A novel heterogeneous synthesis of acyl cyanides catalyzed by PEG400 and zinc iodide

Article abstract of DOI:10.1081/SCC-200026646

Aroyl cyanides were readily synthesized in moderate yields by the cyanation of aroyl chlorides with dry powdered potassium cyanide under the catalysis of PEG400 and zinc iodide in dichloromethane at room temperature. A preliminary study on the one-pot preparation of acetyl cyanide was also reported.

Full text of DOI:10.1081/SCC-200026646

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A Novel Heterogeneous
Synthesis of Acyl Cyanides
Catalyzed by PEG400 and Zinc
Iodide
a
a
a
Yu‐Qing Cao , Yun‐Fei Du , Bao‐Hua Chen
&
a
Ji‐Tai Li
a
College of Chemistry and Environmental
Science , Hebei University , Baoding, 071002, P.R.
China
Published online: 06 Jan 2011.
To cite this article: Yu‐Qing Cao , Yun‐Fei Du , Bao‐Hua Chen & Ji‐Tai Li (2004)
A Novel Heterogeneous Synthesis of Acyl Cyanides Catalyzed by PEG400 and
Zinc Iodide, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:16, 2951-2957, DOI: 10.1081/
SCC-200026646
To link to this article: http://dx.doi.org/10.1081/SCC-200026646
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SYNTHETIC COMMUNICATIONS
Vol. 34, No. 16, pp. 2951–2957, 2004
A Novel Heterogeneous Synthesis of Acyl
Cyanides Catalyzed by PEG400 and
Zinc Iodide
*
Yu-Qing Cao, Yun-Fei Du, Bao-Hua Chen, and Ji-Tai Li
College of Chemistry and Environmental Science, Hebei University,
Baoding, P.R. China
ABSTRACT
Aroyl cyanides were readily synthesized in moderate yields by the
cyanation of aroyl chlorides with dry powdered potassium cyanide
under the catalysis of PEG400 and zinc iodide in dichloromethane at
room temperature. A preliminary study on the one-pot preparation of
acetyl cyanide was also reported.
Key Words: Aroyl cyanides; Aroyl chlorides; KCN; PEG400.
*
Correspondence: Yu-Qing Cao, College of Chemistry and Environmental Science,
Hebei University, Baoding 071002, P.R. China; E-mail: pharm_hbu@yahoo.com.
2
951
DOI: 10.1081/SCC-200026646
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

2
952
Cao et al.
INTRODUCTION
Acyl cyanides have played important roles in organic synthesis which
allow numerous transformations to such compounds as a-ketoacids, 1-amino-
-ethanol derivatives, and a wide range of heterocyclic compounds, further-
more, some of them even show significant biological activity in agricultural
2
[1]
use and are useful as mild and selective acylating agents. Literature
survey indicates that only a small number of methods have been reported
for the preparation of this useful class of compounds, and seldom of them
can be regarded as fairly satisfactory. Benzoyl cyanide was first prepared in
[
2]
1
832 by the reaction of benzoyl chloride with mercuric cyanide. Later on,
[
3]
silver cyanide and cuprous cyanide were used as cyanogen sources in the
cyanating reaction of acyl chlorides, which only afforded moderate yields.
[5]
It was not until trimethylsilyl cyanide (TMSCN), acyl iodide, and
[4]
[1]
tributyltin cyanide were used that the satisfactory yields were obtained.
However, none of those reagents is readily available and some of them
even pose potential danger to the health and generate severe pollution to the
environment. In this respect, some other cheaper or more available cyanogen
sources, such as hydrogen cyanide, sodium cyanide, and potassium cyanide
should be preferable.
The cyanation of aroyl chlorides with potassium cyanide was ever per-
[6]
formed in acetonitrile, catalyzed either by small amount of water or ultra-
[7]
sonic radiation. However, the presence of water or the ultrasound will
lead to the formation of more aroyl cyanide dimers [R–CO–OC(CN) –R]
2
and colorful polymers, which are the main reasons for the low yields. On
the other hand, the catalytic water will be partially consumed by the aroyl
chlorides at the reflux temperature in acetonitrile, which will greatly decrease
the catalytic efficiency of the water as well as the overall yields of the aroyl
cyanides. Tetrabutyl ammonium bromide has been used as phase transfer cata-
lyst (PTC) in the two-phase reaction of aroyl chlorides with aqueous potassium
cyanide. However, lower temperature was needed to reduce the hydrolysis
of the aroyl chlorides and aroyl cyanides, both of which are sensitive to
water. In addition, a larger amount of dimers were formed in the presence
[2]
of water.
Polyethylene glycols (PEGs) can be regarded as the acyclic crown-ether
and have been used as PTC in many organic reactions owing to their stability,
[
8–10]
low cost, poisonlessness, and easy availability.
PEG400 has been used as PTC for the synthesis of primary aliphatic and
In our previous work,
[11]
aromatic nitriles.
In the continuation of our investigation on the research
of using PEGs as PTC, we herein report an alternative and an efficient
method for the preparation of aroyl cyanides by the cyanation of aroyl chlor-
ides with KCN catalyzed by PEG400 (Sch. 1). We also introduced catalytic

