Task specific dicationic acidic ionic liquids catalyzed efficient and rapid synthesis of benzoxanthenones derivatives

Article abstract of DOI:10.1016/j.molliq.2016.07.128

A rapid and straightforward approach to the synthesis of dibenzo[a,j]xanthenes and 1,8-dioxo-octahydroxanthenes using task specific dicationic acidic ionic liquids as a highly efficient and readily available catalyst under solvent-free condition have been

Full text of DOI:10.1016/j.molliq.2016.07.128

Journal of Molecular Liquids 222 (2016) 783–787
Contents lists available at ScienceDirect
Journal of Molecular Liquids
journal homepage: www.elsevier.com/locate/molliq
Task specific dicationic acidic ionic liquids catalyzed efficient and rapid
synthesis of benzoxanthenones derivatives
Najmedin Azizi ⁎, Fatemeh Shirdel
Department of green chemistry, Chemistry and Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 July 2016
Received in revised form 27 July 2016
Accepted 27 July 2016
Available online 28 July 2016
A rapid and straightforward approach to the synthesis of dibenzo[a,j]xanthenes and 1,8-dioxo-
octahydroxanthenes using task specific dicationic acidic ionic liquids as a highly efficient and readily available
catalyst under solvent-free condition have been developed. A series of Brønsted–Lewis acidic ionic liquid were
prepared and investigated their catalytic activity for synthesis of various xanthenes derivatives from aldehydes
and 2-naphthol or dimedone. The ease of the product separation without organic solvent and column chroma-
tography and reusability of acidic ionic liquid catalyst makes this method economically affordable for large-
scale synthesis.
Keyword:
Benzoxanthenones
Recyclable catalyst
Task specific dicationic acidic ionic liquids
Green chemistry
© 2016 Published by Elsevier B.V.
Dimedone
1
. Introduction
Multicomponent reactions (MCRs) under catalytic solvent-free con-
high acid density, easy separation, and reusability [19]. In this context,
acidic ILs is now widely acknowledged as a new class of advanced acidic
catalyst for many organic transformations [20].
ditions not only a powerful tool in organic synthesis; they also represent
an ideal protocol for the construction of different heterocycles and
natural products [1]. Multicomponent reaction is a very significant
tool for atom economic synthesis of highly valuable products with
good to excellent yields from cheap and readily available starting mate-
rials in organic chemistry [2]. Furthermore, MCRs have to be a benefit of
time saving, environmental friendly, cost-effectiveness and the impor-
tant source of molecular diversity for academic and industrial synthetic
chemists [3–6].
A new emerging type of greener solvents and catalysts that have re-
ceived widespread attention as an eco-friendly reaction medium is ionic
liquids (ILs) [7]. ILs are an emerging class of advanced materials due to
their particular properties such as negligible vapor pressure, wide liquid
range, excellent solubility, and good selectivity [8]. The unusual proper-
ties of ILs have made a variety of applications such as solvent, catalysts,
gas adsorbents, and chromatography stationary phases in recent years
Benzoxanthenones and its derivatives have a great deal of impor-
tance due to their numerous biological activities, including their anti-
bacterial and anti-inflammatory in medicinal chemistry and biology
[21]. They are used as fluorescent compounds in laser technology and
widely used as building blocks in dye chemistry [22]. The simplest and
practical preparation of benzoxanthenones and its derivatives, involve
the construction of the C\\O bond via condensation reaction of carbonyl
compounds with naphthol derivatives in the presence of acidic catalysts
[23]. In light of their wide range of industrial applications, numerous
protocols have been reported in the preparation of biologically
important 14-aryl-14H -dibenzo[a,j]xanthenes [24–33] and 1,8-dioxo-
octahydro-xanthene [34–38] using a variety of catalysts or promoter
in the literature. However, the majority of acid catalysts are highly
corrosive and are not easy to recover for reuse. Therefore, it is still
necessary to develop green and reusable catalysts for environmentally
benign synthesis of benzoxanthenone derivatives using simple starting
materials.
[
(
9–13]. Acidic ionic liquids; ionic liquids with acidic properties
Brønsted-type and Lewis-type) is an important ionic liquid derivatives
that are replaced with the most common acids used in labs and in indus-
try [14–18]. Furthermore, acidic ILs possesses the advantages of both
liquid acid and solid acid catalysts such as water solubility, recyclable,
2
. Experimental
2.1. General
All starting materials and task specific dicationic acidic ionic liquids
⁎
Corresponding author.
E-mail address: azizi@ccerci.ac.ir (N. Azizi).
components such as aldehydes, dimedone, β-naphtols, H
2 4 2
SO , ZnCl ,
http://dx.doi.org/10.1016/j.molliq.2016.07.128
167-7322/© 2016 Published by Elsevier B.V.
0

