Direct synthesis of aromatic nitriles from aldehydes using hydroxylamine and oxalyl chloride

Article abstract of DOI:10.1080/00397910601055198

Various aromatic and heterocyclic nitriles were prepared in good to high yields in a direct one-pot process by heating the corresponding aldehydes with hydroxylamine and oxalyl chloride as reagents. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910601055198

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Direct Synthesis of Aromatic Nitriles from
Aldehydes Using Hydroxylamine and Oxalyl
Chloride
a b
a
Barahman Movassagh
& Azadeh Fazeli
a
Department of Chemistry, K. N. Toosi University of Technology, Tehran,
Iran
b
Kermanshah Oil Refining Company, Kermanshah, Iran
Version of record first published: 06 Mar 2007.
To cite this article: Barahman Movassagh & Azadeh Fazeli (2007): Direct Synthesis of Aromatic Nitriles from
Aldehydes Using Hydroxylamine and Oxalyl Chloride, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 37:4, 623-628
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Synthetic Communications , 37: 623–628, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601055198
Direct Synthesis of Aromatic Nitriles
from Aldehydes Using Hydroxylamine and
Oxalyl Chloride
Barahman Movassagh
Department of Chemistry, K. N. Toosi University of Technology,
Tehran, Iran and Kermanshah Oil Refining Company, Kermanshah, Iran
Azadeh Fazeli
Department of Chemistry, K. N. Toosi University of Technology,
Tehran, Iran
Abstract: Various aromatic and heterocyclic nitriles were prepared in good to high
yields in a direct one-pot process by heating the corresponding aldehydes with hydro-
xylamine and oxalyl chloride as reagents.
Keywords: aldehydes, hydroxylamine hydrochloride, nitriles, oxalyl chloride,
triethylamine
Nitriles are key constituents in numerous natural products and a variety of
[
1]
biologically active compounds.
They are used for the preparation
[4]
and 2-oxazolines. A number
[
of oxazoles, tetrazoles, thiazoles,
2]
[3]
[1a]
of methods have been reported in the literature for the preparation of
nitriles from aldehydes including dehydration of the corresponding
[
5]
aldoximes
and using reagents such as sodium azide and aluminum
[
chloride, trimethylsilyl azide, 1-nitropropane and ammonium hydrogen-
6]
[7]
[
8]
[9]
[10]
phosphate,
triazidochlorosilane,
S,S-dimethylsulphurdiimide,
O-(2-
Received in the U.K. January 23, 2006
Address correspondence to Barahman Movassagh, Department of Chemistry, K. N.
Toosi University of Technology, P.O. Box 15875-4416, Tehran, Iran. E-mail:
bmovass1178@yahoo.com
6
23

6
24
B. Movassagh and A. Fazeli
[
11]
aminobenzoyl) hydroxyamine,
monoperoxyphthalate hexahydrate,
N,N-dimethylhydrazine and magnesium
[13]
[12]
and ammonia and iodine
However, many of these methods have limitations including
or lead
[
14]
tetraacetate.
long reaction times, low yields, and expensive or commercially unavailable
reagents. Very recently, we have developed an efficient and convenient
[15]
route for conversion of aldehydes into nitriles using KF/Al O .
2
3
Herein, we report a new, simple, and efficient one-pot preparation of
aromatic nitriles from the corresponding aldehydes using hydroxylamine
and oxalyl chloride in refluxing acetonitrile (Scheme 1).
In this procedure, a mixture of aromatic aldehyde, hydroxylamine hydro-
chloride, and triethylamine was primarily heated under reflux in dry aceto-
nitrile for 2 h; the reaction mixture was then treated with oxalyl chloride,
leading to the corresponding nitriles. Representative examples of this one-
pot procedure are listed in Table 1, including the synthesis of aromatic
(
entries 1–8, Table 1) and heterocyclic (entries 9–12, Table 1) nitriles.
This method can also be applied to aldehydes containing a double bond
entry 13, Table 1). The reaction was not successful for the conversion of
-furaldehyde into the corresponding nitrile (entry 10, Table 1), for which
(
2
poor yield (10%) of 2-furonitrile was obtained after 10 min; this could be
due to the ring opening of 2-furaldehyde in the presence of the hydrogen
chloride produced during the course of reaction. We found that aryl
aldehydes were readily converted to give the corresponding nitriles in good
to high yields using hydroxylamine hydrochloride, triethylamine, and oxalyl
chloride (1 : 1 : 1) in dry acetonitrile under reflux. A limitation of the
reagent for such a transformation is that the reaction is unsuccessful with
aliphatic aldehydes.
The mechanism of our method can be briefly proposed as follows: (1)
hydroxylamine is released from its hydrochloride salt by triethylamine, (2)
the reaction with aldehydes to give aldoximes, and (3) the aldoximes
undergo rapid dehydration in the presence of oxalyl chloride to produce
nitriles. In the case of aliphatic aldehydes, the corresponding aldoximes
were formed, as detected by thin-layer chromatography (TLC), but upon
addition of oxalyl chloride several unidentified products were obtained,
none of which were the expected product.
In summary, an efficient, simple, and novel methodology for one-pot con-
version of aromatic aldehydes into nitriles without the isolation of aldoximes
has been developed. The good to high yields, relatively short reaction times,
and utilization of a readily available reagent are great advantages of the
present procedure.
Scheme 1.

