Ionic liquid [bmim]BF4 as an efficient and recyclable reaction medium for the synthesis of O-acetyl cyanohydrin via one-pot condensation of aldehyde, TMSCN, and Ac2O

Article abstract of DOI:10.1080/00397910802431172

Ionic liquid [bmim]BF4 has been demonstrated to be an efficient and environmentally friendly reaction medium as well as reaction promoter for the synthesis of O-acetyl cyanohydrin via one-pot condensation of aldehyde, TMSCN, and Ac2O without Lewis acid or

Full text of DOI:10.1080/00397910802431172

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Ionic Liquid [bmim]BF as
4
an Efficient and Recyclable
Reaction Medium for the
Synthesis of O-Acetyl
Cyanohydrin via One-Pot
Condensation of Aldehyde,
TMSCN, and Ac O
Zhi-Liang Shen & Shun-Jun Ji
a
2
a
a
Key Laboratory of Organic Synthesis of Jiangsu
Province, College of Chemistry and Chemical
Engineering, Suzhou (Soochow) University , Suzhou,
China
Published online: 29 Jan 2009.
To cite this article: Zhi-Liang Shen & Shun-Jun Ji (2009) Ionic Liquid [bmim]BF as an
4
Efficient and Recyclable Reaction Medium for the Synthesis of O-Acetyl Cyanohydrin
via One-Pot Condensation of Aldehyde, TMSCN, and Ac O, Synthetic Communications:
2
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
39:5, 808-818, DOI: 10.1080/00397910802431172
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1
Synthetic Communications , 39: 808–818, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802431172
Ionic Liquid [bmim]BF as an Efficient and
4
Recyclable Reaction Medium for the Synthesis of
O-Acetyl Cyanohydrin via One-Pot Condensation
of Aldehyde, TMSCN, and Ac O
2
Zhi-Liang Shen and Shun-Jun Ji
Key Laboratory of Organic Synthesis of Jiangsu Province, College of
Chemistry and Chemical Engineering, Suzhou (Soochow) University,
Suzhou, China
Abstract: Ionic liquid [bmim]BF has been demonstrated to be an efficient and
4
environmentally friendly reaction medium as well as reaction promoter for the
synthesis of O-acetyl cyanohydrin via one-pot condensation of aldehyde,
TMSCN, and Ac O without Lewis acid or any special activation. In addition,
2
the recovered ionic liquid could be reused for subsequent runs without the loss
of activity.
Keywords: Acylation, ionic liquids, O-acetyl cyanohydrin, one-pot reaction,
recycle
O-Protected cyanohydrins serve as versatile synthetic intermediates in
organic synthesis for the preparation of a wide variety of organic com-
pounds such as a-hydroxyacids, a-hydroxy ketones, a-amino acids, and
[1]
b-amino alcohols. Among the methods reported for the preparation
of O-protected cyanohydrins, a one-pot condensation of carbonyl com-
pound, cyanide source, and Ac O catalyzed by Lewis acid proved to be
2
[2,3]
[4]
simple and effective. Recently, Sugai and Oriyama have reported
SnBr - and FeCl -promoted one-pot synthesis of O-acetyl cyanohydrin
2
3
Received May 20, 2008.
Address correspondence to Shun-Jun Ji, Key Laboratory of Organic Synthesis
of Jiangsu Province, College of Chemistry and Chemical Engineering, Suzhou
(
Soochow) University, Suzhou 215123, China. E-mail: chemjsj@suda.edu.cn
8
08

