A facile one-pot conversion of aldehydes into nitriles

Article abstract of DOI:10.1080/00397910902788174

A facile one-pot synthesis of nitriles starting with aldehydes has been developed employing hydroxylamine hydrochloride in dimethylsulfoxide at 100C.

Full text of DOI:10.1080/00397910902788174

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A Facile One-Pot Conversion of
Aldehydes into Nitriles
Samuel T. Chill a & Robert C. Mebane a
a Department of Chemistry, University of Tennessee
at Chattanooga, Chattanooga, Tennessee, USA
Published online: 08 Sep 2009.
To cite this article: Samuel T. Chill & Robert C. Mebane (2009) A Facile One-Pot
Conversion of Aldehydes into Nitriles, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 39:20, 3601-3606,
DOI: 10.1080/00397910902788174
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Synthetic Communications1, 39: 3601–3606, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902788174
A Facile One-Pot Conversion of Aldehydes
into Nitriles
Samuel T. Chill and Robert C. Mebane
Department of Chemistry, University of Tennessee at Chattanooga,
Chattanooga, Tennessee, USA
Abstract: A facile one-pot synthesis of nitriles starting with aldehydes has been
developed employing hydroxylamine hydrochloride in dimethylsulfoxide at
100ꢀC.
Keywords: Aldehyde, aldoxime, dehydration, nitrile, tandem reaction
Organic nitriles are versatile synthetic intermediates that can easily be
converted into a variety of other functional groups.[1,2] Nitriles have been
used in a variety of processes including the production of pharmaceuti-
cals, agrochemicals, and biologically important compounds.[3–6] Thus,
methods for preparing organic nitriles are highly desirable.
One of the more widely used methods for preparing nitriles and one
that has received much recent attention involves the dehydration of
aldoximes. A number of dehydration agents have been employed includ-
ing trichloromethyl carbonchloridate,[7] di-2-pyridyl sulfite,[8] thionyl
chloride,[9] dialkyl hydrogen phosphonates=triethylamine,[10] diphosphor-
ous tetraiodide,[11] 1,10-dicarbonylbisimidazole,[12] chlorothionfor-
mate,[13] and triphenylphosphine=I2,[14] to name a few. In addition,
metals and metal complexes have been used including iron porphyrins,[15]
titanium tetrachloride,[16] cetyltrimethylammonium dichromate,[17]
copper(II) acetate,[18] and certain ruthenium-based catalysts.[19,20]
Received November 17, 2008.
Address correspondence to Robert C. Mebane, Department of Chemistry,
#2252, University of Tennessee at Chattanooga, 615 McCallie Ave., Chattanooga,
TN 37403-2598, USA. E-mail: robert-mebane@utc.edu
3601

3602
S. T. Chill and R. C. Mebane
Although these methods may be effective at dehydrating aldoxidmes,
they have disadvantages too in that the reagents may be expensive, hazar-
dous, or inconvenient to use.
Recently, we demonstrated that aldoximes are readily dehydrated to
nitriles with Raney nickel in refluxing 2-propanol.[21] Unfortunately, we
also found that the Raney nickel catalyst was poisoned in the reaction
and could not be reused. During our systematic study directed at regen-
erating the catalyst and exploring other possible dehydrating metal cata-
lysts, surprisingly we discovered that aldoximes readily dehydrate in
dimethylsulfoxide (DMSO) solvent at 100ꢀC. Knowing that aldoximes
are readily prepared from aldehydes and hydroxylamine hydrochlor-
ide,[22] we extended this reaction into a one-pot tandem conversion of
aldehydes into nitriles, which we report herein.[23]
The experimental procedure for the one-pot synthesis of nitriles is
simple and straightforward and generally affords nitriles in good isolated
yields (Table 1). (Aldehyde to nitrile conversion was quantitative as
1
determined by gas chromatography, and H NMR showed that all the
nitriles made in this study had a purity of >95%. Loss of material during
solvent removal may explain the lower isolated yields for entries 1, 5, and
6.) As an illustrative example, octanal (2.0 mmol) was added to a solution
of hydroxylamine hydrochloride (3.7 mmol) in DMSO (4 mL), and the
resulting reaction solution was stirred and heated for 30 min in a sand
bath maintained at 100ꢀC. After cooling to room temperature, water
(20 mL) was added to the reaction mixture, which was then extracted with
diethyl ether (5 ꢁ 20 mL). The combined ether layers were washed with
water (4 ꢁ 20 mL) and dried (K2CO3). Removal of the ether by rotary
evaporation and high vacuum yielded octanenitrile as a light oil
1
(1.9 mmol, 93%) whose mass spectrum and H and 13C NMR spectra
were identical to authentic octanenitrile. (The nitriles prepared in this
1
study are known and were identified by comparing their H and 13C
NMR spectra and mass spectra.)
As seen in Table 1, the reaction is general for the preparation of both
aliphatic and aromatic nitriles. The reaction time can be shortened to less
than 2 min when performed in refluxing DMSO; however, for several of
the aromatic aldehydes, prolonged heating in refluxing DMSO resulted in
minor reversion of nitrile to aldehyde.
Not surprisingly, we have determined that the oxime dehydration is
favored by acidic conditions. Thus, when benzaldehyde oxime (2.0 mmol)
was heated in just refluxing DMSO (4 mL) for 2 min, little conversion
(<3%) to nitrile was observed, and only 34% conversion was realized
after 30 min of reflux. Complete conversion to benzonitrile was observed
in just 2 min when benzaldehyde oxime (2.0 mmol) was heated in reflux-
ing DMSO containing hydrochloric acid (3.7 mmol).

Conversion of Aldehydes into Nitriles
3603
Table 1. Conversion of aldehydes into nitriles via the dehydration of aldoximes
Entry
1
Aldehyde
Nitrile
% Yielda,b Timec
72
93
87
96
30
30
30
30
2
3
4
5
71
60
6
7
74
91
60
60
8
9
91
97
92
60
30
60
10
(Continued )

3604
S. T. Chill and R. C. Mebane
Table 1. Continued
Entry
Aldehyde
Nitrile
% Yielda,b Timec
11
97
92
30
30
12
13
94
60
aIsolated yields.
1
bNitrile purities >95% as determined by H-NMR.
cMonitored by GC-MS.
In conclusion, we have demonstrated that aldehydes can be readily
converted into nitriles upon heating at 100ꢀC in DMSO containing
hydroxylamine hydrochloride. We are extending this methodology to a
one-pot tandem synthesis of amides and esters and will report our results
shortly.
ACKNOWLEDGMENT
The authors gratefully acknowledge financial support from the Research
Corporation, the University of Chattanooga Foundation, and the Grote
Chemistry Fund.
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