Conversion of aldoximes into nitriles with raney nickel in refluxing 2-propanol

Article abstract of DOI:10.1080/00397910802238676

Aldoximes are readily dehydrated to nitriles with Raney nickel in refluxing 2-propanol. Copyright Taylor & Francis Group, LLC.

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Conversion of Aldoximes into
Nitriles with Raney Nickel in
Refluxing 2-Propanol
Daniel R. Zuidema a , Ami L. Dennison a , Elizabeth
Y. Park b & Robert C. Mebane b
a Department of Chemistry, Covenant College,
Lookout Mountain, Georgia, USA
b Department of Chemistry, University of Tennessee
at Chattanooga, Chattanooga, Tennessee, USA
Available online: 14 Oct 2008
To cite this article: Daniel R. Zuidema, Ami L. Dennison, Elizabeth Y. Park & Robert
C. Mebane (2008): Conversion of Aldoximes into Nitriles with Raney Nickel in
Refluxing 2-Propanol, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 38:21, 3810-3815
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Synthetic Communications1, 38: 3810–3815, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802238676
Conversion of Aldoximes into Nitriles with Raney
Nickel in Refluxing 2-Propanol
Daniel R. Zuidema,1 Ami L. Dennison,1 Elizabeth Y. Park,2
and Robert C. Mebane2
1Department of Chemistry, Covenant College, Lookout Mountain,
Georgia, USA
2Department of Chemistry, University of Tennessee at Chattanooga,
Chattanooga, Tennessee, USA
Abstract: Aldoximes are readily dehydrated to nitriles with Raney nickel in
refluxing 2-propanol.
Keywords: Dehydration of aldoximes, nitrile preparation, Raney nickel
Raney nickel is a well-known heterogeneous catalyst for effecting func-
tional group transformations, particularly hydrogenation reactions.[1–3]
We and others have employed Raney nickel in catalytic transfer hydroge-
nations (CTH) using 2-propanol as a hydrogen donor to reduce a variety
of organic compounds including ketones,[4–6] aldehydes,[7] nitriles,[8] iodo-
[5]
lactones,[9] aromatic alcohols,[10] phenols,
olefins,[5] aromatic nitro
compounds[11] and certain aromatic hydrocarbons.[5,12] Knowing that
primary amines can be prepared by the Raney nickel–catalyzed reduction
of aldoximes with hydrogen,[13,14] we recently attempted to reduce aldox-
imes by CTH. Much to our surprise, treatment of aldoximes with Raney
nickel in refluxing 2-propanol led to dehydration of the aldoxime
to afford nitriles. In light of the importance of nitriles as synthetic
intermediates[15,16] and the recent interest in method development for
Received October 17, 2007.
Address correspondence to Robert C. Mebane, Department of Chemistry,
University of Tennessee at Chattanooga, #2252, 615 McCallie Ave.,
Chattanooga, TN 37403-2598. E-mail: robert-mebane@utc.edu
3810

Conversion of Aldoximes into Nitriles
3811
Figure 1. Conversion of aldoximes to nitriles by dehydration with Raney nickel in
reflusing 2-propanol.
the dehydration of aldoximes to nitriles,[17–19] we report herein the results of
our investigation employing Raney nickel to dehydrate aldoximes.
The experimental procedure for dehydrating aldoximes with Raney
nickel in refluxing 2-propanol is simple and straightforward and gen-
erally results in quantitative conversion of the aldoxime into nitrile
(Fig. 1) as conveniently determined by gas chromatography-mass
spectrometry (GC-MS). In the cases of hexanal oxime (entry 1) and
bicyclo[2.2.1]hept-5-ene-2-carbaldehyde oxime (entry 8), the reactions
were stopped prior to completion because minor side products would
appear as the reactions approached completion. As seen in Table 1,
isolated yields for the less volatile nitrile products were quite good
(entries 3, 5–7) but less so for the more volatile nitriles because
of product loss while removing the 2-propanol solvent by rotary
Table 1. Conversion of aldoximes into nitriles with Raney nickel in refluxing
2-propanol
Timea Yieldb
Entry
Aldoxime
Hexanal oxime
Heptanal oxime
Octanal oxime
Benzaldehyde oxime
Product
Hexanenitrile
Heptanenitrile
Octanenitrile
Benzonitrile
(min)
(%)
1c
2d
3c
4c
5d
6d
7c
8e
35
50
5
15
15
30
60
75
26f
47f
89
40f
76
85
67
39
4-Isopropylbenzaldehyde oxime 4-Isopropylbenzonitrile
1-Naphthaldehyde oxime
trans-Cinnamaldehyde oxime
Bicyclo[2.2.1]hept-5-ene-
2-carbaldehyde oxime
1-Naphthonitrile
trans-Cinnamonitrile
Bicyclo[2.2.1]hept-
5-ene-2-carbonitrile
aTime to reach complete conversion as determined by GC.
bIsolated yields. Product nitriles were compared to authentic spectra or literature refer-
ence spectra and confirmed by 1H NMR and 13C NMR spectroscopy and GC-MS.
cSubstrate=Raney nickel, 1=2.5 (w=w).
dSubstrate=Raney nickel, 1=5 (w=w).
eSubstrate=Raney nickel, 1=7.5 (w=w).
fProduct loss observed during rotary evaporation due to volatility of nitrile.

