Poly(ethylene glycol)–bound sulfonyl chloride as an efficient catalyst for transformation of aldoximes to nitriles

Article abstract of DOI:10.1080/00397911.2016.1261163

An operationally simple, efficient, and environmentally benign preparation of nitriles in good to excellent yields from various aldoximes in the presence of recyclable poly(ethylene glycol)–bound sulfonyl chloride is described.

Full text of DOI:10.1080/00397911.2016.1261163

Poly(Ethylene Glycol) Bound Sulfonyl Chloride as an Efficient Catalyst for
Transformation of Aldoximes to Nitriles
Xiao-Lan Zhang1, Xiao-Ling Liu2, Xiao-Yan Sang1, Shou-Ri Sheng2
1College of Chemistry and Chemical Engineering, Shangrao Normal University,
Shangrao, P. R. China
2College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang,
P. R. China
Address correspondence to Xiao-Ling Liu, College of Chemistry and Chemical
Engineering, Jiangxi Normal University, Nanchang, China. E-mail:
liuxiaoling@jxnu.edu.cn
Abstract
An operationally simple, efficient and environmentally benign preparation of nitriles in
good to excellent yields from various aldoximes in the presence of recyclable
poly(ethylene glycol) bound sulfonyl chloride is described.
Graphical Abstract
KEYWORDS: Nitrile; aldoxime; dehydration; poly(ethylene glycol) bound sulfonyl
chloride
1

INTRODUCTION
Nitriles represent an important class of organic compounds with a wide range of
applications. They are not only key components of numerous natural products and
intermediates for several pharmaceuticals, agrochemicals, dyes, and electro-optical
materials,[1] but also versatile precursors for the synthesis of a variety of compounds such
as acids, esters, aldehydes, amines, amides, imidoesters, benzamidines and
nitrogen-containing heterocycles.[2] For these reasons, many methods have been
developed for the synthesis of nitriles. The classical methods for their preparation include
cyanation of aromatic halides,[3] and reaction of halides with sodium cyanide,[4] etc. To
date, numerous methods for the synthesis of nitriles have been reported in the literature,
such as Sandmeyer reaction of diazonium salts,[5] hydrocyanation of alkenes,[6]
metal-catalyzed cyanation of aryl halides,[7] dehydration of amides[8] or oximes,[9]
Schmidt reaction of aldehydes,[10] as well as oxidation of azides [11] and alcohols.[12]
Among them, the dehydration of aldoximes to nitriles is one of the most common routes
for the preparation of nitriles owing to the availability of starting material and the
avoidance of very toxic cyanide ion. In recent years, many methods have been developed
for this conversion.[13–26] Although most of these synthetic methods possess useful value,
the search for a simple, mild, environmentally friendly, and universally applicable
method for the conversion of aldoximes into nitriles is still in demand. In the past years,
there has been a considerable growth in interest in the use of soluble polymer-supported
catalysts and reagents in organic synthesis because of their low cost, easy of preparation,
2

simple workup and recoverablity of catalysts.[27] Polyethylene glycol (PEG), as a
inexpensive polymer, is an ideal soluble support since it is soluble in a wide range of
solvents including N,N-dimethylformamide, dichloromethane, toluene, acetonitrile, and
water at room temperature and can be recovered by solvent precipitation and filtration
with addition of hexane, diethyl ether, tert-butylmethyl ether isopropyl alcohol, or cold
ethanol into the reaction mixture.[28] Furthermore, the PEG-bound products can be
1
adequately characterized by using routine analytical techniques like TLC, IR and H
NMR.[29] With our continued research interest in developing novel methodologies in
organic synthesis using PEG-bound reagent,[30] we report herein a new convenient
method for the dehydration of aldoximes to nitriles using PEG-bound sulfonyl chloride
(PEG-SO2Cl) as an efficient and recyclable catalyst under mild conditions, as outlined in
Scheme 1.
Firstly, the conversion of benzaldehyde oxime 1a to benzonitrile 2a with PEG-SO2Cl was
chosen as a model reaction for the optimization reaction conditions, and the results were
summarized in Table 1. As seen from Table 1, some solvents such as
N,N-dimethylformamide, acetonitrile, tetrahydrofuran, toluene and dichloromethane are
all applicable for this conversion. But considering the ease of product separation,
dichloromethane was selected to be the solvent of choice. After further altering amount of
catalyst, reaction temperature and time, the better result for this conversion was
3