Synthesis of Acyl Cyanides
2953
Scheme 1.
amount of zinc iodide to increase the reaction rate based on the fact that iodide
anion, as both a strong nucleophilic reagent and a good leaving group, had
been extensively used in the S 2 substitution reactions. The experimental
N
results were listed in Table 1.
Benzoyl chloride was used as substrate to study the catalytic efficiency. It
was found that lower dosage of PEG400 could not catalyze the reaction effec-
tively, and higher dosage would undoubtedly lead to more loss of products
during the washing procedure. Compared with the case without the partici-
pation of ZnI , the reaction rate was greatly enhanced with the introduction
2
of ZnI . Based on the results of the comparative experiments, we suggest an
2
amount of 4 mol% PEG400 and 1.6 mol% ZnI to be used and an excess
2
(20%) of dried and fine powdered potassium cyanide was necessary for ensur-
ing the complete conversion of the acyl chlorides.
Both TLC and GC showed that only a negligible amount of colorful
dimers was found for the substrates in all cases except for the ones in
entries 6 and 7. Generally, it supported the idea that potassium cyanide was
a close ion pair in the reaction system, which greatly decreased the formation
[10]
of the dimers. However, when it came to the entries 6 and 7, the formation
of dimers could not be neglected, which was found to be the major reason that
Table 1. Cyanation of aroyl chlorides to the corresponding aroyl cyanides.
M.p. (8C) or b.p. (8C/mmHg)
a
Time
(hr)
Yield
(%)
[
7]
Entry
R
Found
31–32
48–49
Lit.
1
2
3
4
5
6
7
8
9
C
6
H
5
4.5
6
76
82
86
78
88
60
64
86
83
31.5–32.5
48.9–49.7
75–76/4
27–28
57–58
41.4–42.1
4-CH C H
3
3
3
6
6
6
4
4
4
2-CH
3-CH
C
C
H
H
6
130–131/30
26–27.5
[
2]
6
4-MeOC
6
4
H
4
7
56.5–57.5
41–42
4-ClC H
6
4
[
4]
4-BrC
2-Furyl
2-Thienyl
6
H
4
4
66–67
145–146/25
53.5–54.5
66–67
86–88/15
54–55
5
[
6]
5
a
Yield of isolated product calculated according to total aroyl chlorides.

2
954
Cao et al.
led to their lower yields. We proposed that this might due to the electron-
withdrawing effect of the halogen groups on the benzene ring, which made
the carbonyl group highly active to react with two cyanides to form dimers or
polymers. While for the substrate in entry 5, because of the electron-donating
effect of the methoxy group, less dimer was formed. However, the less reac-
tivity of the substrate required longer reaction time.
It was shown by GC and TLC that nearly 30% of PEG400 was acylated by
aroyl chloride to form esters in the comparative experiment concerning the
reaction of PEG400 with benzoyl chloride catalyzed by zinc iodide performed
at room temperature covering a period of time of 12 hr. However, the exper-
iment indicated that the acylated PEG400 still possesses certain ability of
phase transfer catalysis, since its structure also resembles that of the acyclic
crown-ether.
However, the experimental results concerning acetyl chloride, propionyl
chloride, and chloroacetyl chloride show that no acyl cyanides were obtained
and nearly 90% of acyl chloride was recovered after the reactions were per-
formed under reflux covering a period of time as long as 24 hr, which might
indicate that the method might not be suitable for the preparation of aliphatic
acyl cyanides.
It has been reported by the previous literature that aliphatic acyl cyanides
[12]
may be prepared by reaction of aliphatic acyl chlorides with TMSCN.
Based on this and our reported method for the preparation of TMSCN cata-
[13]
lyzed by PEG400,
we launched an investigation on a one-pot synthesis
of aliphatic acyl cyanide using TMSCl as catalyst, since it was easily con-
ceived that the formed TMSCN in the first step could be converted back
into TMSCl in the second step, which could be used circularly (Sch. 2).
The readily available acetyl chloride was used as substrate in our preliminary
study. However, it was found that catalytic amount of TMSCl could not afford
acetyl cyanide at all. In the case, the majority of acetyl chloride (85%) was
recovered, similar to the case without the participation of TMSCl discussed
above. Equal molar ratio of TMSCN and acetyl chloride (1 : 1) was finally pro-
posed to participate in the second-step conversion. With the formation of
TMSCN completed, acetyl chloride was added dropwise and kept the
mixture refluxing for 2 hr. After the removal of the inorganic salts by filtration
Scheme 2.

