Mild and efficient method for the synthesis of nitriles

Article abstract of DOI:10.1081/SCC-120030750

The treatment of aldoximes with a mixture of DMAD and triethylamine serve as an efficient and mild method for the synthesis of aromatic and α,β-unsaturated nitriles in high yields at room temperature.

Full text of DOI:10.1081/SCC-120030750

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Mild and Efficient Method for the Synthesis of
Nitriles
a
Necdet Coşkun
a
Department of Chemistry, Uludağ University, 16059, Görükle Bursa, Turkey
Published online: 16 Aug 2006.
To cite this article: Necdet Coşkun (2004): Mild and Efficient Method for the Synthesis of Nitriles, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 34:9, 1625-1630
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w
SYNTHETIC COMMUNICATIONS
Vol. 34, No. 9, pp. 1625–1630, 2004
Mild and Efficient Method for the
Synthesis of Nitriles
*
Necdet Co s¸ kun
Department of Chemistry, Uluda g˘ University, G o¨ r u¨ kle Bursa, Turkey
ABSTRACT
The treatment of aldoximes with a mixture of DMAD and triethylamine
serve as an efficient and mild method for the synthesis of aromatic and
a,b-unsaturated nitriles in high yields at room temperature.
Key Words: Nitriles; Hydrazine; DMAD; Oximes.
RESULTS AND DISCUSSION
The carbon–nitrogen triple bond formation may be achieved by aldoxime
dehydration, O-acyloxime pyrolysis, base catalyzed decomposition of aldox-
ime O-2,4-dinitrophenyl ethers, elimination of amines from aldehyde hydra-
[1]
zones or hydrazonium salts, etc. The use of dimethyldioxirane, for the
conversion of aldehyde N,N-dimethylhydrazones into the corresponding
*
Correspondence: Necdet Co s¸ kun, Department of Chemistry, Uluda g˘ University,
6059-G o¨ r u¨ kle Bursa, Turkey; E-mail: coskun@uludag.edu.tr.
1
1
625
DOI: 10.1081/SCC-120030750
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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1
626
Co s¸ kun
[2]
nitriles under mild conditions was reported. In all of these methods the start-
ing material is an isolated oxime, O-substituted oxime, or aldehyde hydrazone
derivative. Nitrile syntheses at the other extreme involve the in situ formation
[
1,3]
and dehydration of the oxime.
verted to the corresponding nitriles in refluxing acetonitrile using hydroxyl-
The aryl and alkyl aldehydes were con-
[4]
amine and phthalic anhydride as reagents in one pot. A conversion of
[5]
aldehydes to nitriles using a solid-supported hydrazine was also reported.
[6]
Recently, we have reported the synthesis of nitriles involving dehydro-
carbamoylation of O-phenylcarbamoylated oximes, easily available by our
[
7]
method. We herein report an easily applicable mild and efficient method
for the conversion of aldoximes to the corresponding nitriles treating them
with 2 equiv. of commercially available DMAD and triethylamine in aceto-
nitrile at room temperature (see Sch. 1).
Aldoximes 1 were treated with DMAD in order to prepare corresponding
adducts 3 (see Fig. 1). We needed them as starting materials in hetero Diels–
Alder reactions. The treatment of the aldoximes with DMAD in the absence of
triethylamine did not lead to any reaction after stirring for 24 hr at room temp-
erature. However, the same reaction led to the formation of nitriles when the
reaction was performed in the presence of triethylamine. The best ratio of the
oxime, amine, and DMAD for the quantitative (see Table 1 for the yields) con-
version of the oxime was found to be 1 : 1 : 2 in the cases of 1b–h and 1 : 2 : 2
in the cases of 1a, i, and j. The aimed products could be detected easily by
HPLC, two peaks with higher retention times than the nitrile and starting
oxime appear at the start of the reaction and gradually disappear within
3
hr. We assume that the amine activates the oxime in the nucleophilic
addition to DMAD leading to the formation of but-2-endioic acid esters
see Fig. 1) which could undergo synchronous elimination via 3 or via the
(
E2 like transition state 4 to give the final product 2 and dimethyloxaloacetate.
Probably the aromatic ring in the aldoximes favor the elimination process.
Attempts to convert propionaldoxime and phenylacetaldoxime to the corres-
ponding nitriles at room temperature failed.
To our knowledge these are the first dehydrations of aldoximes with
triethylamine–DMAD mixture reported. The extremely high yields and
Scheme 1.