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N. Azizi, F. Shirdel / Journal of Molecular Liquids 222 (2016) 783–787
1H NMR (500 MHz, D
2
O): δ 1.74–1.76 (m, 4H), 1.90–192 (m, 4H),
2
4
.93 (t, J = 7.2 Hz, 4H), 3.20 (s, 12H), 3.41 (t, J = 8.1 Hz, 4H), 3.85 (s,
H), 4.48 (OH), FTIR KBr, cm : 1050 and 930 (\\SO H), 1160
3
−
1
(
C\\N), 3379 (O\\H).
IL2 was synthesized according to the same procedure, only instead
of H SO , HCl and ZnCl were added (Scheme 1).
2
4
2
2.3. Typical experimental procedure
Scheme 1. Preparation of acidic ionic liquid.
To a mixture of aldehyde (0.5 mmol) and β-naphthol (1 mmol) or
dimedone (1 mmol) was added acidic ionic liquid (1 mol%) and this
reaction mixture were heated at 110 °C with vigorously stirring for
tetramethylethylenediamine TMEDA and 1,4-butane sultone were
1
0–40 min. After completion of the reaction, the mixtures were cooled
commercially available. Melting points were determined on Buchi 535
melting point apparatus. 1H and 13C NMR spectra was recorded on
to room temperature and washed with water to get the crude product.
The crude product was recrystallized from ethanol to afford the pure
product which required no further purification. All compounds were
characterized as the basis of their spectroscopic data (NMR) and melt-
ing point by comparison with those reported on the literature.
5
6
00 MHz NMR spectrometer using DMSO-d as solvent. Chemical shifts
were expressed in (ppm) downfield from TMS. All the reactions were
monitored by thin layer chromatography (TLC) with UV light as detect-
ing agents.
2
.3.1. Selected spectral data
2
.2. Acidic ionic liquid preparations
1
3
a: H NMR (500 MHz, DMSO-d
.58 (m, 6H), 7.53–700 (m, 7H), 6.32 (s, 1H)· C NMR (125 MHz,
): δ = 147.9, 144.2, 130.9, 130.1, 127.9, 127.1.2, 126.8, 126.2,
25.8, 125.3, 124.7121.8, 116.4, 116.2, 39.8.
6
): δ = 8.20 (d, J = 7.8 Hz, 2H), 7.82–
13
7
IL1 and IL4-IL8 were prepared according to our previous paper [39].
DMSO-d
1
6
1
2
.2.1. Preparation of IL3
Acidic ionic liquids (IL3) were synthesized by known methods re-
3c: H NMR (500 MHz, DMSO-d
6
): δ = 8.40 (d, J = 7.8 Hz, 2H), 7.72–
13
6.71 (m, 14H), 6.12 (s, 1H), 3.72 (s, 3H). C NMR (125 MHz, DMSO-d ):
6
ported on the literature [40] with little modification (Scheme 1). The
obtained acidic ILs were characterized by H NMR and FTIR spectrum
the results were compared to the literature data. A 25 mL round-bottom
flask with a magnet was vacuum dried and cooled under argon and
charged with tetramethylethylenediamine TMEDA (14.9 mL,
157.9, 148.6, 136.4, 133.8, 130.9, 130.1, 129.4, 129.2, 127.2, 123.8, 123.2,
1
117.8, 117.1, 113.8, 53.8, 37.1.
1
3e: H NMR (500 MHz, DMSO-d
6
): δ = 8.39 (d, J = 7.8 Hz, 2H), 8.01–
) δ = 154.9,
7.46 (m, 14H), 6.46 (s, 1H). 13C NMR (125 MHz, DMSO-d
6
146.8, 131.9, 130.8, 128.9, 128.1, 127.8, 127.1, 125.9, 125.3, 123.8,
1
00 mmol) and 1,4-butane sultone (30 mL, 300 mmol) and stirred
118.7, 117.7, 116.9, 32.8.
5a: H NMR (500 MHz, DMSO-d
6
1H), 2.42–2.6 (m, 8H), 1.01 (s, 6H). C NMR (125 MHz, DMSO-d )
1
under 80 °C for 6 h until white zwitterion solid was obtained. This zwit-
terion salt was washed with ethyl acetate and dried under vacuum to
obtain the pure zwitterion solid in a good yield (90%). Then two equi-
molar concentrated sulfuric acid (98%) was added dropwise to the zwit-
terion and the mixture was stirred magnetically for 10 h at 60 °C to form
the honey like viscous liquid. The resulting liquid was washed repeated-
ly with ethyl acetate and dried in a high vacuum at 120 °C for 8 h until
pure ionic liquid were obtained.
6
): δ = 7.24–7.11 (m, 5H), 4.40 (s,
1
3
δ = 196.2, 161.8, 136.1, 128.9, 127.8, 113.4, 53.8, 50.8, 48.7, 32.0, 31.8,
28.1, 25.6.
1
5b: H NMR (500 MHz, DMSO-d
6
): δ = 7.10 (d, J = 7.2 Hz, 2H), 6.82
(d, J = 7.2 Hz, 2H), 4.62 (s, 1H), 3.70 (s, 3H), 2.42–2.17 (m, 8H), 0.98–
1.05 (m, 12H). 13C NMR (125 MHz, DMSO-d
) δ = 195.8, 160.9, 157.1,
128.6, 128.1, 113.8, 55.2, 50.2, 40.1, 37.4, 34.2, 31.9, 30.2, 27.5, 26.9.
6
Table 1
Optimization of reaction condition.
entry
IL (1 mol%)
Temp. (°C)
110
110
110
110
110
110
110
25
40
60
80
100
25
Yields (%)a
1
2
3
4
5
6
7
8
9
IL1
IL2
IL3
IL4
IL5
IL6
IL7
IL8
IL3
IL3
IL3
IL3
–
45
93
95
90
75
64
81
72
20
58
82
90
00
28
10
11
12
13
14
–
110
a
Isolated yields.