3812
D. R. Zuidema et al.
evaporation. All reactions initially consisted of an aldoxime-to-catalyst
ratio of 1=2.5 (w=w), but several reactions required additional amounts
of Raney nickel catalyst (entries 2, 5, and 6 required 1=5, and entries
3, 4, and 7 required 1=7.5) to reach completion in the times indica-
ted in Table 1. All reaction products were confirmed by comparison
of NMR and mass spectra data with authentic samples or literature
spectra.
To demonstrate that Raney nickel was indeed required as the catalyst
for these dehydration reactions, a series of control experiments was run.
First, benzaldehyde oxime (8.25 mmol) was stirred in refluxing 2-
propanol (20 mL) for 5.5 h (no Raney nickel added). No conversion to
benzonitrile was observed. This established that in order for the reaction
to proceed, some kind of catalyst was necessary. A separate trial was run
in which powdered nickel metal (non-Raney) (2.634 g), 2-propanol
(20 mL), and benzaldehyde oxime (8.22 mmol) were combined and
warmed to reflux. After 48 h, no change was observed. Furthermore, to
demonstrate that the reaction was not attributable to residual aluminum
remaining in the Raney nickel, an experiment was set up in which alumi-
num filings (2.453 g), 2-propanol (20 mL), and benzaldehyde oxime (ꢀ8.3
mmol) were combined and warmed to reflux. After 48 h, no change was
observed. Finally, to further establish that the dehydration was not attri-
butable to the presence of Ni=Al alloy, benzaldehyde oxime (ꢀ8.3 mmol)
was stirred in a suspension of Ni=Al alloy (50:50) in 2-propanol (20 mL)
at reflux for 3 h. No conversion to benzonitrile was observed.
Although we believe that the Raney nickel catalyzed the dehydration
of aldoximes, we were not able to show that the catalyst could be
recycled. In an extensive study describing the poisonous effects of organic
compounds on Raney nickel, Horner et al.[20] showed that nitriles
strongly poison Raney nickel toward hydrogenations. This same poison-
ing effect may explain our results as well. In the past, our research group
has had success in regenerating poisoned Raney nickel catalyst by thor-
oughly washing the used Raney nickel with 2-propanol[7] or by refluxing
the used catalyst in a solution of KOH in 2-propanol.[9] Our attempts to
apply these methods and others (acid wash) to our poisoned catalyst did
not result in catalyst regeneration. We continue to explore the regenera-
tion of the catalyst.
Because aldoximes are readily prepared from aldehydes and hydro-
xylamine hydrochloride, we explored the possibility of developing a
one-pot tandem synthesis of nitriles from aldehydes. Thus, when a slurry
of heptanal (8.72 mmol) and hydroxylamine hydrochloride (11.7 mmol)
was refluxed with Raney nickel (2.5 g) in 2-propanol (20 mL), complete
conversion to heptanenitrile was realized in 30 min (95% isolated yield).
Octanal and nonanal were also completely converted into their

