An efficient and reusable ionic liquid catalyst for the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes under solvent-free conditions

Article abstract of DOI:10.1039/c4ra06521b

In this work, it was found that acidic protic ionic liquid N,N-dimethylaminoethanol hydrosulfate ([DMEA][HSO₄]) was an efficient and reusable catalyst for the one-pot synthesis of 14-aryl-14H-dibenzo[a,j] xanthenes under solvent-free conditions. This ionic liquid is very cheap, air and water stable, and can be easily recovered and reused for at least six cycles. The catalytic system described here is a green protocol since in the one-pot synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes, the yield of the target compounds is excellent, operation and work-up procedures are simple, and no volatile organic solvents have been used. It is suggested that the synergetic effect of the cation and the anion of this ionic liquid is the main reason for the high catalytic activity and high chemo-selectivity. Scale-up experiments also suggest that this catalytic system has potential in industrial application. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra06521b

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An efficient and reusable ionic liquid catalyst for
the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes
under solvent-free conditions†
Cite this: RSC Adv., 2014, 4, 36031
Anlian Zhu, Shukun Bai, Wei Jin, Ruixia Liu, Lingjun Li, Yang Zhao and Jianji Wang*
In this work, it was found that acidic protic ionic liquid N,N-dimethylaminoethanol hydrosulfate ([DMEA]-
4
[HSO ]) was an efficient and reusable catalyst for the one-pot synthesis of 14-aryl-14H-dibenzo[a,j]-
xanthenes under solvent-free conditions. This ionic liquid is very cheap, air and water stable, and can be
easily recovered and reused for at least six cycles. The catalytic system described here is a green
protocol since in the one-pot synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes, the yield of the target
compounds is excellent, operation and work-up procedures are simple, and no volatile organic solvents
have been used. It is suggested that the synergetic effect of the cation and the anion of this ionic liquid
is the main reason for the high catalytic activity and high chemo-selectivity. Scale-up experiments also
suggest that this catalytic system has potential in industrial application.
Received 2nd July 2014
Accepted 4th August 2014
DOI: 10.1039/c4ra06521b
www.rsc.org/advances
It has been recognized that choline-based ionic liquids (ILs)
are much more biocompatible than their traditional imidazo-
Introduction
The derivatives of benzoxanthenes have received great lium-based companions, and they also benet from wide
1
2
21–24
attention due to their antibacterial, anti-inammatory and resources and low preparation cost.
Therefore, these ILs
3
antiviral properties, and have been used in a wide range of have received increasing attention in organic catalysis and
As our continuous work on the
treatment of tumor cells, laser technology, visualization of synthesis and utilization of choline-based ionic liquids in
biomolecules, and others. Recently, various methodologies sustainable catalysis, the catalytic performances of a series of
have been developed for the synthesis of benzoxanthenes, choline-based ionic liquids on the synthesis of benzoxanthenes
and the most frequently used procedure is through the were investigated in the present work. For the sake of easy
reaction of 2-naphthol with various aldehydes in the pres- understanding, the structures for the cations of typical choline-
based ionic liquids are shown in Scheme 1. It was shown that
wet cyanuric chloride, tungstophosphoric acid–zirconia the catalytic activity and chemical selectivity of the reaction
25–30
applications in areas including photodynamic therapy for the synthesis in recent years.
4
5
6
7
8
9
ence of catalyst such as molecular iodine, amberlyst-15,
1
0
1
1
12
composites,
WCl
6
,
SO
3
H-functionalized acidic ionic between 2-naphthol and aldehydes were signicantly inu-
1
3
14
liquid,
silica sulfuric acid,
glycol and among others.
sulfonated polyethylene enced by the combination of cation and anion of the ionic
Although this one-pot proce- liquids. The ionic liquid with acidic anion of hydrogen sulfate
1
5
16–20
4
dure makes various benzoxanthenes available, almost all of ([HSO ]) and protic cation of N,N-dimethylaminoethanol
these catalytic systems suffered from one or more disadvan- ([DMEA]) was found to be an efficient and reusable catalyst for
tages such as low yield, long reaction time, tedious work-up the one-pot preparation of a series of 14-aryl-14H-dibenzo[a,j]-
procedure, use of special apparatus, excess reagents and xanthenes under solvent-free conditions. The reaction
expensive/un-reusable catalysts. Thus, the development of mechanism was suggested based on the successful detection
efficient, economical and environmentally benign methods of an intermediate and it was shown that cation and anion of
for the preparation of benzoxanthenes is still in a great the ionic liquid have synergetic effect on its catalytic
necessity.
performance.
Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine
Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of
Education, School of Chemistry and Chemical Engineering, Henan Normal
University, Xinxiang, Henan 453007, P. R. China. E-mail: jwang@henannu.edu.cn;
Fax: +86-0373-3329030; Tel: +86-0373-3325805
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/c4ra06521b
1
Scheme 1 The structures for the cations of typical ionic liquids.