Direct Synthesis of Aromatic Nitriles
625
Table 1. Conversion of aromatic aldehydes to nitriles using hydroxylamine hydro-
a
chloride and oxalyl chloride
Time
(min)
Yields
b
(%)
Entry
Aldehydes
Nitriles
1
2
3
4
5
6
7
8
9
3-Methylbenzaldehyde
2-Methoxybenzaldehyde
4-Chlorobenzaldehyde
3-Bromobenzaldehyde
4-Methoxybenzaldehyde
1-Naphthaldehyde
40
195
480
420
20
3-Methylbenzonitrile
2-Methoxybenzonitrile
4-Chlorobenzonitrile
3-Bromobenzonitrile
4-Methoxybenzonitrile
1-Cyanonaphthalene
3-Nitrobenzonitrile
4-Nitrobenzonitrile
2-Pyridinecarbonitrile
2-Furonitrile
81
89
72
73
89
82
92
84
65
10
65
60
89
30
30
3-Nitrobenzaldehyde
4-Nitrobenzaldehyde
2-Pyridinecarbaldehyde
2-Furaldehyde
30
10
1
1
1
1
0
1
2
3
10
15
2-Thiophenecarbaldehyde
3-Pyridinecarbaldehyde
Cinnamaldehyde
2-Thiophenecarbonitrile
3-Pyridinecarbonitrile
Cinnamonitrile
20
15
a
All the products are known in the literature and were characterized by comparison
of their physical and spectral data with those of authentic samples.
b
Yields of isolated pure products.
EXPERIMENTAL
All products were characterized by comparison of their spectral and physical
data with those of known samples. NMR spectra were recorded on Bruker
AQS-300 Avance NMR spectrometer. IR spectra were obtained using a
Shimadzu IR-408 spectrophotometer. Melting points were determined by an
Electrothermal 9100 apparatus.
General Procedure
Triethylamine (1.05 mmol) and aldehyde (1 mmol) were added to a stirred
solution of hydroxylamine hydrochloride (1.05 mmol) in anhydrous aceto-
nitrile (10 mL) and refluxed for about 2 h. Then oxalyl chloride (1 mmol)
was added dropwise at that temperature. The refluxing mixture was also
heated at reflux for the time specified in Table 1. Progress of the reaction
was monitored by TLC. When the reaction was complete, acetonitrile was
evaporated, chloroform (25 mL) was added, the mixture was washed with
water (3 Â 20 mL), and the organic layer was dried over anhydrous
Na SO . The solvent was evaporated in vacuo to give the corresponding
2
4
nitrile, which was purified by preparative TLC (silica gel, eluent petroleum
ether–EtOAc ¼ 3 : 1).

6
26
B. Movassagh and A. Fazeli
Spectral Data
[
16]
4-Chlorobenzonitrile (3)
[
16]
21 1
mp: 928C); IR (nmax, KBr): 2239, 1596, 1485 cm . H
Mp: 948C (lit.
NMR (300 MHz, CDCl ): d 7.62 (d, 2H, J ¼ 8.5 Hz), 7.49 (d, 2H,
3
1
3
J ¼ 8.5 Hz). C NMR (75 MHz, CDCl ): d 138.52, 132.38, 128.69, 116.94,
3
109.79.
[
15]
3-Bromobenzonitrile (4)
21 1
IR (nmax, neat): 2233, 1562, 1471 cm . H NMR (300 MHz, CDCl ): d 7.81
3
(
s, 1H), 7.76 (d, 1H, J ¼ 8.7 Hz), 7.62 (d, 1H, J ¼ 8.4 Hz), 7.38 (t, 1H,
1
3
J ¼ 8.5 Hz). C NMR (75 MHz, CDCl ): d 135.12, 133.76, 129.71, 129.61,
3
1
21.92, 116.28, 113.23.
[
15]
4-Methoxybenzonitrile (5)
[
15]
21 1
mp: 598C); IR (nmax, KBr): 2227, 1602, 1494 cm . H
Mp: 608C (lit.
NMR (300 MHz, CDCl ): d 7.60 (d, 2H, J ¼ 8.8 Hz), 6.97 (d, 2H,
3
1
3
J ¼ 8.8 Hz), 3.87 (s, 3H, CH ). C NMR (75 MHz, CDCl ): d 160.76,
3
3
131.86, 117.16, 112.68, 101.75, 53.48.
[
17]
1-Cyanonaphthalene (6)
[
17]
21 1
mp: 36.5–37.58C; IR (nmax, CHCl ): 2223, 1589, 1509 cm . H
Oil, lit.
NMR (300 MHz, CDCl ): d 8.22 (d, 1H, J ¼ 8.1 Hz), 8.05 (d, 1H,
3
3
J ¼ 8.4 Hz), 7.91 (d, 1H, J ¼ 7.6 Hz), 7.88 (d, 1H, J ¼ 6.8 Hz), 7.68 (t, 1H,
1
3
J ¼ 8.3 Hz), 7.61 (t, 1H, J ¼ 6.8 Hz), 7.50 (t, 1H, J ¼ 7.6 Hz). C NMR
(
75 MHz, CDCl ): d 131.03, 130.61, 130.35, 130.03, 126.41, 126.32,
3
1
25.28, 122.81, 122.65, 115.58, 107.83.
[
16]
Cinnamonitrile (13)
[
16]
21
Oil, lit.
1
mp: 248C; IR (nmax, CHCl ): 2216, 1618, 1576, 1494, 1448 cm
.
H NMR (300 MHz, CDCl ): d 7.45 (m, 5H, aromatic), 7.40 (d, 1H,
3
3
1
3
J ¼ 16.7 Hz, 55 CH), 5.89 (d, 1H, J ¼ 16.7 Hz, 55 CH). C NMR (75 MHz,
CDCl ): d 150.60, 133.53, 131.26, 129.15, 127.41, 118.24, 96.34.
3
ACKNOWLEDGMENTS
We thank the K. N. Toosi University of Technology Research Council and
Kermanshah Oil Refining Company for financial support.

Direct Synthesis of Aromatic Nitriles
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