Microwave-assisted efficient one-pot synthesis of nitriles from aldehydes in the presence of P2O5/SiO2 in solvent-free media

Article abstract of DOI:10.1080/104265090517460

A rapid and efficient procedure is developed for a one-pot synthesis of nitrites by condensation of aldehydes with hydroxylamine hydrochloride in the presence of P₂O₅/SiO₂ in solvent-free media under microwave irradiation. Copyright Taylor & Francis Inc.

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Microwave-Assisted Efficient
One-Pot Synthesis of Nitriles
From Aldehydes in the
Presence of P2O5/SiO2 in
Solvent-Free Media
Hossein Eshghi a & Zinat Gordi b
a Department of Chemistry , Ferdowsi University of
Mashhad , Mashhad, Iran
b Department of Chemistry , Sistan and Baluchestan
University , Zahedan, Iran
Published online: 21 Dec 2010.
To cite this article: Hossein Eshghi & Zinat Gordi (2005) Microwave-Assisted Efficient
One-Pot Synthesis of Nitriles From Aldehydes in the Presence of P2O5/SiO2 in Solvent-
Free Media, Phosphorus, Sulfur, and Silicon and the Related Elements, 180:2, 619-623,
DOI: 10.1080/104265090517460
To link to this article: http://dx.doi.org/10.1080/104265090517460
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Phosphorus, Sulfur, and Silicon, 180:619–623, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090517460
Microwave-Assisted Efficient One-Pot Synthesis of
Nitriles From Aldehydes in the Presence of P2O5/SiO2
in Solvent-Free Media
Hossein Eshghi
Department of Chemistry, Ferdowsi University of Mashhad,
Mashhad, Iran
Zinat Gordi
Department of Chemistry, Sistan and Baluchestan University,
Zahedan, Iran
A rapid and efficient procedure is developed for a one-pot synthesis of nitriles by
condensation of aldehydes with hydroxylamine hydrochloride in the presence of
P2O5/SiO2 in solvent-free media under microwave irradiation.
Keywords Aldehydes; aldoximes; microwave irradiation; nitriles; phosphorus pentoxide
INTRODUCTION
Nitriles, important reagents for organic synthesis have been known to
chemist for a long time. In recent reports, it was shown that nitriles
are very useful starting materials for the synthesis of various bioac-
tive molecules.1,2 Furthermore, nitriles can be converted to amides,
carboxylic acids, amines, ketones, and esters.3 For example, vanilly-
lamine readily obtained by the reduction of vanillylonitrile,4 could be
reacted with acyl chlorides to give capsaicinoids.
Several procedures are available for the one-step conversion of alde-
hydes into nitriles using different chemical reagents and hydroxy-
lamine hydrochloride.5,6 However, most the methods suffer from serious
drawbacks which include the use of hazardous and expensive or com-
mercially unavailable reagents, long reaction times, low yields, drastic
reaction conditions, and tedious workup procedure.
The efficiency of microwave irradiation (MW) in organic synthesis
is currently under intensive study.7 There are just a few publications
Received April 6, 2004; in final form July 29, 2004.
Address correspondence to Hossein Eshghi, Department of Chemistry, Ferdowsi Uni-
versity of Mashhad, Mashhad, 91774-1436, Iran. E-mail: heshghi@hamoon.usb.ac.ir
619

620
H. Eshghi and Z. Gordi
describing the use of microwave irradiation for preparations of ni-
triles from aldehydes and hydroxylamine hydrochloride.8 Our projects
have been to develop new synthetic methods using the P2O5/SiO2 in
solvent-free media.9 Having the above facts in mind, we wish to re-
port a very simple and efficient method for one-pot synthesis of ni-
triles from both alkyl and aryl aldehydes using P2O5/SiO2 and hy-
droxylamine hydrochloride in solvent-free media under microwave
irradiation.
RESULTS AND DISCUSSION
In order to prepare nitriles, various types of aldehydes were mixed with
hydroxylamine hydrochloride in the presence of P2O5/SiO2 reagent us-
ing microwave irradiation in solvent-free media. In this approach, ni-
triles were obtained instead of oximes. The general reaction is illus-
trated in Scheme 1 and the results are reported in Table I. All reactions
were performed in one minute. As shown in the Table I several struc-
turally different aldehydes underwent cleanly and remarkably fast the
one-pot reaction to the corresponding nitriles. This mild and versatile
method which results in yields of 75–95% can also be applied to alde-
hydes containing other reactive functional groups, such as double bond
and hydroxyl group. Even 2-furaldehyde gives a good yield of product
in spite of the literature10 which claims that such a reaction was not
successful.
P2O5/SiO2
RCHO + NH2OH·HCl
−→ RCN + H2O
MW, 1 min.
SCHEME 1 One-pot preparation of nitriles.
In the absence of microwave irradiation, after 10 min grinding of
the mixture the corresponding aldoximes were exclusively formed in
good yields.9d,e This clearly indicates that aldoxime may be an inter-
mediate in the conversion of aldehydes to nitriles. Also, aldoximes are
dehydrated to the corresponding nitriles in high yields under the same
conditions. The general reaction is illustrated in Scheme 2 and the
SCHEME 2 Conversion of aldoximes to nitriles.