RSC Adv., 2014, 4, 36031–36035 | 36031
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Results and discussion
In order to study the catalytic activity of choline-based ionic
liquids with different combination of cation and anion on
the condensation reactions, the reaction between p-nitro-
benzaldehyde and 2-naphthol was initially selected as a model
reaction, and the catalytic results were collected in Table 1. It
was shown that when the ionic liquids with neutral anions,
such as [choline][C ] and [C -choline][Cl] (entries 1 and 2, Table
l
4
ꢀ
1
), were used to promote this reaction at 100 C, no products
can be detected aer 10 hours. When the ionic liquids with
basic anions, such as [choline][Ac] and [DMEA][Ac] (entries 3
and 4, Table 1), were used as catalyst, the model reaction can
proceed uently at room temperature. Aer 10 hours, p-nitro-
benzaldehyde could be completely used up as monitored by
Scheme 2 Chemical structures for target compound 3a and inter-
mediate 4a.
TLC, but 2-naphthol was still in the reaction mixtures. Then, the compared with that of the latter. The above information
mixtures were recrystallized using 95% ethanol and a pure suggests that in this multi-steps reactions, the rst step is both
ꢀ
product (pale brown color) with the melting point of 210 C was acid and basic favorable, but the subsequent step is acid
1
obtained. H NMR detection suggested that only one 2-naphthol favorable.
was reacted with p-nitrobenzaldehyde and 4a (Scheme 2) was
4
The inuence of the amount of [DMEA][HSO ] catalyst on the
the sole product. It was noted that as the reaction temperature reaction was also studied using the model reaction, and the
ꢀ
was increased up to 125 C, another product was produced with results were included in Table 2. It can be seen that with
ꢀ
1
melting point of 310 C (entry 5, Table 1). H NMR detection increasing molar ratio of [DMEA][HSO
indicated that this is the target compound 3a (Scheme 2), but its to 0.1, the yield for the target compound increased signicantly,
nal isolated yield was only 70%. Interestingly, as ionic liquid but further increase of the molar ratio did not have inuence on
with acidic anion such as [DMEA][HSO ] or [choline][HSO ] the yield. Therefore, the molar ratio of the ionic liquid to
4
] to substrates from 0.02

4
4
(
entries 6 and 7, Table 1) was used as catalyst, the product was a substrates was kept at 0.1 : 1 for the further experiments.
ꢀ
mixture of 3a and 4a aer 20 min reaction at 125 C. Never-
4
Using [DMEA][HSO ] as catalyst, the reactions of 2-naphthol
theless, as the reaction time was extended to 1 hour, 4a dis- with different aldehydes were used to investigate the scope of
appeared and turned to the target compound 3a. It was clearly the substrates, and the results were given in Table 3. It can be
indicated that catalytic activity and chemical selectivity of seen that the benzaldehydes and aromatic aldehydes with
[
DMEA][HSO ] for the reaction were higher than those of electron-withdrawing or weak electron-donating substituents
4
30
[
choline][HSO ] due to the stronger acidity of the former
such as –NO , –CH , –OH and halogens could react smoothly to
2 3
4
Table 1 The catalytic activity of different choline-based ionic liquids on the synthesis of 14-(4-nitrophenyl)-14H-dibenzo[a,j]xanthene
a
o
Entry
IL
Reaction temperature ( C)
Reaction time
Product (yield)
1
2
3
4
5
6
7
[Choline][Cl]
[C -choline][Cl]
[Choline][Ac]
[DMEA][Ac]
rt/125
rt/125
rt
10 h
10 h
10 h
10 h
2 h
20 min, 1 h
20 min, 1 h
—
—
4
4a (90%)
4a (92%)
3a (70%)
3a + 4a (15% + 45%), 3a (85%)
3a + 4a (30% + 50%), 3a (99%)
rt
[DMEA][Ac]
125
125
125
[Choline][HSO
4
]
4
[DMEA][HSO ]
a
The molar ratio of ionic liquid to substrates was kept at 0.1.
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Table 2 The influence of the IL amount on the catalytic performance
Entry
Molar ratio (IL : aldehyde)
Reaction time
Isolated yield (%)
1
2
3
4
5
6
0.02 : 1
0.05 : 1
0.1 : 1
0.5 : 1
2 : 1
1 h
1 h
1 h
1 h
40 min
40 min
80
90
99
99
99
99
5 : 1
a
Table 3 Preparation of 14-aryl-14H-dibenzo[a,j]xanthenes catalyzed by [DMEA][HSO
4
] under solvent free conditions
ꢀ
ꢀ
Entry
R
Time
Product
Isolated yield (%)
Mp ( C)
Lit. mp ( C)
1
2
3
4
5
6
7
8
4-NO
2
C
6
6
H
H
4
4
1 h
1 h
1 h
4 h
1 h
1 h
1 h
5 min
3a
3b
3c
3d
3e
3f
99
90
98
74
90
92
95
90
310–312
178
233–234
140–142
228
300–301
298
250–252
311–312 (ref. 13)
181 (ref. 20)
235–237 (ref. 20)
140 (ref. 14)
227–228 (ref. 13)
300–302 (ref. 20)
295–297 (ref. 12)
238–240 (ref. 13),
C
6
H
5
3-NO
2
C
4-OHC
4-CH
4-ClC
4-BrC
4-FC
6
H
4
3
C
6
H
4
6
H
4
6
H
4
3g
3h
6
H
4
265–267 (ref. 20)
9
1
1
4-CH
4-(OH)C
4-CHOC
3
OC
6
H
4
3 h
4 h
1 h
3i
3j
3k
65
45
91
206
198–201
328
203–205 (ref. 12)
—
—
0
1
6
H
3
-3-(OCH
3
)
6
H
4
a
The sixth run of the recovered ionic liquid.
