One-step synthesis of α,β-unsaturated arylsulfones by a novel multicomponent reaction of aromatic aldehydes, chloroacetonitrile, benzenesulfinic acid sodium salt

Article abstract of DOI:10.1016/j.cclet.2012.10.013

A new and green method for the synthesis of α,β-unsaturated arylsulfones had been achieved through the condensation of aromatic aldehydes, chloroacetonitrile, benzenesulfinic acid sodium salt in the presence of 1-butyl-3-methyl imidazolium hydroxide ([bmim]OH) in EtOH under reflux. The ionic liquid was recovered and recycled for subsequent reactions. The advantages of this protocol were non-toxic, easy work-up and good yields.

Full text of DOI:10.1016/j.cclet.2012.10.013

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 1352–1354
www.elsevier.com/locate/cclet
One-step synthesis of a,b-unsaturated arylsulfones by a novel
multicomponent reaction of aromatic aldehydes,
chloroacetonitrile, benzenesulfinic acid sodium salt
*
Lei Zhang, Mao Hua Ding, Hong Yun Guo
College of Chemical Engineering and Materials, Zhejiang University of Technology, Hangzhou 310014, China
Received 10 July 2012
Available online 16 November 2012
Abstract
A new and green method for the synthesis of a,b-unsaturated arylsulfones had been achieved through the condensation of
aromatic aldehydes, chloroacetonitrile, benzenesulfinic acid sodium salt in the presence of 1-butyl-3-methyl imidazolium
hydroxide ([bmim]OH) in EtOH under reflux. The ionic liquid was recovered and recycled for subsequent reactions. The
advantages of this protocol were non-toxic, easy work-up and good yields.
# 2012 Hong Yun Guo. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Ionic liquids; Benzenesulfinic acid sodium salt; a,b-Unsaturated arylsulfones
The application of sulfones as intermediates in organic synthesis has increased considerably in the last years [1].
This interest comes from the fact that arylsulfonyl groups can stabilize adjacent carbanions [2] and may easily be
removed by hydrolysis, reduction or elimination [3], and when appropriate, may be eliminated to introduce carbon–
carbon double bonds into organic molecules [4]. Thus they are useful in temporary activating groups for alkylation [5],
acylation [6] and addition [7] reactions.
To the best of our knowledge, the knoevenagel condensation [8] of arylsulfones and aldehydes is one of the most
popular methods for the synthesis of unsaturated arylsulfones. However, there is no report for the synthesis of a,b-
unsaturated arylsulfones achieved through the condensation of aromatic aldehydes, chloroacetonitrile, benzene-
sulfinic acid sodium salt. Furthermore, these methods required strong bases such as sodium hydride [9], butyl lithium
[10] or lithium diisopropylamide (LDA) [11].
As a continuation of our efforts on synthesizing these compounds with efficient and green approaches. Herein, we
would like to report a novel synthetic method through the condensation of aromatic aldehydes, chloroacetonitrile,
benzenesulfinic acid sodium salt in ethanol catalyzed by ionic liquids (Scheme 1).
Initially, the reaction of 4-chlorobenzaldehyde (1b, 1 mmol), chloroacetonitrile (2, 1 mmol) and benzenesulfinic
acid sodium salt (3, 1 mmol) was carried out in ethanol in the presence of different ionic liquids (10% mol) under
reflux. As illustrated in Table 1, [bmim]OH was preferred as the optimal catalyst (Table 1, entry 4). Moreover, the
* Corresponding author.
E-mail address: guohy63@163.com (H.Y. Guo).
1001-8417/$ – see front matter # 2012 Hong Yun Guo. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2012.10.013

L. Zhang et al. / Chinese Chemical Letters 23 (2012) 1352–1354
1353
SO2Na
H
SO2Ph
CN
N
CN
N
OH
Solvent (reflux)
CHO
+
+
R
Cl
2
R
1
3
4
Scheme 1. The synthetic route of a,b-unsaturated arylsulfones.
Table 1
Reaction conditions optimization for the synthesis of 4b.
Entrya
Catalysts
Solvent
Time (h)
Yieldb (%)
1
2
[bmim]PF6
[bmim]BF4
HEAA
EtOH
EtOH
EtOH
EtOH
Water
DMF
12
12
8
33
40
66
85
38
66
83
54
74
79
60
74
3
4
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
[bmim]OH
6
5
12
12
6
7
MeOH
CH3CN
DMSO
CH3Cl
CCl4
6.5
8
10.5
7.5
8
9
10
11
12
12
10
CH2Cl2
a
All reaction were run with 4-chlorobenzaldehyde (1b, 1 mmol), chloroacetonitrile (2, 1 mmol) and benzenesulfinic acid sodium salt (3, 1 mmol),
and 2 mL solvent.
b
Isolated yield.
solvent had a great influence on the model reaction. The reactions were carried out at different solvent. The yield of
product 4b was increased and the reaction time was shortened when the solvent was ethanol (Table 1, entries 4–12).
The reason maybe is starting materialist dissolve easily in ethanol. So the starting materials in EtOH have larger
contact area, shorter reaction time and higher yield.
Based on the optimized reaction conditions, a series of a,b-unsaturated arylsulfones derivatives were synthesized.
The results were summarized in Table 2, showing that the reaction in the presence of [bmim]OH (10% mol) under
reflux gave the corresponding products in moderate to good yields. It is obvious that this protocol could be applied to
various aromatic aldehydes with electron-withdrawing groups or electron-donating groups. Besides, the results
suggest that the substrates bearing electron-withdrawing groups on the aromatic ring increases the reactivity (higher
Table 2
Synthesis of 4 using [bmim]OH as catalyst in ethanol.
Entry
R
Products
Time (h)
Yielda (%)
1
2
C6H5–
4a
4b
4c
4d
4e
4f
9
6
74
85
89
74
69
64
61
84
63
78
77
60
NR
4-Cl–C6H4–
4-NO2–C6H4–
4-F–C6H4–
3
6
4
8
5
4-CH3–C6H4–
4-MeO–C6H4–
4-OH–C6H4–
2-NO2–C6H4–
2-Furyl–
10
11
12.5
6
6
7
4g
4h
4i
8
9
12
8
10
11
12
13
2,4-Cl2–C6H3–
2-Naphthyl–
3-OMe-4-OH–C6H3–
n-Butyl–
4j
4k
4l
6
12
12
4m
a
Isolated yield.

