A rapid and facile conversion of primary amides and aldoximes to nitriles and ketoximes to amides with triphenylphosphine and N-chlorosuccinimide

Article abstract of DOI:10.1081/SCC-120005936

Primary amides and aldoximes are easily converted to their corresponding nitriles using a mixture of triphenylphosphine and N-chlorosuccinimide in dichloromethane at room temperature. The reaction of aldoximes occurs almost immediately and primary amides in 0.5h by this method. By this procedure secondary amides are produced by Beckmann rearrangement of ketoximes.

Full text of DOI:10.1081/SCC-120005936

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A RAPID AND FACILE CONVERSION OF PRIMARY
AMIDES AND ALDOXIMES TO NITRILES AND KETOXIMES
TO AMIDES WITH TRIPHENYLPHOSPHINE AND N-
CHLOROSUCCINIMIDE
N. Iranpoor a , H. Firouzabadi b & G. Aghapour a
a Chemistry Department, College of Sciences, Shiraz University, Shiraz, 71454, Iran
b Chemistry Department, College of Sciences, Shiraz University, Shiraz, 71454, Iran
Version of record first published: 16 Aug 2006.
To cite this article: N. Iranpoor , H. Firouzabadi & G. Aghapour (2002): A RAPID AND FACILE CONVERSION OF PRIMARY AMIDES
AND ALDOXIMES TO NITRILES AND KETOXIMES TO AMIDES WITH TRIPHENYLPHOSPHINE AND N-CHLOROSUCCINIMIDE, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:16, 2535-2541
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 16, pp. 2535–2541, 2002
A RAPID AND FACILE CONVERSION OF
PRIMARY AMIDES AND ALDOXIMES TO
NITRILES AND KETOXIMES TO AMIDES
WITH TRIPHENYLPHOSPHINE AND
N-CHLOROSUCCINIMIDE
*
N. Iranpoor, H. Firouzabadi, and G. Aghapour
*
Chemistry Department, College of Sciences, Shiraz
University, Shiraz 71454, Iran
ABSTRACT
Primary amides and aldoximes are easily converted to their
corresponding nitriles using a mixture of triphenylphosphine
and N-chlorosuccinimide in dichloromethane at room tem-
perature. The reaction of aldoximes occurs almost immedi-
ately and primary amides in 0.5 h by this method. By this
procedure secondary amides are produced by Beckmann re-
arrangement of ketoximes.
Key Words: Amide; Aldoxime; Nitrile; Triphenylphosphine;
N-chlorosuccinimide
Nitriles are important intermediates for fine chemicals such as medi-
cines, agricultural chemicals and dyes. One of the most general methods for
synthesis of nitriles is the nucleophilic substitution reaction of alkyl halides
with inorganic cyanides. However, due to violent poisons of cyanide, the
*Corresponding authors. E-mail: iranpoor@chem.susc.ac.ir
2535
DOI: 10.1081/SCC-120005936
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2536
IRANPOOR, FIROUZABADI, AND AGHAPOUR
conversion of primary amides and aldoximes into nitriles has gained
important synthetic application for this transformation. Several methods
have been used for dehydration of aldoximes to nitriles.[1–9] However,
many of these methods are deficient in some respect such as tedious
work-up, vigorous reaction conditions, unsatisfactory yields and use of
great excess of reagents. Reagents such as triethylamine/sulfur dioxide[10]
and sulfuryl chloride fluoride[11] allow the rapid and mild dehydration of
aldehyde oximes but the preparation of the reagents is inconvenient (at
ꢀ78ꢁC). Dehydration with zeolite (CsX) suffers from high temperatures
(350ꢁC)[12] and reagents like phosgene,[13] diphosgene[14] and triphosgene[15]
are hazardous to use. Also, the use of Envirocat EPZGR has long reaction
times for this transformation.[16] Some methods have also been reported for
the conversion of amides into nitriles. Recent developed procedures for this
reaction include Vilsmeier reagent,[17] cyanuric chloride/DMF,[18] triethoxy-
diiodophosphorane[19] and trifluoroacetic anhydride.[20] However, these
reagents still have some disadvantages regarding difficulty in handling
or unsatisfactory yields. Also, the Beckmann rearrangement has been of
tremendous interest to all practicing organic chemists as the reaction
effects a nitrogen insertion into a carbon framework.[21] The conventional
Beckmann rearrangement usually requires the use of excess amounts of
strongly Bronsted acid such as conc. H2SO4 or polyphosphoric acid
(PPA) which cause serious problems such as product decomposition and
formation of large amount of inorganic salts caused by neutralization. To
circumvent these problems, during recent years, different solid catalysts
such as metal oxides,[22] metal phosphates,[23] supported boria,[24] zeolite,[25]
aluminosilicate[26,27] including clay are being used. However, most of these
reactions are vapor phase reactions or are carried out at very high tempera-
tures (523 Kꢁ). Therefore, there is still a need for research to introduce
more convenient and generally applicable methods for these important
synthetic transformations. In continuation of our previous work on pre-
paration of nitriles,[28] and introducing new applications for Ph3P,[29a,b]
we wish to report a rapid and facile method for dehydration of primary
amides and aldoximes to their corresponding nitriles and Beckmann rear-
rangement of ketoximes to secondary amides by use of triphenylphosphine/
N-chlorosuccinimide, (PPh3/NCS), as efficient reagent under mild reaction
conditions.
First, we studied the reaction of phenylacetamide with Ph3P in the pres-
ence of various electrophilic halogen sources such as N-chlorosuccinimide
(NCS), N-bromosuccinimide (NBS), and also 2,4,4,6-tetrabromo-2,5-cyclo-
hexadienone (TABCO).[30] The results are shown in Table 1.
Results of Table 1 show that the use of Ph3P/NCS as source of elec-
trophilic halogen is more efficient than using Ph3P/NBS and Ph3P/TABCO.