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Synthesis of Nitriles
1627
Figure 1. Suggested transition states for the fragmentation of N-benzilidenaminoxy-
but-2-endioic acid esters.
the mild conditions and the formation of easily separable mixture are the
advantages of the method developed. The isolation of the product involves
only an extraction where the by-products remain in the water phase. The
evaporation of the solvent gave nearly pure nitrile, which is further purified
by recrystallization or flash column chromatography or simply by filtering
a
Table 1. Synthesis of nitriles 2a–j.
R
Yield (%) Mp (8C)
R
Yield (%) Mp (8C)
b
c
2
a Ph
b 4-MeOC
92
100
Oil
d
60
2f 3-NO
2g 4-ClC
2
C
6
H
4
98
99
116
93–94
d
2
6
H
4
6
H
4
d
2
c 2,3-(MeO)
2
C
6
6
H
3
3
96
47
2h
90
Oil
d
e
d
80
2
d 3,4-(MeO)
2
C
H
95
98
68
2i
2j
98
c
2
e 2-NO
2
C
6
H
4
111
97
Oil
a
All prepared nitriles are known in literature and were identified by comparing their
physical and spectral data with those of authentic samples.
b
The yields were also determined by HPLC and were nearly quantitative for all of the
cases.
c
Recrystallized from water.
d
Recrystallized from acetonitrile-water.
In the cases of benzaldoxime and pyridine aldoximes the ratio of the oxime, amine and
DMAD is 1 : 2 : 2.
e

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628
Co s¸ kun
through short silica packed column. The prepared nitriles 2a–j were
identified by comparison of their physical constants and spectral character-
istics with those of commercially available or prepared by our previous
[
6]
method.
EXPERIMENTAL
Melting points were determined on an Electrothermal Digital melting
1
point apparatus. IR spectra were recorded on a Mattson 1000 FTIR. H
NMR spectra were recorded on a Varian 200 MHz spectrometer. Commer-
cially available oximes or prepared from the corresponding aldehydes were
used as starting materials. The reactions were monitored by HPLC using
C18 column and UV detector. Water–acetonitrile (60 : 40) was used as a
mobile phase.
General Procedure
To a solution of aldoxime 2 (3 mmol) in acetonitrile (15 mL) triethyl-
amine (0.303 g, 3 mmol) and DMAD (0.852 g, 6 mmol) were added and the
mixture stirred at room temperature for 3 hr. The solvent was evaporated
a
under vacuum and water (50 mL) was added to the residue and then extracted
with chloroform (3 Â 15 mL). The combined extracts were washed with water
(
2 Â 15 mL) and dried (anh. Na SO ), filtered, and the solvent evaporated.
2
4
The crude products were purified by crystallization or flash column chroma-
tography or filtering through short silica gel packed column using ethyl acetate
hexane mixture as eluent.
Benzonitrile (2a). See Table 1 for the yields and melting points. IR
2
1
(
neat) nCN 2229 cm
-Methoxybenzonitrile (2b). IR (KBr) nCN 2238 cm ; H NMR CDCl3
d ppm 3.91 (3H, s), 6.95–7.83 (4H, m); Anal. Calcd for C H NO (133,15):
.
2
1 1
4
8
7
C, 72.17; H, 5.30; N, 10.52; Found: C, 72.20; H, 5.25; N, 10.45.
21 1
2,3-Dimethoxybenzonitrile (2c). IR (KBr) nCN 2238 cm ; H NMR
CDCl d ppm 3.91 (6H, s), 7.02–7.60 (3H, m); Anal. Calcd for C H NO
3
9
9
2
(
163,18); C, 66.25; H, 5.56; N, 8.58; Found: C, 66.30; H, 5.50; N, 8.63.
a
The 4-chlorobenzonitrile crystallises as white needles after adding of water directly to
the acetonitrile solution and could be separated by filtration.