Synthesis of Acyl Cyanides
2955
and dichloromethane by distillation, 70% of TMSCl was recovered and 55%
of acetyl cyanide was obtained. Surprisingly, a-[(trimethylsilyl)oxy] acrylo-
nitrile was further separated by distillation under reduced pressure, and the
structure was confirmed by comparing its IR and H NMR with that of the
[14]
pure sample prepared according to the previous literature.
concerning its formation is under investigation.
The mechanism
The experimental results indicated that the present procedure for the prep-
aration of aroyl cyanide compared favorably well with the previous methods
for its high yield, mild reaction condition, and availability of the starting
materials. The method described for the preparation of acetyl cyanide
should also be applicable to the preparation of other aliphatic acyl cyanides,
the results as well as the mechanism will be discussed in due course.
EXPERIMENTAL
GC-17A is a column packed with SE30 on Chromsorb using o-terphenyl
as an internal standard. TLC was GF254 thin layer chromatography with pet-
roleum ether/ethyl acetate (10/1) as eluent. Melting points were determined
on microscopy apparatus and were uncorrected. Potassium cyanide was dried
at 1208C under vacuum for 24 hr and finely powdered. All the glass apparatus
were oven-dried before use and all the reactions were performed in a hood
with good ventilation.
Typical Procedure for the Preparation of Benzoyl Cyanide
A 100 mL three-necked, round-bottomed flask equipped with a magnetic
bar and nitrogen inlet tube was charged with 0.5 g (0.0016 mol) ZnI , 30 mL of
2
CH Cl , 1.5 g (0.004 mol) of PEG400, and 7.8 g (0.12 mol) of KCN, after
2
2
stirring for 20 min, 14 g (0.100 mol) of benzoyl chloride was added.
Then the mixture was vigorously stirred under nitrogen at room temperature.
The process of the reaction was monitored by TLC. When the spot of the
benzoyl chloride on the TLC was completely disappeared, the stirring was
continued for half-an-hour. The solid residue was filtered off and washed
with dichloromethane, and the filtrate was washed with cold water
(
2 Â 30 mL). The dichloromethane layer was separated, dried over mag-
nesium sulfate, filtered and distilled to give the crude benzoyl cyanide
which was further purified by recrystallization from hexane, 11.2 g of color-
less crystal was obtained. Yield, 76%, m.p. 31–328C.

2
956
Cao et al.
Typical Procedure for the Preparation of Acetyl Cyanide and
a-[(Trimethylsilyl)oxy] Acrylonitrile
A 0.5 g of ZnI , 30 mL of CH Cl , 2g (0.005 mol) of PEG400, 7.8 g
2
2
2
(0.12 mol) of potassium cyanide, and 12 g (0.11 mol) of TMSCl were added to
a 100 mL three-necked, round-bottomed flask equipped with a magnetic bar
and nitrogen inlet tube. The mixture was stirred under nitrogen at room temp-
erature for 20 hr. With the filtering off the inorganic salts, the liquid filtrate
was fed back to the original flask, and 7.9 g (0.10mol) of acetyl chloride was
added dropwise under nitrogen atmosphere. The mixture was kept reflux for
2
3
hr. After the removal of CH Cl , 8.4g of TMSCl was recycled (70%) and
2 2
[15]
.8 g of acetyl cyanide was obtained. Yield, 55%, b.p. 91–938C (Lit. 938C).
A 2.1 g of a-[(trimethylsilyl)oxy] acrylonitrile was further collected by dis-
tillation at reduced pressure. Yield, 15%, calculated based on acetyl chloride.
[
14]
B.p. 80–828C/50 mmHg (Lit.
based on IR and H NMR spectroscopies. n
58–598C/40 mmHg). Identification was
IR (KBr): 2950, 2230, 1600,
max
1
210, 1050, 800, 750. H NMR (CDCl , 400 MHz): d 0.29 (s, 9 H), 5.03 (s, 1
1
H), 5.09 (s, 1 H).
3
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2
3
4
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1
Received in Japan January 19, 2004