PCC-Promoted dehydration of aldoximes: A convenient access to aromatic, heteroaromatic, and aliphatic nitriles

Article abstract of DOI:10.1080/00397911.2012.738459

A simple and convenient procedure for the synthesis of nitriles by dehydration of aldoximes using a PCC (pyridiniumchlorochromate) has been developed. A variety of aromatic, heteroaromatic, and aliphatic aldoximes are converted. Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the full spectral details.

Full text of DOI:10.1080/00397911.2012.738459

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PCC-Promoted Dehydration of
Aldoximes: A Convenient Access to
Aromatic, Heteroaromatic, and Aliphatic
Nitriles
S. Chandrappa a , T. S. R. Prasanna b , K. Vinaya a , D. S. Prasanna a
& K. S. Rangappa a
a Department of Studies in Chemistry , University of Mysore,
Manasagangotri , Mysore , India
b Synthetic Polymer Laboratory, Department of Polymer Science and
Technology , Sri Krisnadevaraya University , Anantapur , India
Published online: 08 Jul 2013.
To cite this article: S. Chandrappa , T. S. R. Prasanna , K. Vinaya , D. S. Prasanna & K. S. Rangappa
(2013) PCC-Promoted Dehydration of Aldoximes: A Convenient Access to Aromatic, Heteroaromatic,
and Aliphatic Nitriles, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 43:20, 2756-2762, DOI: 10.1080/00397911.2012.738459
To link to this article: http://dx.doi.org/10.1080/00397911.2012.738459
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Synthetic Communications1, 43: 2756–2762, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.738459
PCC-PROMOTED DEHYDRATION OF ALDOXIMES: A
CONVENIENT ACCESS TO AROMATIC,
HETEROAROMATIC, AND ALIPHATIC NITRILES
S. Chandrappa,1 T. S. R. Prasanna,2 K. Vinaya,1
D. S. Prasanna,1 and K. S. Rangappa1
1Department of Studies in Chemistry, University of Mysore,
Manasagangotri, Mysore, India
2Synthetic Polymer Laboratory, Department of Polymer Science and
Technology, Sri Krisnadevaraya University, Anantapur, India
GRAPHICAL ABSTRACT
Abstract A simple and convenient procedure for the synthesis of nitriles by dehydration of
aldoximes using a PCC (pyridiniumchlorochromate) has been developed. A variety of aro-
matic, heteroaromatic, and aliphatic aldoximes are converted.
Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications1 for the full spectral details.
Keywords Aldoxime; carbonyl group; dehydration; nitrile; oxidizing agent; PCC
INTRODUCTION
Organic nitriles are very important in organic synthesis as they are versatile
intermediates in the synthesis of amines, carboxylic acids, esters, and ketones, which
are useful raw materials for pharmaceuticals, 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,[1] whereas aromatic nitriles are produced by the Sandmeyer
reaction and ammoxidation.[3] However, these methods are associated with the use
of NaCN=KCN=metal cyanides, which are in general highly poisonous, and
heavy-metal cyanides such as zinc cyanide, which leave residues of heavy-metal salts.
Received September 7, 2012.
Address correspondence to K. S. Rangappa, Department of Studies in Chemistry, University of
Mysore, Manasagangotri, Mysore 570 006, India. E-mail: rangappaks@gmail.com; rangappaks
@chemistry.uni-mysore.ac.in
2756