O-Acetyl Cyanohydrin Synthesis
809
using trimethylsilyl cyanide (TMSCN), an efficient and easily handled
cyanation reagent, to replace other cyanide sources, especially highly
toxic gaseous HCN. Although the synthesis of O-acetyl cyanohydrin
[
2,4]
using a one-pot procedure has been investigated,
the searching for a
more general method that could proceed smoothly at ambient conditions
in the absence of Lewis acid or any special activation is still highly sought
after in the synthetic community.
[5,6]
Recently, ionic liquids
have emerged as promising solvents with
unique properties such as tunable polarity, high thermal stability, negli-
gible vapor pressure, and recyclability. Their high polarity and the ability
to solubilize both inorganic and organic compounds can result in both
enhanced reaction rate and higher selectivity of chemical process in con-
trast with conventional solvents. Therefore, they are emerging as attrac-
tive alternatives to conventional volatile solvents in organic synthesis. In
continuation of our efforts to apply ionic liquids as both reaction solvent
and reaction promoter to organic transformations under mild conditions,
herein we report an efficient method for the synthesis of O-acetyl cyano-
hydrins via one-pot condensation of aldehydes, TMSCN, and Ac O in
2
ionic liquid [bmim]BF (Scheme 1).
4
Initial studies were focused on the one-pot reaction of benzaldehyde,
TMSCN, and Ac O using different imidazolium-based ionic liquids at
2
room temperature. All the results are summarized in Table 1.
As shown in Table 1, in the presence of different ionic liquids, the
one-pot reactions of benzaldehyde, TMSCN, and Ac O proceeded
2
smoothly at room temperature to give the desired product O-acetyl
cyanohydrin in moderate to excellent yields. No Lewis acid or special
activation were needed. In addition, the highest yield (99%) was obtained
when ionic liquids [omim]Br or [bmim]BF were used as reaction media
4
(
entries 3 and 4). However, without Lewis acid or any special activation,
our attempt to carry out the one-pot reaction in a conventional organic
solvent such as THF failed. No desired product was obtained under
the same conditions.
In the following work, using ionic liquid [bmim]BF as both reaction
4
solvent and promoter for the one-pot reactions of TMSCN, Ac O, and
2
various aldehydes was investigated. All the results are listed in Table 2.
Scheme 1. One-pot synthesis of O-acetyl cyanohydrin in ionic liquid.

810
Z.-L. Shen and S.-J. Ji
Table 1. Investigation of a one-pot reaction of benzaldehyde,
TMSCN, and Ac
2
O employing various ionic liquids
a
Entry
Ionic liquid
Yield (%)
1
2
3
4
5
6
7
8
[hmim]Cl (n ¼ 5)
[omim]Cl (n ¼ 7)
[omim]Br (n ¼ 7)
62
96
99
99
87
95
89
96
[bmim]BF
[hmim]BF
4
4
(n ¼ 3)
(n ¼ 5)
[omim]BF (n ¼ 7)
4
[bmim]PF
[omim]PF
6
6
(n ¼ 3)
(n ¼ 7)
a
Isolated yield.
As shown in Table 2, in all cases, the reactions proceeded efficiently
in ionic liquid [bmim]BF at ambient temperature to afford the corre-
4
sponding products in good to excellent yields. Even for less reactive
aliphatic aldehyde hydrocinnamaldehyde, 83% yield of the desired pro-
duct was furnished (entry 10). Moreover, our attempt to use acetyl chlor-
ide in place of acetic anhydride as an acylating reagent could also give the
desired product a-acetoxyphenylacetonitrile in 96% yield in ionic liquid
[
bmim]BF at room temperature.
One thing should be noted: our procedure also demonstrated that
4
O-TMS-protected cyanohydrin, derived from cyanation reaction of alde-
hyde with TMSCN in the presence of ionic liquid in the first step, could
be acylated directly by acetic anhydride without the need to transform it
[7]
into cyanohydrin first.
With the success of these transformations, we continued our task to
study the recyclability of the ionic liquid. The remaining ionic liquid
[
bmim]BF was recovered and reused several times in subsequent runs
4
without observing any loss of activity (Table 3). For example, the recy-
cling procedure using benzaldehyde as substrate yielded the product in
9
9% (run 1), 94% (run 2), 95% (run 3), 96% (run 4), and 92% (run 5),
respectively.
In summary, we have developed a convenient, efficient, and environ-
mentally friendly method for the synthesis of O-acetyl cyanohydrins via
one-pot reaction of aldehydes, TMSCN, and Ac O using ionic liquid
2
[
bmim]BF as both reaction media and promoter. This method is quite
4
general and works with a wide variety of aldehydes at room temperature
in the absence of Lewis acid or any special activation. In addition, the
ionic liquid can be easily recycled for subsequent runs without loss of
activity. The mild reaction conditions, good yields, the simplicity of the

O-Acetyl Cyanohydrin Synthesis
811
Table 2. One-pot condensation of TMSCN, Ac
liquid [bmim]BF
2
O, and various aldehydes in ionic
4
a
Entry
1
Aldehyde
Yield (%)
96
2
3
99
91
4
5
6
7
92
79
93
76
8
9
87
91
83
1
0
a
Isolated yield.

