Mild, efficient, and rapid dehydration of aldoximes to nitriles mediated by phthalic anhydride under microwave irradiation

Article abstract of DOI:10.1007/s007060270013

Aldoximes can be efficiently and rapidly dehydrated to nitriles by treatment with phthalic anhydride under microwave irradiation.

Full text of DOI:10.1007/s007060270013

Monatshefte f uÈ r Chemie 133, 111±114 (2002)
Mild, Ef®cient, and Rapid Dehydration
of Aldoximes to Nitriles Mediated by Phthalic
Anhydride Under Microwave Irradiation
Ã
Rahim Hekmatshoar , Majid M. Heravi, Yahya S. Beheshtiha,
and Karim Asadolah
Department of Chemistry, School of Science, Azzahra University, Vanak, Tehran, Iran
Summary. Aldoximes can be ef®ciently and rapidly dehydrated to nitriles by treatment with phthalic
anhydride under microwave irradiation.
Keywords. Aldoximes; Phthalic anhydride; Nitriles; Microwave Irradiation.
Introduction
Nitriles have been used in organic synthesis for a long time as precursors of biolog-
ically active compounds such as antipecurnavirus tetrazole analogues [1], 1,2-
diarylimidazoles as potent anti-in¯ammatory agents [2], triazolo[1,5-c]primidines
with potent antiasthma activity, and benzamidine with ®brinogen antiagonistic
activity [4]. Another application of nitriles is their reaction with ꢀ-aminoalcohol in
the presence of a catalyst to give 2-oxazolines, which are used as chiral auxiliaries
in asymmetric synthesis [5]. The most common route to nitriles starts from alde-
hydes [6]. Very recently, aldehydes have been converted into nitriles using ammonia
and hydrogen peroxides [7].
Oximes are extensively employed for the puri®cation of carbonyl compounds
8]. In addition, oximes can be synthesized from non-carbonyl compounds [9].
[
Therefore, direct conversion of oximes to nitriles offers an alternative and promis-
ing route. In spite of this possibility, only few reports exist in literature dealing with
0
this reaction. The use of trimethylsilyl iodide [10], 1,1 -oxalyldiimidazole [11], and
carbon monoxide/water in the presence of a Rh carbonyl cluster [12] have been
reported. Recently, a new enzymatic method for the conversion of aldoximes to
nitriles has been described [13].
Results and Discussion
Microwave irradiation is a useful technique in organic synthesis [14]. In connection
with our interest using microwave irradiation to implement and increase reaction
à Corresponding author. E-mail: mmheravi@azzahra.ac.ir

1
12
R. Hekmatshoar et al.
Table 1. Conversion of aldoximes to nitriles with phthalic anhydride under microwave irradiation
a
ꢀ
ꢀ
b
Yield %
Entry
Oxime (1)
Nitrile (2)
Reaction M.p./ C or b.p./ C (torr)
time
reported found
min)
(
1
2
3
4
3
5
121 (100) 123.5 (100)
90
87
86
116
115±117
254 (760) 251±252 (760)
4
5
6
4
84
93
85±87
92±93
85
90
92
10
8
30
26±28
7
8
9
12
5
109
112±114
80
86
78
142 (760) 146±149 (760)
15
144
110
146±149
110±112
1
0
7
94
a
Oximes were synthesized according to reported procedures
Yields refer to isolated products
b
rates [15], in this communication we report that phthalic anhydride, an inexpen-
sive and readily available reagent, can convert aldoximes to nitriles rapidly and
ef®ciently in acetonitrile under microwave irradiation. When benzaldoxime and
phthalic anhydride were dissolved in CH CN and treated with microwaves for less
3

Rapid Dehydration of Aldoximes to Nitriles
113
than 4 min, benzonitrile was obtained almost quantitatively. To assess the general-
ity of the method, a variety of aldoximes were converted to the corresponding nitriles
in very short reaction times and high yields under the same conditions (Table 1).
In conclusion, we have developed a mild, ef®cient, inexpensive, and rapid
method for the direct conversion of aldoximes to nitriles.
Experimental
All products are known compounds; their physical data agreed with those of authentic samples.
General procedure
3
mmol of an appropriate oxime 1 and 5.05 mmol phthalic anhydride were added to 10 cm of
5
anhydrous acetonitrile. The resulting mixture was immediately placed into a microwave oven operat-
ing at medium to high power for the time indicated (Table 1). Then, the solvent was evaporated, and
3
the resulting residue was extracted with 3 Â 30 cm of CH Cl . The organic layer was washed with
2
2
5
% NH and an excess of H O to remove phthalic acid. The organic layer was dried over MgSO and
3 2 4
then evaporated. The residue was recrystallized from n-hexane/ethylacetate (Table 1, entries 2, 4±7,
9
, 10) or puri®ed by passing through a short silicagel column using CHCl as eluent (Table 1, entries
3
1
, 3, 8) to give pure nitrile 2.
References
[
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[
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[
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R. Hekmatshoar et al.: Rapid Dehydration of Aldoximes to Nitriles
[
[
[
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Received April 18, 2001. Accepted (revised) June 7, 2001

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