Ionic liquid-promoted dehydration of aldoximes: a convenient access to aromatic, heteroaromatic and aliphatic nitriles

Article abstract of DOI:10.1016/j.tetlet.2009.08.069

A simple and convenient procedure for the synthesis of nitriles by dehydration of aldoximes using an ionic liquid, 1-pentyl-3-methylimidazolium tetrafluoroborate, [pmim]BF₄ under organic solvent-free condition, has been developed. A variety of aromatic, heteroaromatic and aliphatic aldoximes are converted to the corresponding nitriles. The ionic liquid is recovered and reused for subsequent reactions.

Full text of DOI:10.1016/j.tetlet.2009.08.069

Tetrahedron Letters 50 (2009) 6088–6091
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Tetrahedron Letters
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Ionic liquid-promoted dehydration of aldoximes: a convenient access
to aromatic, heteroaromatic and aliphatic nitriles
*
Debasree Saha, Amit Saha, Brindaban C. Ranu
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and convenient procedure for the synthesis of nitriles by dehydration of aldoximes using an
ionic liquid, 1-pentyl-3-methylimidazolium tetrafluoroborate, [pmim]BF4 under organic solvent-free
condition, has been developed. A variety of aromatic, heteroaromatic and aliphatic aldoximes are con-
verted to the corresponding nitriles. The ionic liquid is recovered and reused for subsequent reactions.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 29 June 2009
Revised 17 August 2009
Accepted 21 August 2009
Available online 26 August 2009
Keywords:
Aldoxime
Nitrile
Dehydration
Ionic liquid
Organic solvent-free reaction
The organicnitriles are ofmuchimportanceinorganicsynthesisas
these are versatile intermediates in the synthesis of amines, carbox-
ylic acids, esters and ketones which are useful raw materials for phar-
maceuticals, agrochemicals and dyes.1 The cyano moiety is also
present in numerous bioactive molecules.2 The classical method for
the synthesis of alkyl cyanide involves nucleophilic substitution of
an alkyl halide with metal cyanides,1a whereas aromatic nitriles are
produced by the Sandmeyer reaction and ammoxidation.3 However,
these methods are associated with the use of NaCN/KCN/metal cya-
nides, which are in general highly poisonous, and heavy metal cya-
nides such as zinc cyanide which leaves residue of heavy metal
salts. Thisisnotdesirableinthecontextofacleanenvironment.Dehy-
dration of aldoximes to nitriles is one of the cleanest routes avoiding
inorganic cyanides. Many methods have been developed for this
transformation4 and some of the recently reported procedures
involvePd(OAc)2/PPh3 inCH3CN,4a benzotriazolephosphoniumhexa-
fluorophosphate derivative/DBU in CH2Cl2,4b N-chlorosuccinimide/
pyridine in CH3CN,4c DMF at 135 °C,4d tungsten–tin mixed hydroxide
in o-xylene at 149 °C,4e diethylchlorophosphate in toluene,4f
molecular sieves under flash vacuum pyrolysis,4g ZnO/CH3COCl,4h
chlorosulfonic acid in toluene,4i dimethylthiocarbonate/Et3N in diox-
ane,4j diethylchlorophosphite in CHCl3,4k zeolite under microwave
irradiation,4l AlCl3Á6H2O/KI/H2O/CH3CN,4m Preyssler’s anion, [NaP5
all these procedures are quite satisfactory; however a majority of
them are restricted to the reactions of aromatic aldoximes. The ali-
phatic aldoximes are addressed by a few methods.4e,i,j,h,f
Moreover, many of them involve hazardous organic solvents
and toxic chemicals, and require long reaction times. Thus, alterna-
tive procedures with more general applicability, considerably fas-
ter reaction and environmentally friendly conditions are still in
demand.
The ionic liquids having low volatility and unique catalytic
activity have received considerable attention as eco-friendly sol-
vents as well as catalysts5a,b and reagents5f–h in the context of
green synthesis.5a As a part of our continued efforts to explore
the potential of ionic liquids for useful reactions,5c–e we report here
the dehydration of aldoximes by an inexpensive and easily acces-
sible ionic liquid, 1-pentyl-3-methylimidazolium tetrafluorobo-
rate, [pmim]BF4 in the absence of any organic solvent and
additive (Scheme 1).
To optimize the reaction conditions and find the right ionic li-
quid, a few experiments were carried out with different ionic liq-
uids at varied temperatures, as illustrated in Table 1. It was
found that the reaction using [pmim]BF4 at 90 °C provided the best
yield (Table 1, entry 3). The analogous ionic liquid, 1-butyl-3-
methylimidazolium tetrafluoroborate, [bmim]BF4 also gave
W30O110] ,
14À 4n Burgess reagent4o and thionyl chloride4p as dehydrat-
ing agents. Among these, only a few are catalytic,4a,e,n and most of
them use stoichiometric amounts of reagents.4b–d,f,h–k,m,o,p In general,
[pmim]BF
90 ºC
4
RCH NOH
RCN
R = aryl , heteroaryl , alkyl
* Corresponding author. Tel: +91 33 24734971; fax: +91 33 24732805.
E-mail address: ocbcr@iacs.res.in (B.C. Ranu).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.08.069