N. Azizi, F. Shirdel / Journal of Molecular Liquids 222 (2016) 783–787
785
Fig. 1. Structure of eight kinds of acidic ionic liquid.
3
. Results and discussion
procedure outlined in literature (Fig. 1) [39,40]. Then the acidic ILs
was applied to catalyze condensation reaction of benzaldehydes and
β-naphthol as test substrates in a 1:2 ratio under solvent-free condi-
tions to investigate the synthesis of benzoxanthenone. For initial stud-
ies, the effects of ionic liquid loading and the nature of the ionic liquid
as well as temperature in a model reaction of 2-naphthol and benzalde-
hydes were investigated in detail and the results are summarized in
Table 1. Control experiments showed that under solvent-free condition
in the absence of IL as catalyst, conversions were very low for reactions
performed at 25–110 °C (Table 1, entries 13, 14). The condensation re-
action of 2-naphthol and benzaldehydes proceeded smoothly in the
presence of one of the IL1-IL8 and gave the desired product in moderate
to excellent yields within 10 min at 110 °C. Because of the solidification
As a result, a simple, effective and green procedure for Brønsted–
Lewis acidic ionic liquid catalyzed dibenzo[a,j]xanthene synthesis with
excellent yields is one of the fundamental challenges and ultimate
goals for green chemistry. In continuation of our work on the applica-
tion of deep eutectic solvent as novel and green catalyst and solvent
[41–43] in organic synthesis, we here report that of benzoxanthenone
can be produced using Brønsted–Lewis acidic ionic liquid an efficient
and novel catalyst via a direct condensation of aldehydes and 2-
naphthol (Table 1). A series ionic liquids containing additional function-
al groups including Brönsted acid ionic liquids, Lewis acid ionic liquid
and Brønsted–Lewis acidic ionic liquid were synthesized following the
Table 2
Synthesis of benzoxanthenones derivatives via three-component reaction aldehyde, and β-naphthol in acidic ionic liquid.
entry
R
C
4-CH
4-CH
4-NO
4-ClC
4-OHC
4-CO MeC
3-NO
2-CH
product
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
Yields a (%)
M.P. (°C) Found Reported [Lit]
190–191
232.-234
207–208
326–328
293–295
145–147
249–251
229–230
1
2
3
4
5
6
7
8
9
6
H
5
95
95
88
84
78
70
82
72
70
58
74
191–192 [39]
233–234 [40]
206–209 [41]
327–329 [39]
293–295 [41]
145–146 [42]
250–252 [39]
233–234 [43]
223–225 [40]
68–70 [32]
3
C
6
H
4
3
OC
6
H
4
2
C
6
H
4
6
H
4
6
H
4
2
6
H
4
2
C
6
H
4
3
C
6
H
4
220–222
66–68
226–228
1
1
0
1
C
7
H
15
229–230[23]
12
3l
80
238–240
240–242 [24]
1
1
3
4
3m
3n
64
00
200–202
198–200[29]
–
–
a
Isolated yields.