PCC-PROMOTED DEHYDRATION
2757
This is not desirable in the context of a clean environment. Dehydration of aldox-
imes to nitriles is one of the cleanest routes, avoiding inorganic cyanides. Many
methods have been developed for this transformation and some of the recently
reported procedures involve Pd(OAc)2=PPh3 in CH3CN,[4] benzotriazole phosphoniu-
hexafluorophosphate derivative 1,8-diaza bicyclo[5.4.0]undec-7-ene (DBU)=in
CH2Cl2,[5] N-chlorosuccinimide=pyridine in CH3CN,[6] dimethyl formamide (DMF)
at 135 ꢀC,[7] tungsten–tin mixed hydroxide in o-xylene at 149 ꢀC,[8] diethylchloropho-
sphate in toluene,[9] molecular sieves under flash vacuum pyrolysis,[10] ZnO=
CH3COCl,[11] chlorosulfonic acid in toluene,[12] dimethylthiocarbonate=Et3N in diox-
ane,[13] diethylchlorophosphite in CHCl3,[14] zeolite under microwave irradiation,[15]
AlCl3 ꢁ 6H2O=KI=H2O=CH3CN,[16] Preyssler’s anion [NaP5W30O110],[17,18] Burgess
reagent, and thionyl chloride as dehydrating agents. Among these, only a few are cata-
lytic, and most of them use stoichiometric amounts of reagents. In general, all these
procedures are satisfactory; however, a majority of them are restricted to the reactions
of aromatic aldoximes. The aliphatic aldoximes are addressed by a few methods.[19]
Moreover, many of them involve expensive and toxic chemicals and require
long reaction times. Thus, alternative procedures with more general applicability,
considerably faster reaction, and easy workup conditions are still in demand.
RESULTS AND DISCUSSION
Pyridiniumchlorochromate (PCC) is a mild oxidizing reagent, a readily avail-
able, stable reagent commonly used for the oxidation of alcohols to aldehydes or
ketones in organic synthesis,[20–25] and it has not been studied and utilized as a
reagent for the preparation of nitriles from aldoximes. Hence, this scenario has
prompted us to envisage an alternative strategy for the dehydration of aldoximes
keeping in view the following significant aspects: (1) use of commercially available
stable PCC reagent, (2) short reaction time leading to overall efficiency, (3) tolerance
of broad functional groups. We studied this unique transformation reaction in more
detail. Herein, we report for the first time a general procedure for the dehydration of
aldoximes to nitriles in the presence of PCC (Scheme 1).
A preliminary examination using benzaldoxime as a model showed that PCC
effectively mediated its conversion into benzonitrile. When a CHCl3 solution of ben-
zaldoxime (1.0 equiv) and PCC (1.1 equiv) was stirred at reflux, the starting material
was consumed in 2 h, as indicated by thin-layer chromatography (TLC). In addition,
it is interesting to note that aliphatic, aromatic, and heteroaromaticoximes bearing
various functionalities such as chloro, bromo, nitro, methyl methoxy, boronate, ole-
fins, amine, and benzyl oxy carbonyl groups survived the reaction and provided good
yields of corresponding nitriles. The results are presented in Table 1. A plausible
mechanism of nitrile synthesis is outlined in Scheme 2.
Scheme 1. Dehydration of aldoximes to nitriles.

2758
S. CHANDRAPPA ET AL.
Table 1. Structure of the synthesized compounds, reaction time, and yield
Entry
Aldoximes
Time (h)
Product
Yield (%)
Ref.
1
2
86
4d
—
2
3
85
3
4
3
82
79
4e
4a
2.5
5
6
7
2.5
3
80
85
86
4e
4e
4e
3
8
9
2
3
90
85
82
4a
4a
4d
10
2.5
11
2.5
86
5
(Continued )

PCC-PROMOTED DEHYDRATION
2759
Table 1. Continued
Entry
Aldoximes
Time (h)
Product
Yield (%)
Ref.
5
12
3
88
13
2.5
80
—
14
15
3
2
79
81
—
6
16
2.5
86
—
17
2.5
83
—
Scheme 2. Plausible mechanism of nitrile synthesis.

