde (1 mmol), aromatic amine
(1 mmol), and 0.1 g PVPP-BF3 in 5 cm3 acetonitrile was
stirred at reflux temperature for the appropriate time as
shown in Table 2. Completion of the reaction was indi-
cated by TLC monitoring. Then, the reaction mixture was
cooled to ambient temperature, and the PVPP-BF3 was
filtered off. The filtrate was concentrated to dryness, and
the crude solid residue was recrystallized from ethanol and
water to afford pure crystals of the proper 1,8-dioxodeca-
hydroacridines in 90–98 % yields. The products were
Experimental
All chemicals were purchased from the Merck chemical
company. Melting points were recorded on an electro-
thermal melting point apparatus. The NMR spectra were
recorded in CDCl3 with TMS as an internal standard on a
Bruker Avance DRX 400 MHz spectrometer. IR spectra
were determined on an SP-1100, P-UV-Com instrument.
Products were separated by simple filtration and identified
by comparison of the obtained FT-IR and 1H NMR spectra
with those reported for authentic samples.
1
characterized by FT-IR, H NMR, and physical constants.
Acknowledgments We are grateful to Islamic Azad University of
Rasht Branch for financial assistance of this work.
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