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N. Azizi, F. Shirdel / Journal of Molecular Liquids 222 (2016) 783–787
Table 3
Synthesis of xanthenes derivatives in acidic ionic liquid.
Entry
ArCHO
Product
Yield (%)a
m.p (°C)
Found
Reported
1
2
3
4
5
C
6
H
5
5a
5b
5c
5d
5e
95
78
92
86
72
203–205
240–242
238–240
214–215
227–228
202–204 [36]
241–243 [36]
240–241 [36]
216–217 [34]
225–227 [35]
4-OMe-C
4-Br-C
4-Me-C
2-Cl-C
6
H
4
6
H
4
6
H
4
6
H
4
a
Isolated yields.
of the reaction mixture at lower temperature such as 80 °C the conver-
sion to the corresponding products was not completed. Among the IL
were tested for this conversation, the IL (IL2, IL3) that involves the
Table 3. The reaction was fast and proceeded smoothly under optimized
condition to give the corresponding substituted xanthenes derivatives 5
from various aromatic aldehydes in good to excellent yields. There were
no remarkable differences in yields and reaction time between aromatic
aldehydes with electron-donating groups and those with electron-
withdrawing groups.
The efficacy of acidic IL was also evaluated on a large scale
(10 mmol). Thus, a mixture of benzaldehyde (20.0 mmol), 2-naphtol
(10 mmol) and acidic IL2 (5 mol%) was taken in a round-bottom flask
(25 mL) and stirred at 110 °C for 20 min. Interestingly, the product 3a
was isolated in excellent yield (90%) without compromising the opti-
mized reaction conditions after simple work-up.
A possible mechanism of the acidic ionic liquid catalyzed reaction is
depicted in Scheme 2. The cation and the anion of acidic ionic liquid
have synergetic effect on its catalytic reaction. The cation of the acidic
ionic liquid act a highly efficient acidic catalyst and activate carbonyl
groups of aldehydes and acidic hydrogen of 2-naphthol. Then, 2-naphtol
attacks the carbonyl carbon of benzaldehyde to form a tetrahedral inter-
3 3 4
SO H functional groups and ZnCl or HSO anion (Table 1, entries 2, 3)
showed higher catalytic activity with lower catalyst loading (1 mol%)
and gave benzoxanthenone (3a) in 93 and 95% isolated yield respective-
ly (Table 1).
With an optimized catalytic system in hand, we set out to probe its
versatility and the generality of the reactions, starting with various
aromatic aldehydes with diverse steric and electronic properties and
β-naphtols under solvent free condition. As shown in Table 2, aldehydes
with different substituents smoothly reacted with β-naphtol and
affording the corresponding products in short reaction times. Various
aldehydes containing electron-rich and electron-deficient substituents
at para-, meta-, or ortho-positions, led to in good to excellent yields of
isolated product (68–95%). The steric hindrance of the methyl group
in ortho position led to the lower conversion than the para-substituted
aldehyde. Furthermore, the reaction work well with aliphatic aldehydes
such as octanal under same reaction conditions and gave the corre-
sponding products in short reaction times. (Table 2, entry 10). In
addition, heteroaromatic aldehydes such as 2-pyridinecarboxaldehyde,
mediate through the loss of H
2
O produces the Knoevenagel product.
Further nucleophilic conjugate addition of 2-naphtole on Knoevnagel
intermediate leads to the acyclic adduct intermediate. SO3H groups
acts as a Brønsted acid to removes water and assist to generate final
products.
4
-pyridinecarboxaldehyde and furfural (Table 2, entries 10–13) can also
serve as a good substrates in this reaction and were converted into
dibenzo[a,j]xanthenes 3k-3m in good yields. However, indole-3-
carboxaldehyde failed to give the corresponding product 3n under
these condition and lead to a mixture of products that separation into
its components was impossible. (Table 2, entry 14).
To test the generality of this procedure, dimedone 4 were treated
with diverse aromatic aldehydes 1 under identical conditions in
the presence of IL3, and representative examples are summarized in
Scheme 2.
Further investigation involved the reusability of the acidic ionic liq-
uid in the reaction between benzaldehyde (6 mmol), and β-naphthol
(3 mmol) in the presence of 3 mol% of IL3 under described reaction con-
ditions reported in Table 2 (entry 1). At the end, water (5 mL) was
added to the reaction media to dissolve a catalyst. The product was re-
covered by filtration, and catalyst washed with ethyl acetate, dried
Scheme 2. Proposed reaction mechanism in the presence of acidic ionic liquid.

N. Azizi, F. Shirdel / Journal of Molecular Liquids 222 (2016) 783–787
787
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