Zinc chloride-catalyzed expeditious route to nitriles

Article abstract of DOI:10.1080/00397910903069657

Zinc chloride has been found to be an excellent catalyst for a one-pot synthesis of nitriles from araldehydes and hydroxylammonium chloride under solvent-free conditions. The features of the present method are short reaction time, easy workup procedure, and good yields of the nitriles.

Full text of DOI:10.1080/00397910903069657

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Zinc Chloride–Catalyzed Expeditious
Route to Nitriles
a
a
M. A. Päsha & Aatika Nizam
a
Department of Studies in Chemistry , Central College Campus,
Bangalore University , Bangalore, India
Published online: 07 Apr 2010.
To cite this article: M. A. Päsha & Aatika Nizam (2010) Zinc Chloride–Catalyzed Expeditious Route to
Nitriles, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 40:9, 1276-1279, DOI: 10.1080/00397910903069657
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Synthetic Communications , 40: 1276–1279, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903069657
ZINC CHLORIDE–CATALYZED EXPEDITIOUS ROUTE
TO NITRILES
M. A. P a¨ sha and Aatika Nizam
Department of Studies in Chemistry, Central College Campus, Bangalore
University, Bangalore, India
Zinc chloride has been found to be an excellent catalyst for a one-pot synthesis of nitriles
from araldehydes and hydroxylammonium chloride under solvent-free conditions. The
features of the present method are short reaction time, easy workup procedure, and good
yields of the nitriles.
Keywords: Aldehydes; hydroxyl ammonium hydrochloride; microwave; nitriles; ZnCl
2
INTRODUCTION
In recent years, increasing interest has been focused on the synthesis of nitriles
because of their importance in organic synthesis, as they serve as intermediates in the
[
1]
synthesis of a variety of pharmaceuticals, pesticides, and dyes.
However, zinc chloride is considered to be a high-quality catalyst in organic
synthesis because of the numerous advantages associated with it: it is an environmen-
tally safe catalyst, readily available, and inexpensive.
Usually the synthesis of nitriles is accomplished by substitution reactions of
[
2]
alkyl and aryl halides with metal cyanides, oxidation of primary amines, dehy-
[3]
[4]
[5]
dration of primary and secondary amides, and dehydration of aldoximes with
dehydrating agents. Other reported methods for the synthesis of nitriles is the
one-pot reaction of aldehydes and hydroxylammonium chloride using various
[6]
[
7]
catalysts.
The reported methods entail problems such as use of catalysts that are
environmentally hazardous, excess catalysts, expensive reagents, tedious workup
procedures, and cumbersome methodologies. Therefore, there is a need for a versa-
tile, simple, and environmentally friendly process for a one-pot synthesis of nitriles
from aldehydes.
During the past decade, microwave heating has become a convenient and
widely used tool in organic synthesis. Microwave irradiation often leads to a remark-
able decrease in reaction time, increased yields, easier workup procedure, and use of
[8,9]
green chemistry protocols.
Received March 2, 2009.
Address correspondence to M. A. P a¨ sha, Department of Studies in Chemistry, Central College
Campus, Bangalore University, Bangalore 560 001, India. E-mail: mafpasha@gmail.com
1
276

ZINC CHLORIDE–CATALYZED EXPEDITIOUS ROUTE TO NITRILES
1277
We previously reported the synthesis of nitriles from primary amides using zinc
[
10]
chloride as catalyst in acetonitrile medium, but there has always been a desire to
synthesize these nitriles from readily available starting materials under solvent-free
conditions. Therefore, we have made use of the readily available aldehydes to synthe-
size nitriles under solvent-free conditions using microwaves.
RESULTS AND DISCUSSION
To find the best catalyst for the synthesis of nitriles, the reaction of anisalde-
hyde and hydroxylammonium chloride was carried out in the absence of catalyst
and in the presence of various Lewis acids, both under thermal conditions and under
microwave irradiation. Best results were obtained when zinc chloride was used as a
catalyst under microwave irradiation.
In a typical experiment, aromatic aldehyde, hydroxylammonium chloride,
and a catalytic amount of ZnCl (10 mol%) were taken in a Pyrex tube, mixed well,
2
and irradiated in a domestic microwave oven at 160 W for less than a minute to get
the nitriles in good to excellent yields (Scheme 1). This was confirmed by recording
the infrared (IR) spectra for the corresponding nitriles and observing a sharp peak
at the frequencies (Table 1).
Encouraged by this success, we attempted the reaction of hydroxyl ammonium
chloride with various aromatic aldehydes under similar conditions (Table 1). This
protocol is suited for both electron-donating and electron-withdrawing substituents
on the aromatic aldehydes.
Scheme 1. Synthesis of various substituted nitriles.
Table 1. One-pot conversion of araldehydes into corresponding nitriles in the presence of cat. ZnCl
60 W of microwave irradiation
2
at
)
1
Time Yield
(s)
IR
(%) (t cm
À1
Entry
Substrate
Product
1
2
3
4
5
6
7
8
9
4-Methoxybenzaldehyde
3-Chlorobenzaldehyde
3-Nitrobenzaldehyde
4-Methoxybenzonitrile
3-Chlorobenzonitrile
3-Nitrobenzonitrile
25
30
30
30
28
28
25
25
28
30
30
85
80
80
78
85
80
88
85
90
80
78
2225.70
2235.30
2235.34
2239.20
2229.56
2227.63
2221.84
2225.70
2226.70
2228.70
2235.34
2-Nitrobenzaldehyde
2-Nitrobenzonitrile
4-Hydroxybenzaldehyde
3,4,5-Trimethoxybenzaldehyde
2,4-Dimethoxybenzaldehyde
4-Hydroxybenzonitrile
3,4,5-Trimethoxybenzonitrile
2,4-Dimethoxybenzonitrile
3-Methoxy-4-hydroxybenzaldehyde 3-Methoxy-4-hydroxybenzonitrile
2-Chlorobenzaldehyde
4-Chlorobenzaldehyde
2,4-Dichlorobenzaldehyde
2-Chlorobenzonitrile
4-Chlorobenzonitrile
2,4-Dichlorobenzonitrile
1
1
0
1

¨
M. A. PASHA AND A. NIZAM
1278
CONCLUSION
In conclusion, we have developed a simple, solvent-free, and efficient method
to get nitriles by the reaction of different aldehydes and hydroxylammonium chlor-
ide in the presence of a catalytic amount of zinc chloride under microwave
irradiation within 30 s.
EXPERIMENTAL
Aldehydes, hydroxylammonium chloride, and other chemicals used were com-
mercial. All the reactions were carried out using a conventional (unmodified) house-
hold microwave oven (LG, 230 V, 160 W). Reactions were monitored by thin-layer
chromatography (TLC) by comparison with the authentic samples. Yields refer to
the isolated yields of the products. The infrared (IR) spectra of the products were
recorded on a Shimatzu Fourier transform (FT)–IR 8400s spectrophotometer.
Procedure for the Preparation of 4-Methoxybenzonitrile
A mixture of anisaldehyde (0.136 g, 1 mmol), hydroxylammonium chloride
0.08 g, 1.2 mmol), and zinc chloride (10 mol%) was taken in a Pyrex cylindrical tube,
(
mixed well, and irradiated in a microwave oven at 160 W for 25 s. The contents were
cooled to room temperature and extracted with dichloromethane (5 ml). The organic
layer was dried over anhydrous sodium sulfate, and the solvent was removed under
vacuum. The crude product was chromatographed on a short column of silica gel
using light petrol as an eluent to get the pure nitrile (0.143 g, 85%).
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