afford the corresponding products with good to excellent iso- hour. When the reaction was completed, the target compound
lated yields (entries 1–8), while the benzaldehydes with strong can be precipitated and the ionic liquid can be recovered by
electron-donating groups such as –OCH showed low reactivity addition of 1 ml of water and then ltrated. It was found that
3
and could only get moderate isolated yields with the prolonged the amount of IL leaching into the product was negligible. The
reaction time (entries 9 and 10). However, it is interesting to IL could be recovered aer drying of its aqueous solution, and
note that when 1,4-phthalaldehyde was used as the substrate,
only one aldehyde group was reacted with 2-naphthol, and
another aldehyde group was kept intact (entry 11).
4
Table 4 The reusability of [DMEA][HSO ] in the model reaction
The scale up effect of this catalytic system has also been
investigated using the model reaction. The results showed that
when the reaction scale was increased to 10 mmol, the target
compound can still give almost quantitative isolated yields in 1
Runs
1
2
3
4
5
6
Yield (%)
99
98
97
96
98
97
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4
Scheme 3 Proposed reaction mechanism for [DMEA][HSO ] catalyzed synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes.
then directly used for the next run. No signicant activity
decrease was observed aer six runs (Table 4), which suggests
that this ionic liquid catalyst is recyclable and reusable.
According to the above discussion, the cation and the anion N,N -Dimethylaminoethanol (DMEA) and 1-chlorobutane were
of this ionic liquid have synergetic effect on its catalytic obtained from Beijing Chem. Reagent Co. and distilled at
performance, and a plausible reaction mechanism is proposed reduced pressure before use. Choline chloride was also
as illustrated in Scheme 3. The ndings that the rst step is obtained from Beijing Chem. Reagent Co. Sulfuric acid (H SO )
Experimental
Synthesis and characterization of the ionic liquids
0
2
4
both acid and basic favorable but the subsequent steps are acid and acetic acid were purchased from Shanghai Reagent Co., and
favorable may provide some important information for the strong basic ion exchange resin (Ambersep 900 OH) was
further catalyst design of the reactions mentioned.
purchased from Alfa Aesar. 2-Naphthol, benzaldehyde and
substituted benzaldehydes were purchased from Aladdin
Reagent Co. All of the commercially available reagents were AR
Conclusions
grade and used as received unless indicated otherwise. The
0
ionic liquids [DMEA][HSO
4
] and N,N -dimethylaminoethanol
In this work, we found that ionic liquid [DMEA][HSO ] is an
4
acetate ([DMEA][Ac]) were synthesized by simple neutralization
efficient and environmentally friendly catalyst for the one-pot
synthesis of a series of 14-aryl-14H-dibenzo[a,j]xanthenes under
solvent-free conditions. This catalytic system benets from easy
operation and work-up procedure, wide substrates tolerance
and high chemical selectivity. In addition, the catalyst is cheap,
feasible, and can be easily recovered and reused for at least six
runs without signicant activity decrease. It is suggested that
the synergetic effect of the cation and anion of the ionic liquid
plays a predominant role in the catalytic activity and chemo-
selectivity. This nding would be constructive for the rational
design of novel catalysts for this type of reactions.
0
of N,N -dimethylaminoethanol with corresponding acids such
as sulfuric acid or acetate acid in an equal molar ratio. Choline
hydrogen sulfate ([choline][HSO
4
]) and choline acetate
([choline][Ac]) were prepared by neutralization of corresponding
acid with choline hydroxide which was obtained by the ion-
exchange of choline chloride using strong basic anion
exchange resin. N,N-Dimethyl-N-butylaminoethanol chloride
0
(
[C -choline][Cl]) was prepared by quaternary amination of N,N -
4
1
dimethylaminoethanol with chlorobutane. H-NMR spectra
were recorded on a BRUKER AV-400 instrument at room
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1
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added as catalyst, and the reaction was monitored by TLC
method. Aer the reaction was completed, the mixtures were
cooled to room temperature and washed with water to get the
crude product. The pure product can be obtained from the
recrystallization using 95% ethanol, and the collected aqueous
solution was concentrated by evaporation to regenerate the
ionic liquid.
1
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Acknowledgements
This work was supported by the National Natural Science
Foundation of China (Grant 21373079, 21172058).
2
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