D. Saha et al. / Tetrahedron Letters 50 (2009) 6088–6091
6089
Table 1
comparable results. However, for our own convenience, [pmim]BF4
has been used. The reaction using a basic ionic liquid, 1-methyl-3-
pentylimidazolium hydroxide did not proceed at all.
Standardization of reaction conditions
CN
CH NOH
Several aldoximes were subjected to dehydration by this proce-
dure6 using [pmim]BF4 to produce the corresponding nitriles. The
results are summarized in Table 2. Both electron-donating and
electron-withdrawing group-substituted aromatic aldoximes pro-
vided uniformly good results. The vinyl aldoximes such as cin-
namyl and acrolyl aldoxime (Table 2, entry 11) also underwent
dehydration without any difficulty. Thus, this protocol provides
an easy access to conjugated nitriles. This procedure is also com-
patible with heteroaryl (Table 2, entry 16) and aliphatic aldoximes
(Table 2, entries 13–15).
Although ionic liquids have been reported to catalyze Beck-
mann rearrangement of ketoximes efficiently,7 their use for dehy-
dration of aldoximes is rather scarce.8 Only two reactions of
aromatic aldoximes have been demonstrated using a complex
task-specific ionic liquid bearing a sulfonyl chloride moiety.8a This
ionic liquid is not readily available and its preparation involves a
number of steps and expensive chemicals. In another report,8b
dehydration of aldoximes was carried out using a combination of
IL, air
3 h
Cl
Cl
Entry
IL
Equiv of IL
Temp (°C)
Yielda (%)
1
2
3
4
5
6
7
8
[pmim]BF4
[pmim]BF4
[pmim]BF4
[pmim]BF4
[pmim]BF4
[bmim]BF4
[pmim]Br
1
1
1
0.5
0.75
1
1
1
25
60
90
90
90
90
90
90
10b
45b
88
40b
65b
82
0c
[pmim]OH
0d
a
Yields refer to those of purified isolated products characterized by spectroscopic
data (IR, 1H and 13C NMR).
b
Besides product, the reaction mixture contains unreacted starting material.
The reaction mixture contains unreacted starting material (aldoxime) only
c
without any product.
d
The reaction mixture contains unreacted starting material (aldoxime) and the
corresponding aldehyde in 1:1 ratio.
Table 2
Dehydration of aldoximes to nitriles by [pmim]BF4
Entry
Aldoxime
Time (h)
4
Product
Yielda (%)
86
Ref.
4d
CN
CH NOH
1
CH NOH
CH NOH
CN
2
3
3
4
4
5
5
4
5
5
88
90
84
82
82
80
82
75
78
11
4e
4a
4e
4e
4e
4k
12
4a
Cl
Br
Cl
Br
CN
3
CH NOH
CN
4
NO
2
NO
2
CH NOH
CH NOH
CN
5
O N
2
O N
2
CN
6
H CO
3
H CO
3
CN
CN
CH NOH
CH NOH
7
H C
3
H C
3
8
HO
HO
OCH
OCH
3
3
CH NOH
CN
9
CN
CH NOH
10
(continued on next page)