Nitriles
621
TABLE I One-Pot Preparation of Nitriles from Aldehydes by Using
P2O5/SiO2 and Hydroxylamine Hydrochloride in Solvent-Free Media
under Microwave Irradiation
Yield
(%)a
Mp or bp (◦C)/
mmHg(lit.)
Entry
Aldehyde
Nitrile
1
2
3
4
5
CH3CHO
C3H7CHO
C5H11CHO
C6H13CHO
CH3CN
C3H7CN
C5H11CN
C6H13CN
75 81/760 (80/760)11
78 113/760 (110/760)11
78 160/760 (162/760)11
75 198/760 (70-71/10)12
95 190/760 (187/760)11
6
7
80 113 (112–114)10
89 82–83 (81)13
8
9
85 74–75 (74–76)12
85 146–147 (148)11
85 116–117 (117)11
10
11
12
85 258/760 (260/760)11
75 147 (147–148)12
aIR, 1H-NMR, and mp or bp confirmed the structures.
results are reported in Table II. As shown in Table II the correspond-
ing nitriles were obtained in 85–95% yields from both alkyl and aryl
aldoximes.
In conclusion, this one-pot synthesis of nitriles from aldehydes, with-
out isolation of aldoximes, offers significant improvements over the ex-
isting procedures and thus makes available a variety of nitriles and
related compounds. Also this simple and readily available reagent af-
fords various nitriles in a short reaction time, with excellent yields,

622
H. Eshghi and Z. Gordi
TABLE II Conversion of Aldoximes to Nitriles by Using P2O5/SiO2 in
Solvent-Free Media under Microwave Irradiation
Yield Mp or bp (◦C)/
Entry
1
Aldoxime
Nitrile
(%)a
mmHg(lit.)
CH3CH=NOH
CH3CN
85
81/760
(80/760)11
113/760
2
3
4
C3H7CH=NOH
C6H13CH=NOH
C3H7CN
88
85
90
(110/760)11
198/760
C6H13CN
(70–71/10)12
190/760
(187/760)11
5
6
95
113
(112–114)10
95 82–83
(81)13
7
8
92
85
74–75
(74–76)12
147
(147–148)12
aIR, 1H-NMR, and mp or bp confirmed the structures.
and good selectivity. Further applications of the P2O5/SiO2reagent in
organic synthesis are under investigation.
EXPERIMENTAL
All melting points recorded are uncorrected open capillary measure-
ments. IR spectra were recorded on a Shimadzu-IR 470 spectropho-
tometer. 1H-NMR spectra were recorded on a Bruker-80 and 500 MHz
instrument using tetramethylsilane (TMS) as an internal standard. Sil-
ica gel 60(230–400 mesh) was obtained from Fluka and was dried in an
oven at 120◦C for 2 h. Irradiation was carried out in a domestic mi-
crowave oven (Electra, 2450 MHz, and 800 W) for an optimized time.
The P2O5/SiO2 reagent was obtained according to the early reported
procedure.9

Nitriles
623
Preparation of Nitriles
General Procedure
In a typical reaction, a mixture of aldehyde (2 mmol), hydroxylamine
hydrochloride (4 mmol) and the P2O5/SiO2 reagent (1 g), or a mix-
ture of aldoxime (2 mmol) and the P2O5/SiO2 reagent (1 g) was ground
thoroughly in the mortar. Usually an immediate colour change was ob-
served. The mortar was covered with a watch glass and put inside the
microwave oven. The mixture was irradiated for one minute and the
completion of the reaction was monitored by TLC. After the completion
of the reaction, the mortar was removed from the oven, the mixture
was cooled to room temperature and then 10 ml of 5% aqueous HCl
was added to the mixture. The resulting solution was extracted with
CH2Cl2 (2 × 10 ml). The extracts were combined and dried over CaCl2.
Evaporation of the solvent under vacuum gave nitriles with high purity
(based on TLC, 1H-NMR, IR and melting point). Column chromatogra-
phy or recrystalization from benzene or benzene-cyclohexane gave pure
products.
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