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Synthesis of Nitriles
1629
21 1
,4-Dimethoxybenzonitrile (2d). IR (KBr) nCN 2238 cm ; H NMR
3
CDCl d ppm 3.90 (6H, s), 7.05–7.60 (3H, m); Anal. Calcd for C H NO
3
9
9
2
3
(
163,18): C, 66.25; H, 5.56; N, 8.58; Found: C, 66.32; H, 5.53; N, 8.61.
2
21 1
-Nitrobenzonitrile (2e). IR (KBr) nCN 2238 cm ; H NMR CDCl
d ppm 7.05–8.30 (4H, m); Anal. Calcd for C H N O (148,12): C, 56.76;
7
4 2 2
H, 2.72; N, 18.91; Found: C, 56.70; H, 2.80; N, 18.95.
3
ppm 7.05–8.30 (4H, m); Anal. Calcd for C H N O (148,12): C, 56.76; H,
21 1
-Nitrobenzonitrile (2f). IR (KBr) nCN 2238 cm ; H NMR CDCl d
3
7
4 2 2
2
.72; N, 18.91; Found: C, 56.75; H, 2.82; N, 18.90.
21 1
-Chlorobenzonitrile (2g). IR (KBr) nCN 2238 cm ; H NMR CDCl d
4
ppm 7.06–8.0 (4H, m); Anal. Calcd for C H ClN (137, 57): C, 61.12; H, 2.93;
3
7
4
N, 10.18; Found: C, 61.15; H, 3.00; N, 10.15.
R)-6,6-Dimethylbicyclo[3.1.1]hept-2-ene-2-carbonitrile (2h). IR (neat)
(
2
1 1
nCN 2238 cm ; H NMR CDCl d ppm 0.83 (3H, s), 1.18 (1H, d, J ¼ 10 Hz)
3
1.41 (3H, s), 2.18 (1H, s), 2.50 (3H, m), 2.87 (1H, m), 6.23 (1H, s); Anal.
Calcd for C H N (147,22): C, 81.59; H, 8.90; N, 9.51; Found: C, 81.65;
H, 8.75; N, 9.60.
1
0 13
2
Isonicotinonitrile (2i). IR (KBr) nCN 2236 cm ; Anal. Calcd for
1
C H N (104,11): C, 69.22; H, 3.87; N, 26.91; Found: C, 69.20; H, 3.88; N,
6
4 2
2
6.90.
Pyridine-2-carbonitrile (2j). IR (neat) nCN 2238 cm ; Anal. Calcd for
C H N (104,11): C, 69.22; H, 3.87; N, 26.91; Found: C, 69.25; H, 3.90; N,
2
1
6
4 2
26.92.
ACKNOWLEDGMENT
The financial assistance of Uluda g˘ University Research Fund is gratefully
acknowledged (Project No. 2000/36).
REFERENCES
1
2
. Barton, D.; Ollis, W.D. Imines, nitrones, nitriles and isocyanides. In Com-
prehensive Organic Chemistry; Pergamon: Oxford, UK, 1979; Vol. 2,
32–535.
5
. Altamura, A.; D’Accolti, L.; Detomaso, A.; Dinoi, A.; Fiorentino, M.;
Fusco, C.; Curci, R. High-yield synthesis of nitriles by oxidation of alde-
hyde N,N-dimethylhydrazones with dimethyldioxirane. Tetrahedron Lett.
1998, 39 (14), 2009–2012.
3. March, J. Eliminations. In Advanced Organic Chemistry; John Wiley and
Sons: N.Y., 1985; 806–807.

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630
Co s¸ kun
4
. Wang, E.C.; Lin, G.J. A new one pot method for the conversion of alde-
hydes into nitriles using hydroxylamine and phthalic anhydride. Tetra-
hedron Lett. 1998, 39 (23), 4047–4050.
5. Baxendale, I.R.; Ley, S.V.; Sneddon, H.F. A clean conversion of aldehydes
to nitriles using a solid-supported hydrazine. Synlett. 2002, 5, 775–777.
6
. Co s¸ kun, N.; Ar y´ kan, N. Direct conversion of aldehydes into nitriles via
O-phenylcarbamoylated aldoximes. Tetrahedron 1999, 55, 11943–11948.
7. Co s¸ kun, N. Reactivity of bis(arylcarbamoyl)-N-arylphenacylamine
oximes. Synthesis of 1,3-dihydroimidazol-2-ones and N-unsubstituted
O-arylcarbamoylhydroxylamines. Tetrahedron 1999, 55 (2), 475–484.
Received in the UK August 22, 2003

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