FeCl3-silica: A green approach for the synthesis of nitriles from oximes

Article abstract of DOI:10.1080/00397911.2016.1167910

A green and suitable protocol for the conversion of aldoximes into nitriles is described. The transformation is carried out under solvent-free conditions using FeCl₃-silica medium. The protocol offers a green, single-step facile procedure with the use of less toxic metal salt to isolate nitriles in good to excellent yields.

Full text of DOI:10.1080/00397911.2016.1167910

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FeCl3-silica: A Green Approach for the Synthesis of
Nitriles From Oximes
Pranab Ghosh, Gyan Chandra Pariyar, Bittu Saha & Raju Subba
To cite this article: Pranab Ghosh, Gyan Chandra Pariyar, Bittu Saha & Raju Subba (2016):
FeCl3-silica: A Green Approach for the Synthesis of Nitriles From Oximes, Synthetic
Communications, DOI: 10.1080/00397911.2016.1167910
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Date: 05 April 2016, At: 08:15

FeCl3-Silica: A Green Approach for the Synthesis of Nitriles from Oximes
Pranab Ghosh1,, Gyan Chandra Pariyar1, Bittu Saha1, Raju Subba1
1Department of Chemistry, University of North Bengal, Darjeeling, West Bengal, India.
Corresponding author: Pranab Ghosh. E-mail: pizy12@yahoo.com
Abstract
A green and suitable protocol for the conversion of aldoximes into nitriles is described.
The transformation is carried out under solvent-free condition using FeCl3-silica medium.
The protocol offers a green, single-step facile procedure with the use of less toxic metal-
salt to isolate nitriles in good to excellent yields.
KEYWORDS: Oximes, Nitriles, Silica, FeCl3, Solvent-free.
INTRODUCTION
Organonitrile derivatives are widely used intermediates for the production of
agrochemicals, pharmaceuticals, polymers, pigments and dyes.1 Moreover, nitriles are
broadly used as starting materials for a wide range of organic synthesis such as amines,
amides, aldehydes, ketones, carboxylic acids and esters.2 The offered classical method for
nitrile synthesis are Sandmeyer reaction,3 ammoxidation of aldehydes,4 Kolbe nitrile
synthesis,5 hydrocyanation of alkenes,6 and Rosenmund–von Braun reaction.7 During the
past few decades, diverse catalytic systems have been reported for synthesis of nitriles
from substrates like alcohols,8 amines,9 amides,10 azides11 and carbonyls.12 These include
oxidative rearrangement of alkene,13 methyl arenes14 and benzyl or allyl halides15 but
these methods result the corresponding higher homologues.
1

Out of several reported methodologies, the transformation of oxime derivatives into
nitriles has received most attention as it does not alter the number of carbons in the
compound. Literature survey reveals that diverse catalytic system has been grown for the
transformation of oxime into nitrile such as Ac2O/K2CO3/DMSO,16 MnO2, 17 HSO3Cl,18
TiCl3(OTf),19 DMAD,20 Fe2(SO4)3,21 N-(p-toluenesulfonyl) imidazole,22 H2SO4/Silica,23
Ranny nickel,24 methyl (carboxysulfamoyl) triethylammonium hydroxide inner-salt,25
BDMS,26 propylphosphonic anhydride,27 silica-supported heteropolyacid,28 Palladium,29
thionyl chloride-benzotriazole,30 chloral,31 diethyl chlorophosphate,32 ArCuCNLi,33 8-
bromocaffeine,34 thiophosphoryl chloride,35 NiCl2,36 Bi(OTf)337 and CuCl2.38
Although a number of synthetic protocols have been reported but the harsh reaction
conditions, longer reaction time, low yield, work-up difficulties and waste of toxic metal-
salt or solvents into the environment made the various existing methodologies avertable
and unattractive under the aspect of green approach. For the ample relevance of nitrile as
credible bioactive material39 [fig 1] and numerous functional group transformations for
designing the functional molecules there is still a requirement for less expensive,
straightforward, and environmentally friendly protocols for their synthesis.
As iron has received a special interest in the area of various organic synthesis due to its
high catalytic activity, high functional group tolerance, low cost and low toxicity, 40
emphasizing on the reduction of toxic waste into the environment and searching for
greener synthetic means, we have chosen the combination of ferric chloride and silica for
2

the facile conversion of aldoxime to nitriles in our present investigation. Although there
are some other modified clean and green known protocols available in literature, but the
use of silica as a reaction medium is one of the significant approach to accomplish the
green process. In recent years, silica gel has been extensively used as reaction medium in
various organic transformations for a possible replacement of traditional hazardous
solvents which might cause a serious threat to chemical pollution into the environment.
The scantiness in existing methodologies could be fulfilled by the solid phase approach
with readily available reagents and which would also be a desirable approach to enhance
synthetic pathway for nitrile synthesis. In this context, the nontoxic nature of silica gel,
its high thermal and chemical stability may be considered as a potential candidate to
provide the present demand of green chemistry approach. Keeping this in mind and in
continuation of our studies for the development of milder eco-friendly synthetic
methodology for nitriles,41 we report herein our findings that finally established a
practical and clean procedure for the synthesis of nitriles directly from aldoximes or with
analogues via one-pot reaction at room temperature. There was no other by-product
detected by analysis of the crude product, the conversion was high and the isolation of the
desired nitrile was achieved in excellent yield. Interestingly, a high functional group
tolerance was observed with excellent conversions to nitriles (Scheme 1).
RESULT AND DISCUSSIONS
To standard the reaction protocol, vanillin oxime was treated as the starting material. The
model reaction comprising vanillin oxime (1.0 mmol) and silica gel (1.0 g) at 50oC on a
magnetic stirrer for 5 h furnished no yield. After raising the temperature up to 100oC, it
3