6090
D. Saha et al. / Tetrahedron Letters 50 (2009) 6088–6091
Table 2 (continued)
Entry
Aldoxime
Time (h)
5
Product
Yielda (%)
76
Ref.
4a
CH NOH
CN
11
12
13
14
15
16
5
4
6
7
5
75
86
90
76
75
14
13
4f
CN
CH NOH
CN
CH NOH
CH NOH
CH NOH
6
5
4
6
CN
CN
5
4g
4d
4
CH NOH
CN
S
S
a
Yields refer to those of purified isolated products characterized by spectroscopic data (IR, 1H and 13C NMR).
AlCl3/[bmim]Br in xylene under microwave irradiation. The use of
AlCl3 is not very desirable as it entails environment pollution. Our
procedure using a very common and readily accessible9 ionic liquid
[pmim]BF4 or [bmim]BF4 without any organic solvent and co-cata-
lyst possesses distinct advantages over the other two. Moreover,
the reactions are relatively fast (3–7 h) and the yields (isolated)
are quite high (75–90%). The ionic liquid works here as a catalyst
as well as a reaction medium. The reaction is also effective using
75 mol % of ionic liquid; however, the reaction is relatively slow.
This procedure is also more general as it is compatible with aro-
matic, heteroaromatic as well as aliphatic aldoximes, and a variety
of functionalities such as Cl, Br, NO2 and OH. The ionic liquid was
recovered after the reaction and recycled for three runs without
any appreciable loss of efficiency.
+
N
N
H
O
H
BF
N
4
-H O
2
R
C
N
H
R
Scheme 2.
carbon of the oxime (C@N bond) leading to the formation of the
corresponding aldehyde (Table 1, entry 8). BrÀ is effective neither
as a base nor as a strong nucleophile as OHÀ, thus producing nei-
ther nitrile nor aldehyde (Table 1, entry 7).
In conclusion, we have developed an ionic liquid-promoted effi-
cient procedure for the dehydration of aldoximes to nitriles under
organic solvent-free condition in an aerobic atmosphere. The sim-
plicity in operation, general applicability, relatively fast reaction,
high yields and recyclability of ionic liquid up to three runs make
this protocol an attractive alternative.
Although we do not have any experimental data regarding the
mechanism of this reaction, we propose a reaction pathway as out-
lined in Scheme 2. The ionic liquid, [pmim]BF4 facilitates the dehy-
dration process through co-ordination of its 2-carbon-H with –OH
of aldoxime,10 followed by abstraction of H+ by BF4À. Here BF4
À
acts as a base rather than as a nucleophile. When [pmim]OH is
used, OHÀ being a stronger nucleophile attacks the sp2 hybridized
Table 3
Recyclability of ionic liquids
Acknowledgements
This work has enjoyed the financial support from DST, New Del-
hi under Grant No. SR/S5/GC-02/2006. D.S. and A.S. thank CSIR,
New Delhi, for their fellowships.
CN
CH NOH
[pmim]BF4
air, 90 ºC, 3h
Cl
Cl
No. of cycles
Supplementary data
Yield (%)
Amount of recovered ionic liquid (mg)
1a
2b
3b
4b
88
82
75
68
192
144
123
93
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.08.069.
References and notes
a
One millimolar (156 mg) of oxime was taken in 1 mmol (240 mg) of [pmim]BF4.
The aldoximes were taken in proportionate molar ratio of the recovered ionic
b
1. (a) Fatiadi, A. J. In Preparation and Synthetic Applications of Cyano Compounds;
Patai, S., Rappaport, Z., Eds.; Wiley: New York, 1983; (b) Miller, J. S.; Manson, J.
liquids.