812
Z.-L. Shen and S.-J. Ji
reaction procedure, and ease of recovery and reuse of this reaction med-
ium make this method attractive for scale-up purposes.
EXPERIMENTAL
1
13
H NMR and C NMR spectra were recorded on a Bruker Avance DPX
00 and Bruker AMX 400 spectrophotometer using TMS as an internal
3
standard. HRMS spectra were obtained using a Finnigan MAT95XP
GC=high resolution mass spectrometry (HRMS) (Thermo Electron Cor-
poration). Infrared (IR) spectra were recorded on a Bio-Rad FTS 165
Fourier transform infrared (FTIR) spectrometer.
General Procedure for the Synthesis of O-Acetyl Cyanohydrin
in Ionic Liquid [bmim]BF4
[bmim]BF (0.5 mL), aldehyde (1.0 mmol), and TMSCN (1.5 mmol) were
4
added to a 10-mL round-bottomed flask. After stirring at room tempera-
ture for 12 h, Ac O (2 mmol) was added to the flask, and it was stirred for
2
another 12 h before extraction with diethyl ether (10 mL ꢀ 5). The com-
bined diethyl ether layers were washed with brine, dried over magnesium
sulfate, and concentrated under vacuum, and the residue was purified by
silica-gel column chromatography using ethyl acetate and hexane as
eluant to give the desired product O-acetyl cyanohydrin. The residual ionic
ꢁ
liquid was dried at 60 C under vacuum before reuse in further reactions.
Spectral and Analytical Data
[
7a]
a-Acetoxy-2-(4-chlorophenyl)acetonitrile (Table 2, Entry 1)
R ¼ 0.51 (ethyl acetate=hexane ¼ 1=4); FTIR (NaCl, neat): n 2250,
f
ꢂ1
1
1
753 cm ; H NMR (300 MHz, CDCl ): d 2.16 (s, 3H), 6.38 (s, 1H),
3
4
Table 3. Recycling of [bmim]BF in one-pot reaction
of benzaldehyde, TMSCN, and Ac
2
O
Run
Isolated Yield (%)
1
2
3
4
5
99
94
95
96
92