1354
L. Zhang et al. / Chinese Chemical Letters 23 (2012) 1352–1354
Table 3
Studies on the reuse of [bmim]OH in the preparation of 4b.
Rounda
1
2
3
4
5
6
Yieldb (%)
85
83
83
82
81
80
a
All reaction were run with 4-chlorobenzaldehyde (1b, 1 mmol), chloroacetonitrile (2, 1 mmol) and benzenesulfinic acid sodium salt (3, 1 mmol),
and 2 mL solvent.
b
Isolated yield.
yields and shorter reaction time). Meanwhile, the presence of electron-donating groups decreases the reaction rate. So,
it is concluded that the electronic nature of the substituents on aldehydes has some effect on this reaction. However,
when the aliphatic aldehyde was applied to this reaction, no expected product obtained, we attributed this to the slow
formation and unstable nature of the product formed from the aliphatic aldehydes examined. In this study, the products
1
4g–l were new compounds, which were characterized by mp, IR, H NMR, 13C NMR, mass spectroscopy [12].
As a green catalyst, the recovery and reuse of ionic liquid was very important in green synthetic process. Therefore,
we studied on the reuse of [bmim]OH on the optimized reaction conditions. As shown in Table 3, the ionic liquid
[bmim]OH could be successively recovered and reused for five times without remarkable loss in the catalytic activity.
In summary, the highly functionalized a,b-unsaturated arylsulfonesare are of intense attention because of their
useful temporary activating groups, and thus an efficient procedure for their synthesis is of high importance. The
present procedure using a novel and convenient multicomponent reaction in the present of green catalyst provides a
high yielding synthesis of a,b-unsaturated arylsulfonesare. The other advantage of this procedure is the reusability of
ionic liquids.
Typical procedure: The mixture of the aromatic aldehyde 1 (1 mmol), chloroacetonitrile 2 (1 mmol),
benzenesulfinic acid sodium salt 3 (1 mmol) and [bmim]OH (10%) in EtOH (2 mL) was stirred under reflux for
the appropriate time (monitored by thin-layer chromatography [TLC]). After completion of the reaction, the solid
product was collected by filtration and recrystallized from ethanol to give the pure compound 4. The filtrate was
poured into 10 mL of water, extracted with diethyl ether several times to remove unreacted aromatic aldehyde,
chloroacetonitrile and other organic contaminations. Then the water was evaporated under reduced pressure and
centrifugated to recover the ionic liquid for subsequent use.
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[12] Some selected data: compound 4k: mp 160–161 8C; 1H NMR (500 MHz, CDCl3): d 9.15 (s, 1H), 8.26 (d, 1H, J = 7.4 Hz), 8.06–8.12 (m, 4H),
7.94 (d, 1H, J = 8.1 Hz), 7.61–7.58 (m, 6H). 13C NMR (CDCl3): d 148.9, 137.8, 134.7, 134.3, 133.5, 131.6, 129.7; 129.3, 128.7, 128.3, 128.2,
127.1, 126.7, 125.3, 122.5, 117.0, 113.0. IR vmax (KBr): 3020, 2200, 1595 cm–1. MS (EI, 70 eV) (m/z, %): 319.3 (M, 25.1), 177.4 (100), 151.5
(9.4), 51.3 (5.5). 4l: mp 179–180 8C; 1H NMR (500 MHz, CDCl3): d 8.12 (s, 1H), 8.03 (d, 2H, J = 8.7 Hz), 7.60–7.41 (m, 5H), 7.01 (d, 1H,
J = 8.2 Hz), 6.29(s, 1H), 3.96 (s, 3H). 13C NMR (CDCl3): d 151.7, 151.5, 147.0, 138.6, 134.3, 129.6, 128.9, 128.4, 122.9, 115.2, 113.9, 111.0,
110.7, 56.2. IR vmax (KBr): d 3059, 2222, 1576 cmÀ1. MS (EI, 70 eV) (m/z, %): 316.2 (M+1, 11.0), 173.3 (100), 158.2 (22.7), 130.3 (7.9), 51.2
(11.0).