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6091
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products are known compounds and were identified by comparison of their
spectroscopic data (IR, 1H NMR and 13C NMR) with those reported (See
references in Table 2). Spectroscopic characterization data (IR, 1H NMR and 13
NMR) of a few selected compounds are provided below as ready reference.
C
Benzonitrile (Table 2, entry 1): colourless liquid; IR (neat): 3065, 2230, 1599,
1491, 1446, 1288 cmÀ1 1H NMR (CDCl3, 300 MHz): d 7.49–7.43 (m, 3H), 7.34–
;
7.29 (m, 2H); 13C NMR (CDCl3, 75 MHz): d 132.57, 131.80 (2C), 128.90 (2C),
118.57, 112.04.
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K. R., Eds.; American Chemical Society: Washington, D.C., 2002. p 474; (b)
Parvulescu, V. I.; Hardacre, C. Chem. Rev. 2007, 107, 2615–2665; (c) Saha, D.;
Saha, A.; Ranu, B. C. Green Chem. 2009, 11, 733–737; (d) Ranu, B. C.; Adak, L.;
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6. Representative experimental procedure for dehydration of aldoximes.
Conversion of benzaldoxime (mixture of cis and trans isomers) to
benzonitrile (Table 2, entry 1): A mixture of benzaldoxime (121 mg, 1 mmol)
and [pmim]BF4 (240 mg, 1 mmol) ([bmim]BF4 may also be used) was stirred at
90 °C in an aerobic atmosphere for 4 h (monitored by TLC). After the reaction
was over, the reaction mixture was extracted with ether (3 Â 10 mL), and the
ether extract was washed with water and dried over Na2SO4. Evaporation of the
solvent left the crude product which was purified by column chromatography
over silica gel (hexane/ether 95:5) to afford pure benzonitrile (89 mg, 86%). The
1H and 13C NMR data of this compound are in good agreement with the
reported data.4d
4-Hydroxy-3-methoxybenzonitrile (Table 2, entry 8): Solid; mp 90 °C; IR (KBr):
3363, 3228, 2228, 1603, 1520, 1371, 1283 cmÀ1 1H NMR (CDCl3, 300 MHz): d
;
7.19 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 6.93 (d, J = 8.1 Hz), 6.44 (br s, 1H), 3.90 (s,
3H); 13C NMR (CDCl3, 75 MHz): d 150.18, 146.91, 126.77, 119.35, 115.62,
115.09, 102.98, 55.96.
2-Naphthalenecarbonitrile (Table 2, entry 10): colourless liquid; IR (neat):
3433, 3062, 2226, 1626, 1593, 1361, 1273 cmÀ1 1H NMR (CDCl3, 300 MHz): d
;
8.00 (s, 1H), 7.73–7.68 (m, 3H), 7.50–7.39 (m, 3H); 13C NMR (CDCl3, 75 MHz): d
134.59, 134.09, 132.18, 129.18, 129.06, 128.39, 128.05, 127.67, 126.27, 119.28,
109.29.
(E)-3-Phenylprop-2-enenitrile (Table 2, entry 11): colourless liquid; IR (neat):
3366, 3060, 2218, 1697, 1618, 1494, 1207 cmÀ1 1H NMR (CDCl3, 300 MHz): d
;
7.34 (br s, 5H), 7.29 (d, J = 16.7 Hz, 1H), 5.79 (d, J = 16.6 Hz, 1H); 13C NMR
(CDCl3, 75 MHz): d 150.64, 133.60, 131.33, 129.21 (2C), 127.50 (2C), 118.33,
96.40.
1-Heptanonitrile (Table 2, entry 14): colourless liquid; IR (neat): 3016, 2959,
2932, 2860, 2247, 1462, 1427, 1379, 1115 cmÀ1 1H NMR (CDCl3, 300 MHz): d
;
2.24 (t, J = 6 Hz, 2H), 1.59–1.50 (m, 2H), 1.39–1.31 (m, 2H), 1.24–1.22 (m, 4H),
0.81 (t, J = 6 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d 119.56, 30.66, 28.05, 25.09,
22.09, 16.76,13.61.
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9. The ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate is
commercially available (Aldrich). The other ionic liquids, [pmim]BF4 and
[pmim]OH were easily prepared by a metathesis reaction of [pmim]Br with
NaBF4 and KOH following reported procedures: (a) Namboodiri, V. V.; Varma, R.
S. Org. Lett. 2002, 4, 3161–3163; (b) Ding, S.; Radosz, M.; Shen, Y.
Macromolecules 2005, 38, 5921–5928; (c) Ranu, B. C.; Banerjee, S. Org. Lett.
2005, 7, 3049–3052. The ionic liquid, [bmim}OH is considerably stable at
100 °C (Ranu, B. C.; Banerjee, S.; Jana R. Tetrahedron 2007, 63, 776–782).
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The ionic liquid, left after extraction of the product was dried under vacuum
and reused for subsequent reactions. The details are outlined in Table 3.
This procedure was followed for all the reactions listed in Table 2. All the