O-Acetyl Cyanohydrin Synthesis
813
1
3
7
1
(
.40–7.48 (m, 4H) ppm; C NMR (75.4 MHz, CDCl ): d 168.7 (C¼O),
3
36.4 (C), 130.2 (C), 129.3 (CHx2), 129.1 (CHx2), 115.7 (CN), 62.0
CH), 20.2 (CH ) ppm; HRMS (EI, m=z): [M] . Calcd. for C H ClNO :
2
þ
3
10
8
2
09.0244; found: 209.0241.
[
7a]
a-Acetoxy-2-phenylacetonitrile (Table 2, Entry 2)
R ¼ 0.50 (ethyl acetate=hexane ¼ 1=4); FTIR (NaCl, neat): n 2250,
f
ꢂ1
1
1
7
6
746 cm ; H NMR (300 MHz, CDCl ): d 2.17 (s, 3H), 6.41 (s, 1H),
.43–7.54 (m, 5H) ppm; C NMR (75.4 MHz, CDCl ): d 20.2 (CH ),
3
1
3
3
3
2.7 (CH), 116.0 (CN), 127.7 (CHx2), 129.1 (CHx2), 130.2 (CH), 131.7
þ
(
C), 168.8 (CO) ppm; HRMS (EI, m=z): [M] . Calcd. for C H NO ;
1
0
9
2
1
75.0633; found: 175.0633.
[
7a]
a-Acetoxy-2-(4-methylphenyl)acetonitrile (Table 2, Entry 3)
R ¼ 0.52 (ethyl acetate=hexane ¼ 1=4); FTIR (NaCl, neat): n 2250,
f
ꢂ1
1
1
747 cm ; H NMR (300 MHz, CDCl ): d 2.12 (s, 3H), 2.36 (s, 3H),
3
6
.35 (s, 1H), 7.23 (d, J ¼ 8.43 Hz, 2H), 7.39 (d, J ¼ 8.01 Hz, 2H) ppm;
1
3
C NMR (75.4 MHz, CDCl ): d 168.8 (C¼O), 140.5 (C), 129.7 (CHx2),
3
128.8 (C), 127.7 (CHx2), 116.2 (CN), 62.6 (CH), 21.1 (CH ), 20.3 (CH )
ppm; HRMS (EI, m=z): [M] . Calcd. for C H NO : 189.0790; found:
3
3
þ
1
1
11
2
1
89.0791.
[
7a]
a-Acetoxy-2-(4-methoxyphenyl)acetonitrile (Table 2, Entry 4)
R ¼ 0.49 (ethyl acetate=hexane ¼ 1=4); FTIR (NaCl, neat): n 2250,
f
ꢂ1
1
1
6
2
1
741 cm ; H NMR (300 MHz, CDCl ): d 2.12 (s, 3H), 3.81 (s, 3H),
3
.34 (s, 1H), 6.94 (dd, J ¼ 6.63, 2.4 Hz, 2H), 7.44 (dd, J ¼ 6.63, 2.4 Hz,
1
3
H) ppm; C NMR (75.4 MHz, CDCl ): d 168.9 (C¼O), 160.9 (C),
3
29.4 (CHx2), 123.7 (C), 116.2 (CN), 114.4 (CHx2), 62.4 (CH), 55.2
þ
(CH ), 20.2 (CH ) ppm; HRMS (EI, m=z): [M] . Calcd. for
C H NO ; 205.0739; found: 205.0738.
3
3
1
1
11
3
[
7a]
a-Acetoxy-2-(4-cyanophenyl)acetonitrile (Table 2, Entry 5)
R ¼ 0.31 (ethyl acetate=hexane ¼ 1=4); FTIR (NaCl, neat): n 2229,
f
ꢂ1
1
1
7
1
744 cm ; H NMR (300 MHz, CDCl ): d 2.22 (s, 3H), 6.49 (s, 1H),
3
1
3
.74 (dd, J ¼ 28.53, 8.01 Hz, 4H) ppm; C NMR (75.4 MHz, CDCl ): d
3
68.7 (C¼O), 136.4 (C), 133.0 (CHx2), 128.4 (CHx2), 117.8 (C), 115.4