2760
S. CHANDRAPPA ET AL.
In summary, the short reaction period, simple workup, good yield, broad sub-
strate scope in tolerating various functional groups, and straightforward approach
should be of further interest in synthetic chemistry.
EXPERIMENTAL
Representative Experimental Procedure for Dehydration of
Aldoximes: Conversion of Benzaldoxime to Benzonitrile (Table 1,
Entry 1)
A mixture of benzaldoxime (121 mg, 1 mmol) and PCC (237 mg, 1.1 mmol) in
CHCl3 was heated to reflux for 2 h (monitored by TLC). After the reaction was over,
the black reaction mixture was filtered through a Celite pad and washed with EtOAc.
Evaporation of the solvent left the crude product, which was purified by column
chromatography over silica gel (hexane=EtOAc, 95:5) to afford pure benzonitrile
1
(89 mg, 86%). The infrared (IR) and H and 13C NMR data of this compound are
in good agreement with the reported data.[4d]
Compounds 1–12 and 15 are known and were identified by comparison of their
spectroscopic data (IR, 1H NMR, and 13C NMR) with those reported (see references
in Table 1). Compounds 13, 14, 16, and 17 were characterized by their spectroscopic
data, which are in agreement with the proposed structures.
1
Representative spectroscopic characterization data (IR, H NMR, and 13C
NMR) for the compounds are provided (compounds 13, 14, 16, and 17).
4-Amino-3-chloro-5-methylbenzonitrile (13)
The general protocol was used for cyclization; 0.35 g of 13 was isolated as
off-white solid; mp: 128–130 ꢀC; 1H NMR (CDCl3, 400 MHz) d: 7.42 (1H, s,
Ar-H), 7.22 (1H, s, Ar-H), 4.5 (2H, br s, -NH2), 2.19 (3H, s, -CH3); dC(100.6 MHz,
DCl3), 145.4, 132.2, 130.9, 123.1, 118.9, 118.2, 100.2, 17.6; IR n max(KBr, cmꢂ1):
3391, 2932, 2235, 1509, 1350, 803, 775; MS (ESI) [M þ 1]þ: 165.2.
5-Methyl-2-nitrobenzonitrile (14)
The general protocol was used for cyclization; 0.21 g of 14 was isolated as pale
yellow solid; mp: 108–111 ꢀC; 1H NMR (CDCl3, 400 MHz) d: 8.02–8.0 (1H, d,
J ¼ 8.4 Hz, Ar-H), 7.67–7.64 (2H, m, Ar-H), 2.6 (3H, s, -CH3); dC (100.6 MHz,
CDCl3), 152.3, 136.5, 134.6, 130.7, 125.2, 116.8, 116.7, 19.9; IR n max (KBr, cmꢂ1):
2942, 2228, 1605, 1455, 833, 793; MS (ESI) [M þ Na]þ: 185.1, [M þ K]þ: 203.1.
4-((2-Phenyl-1H-benzoimidazol-1-yl)methyl)benzonitrile (16)
The general protocol was used for cyclization; 0.56 g of 16 was isolated as pale
1
yellow solid; mp: 119–121 ꢀC; H NMR (CDCl3, 400 MHz) d: 7.94–7.92 (1H, d,
J ¼ 8.0 Hz, Ar-H), 7.76–7.64 (4H, m, Ar-H), 7.54–7.48 (3H, m, Ar-H), 7.41–7.37
(1H, m, Ar-H), 7.36–7.30 (1H, m, Ar-H), 7.26–7.24 (2H, d, J ¼ 8.4 Hz, Ar-H),
7.21–7.19 (1H, d, J ¼ 8.0 Hz, Ar-H), 5.55 (2H, S, -CH2); dC(100.6 MHz, CDCl3),
154, 143, 141.6, 135.6, 132.9, 132.5, 130.2, 129.6, 129.1, 126.7 123.4, 123.1, 120.2,

PCC-PROMOTED DEHYDRATION
2761
118.2, 112, 110, 48; IR n max (KBr, cmꢂ1): 2926, 2229, 1559, 1460, 829, 745; MS
(ESI) [M þ 1]þ: 310.1.
Benzyl-1-cyanocyclobutylcarbamate (17)
The general protocol was used for cyclization; 0.192 g of 17 was isolated as pale
yellow solid; mp: 99–101 ꢀC; 1H NMR (DMSOd6, 400 MHz) d: 8.4 (1H, br s, -NH),
7.36–7.29 (5H, m, Ar-H), 5.07 (2H, S, -CH2), 2.55–2.48 (2H, m, -CH2), 2.34–2.27
(2H, m, -CH2), 1.99–1.95 (2H, m, -CH2); dC (100.6 MHz, DMSOd6), 154.4, 136.3,
128.3, 128.2, 127.9, 121.5, 65.8, 47.3, 32.8, 15.4; IR n max (KBr, cmꢂ1): 2912,
2232, 1649, 1362, 803; MS (ESI) [M þ 1]þ: 230.1, [M þ Na]þ: 253.1.
SUPPORTING INFORMATION
1
Compound characterization data and copies of H NMR and 13C NMR for
compounds (see Table 1; 13, 14, 16, and 17) described in Scheme 1 can be found
via the Supplementary Content section of this article’s webpage.
ACKNOWLEDGMENT
The authors are grateful to the University Grants Commission, Government of
India, for financial support to K. S. R. under Project No. F. 31-143=2005(SR).
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