SHORT PAPER
1997
Convenient Conversion of Aldoximes into Nitriles with N-Chlorosuccinimide
and Pyridine
Synthesis of
N
itrile
s
irosław Gucma, W. Marek Gołębiewski*
Institute of Industrial Organic Chemistry, 6 Annopol St., 03-236 Warsaw, Poland
Fax +48(22)8110799; E-mail: golebiewski@ipo.waw.pl
Received 27 February 2008; revised 10 March 2008
triflic anhydride involve inconveniently low temperatures
Abstract: Benzaldehyde oximes substituted with electron-donating
groups are dehydrated to the corresponding benzonitriles by N-
chlorosuccinimide/pyridine in acetonitrile. Benzaldehyde oxime it-
self and alkanal oximes afford the corresponding aldehydes.
(–78 °C); on the other hand some reactions suffer from
high temperatures. The drawback of recently published
method of primary amides and aldoximes dehydration
with a mixture of triphenylphosphine and N-chlorosuccin-
imide is the requirement for chromatographic separation
of the products from triphenylphosphine oxide.2 There-
fore, there is still a need to develop a new, mild, and effi-
cient method for this conversion. Herein we present a new
application of N-chlorosuccinimide in nitrile synthesis by
dehydration of various aldoximes.
Key words: aldoxime, aryl nitrile, N-chlorosuccinimide, pyridine,
dehydration
In continuation of our interest in the application of N-
chlorosuccinimide in organic synthesis we have examined
the reaction of benzaldehyde oximes with N-chlorosuc-
cinimide.1 This reagent was recently used in combination
with triphenylphosphine to accomplish dehydration of al-
doximes and primary amides to nitriles.2
Following our studies on the 1,3-dipolar cycloaddition re-
action of nitrile oxides to a,b-unsaturated compounds,29
we examined the reaction of aldoximes with N-chlorosuc-
cinimide. The reaction of aldoximes 1a–h with N-chloro-
succinimide leads to the nitriles 2a–h (Scheme 1 and
Table 1). N-Chlorosuccinimide is the most popular re-
agent for the conversion of aldoximes into hydroximoyl
chlorides,30 which by treatment with base in situ generate
nitrile oxides.31 The original procedure for the synthesis
of hydroximoyl chlorides with N-chlorosuccinimide using
N,N-dimethylformamide as a solvent has limitations for
strongly activated aldoximes, because it affords mixtures
of ring chlorinated oximes and hydroximoyl chlorides. As
a solution to this problem French chemists proposed the
use of pyridine in chloroform as a solvent to quench the
unwanted electrophilic nuclear chlorination favored by
acidic catalyst (formed, e.g., by hydrolysis of NCS).32
However, in our case, this approach resulted in the forma-
tion of a mixture of several products as well. We then test-
ed different solvents and bases and were surprised to find
that in several solvents (CH2Cl2, THF, and MeCN) the
main products were, unexpectedly, nitriles. The best re-
sults were obtained with acetonitrile as a solvent and py-
ridine as a base (half molar equivalent). Promotion of
aldoxime dehydration by acetonitrile has been previously
reported.33 The reaction was successfully carried out for
benzaldehyde oximes substituted with electron-donating
groups, such as methoxy, dialkylamino, or alkyl. Usually
a small excess of N-chlorosuccinimide was required to
carry the reaction to completion, which took 1–2 hours.
Nitriles are useful intermediates in the synthesis of
amines, carboxylic acids, esters, and ketones. General
methods of nitrile synthesis comprise direct cyanation of
aromatic rings with trichloroacetonitrile, 3 reaction of aryl
halides with copper(I) cyanide4 or alkali cyanides in N,N-
dimethylformamide in the presence of palladium(II)
salts,5 replacement of the diazonium group by the cyano
group (Sandmeyer reaction);6 these methods are not free
from health hazards. There are many methods for conver-
sion of aldehydes into nitriles via aldoximes. The most
common reagent for aldoxime dehydration is acetic
anhydride7 and other similar compounds such as phthalic8
and triflic anhydride.9 Other methods involve treatment
with lower organic acids such as formic,10 or oxalic acid,11
use of strong mineral acids (H2SO4, ClSO3H),12 the com-
bination of acyl,13 thionyl, silyl, or sulfonyl chloride and a
base,14 trivalent organophosphorus compounds, e. g. di-
ethyl chlorophosphite15 or triphenylphosphine iodine16
(the driving force is the formation of a strong P=O
bond), polychloroheteroaromatic compounds such as
tetrachloropyridine17 or trichlorotriazine,18 quaternary
ammonium,19 or imidazolium salts,20 Lewis acids,21,22 ion
exchangers,23 modified24 or unmodified montmorillonite
clays,25 enzymatic systems,26 or heating without27 or with
a catalyst.28 Some of these methods have only limited
value due to low yields, expensive or not readily available
reagents, use of strong acids or bases, drastic reaction con-
ditions, or tedious workup. The use of clays generally re-
quires long reaction times, reactive chemicals such as
O
O
py
ArCH NOH
+
py⋅HCl
ArCN
+
+
NCl
NH
MeCN
SYNTHESIS 2008, No. 13, pp 1997–1999
Advanced online publication: 21.05.2008
x
x.
x
x
.
2
0
0
8
O
O
Scheme 1
DOI: 10.1055/s-2008-1067106; Art ID: P02908SS
© Georg Thieme Verlag Stuttgart · New York
Gucma, Miroslaw