Conversion of Aldoximes into Nitriles
3813
corresponding nitriles (octanenitrile, 20 min, 74% yield, and nonaneni-
trile, 60 min, 65% yield). Aromatic aldehydes gave only partial conversion
to nitriles with this one-pot method.
In conclusion, aldoximes are readily dehydrated to nitriles with
Raney nickel in refluxing 2-propanol. The procedure was easily adapted
into a one-pot tandem synthesis of nitriles starting with simple aliphatic
aldehydes. Future work will elaborate on the scope of the reaction as to
what types of functional groups are tolerated in the reaction.
EXPERIMENTAL
Raney 2800 nickel (undigested, ꢀ89% Ni and 6–9% Al) was obtained
from W. R. Grace Company, Chattanooga Davison. The catalyst was
1
washed prior to use with distilled water (3ꢁ) and 2-propanol (3ꢁ). H
and 13C NMR spectra were recorded on a Jeol 400-MHz spectrometer
using tetramethylsilane (TMS) as an internal reference. Mass spectra
were recorded on a ThermoElectron PolarisQ GC-MS. The NMR spec-
tra and mass spectra of the nitriles prepared in this work were identical to
authentic spectra.
As an illustrative example of the dehydration procedure, octanal
oxime (0.972 g, 6.79 mmol) was refluxed in a magnetically stirred suspen-
sion of Raney nickel (2.5 g) in 2-propanol (20 mL) for 5 min with the con-
denser open to the atmosphere. After cooling to room temperature, the
reaction solution was decanted from the Raney nickel, and the catalyst
was washed with 2-propanol (3 ꢁ 10 mL). (Raney nickel is paramagnetic
and sticks to the magnetic stir bar, which facilitates decantation.) The
combined organic layers were filtered through Celite1 and the solvent
was removed by rotary evaporation and high vacuum to give octaneni-
1
trile as an oil in 89% yield. H NMR: d 0.87 (t, J ¼ 7 Hz, 3H), 1.25–
1.35 (m, 6H), 1.43 (m, 2H), 1.64 (m, 2H), 2.32 (t, J ¼ 7 Hz, 2H).[21]
Hexanenitrile (entry 1). 1H NMR: d 0.93 (t, J ¼ 7 Hz, 3H), 1.24–1.49
(m, 4H), 1.66 (m, 2H), 2.34 (t, J ¼ 7 Hz, 2H).[21]
Heptanenitrile (entry 2). 1H NMR: d 0.85 (t, J ¼ 7 Hz, 3H), 1.20–1.31
(m, 4H), 1.41 (m, 2H), 1.61 (m, 2H), 2.29 (t, J ¼ 7 Hz, 2H).[21]
1
Benzonitrile (entry 4). H NMR: d 7.40–7.65 (m, 5H).[21]
1
4-Isopropybenzonitrile (entry 5). H NMR: d 1.20 (d, J ¼ 7 Hz, 6H),
2.80–2.90 (septet, J ¼ 7 Hz, 1H), 7.47–7.52 (m, 4H).[22]
1
1-Naphthonitrile (entry 6). H NMR: d 7.41 (t, J ¼ 7 Hz, 1H), 7.50–
7.62 (m, 2H), 7.78–7.82 (m, 2H), 7.96 (d, J ¼ 8 Hz, 1H), 8.15 (d, J ¼ 8 Hz,
1H).[21]
1
trans-Cinnamonitrile (entry 7). H NMR: d 5.87 (d, J ¼ 17 Hz, 1H),
7.35–7.48 (m, 6H).[21]

3814
D. R. Zuidema et al.
Bicyclo[2.2.1]hept-5-ene-2-carbonitrile (entry 8, mixture of isomers).
1H NMR: d 1.29–1.59 (m, 3H), 1.95–2.19 (m, 1H), 2.79–3.26 (m, 3H),
5.99–6.35 (m, 2H).[23]
ACKNOWLEDGMENTS
D. R. Z. gratefully acknowledges financial support a National Science
Foundation=Research Site for Educators in Chemistry grant (CHE-
9974734) and a Covenant College research grant. R. C. M. gratefully
acknowledges financial support from the Research Corporation, the
University of Chattanooga Foundation, and the Grote Chemistry Fund.
In addition, we are indebted to W. R. Grace Company, Chattanooga,
Tennessee, for the generous donation of Raney catalysts.
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Conversion of Aldoximes into Nitriles
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