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TRIPHENYLPHOSPHINE AND N-CHLOROSUCCINIMIDE
2537
Table 1.
O
k
r:t:0:5 h
BnCNH2 ꢀꢀꢀꢀꢀ! BnCN
CH2Cl2
Molar Ratio
(Amide : PPh3 : NXS)
Yield
(%)a
Entry
Reagent
1
2
3
4
5
6
7
8
PPh3/NCS
PPh3/NCS
PPh3/NCS
PPh3/NCS
PPh3/NBS
PPh3/NBS
PPh3/TABCOb
PPh3/TABCO
1 : 1.2 : 1.2
1 : 1.5 : 1.2
1 : 1.2 : 1.5
1 : 1.6 : 1.6
1 : 1.2 : 1.2
1 : 1.6 : 1.2
1 : 1.2 : 1.2
1 : 1.6 : 1.2
71
73
74
91
51
71
34
54
aBy NMR analysis.
b2,4,4,6-Tetrabromo-2,5-cyclohexadienone was prepared according to the literature.[30]
The reaction of phenyl acetamide with PPh3/NCS occurs at room tempera-
ture in CH2Cl2 and produces benzyl nitrile in excellent yield (Table 1,
Entry 4), however, the same reaction with Ph3P/NBS and Ph3P/TABCO
produce phenyl acetamide in only 51 and 34% yields, respectively. We
therefore extended this procedure for dehydration of other primary
amides and also aldoximes (Table 2).
As shown in this table, aldoximes and primary amides easily convert to
their corresponding nitriles. The reaction of aldoximes occurs almost im-
mediately and amides react in 0.5 h with this reagent. In comparison with
the reaction of Ph3P/CCl4 in CH3CN with aldoximes and primary ami-
des,[9d] the present reaction using Ph3P/NCS requires shorter reaction
time. In addition, the use of Ph3P/CCl4 in acetonitrile for this conversion
suffers from the use of excess Ph3P (four equimolar).
The Beckmann reaction of ketoximes with Ph3P/NCS occurs also at
room temperature almost immediately and their corresponding secondary
amides are obtained in high yields (Table 2).
Dehydration reactions of aldoximes and primary amides with
Ph3P/NCS can occur through their reaction with (1) to produce the inter-
mediates (2) and (3), respectively. These intermediates can then convert to
nitrile by the formation of triphenyl phosphine oxide.