conveniently achieved in 97 % isolated yield of benzonitrile 2a in the presence 15 mol %
of PEG-SO2Cl in refluxing dichloromethane for 50 min (entry 6).
Secondly, to further show the generality and scope of this synthesis protocol, the
substrate scope of a variety of aldoximes was investigated through this procedure, and the
results were listed in Table 2. Seen from Table 2, various kinds of structurally diverse
aldoximes were smoothly converted to nitriles in good to excellent yields. Not only
aromatic aldoximes (Table 2, entries 1–11) but also aliphatic ones could be transformed
to the corresponding nitriles (Table 2, entries 12 and 13). The difference is that the
conversion rate of aliphatic aldoximes was slower than that of aromatic aldoximes. It is
also noteworthy to mention that the ortho-substituted aromatic aldoximes (Table 2,
entries 4, 8 and 10) gave the corresponding nitriles in relatively low yields than those
with the same substituents at the para and/or meta positions, and the reaction time needs
to be slightly prolonged, possibly due to the stereo-hindrance effect of the
ortho-substituted groups. The heteroaromatic aldoximes such as 2-furaldoxime and
2-thiophenealdoxime (Table 2, entries 14 and 15) were found to be compatible with the
employed reaction conditions and the reaction proceeded smoothly to afford 91–92 %
yield without forming any side products. In addition, as a typical olefinic aldoximes,
trans-cinnamaldoxime was conveniently converted into the corresponding nitriles with
stereochemical retention of the double bond (Table 2, entry 16). Moreover, a substrate
4

bearing bis-aldoxime was also readily dehydrated to give 1,4-dicyanobenzene in
excellent yield (Table 2, entry 17).
The reaction mechanism for conversion of aldoxime to nitrile in the presence of
PEG-SO2Cl could be briefly proposed in Scheme 2. It includes reaction of the aldoximes
with PEG-SO2Cl to form O-sulfonyl-oxime, which undergoes thermal elimination
subsequently to produce the nitrile compounds and PEG-bound sulfonic acid.
The recovered PEG-bound sulfonic acid was obtained by precipitation from the reaction
mixture with cold diethyl ether. After washing with diethyl ether and drying in vacuo, it
could be easily converted to PEG-SO2Cl again by treatment with thionyl chloride in
N,N-dimethylformamide according to our reported procedure. The recycling of the
regenerated PEG-SO2Cl was also tested through the model reaction under the same
conditions (Table 3, entries 1–4). As observed, the efficiency of the PEG-SO2Cl catalyst
on the dehydration was maintained up to the third consecutive run, and after that its
activity got diminished to some extent. Furthermore, the conversion took slightly longer
to get a complete along with the gradually slight decrease in the yield of benzonitrile 2a.
In summary, a new facile method has been established for the conversion of aldoximes to
the corresponding nitriles using recyclable poly(ethylene glycol) bound sulfonyl chloride
as dehydration agent. The availability of the catalyst, mild reaction conditions, simple
5

experimental procedure, relatively high yields of products, generality, and versatility are
advantages of the current method.
EXPERIMENTAL
Melting points were uncorrected. 1H NMR spectra were recorded on a Bruker Avance
(400 MHz) spectrometer, using CDCl3 as the solvent and TMS as internal reference.
Mass spectra (EI, 70eV) were recorded on a HP5989B mass spectrometer. IR spectra
were taken on a Perkin-Elmer SP One FTIR spectrophotometer. Difunctionalised
polyethylene glycol bound sulfonyl chloride (PEG-SO2Cl) (loading: 0.46 mmol Cl/g) was
prepared from PEG polymer (average mass 4000) according to our report method.[30] All
aldoximes are known compounds and were prepared by reaction of hydroxylamine
hydrochloride with the corresponding aldehydes through the reported method.[21] Diethyl
ether was distilled from sodium-benzophenone immediately before use and
Dichloromethane was distilled from phosphorous pentoxide immediately prior to use.
General Procedure For The Preparation Of Nitriles
To a stirred solution of aldoxime (1.0 mmol) in freshly distilled dichloromethane (10 mL)
was added PEG-SO2Cl (0.15 mmol, 326 mg) and the reaction mixture stirred at reflux
temperature for the given time in Table 2. After completion of the reaction (monitored by
TLC), The solution was concentrated by rotary evaporation and diluted with slow
addition of an excess of cold ether with vigorous stirring. The precipitate was filtered
6