814
Z.-L. Shen and S.-J. Ji
þ
(CN), 114.2 (CN), 62.0 (CH), 20.3 (CH ) ppm; HRMS (EI, m=z): [M] .
Calcd. for C H N O : 200.0586; found: 200.0583.
3
11
8
2
2
[
6j]
a-Acetoxy-2-(3,4-methylenedioxyphenyl)acetonitrile (Table 2, Entry 6)
R ¼ 0.42 (ethyl acetate=hexane ¼ 1=4); FTIR (NaCl, neat): n 2252,
f
ꢂ1
1
1
6
751 cm ; H NMR (300 MHz, CDCl ): d 2.14 (s, 3H), 6.00 (s, 2H),
3
1
3
.30 (s, 1H), 6.83 (d, J ¼ 8.01 Hz, 1H), 6.97–7.02 (m, 2H) ppm;
C
NMR (75.4 MHz, CDCl ): d 168.8 (C¼O), 149.2 (C), 148.2 (C), 125.2
3
(
C), 122.2 (CH), 116.1 (CN), 108.4 (CH), 108.0 (CH), 101.7 (CH ),
2
þ
6
C H NO : 219.0532; found: 219.0532.
2.5 (CH), 20.3 (CH ) ppm; HRMS (EI, m=z): [M] . Calcd. for
3
1
1
9
4
[
8a]
a-Acetoxy-1-naphthylacetonitrile (Table 2, Entry 7)
R ¼ 0.54 (ethyl acetate=hexane ¼ 1=4); FTIR (NaCl, neat): n 2251,
f
ꢂ1
1
1
7
8
746 cm ; H NMR (300 MHz, CDCl ): d 2.10 (s, 3H), 6.99 (s, 1H),
3
.41–7.60 (m, 3H), 7.76 (d, J ¼ 7.2 Hz, 1H), 7.87 (t, J ¼ 8.4 Hz, 2H),
1
3
.00 (d, J ¼ 8.01 Hz, 1H) ppm; C NMR (75.4 MHz, CDCl ): d 168.9
3
(
C¼O), 133.8 (C), 131.3 (CH), 129.9 (C), 129.0 (CH), 127.5 (CH),
1
2
2
27.4 (CH), 126.9 (C), 126.5 (CH), 125.0 (CH), 116.1 (CN), 61.2 (CH),
0.2 (CH ) ppm; HRMS (EI, m=z): [M] . Calcd. for C H NO :
þ
3
14 11
2
25.0790; found: 225.0788.
[
8b]
a-Acetoxy-2-(5-methyl-2-furyl)acetonitrile (Table 2, Entry 8)
R ¼ 0.47 (ethyl acetate=hexane ¼ 1=4); FTIR (NaCl, neat): n 2215,
f
ꢂ1
1
1
751 cm ; H NMR (300 MHz, CDCl ): d 2.15 (s, 3H), 2.32 (s, 3H),
3
6
.03 (q, J ¼ 1.33 Hz, 1H), 6.40 (s, 1H), 6.55 (d, J ¼ 3.21 Hz, 1H) ppm;
1
3
C NMR (75.4 MHz, CDCl ): d 168.7 (C¼O), 155.3 (C), 142.0 (C),
3
114.2 (CN), 113.6 (CH), 107.1 (CH), 55.7 (CH), 20.2 (CH ), 13.4 (CH )
ppm; HRMS (EI, m=z): [M] . Calcd. for C H NO : 179.0582; found:
3
3
þ
9
9
3
1
79.0587.
[
3i]
a-Acetoxy-2-(2-thienyl)acetonitrile (Table 2, Entry 9)
R ¼ 0.56 (ethyl acetate=hexane ¼ 1=4); FTIR (NaCl, neat): n 2255,
f
ꢂ1
1
1
7
1
754 cm ; H NMR (300 MHz, CDCl ): d 2.14 (s, 3H), 6.62 (s, 1H),
3
.04 (q, J ¼ 2.8 Hz, 1H), 7.34 (t, J ¼ 1.8 Hz, 1H), 7.45 (q, J ¼ 2.14 Hz,
1
3
H) ppm; C NMR (75.4 MHz, CDCl ): d 168.7 (C¼O), 133.3 (C),
3

O-Acetyl Cyanohydrin Synthesis
815
1
ppm; HRMS (EI, m=z): [M] . Calcd. for C H NO S: 181.0197; found:
29.5 (CH), 128.9 (CH), 127.1 (CH), 115.4 (CN), 58.0 (CH), 20.2 (CH )
3
þ
8
7
2
1
81.0197.
[
7b]
a-Acetoxy-4-phenylbutanenitrile (Table 2, Entry 10)
R ¼ 0.68 (ethyl acetate=hexane ¼ 1=4); FTIR (NaCl, neat): n 2249,
f
ꢂ1
1
1
749 cm ; H NMR (300 MHz, CDCl ): d 2.09 (s, 3H), 2.20 (m, 2H),
3
2
.81 (t, J ¼ 7.64 Hz, 2H), 5.24 (t, J ¼ 6.83 Hz, 1H), 7.16–7.33 (m, 5H)
1
3
ppm; C NMR (75.4 MHz, CDCl ): d 168.9 (C¼O), 139.0 (C), 128.62
3
(
(
CHx2), 128.19 (CHx2), 126.5 (CH), 116.6 (CN), 60.4 (CH), 33.6
CH ), 30.6 (CH ), 20.1 (CH ) ppm; HRMS (EI, m=z): [M] . Calcd.
þ
2
2
3
for C H NO : 203.0946; found: 203.0951.
1
2
13
2
ACKNOWLEDGMENT
This work was partially supported by the Key Laboratory of Organic
Synthesis of Jiangsu Province at Suzhou University (No. S8109108),
the Natural Science Foundation of Jiangsu Province (No. BK2006048),
the National Science Foundation of China (Nos. 20472062 and
2
0672079), the Nature Science Key Basic Research of Jiangsu Province
for Higher Education (Nos. 06KJA15007 and 05KJB150116), the Jiangsu
Provincial Key Laboratory of Fine Petrochemical Technology (KF0402),
and a research grant from the Innovation Project for Graduate Students
of Jiangsu Province.
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