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2538
IRANPOOR, FIROUZABADI, AND AGHAPOUR
Table 2. Treatment of Amides and Oximes with PPh3/NCS at Room Temperaturea
Entry
Substrate
Molar Ratiob
Productc
Yield (%)d
1
2
3
4
5
6
7
8
9
CH3CH2CONH2
BnCONH2
PhCONH2
PhCH¼NOH
1 : 1.4 : 1.4
1 : 1.6 : 1.6
1 : 1.5 : 1.5
1 : 1.5 : 1.5
1 : 1.2 : 1.2
1 : 1.3 : 1.3
1 : 1.4 : 1.4
1 : 1.3 : 1.3
1 : 1.2 : 1.2
1 : 1.4 : 1.4
1 : 1.3 : 1.3
1 : 1.3 : 1.3
CH3CH2CN
BnCN
PhCN
90e
70 (90)f
75e
PhCN
97e
p-ClC6H4CH¼NOH
o-ClC6H4CH¼NOH
p-BrC6H4CH¼NOH
p-O2NC6H4CH¼NOH
o-O2NC6H4CH¼NOH
p-CH3C6H4CH¼NOH
Ph2C¼NOH
p-ClC6H4CN
o-ClC6H4CN
p-BrC6H4CN
p-O2NC6H4CN
o-O2NC6H4CN
p-CH3C6H4CN
PhCONHPh
CH3CONHPh
84
92
94
91
95
77
10
11
12
82
75 (95)f
Ph(CH3)C¼NOH
aThe reaction time for oximes is immediately and for amides is 0.5 h.
bThe molar ratio of oxime or amide : PPh3 : NCS.
cAll the products are known compounds.[9a,16,32]
dIsolated yield.
eYield is based on GC analysis using n-heptane as internal standard.
fYield is based on NMR analysis using toluene or anisole as internal standard.
The reaction of (1) with ketoximes can form the intermediate (4).
Beckmann rearrangement of (4) with loses of Ph3PO produce (5), which
can be attacked by a molecule of water in the work-up procedure to form
the rearranged product.
In conclusion, PPh3/NCS is a mild and efficient reagent for the con-
version of primary amides and aldoximes into nitriles. The use of this
reagent provides also a very mild and efficient method for the conversion

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TRIPHENYLPHOSPHINE AND N-CHLOROSUCCINIMIDE
2539
of ketoximes into secondary amides. Simple work-up, availability of the
reagents, high yields, short reaction times and occurrence of the reactions
at room temperature could also be considered as advantages of the present
method.
EXPERIMENTAL
All oximes were prepared from aldehydes or ketones according to the
literature.[31] All products are known compounds and were characterized by
comparison of their physical data with literature values. IR spectra were
1
recorded on a Perkin Elmer 781 spectrometer. H and 13C-NMR spectra
were recorded on Bruker Advance DPX-250 spectrometer. Mass spectra
were recorded on Shimadzu GCMS-QP 1000 EX instrument.
Typical Procedure
To a solution of PPh3 (0.315 g, 1.2 mmol) and NCS (0.16 g, 1.2 mmol)
in dichloromethane (5 mL) was added 2-nitrobenzaldehyde oxime (0.166 g,
1 mmol). The mixture was well stirred at room temperature. TLC monitor-
ing showed the immediate completion of the reaction. After evaporation of
the solvent, the crude product was purified by column chromatography
using n-pentane/ethyl acetate as eluent to give 2-nitrobenzonitrile as pale
yellow crystals, 0.14 g, 95% yield, m.p. 109–110ꢁC, Lit.[16] 111ꢁC.
ACKNOWLEDGMENT
We gratefully acknowledge the partial support of this work by Shiraz
University Research Council.
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2540
IRANPOOR, FIROUZABADI, AND AGHAPOUR
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TRIPHENYLPHOSPHINE AND N-CHLOROSUCCINIMIDE
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Received in the UK May 1, 2001

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