through a fritted funnel, washed with ether and dried well to furnish the PEG bound
sulfonic acid in excellent yield and then converted into the PEG-SO2Cl for the recycling.
The filtrate was concentrated in a rotary evaporator, and finally the crude product was
purified by column chromatography eluted with 10–20 % ethyl acetate in hexane for their
structure analysis.
SUPPORTING INFORMATION
Characterization data of all target compounds, copies of 1H NMR and 13C NMR spectra
of all compounds. This material can be found via the “Supplementary Content” section of
this article’s webpage.
ACKNOWLEDGEMENTS
We gratefully acknowledge financial support from the National Natural Science
Foundation of China (No. 21062007), the Opening Foundation of National Research
Center for Carbohydrate Synthesis (No. GJDTZX-KF-201414), the Opening Foundation
of Key Laboratory of Functional Small Organic Molecule, Ministry of Education (No.
KLFS-KF-201411) and the Research Program of Jiangxi Province Department of
Education (No. GJJ11380).
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Table 1. Catalytic conversion of benzaldehyde oxime to benzonitrile a
Entry
Solvent
DMF
Time (min)
220
Yield (%) b
1
2
3
4
5
6
7
92
MeCN
THF
200
91
230
92
PhCH3
CH2Cl2
CH2Cl2
CH2Cl2
210
90
180
91
50
97 c
94 d
40
a Benzaldehyde oxime (1.0 mmol), PEG-SO2Cl (326 mg, 0.15 mmol), solvent (10 mL),
rt.
b Isolated yield.
c At refluxing temperature.
d PEG-SO2Cl (435 mg, 0.20 mmol) was used at refluxing temperature.
13

Table 2. Dehydration of various aldoximes to nitriles catalyzed by PEG-SO2Cl a
Entry
Aldoxime (1)
Time
(min)
50
Nitrile (2) Yield (%)
b
c
1
2
3
4
5
6
7
Benzaldehyde oxime (1a)
2a
2b
2c
2d
2e
2f
97
94
93
85
96
94
97
4-Nitrobenzaldehyde oxime (1b)
3-Nitrobenzaldehyde oxime (1c)
60
60
2-Chlorobenzaldehyde oxime (1d) 70
4-Chlorobenzaldehyde oxime (1e) 50
4-Bromobenzaldehyde oxime (1f) 50
4-Methoxybenzaldehyde oxime
55
2g
(1g)
8
2-Methylbenzaldehyde oxime (1h) 65
3-Methylbenzaldehyde oxime (1i) 50
2h
2i
86
96
88
9
10
2-Hydroxybenzaldehyde oxime
(1j)
40
2j
11
4-Hydroxybenzaldehyde oxime
(1k)
45
2k
98
12
13
14
Heptaldehyde oxime (1l)
Phenylacetaldehyde oxime (1m)
2-Furaldoxime (1n)
90
80
50
2l
91
92
92
2m
2n
14

15
16
17
2-Thiophenealdoxime (1o)
Cinnamaldehyde oxime (1p)
50
60
2o
2p
2q
91
92
97
Terephthalaldehyde bisoxime (1q) 60
a Reaction of aldoxime (1.0 mmol) in CH2Cl2 (10 mL) at refluxing temperature in the
presence of PEG-SO2Cl (326 mg, 0.15 mmol).
b All products are known compounds, and were characterized by comparison of their IR
and 1H NMR spectra or mp data, with those of authentic samples.
c Isolated yield.
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Table 3. Recyclability of PEG-SO2Cl a
Entry
Yield (%) b
Time (min)
Catalyst recovery (%)
1st run
97
50
60
70
90
98
96
92
85
2nd run c
3rd runc
4th runc
95d
92 e
88 f
a Reaction of benzaldoxime 1a (1.0 mmol) in CH2Cl2 (10 mL) at refluxing temperature in
the presence of PEG-SO2Cl (326 mg, 0.15 mmol).
b Isolated yield.
c The generated catalyst was used under identical reaction conditions to those for the 1st
run.
16

Scheme 1. PEG-SO2Cl catalyzed conversion of aldoximes to nitriles.
17

Scheme 2. Plausible mechanism for conversion of aldoximes to nitriles with PEG-SO2Cl.
18