yielded only carbonyl compound instead of the nitrile. The next reaction was then set up
by combining vanillin oxime (1.0 mmol), silica gel (1.0 g) and 10 mol% anhydrous
FeCl3. The reaction was monitored from room temperature to 100oC but only 18%
desired product could be isolated at 100oC in 5 h (table 1). The quantity of FeCl3 and the
reaction temperature was then raised. The isolated desired product at 110oC and 20 mol%
FeCl3 in 5 h was only 32% (table 1). With same reaction condition and time, at 40 mol%
FeCl3, the isolated desired product was 56% (table 1). The sharp increase in the quantity
of nitrile with the increase in amount of FeCl3 at the same reaction condition clearly
indicates the requirement of more amount of FeCl3 for excellent transformation whereas
no such outcome was observed by lengthening the reaction time (entry 6, table 1). When
the reaction was carried out with 75 mol% FeCl3, the yield of the desired product was
more than 90%. Finally the reactant and FeCl3 ratio was put at 1:1 in silica (1.0 g) which
furnished 98% desired product (entry 8, table 1). Again maintaining all parameters
similar, an excellent yield was found by shortening the reaction time (2 h) (entry 12, table
1). Again, the decrease in % of yield was observed when the time was shortened from 2 h
to 1 h (entry 13, table 1). Finally, optimization of the reactant ratio and condition showed
aldoxime (1.0 mmol), anhydrous FeCl3 (1.0 mmol) and silica gel 60-120 mesh (1.0 g) at
110 oC to be the best combination to furnish maximum yield of the desired product (98%)
in 2 h (entry 12, table 1). For the generalization of our scheme, the aldoximes 1a-l was
successfully converted to the corresponding nitriles 2a-l under optimized condition (table
2). The oximes having various substituents have been converted into nitriles. Those
having electron releasing groups such as –OH, -OCH3, -N(CH3)2 furnished an excellent
yield whereas oximes having electron withdrawing groups offered comparatively lower
4

yield by minimal difference (table 2). Increasing hydrophobic moiety to neutral oximes
provide a lower yield of the desired product (entry 1a, 1k, 1l, table 2). The overall
applicability of the protocol is highly suitable for the desired conversion under the
aspects of sustainable development and green chemistry.
EXPERIMENTAL
Procedure for the synthesis of nitrile from aldoxime: Aldoxime (1.0 mmol) and
anhydrous FeCl3 (1.0 mmol) were intimately mixed with silica gel 60-120 mesh (1.0 g) in
mortar and pestle. The resulting solid mixture was poured into a round bottom flask (50
ml) and allowed to stir on magnetic stirrer at 110oC for appropriate time (table 2). The
progress of the reaction was monitored by TLC. After completion of the reaction, the
reaction mixture was extracted with ethyl acetate (3x15 ml), washed several times with
water. The combined organic mixture was dried over anhydrous Na2SO4, concentrated,
and purified by column chromatography on silica gel 60-120 mesh using petroleum
ether/ethyl acetate as eluent to afford pure nitrile. The desired isolated products were
characterized by IR, 1H NMR and 13C NMR spectroscopy.
CONCLUSION
In conclusion, we have developed a solvent free and environmentally benign protocol for
the single-step facile synthesis of nitriles from aldoximes (1.0 mmol) by using anhydrous
FeCl3 (1.0 mmol) on silica gel (1.0 g). The reaction protocol includes the use of
inexpensive and less toxic reagent, one-pot excellent yield of the desired products, simple
and easy reaction conditions and effortless work-up process.
5

ACKNOWLEDGEMENT
Authors are thankful to UGC, New Delhi for financial support.
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Table 1. Optimization of reactiona
Entry
1
FeCl3 (mol %)
Temp (oC)
Time (h)
Yield (%)b
Nil
-
50
5
Nil
Nil
18
32
56
56-57
>90
98
-
2
90
5
3
10
20
40
40
75
100
-
100
5
4
110
5
5
110
5
6
-
-
-
-
-
-
-
-
6.5
5
7
8
-
9
4
10
11
12
13
-
3
-
-
2.5
2
-
-
98c
93
-
1
a Reaction of vanillin oxime (1.0 mmol), anhydrous FeCl3 (0-100 mol %) and silica gel
60-120 mesh (1.0 g) on a magnetic stirrer in different time interval at 110 oC.
bIsolated yield.
cOptimized reaction condition.
11

Table 2. FeCl3-silica mediated synthesis of nitriles
Entry
a
Aldoximes (1)
Time (h)
3
Product (2)
Yield%b
95
OH
CN
N
OH
CN
b
c
d
e
f
5
81
79
90
87
90
89
88
N
NO2
NO2
OH
CN
5
N
O2N
O2N
OH
CN
4
N
Me2N
Me2N
OH
OH
CN
OH
4
N
OH
CN
3.5
3
N
OMe
OMe
OH
CN
g
h
N
HO
HO
OH
CN
3.5
N
MeO
MeO
12

OH
CN
i
1.5
2.0
3
98
97
87
86
N
HO
HO
OCH3
OCH3
OH
CN
OH
j
N
OH
OCH3
OCH3
OH
CN
k
l
N
CN
OH
N
3
bIsolated yield.
13

Scheme 1. Synthesis of nitriles from oximes R = H, 3-NO2, 4-NO2, 4-N(CH3)2, 2-OH, 3-
OCH3, 4-OH, 4-OCH3, 3-OCH3-4-OH, 2-OH-3-OCH3, 2-Napthyl, 1-Napthyl.
14

Figure 1. Potent bioactive organonitrile derivatives
15