Microwave promoted rapid dehydration of aldoximes to nitriles using melamine-formaldehyde resin supported sulphuric acid in dry media

Article abstract of DOI:10.1016/j.cclet.2011.01.008

A simple and convenient procedure for the synthesis of nitriles by dehydration of aldoxime using supported sulphuric acid on melamine-formaldehyde resin (MFR) under solvent-free condition has been developed. A variety of aromatic and aliphatic aldoximes were converted to the corresponding nitriles. The resin was recovered and reused for subsequent reactions.

Full text of DOI:10.1016/j.cclet.2011.01.008

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 815–818
www.elsevier.com/locate/cclet
Microwave promoted rapid dehydration of aldoximes
to nitriles using melamine-formaldehyde resin
supported sulphuric acid in dry media
*
Ramin Rezaei , Marzeih Karami
Department of Chemistry, Islamic Azad University, Firouzabad Branch, P.O. Box 74715-117, Firouzabad, Iran
Received 27 October 2010
Available online 19 April 2011
Abstract
A simple and convenient procedure for the synthesis of nitriles by dehydration of aldoxime using supported sulphuric acid on
melamine-formaldehyde resin (MFR) under solvent-free condition has been developed. A variety of aromatic and aliphatic
aldoximes were converted to the corresponding nitriles. The resin was recovered and reused for subsequent reactions.
#
2011 Ramin Rezaei. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Aldoximes; Nitriles; Melamine-formaldehyde resin; Sulphuric acid; Solvent-free
Nitriles are versatile synthetic intermediates for pharmaceuticals, agricultural chemicals and dyes [1]. The most
common and well-known procedure for the preparation of nitriles is the nucleophilic displacement of substrates with
suitable leaving groups such as halogen compounds, aryl sulfonates, alcohols, esters, ethers, nitro or amino
compounds and diazonium salts with inorganic cyanide ions [2]. The other alternative procedures are dehydration of
amides [3] and aldoximes [4], conversion of alcohols [5], aldehydes [6] and carboxylic acids [7] to nitriles using
various reagents and direct conversion of amines [8].
The dehydration of aldoximes which are easily prepared from the corresponding aldehydes is a candidate for clean
nitrile synthesis and various procedures have been reported [9]. However, selective dehydration to the corresponding
nitriles is very difficult and many reported procedures require the use of reactive reagents in stoichiometric amounts,
such as the Burgess reagent [10], N-chlorosuccinimide/PPh [11] and thionyl chloride [12]. Such reagents present a
3
severe drawback for scaled-up and industrial application. Therefore, efficient catalytic procedures for the dehydration
of aldoximes are still in great demand. Oxorhenium(VII) complexes [13], Ga(OTf) [14], InCl [15], TiCl (OTf) [15]
and Cu (OAc) [16] have been reported to catalyze the dehydration homogeneously, for example. Although
3
3
3
2
heterogeneous dehydration systems are environmentally and technologically the most desirable procedures, widely
usable truly heterogeneous catalysts are unprecedented.
Herein we report a simple and efficient process for the dehydration of aldoximes to nitriles using supported
sulphuric acid on melamine-formaldehyde resin (MFR) under microwave irradiation and solvent-free condition.
Simplicity of operation, easy work-up and high yields are some advantages of this method.
*
Corresponding author.
E-mail address: rezaieramin@yahoo.com (R. Rezaei).
1001-8417/$ – see front matter # 2011 Ramin Rezaei. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.01.008

816
R. Rezaei, M. Karami / Chinese Chemical Letters 22 (2011) 815–818
Table 1
Effect of various support-H
2
SO
4
on conversion of benzaldoxime into benzonitrile under microwave irradiation.
Supportted-H SO4
2
H
C
N
C
N
OH
Microwave (50 W)
a
Yield (%)
Entry
Support
Time (min)
1
2
3
4
5
6
7
8
None
30
5
50
80
80
75
60
70
55
75
MFR
Silica gel
Alumina
7
10
15
18
15
10
Montmorillonite k-10
Clay
Kaolin
Zeolite
a
Isolated yield.
First, the dehydration of benzaldoxim as a model substrate was carried out with various supports, including
previously reported solid supports (Table 1). Melamine-formaldehyde resin showed the highest catalytic activity for
the dehydration of benzaldoxime among various supports tested (Table 1, entry 2). In the absence of support, the
reaction was achieved; however, moderate yield of nitrile was attained after longer reaction time (Table 1, entry 1).
Other supports such as silica gel, alumina, montmorillonite k-10, clay, kaolin and zeolite (Table 1, entries 3–8) also
afford good yields of nitrile in longer reaction times.
The best ratio for H SO and MFR was found 10 mmol H SO per a gram of MFR.
2
4
2
4
To realize the superiority of the microwave assisted method in comparison with conventional heating method, we
compared the model reaction in four different solvents with different polarity and different boiling points. In DMSO and
DMF, higher power outputs provide high temperatures because solvents with high enough boiling points were used. The
reactions show similar effects of temperature on the yields to those observed under thermal conditions. Similar results
were observed in MeCN, because the reaction temperature was maintained by the boiling point of MeCN.
In THF solvent system the results indicate that no obvious effect of microwave irradiation on the yield was
observed, because the reactants and their intermediates should locate in microscopic hot spots in the reaction system
and their actual temperature is somewhat higher than solvent [17].
Several aldoximes were subjected to dehydration by this procedure using MFR-H SO to produce the
2
4
corresponding nitriles. The results are summarized in Table 2. Both electron-donating and electron-withdrawing
group-substituted aromatic aldoximes provided uniformly good results (Table 2, entries 2–9). This procedure is also
compatible with heteroaryl (Table 2, entry 10) and aliphatic aldoximes (Table 2, entry 11) and a variety of
functionalities such as Cl, NO and OH.
2
A plausible mechanism for the MFR-H SO catalyzed reaction to form nitrile derivatives was illustrated in Scheme
4
2
1
followed by abstraction of H by HSO .
. The MFR-H SO facilitates the dehydration process through co-ordination of its N–H with – OH of aldoxime,
2 4
+
À
4
In summary, we have developed an efficient and mild protocol for the synthesis nitriles via dehydration of
aldoximes using supported H SO –melamine-formaldehyde resin under solvent-free condition. Furthermore, the
2
4
reaction is a green process and the catalyst is recyclable for several uses. The advantages of the present method in
terms of facile manipulation, fast reaction rates and formation of cleaner products under neat reaction conditions
should make this protocol as a valuable alternative to the existing methods.
1
. Experimental
All chemicals and analytical grade solvents were purchased from Merck or Fluka chemical company. Melting
1
points of all nitriles were determined in open glass capillaries on Mettler FP51 melting point apparatus. H NMR
spectra were recorded on an Bruker AVANCE DRX 500 spectrometer. A stars SYNTH microwave oven was used at
different power levels for all the experiments. The reaction was monitored by TLC using pre-coated plates (Merck).

R. Rezaei, M. Karami / Chinese Chemical Letters 22 (2011) 815–818
817
Table 2
Dehydration of aldoximes to nitriles in the presence of MFR-H
2
4
SO .
a
b
Yield (%)
Entry
Aldoxime
Nitrile
MP (lit) [18]
Reaction time (min)
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
H
C
c
1
NOH
191
80
5
C
N
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
H
c
2
3
H3C
C
NOH
H3C
C
N
216 (218)
85
90
4
4
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
H
O N
2
C
NOH
152 (149)
109 (110)
O N
2
C
N
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
4
H
75
5
HO
C
NOH
HO
C
N
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
H
5
6
91 (93)
40 (43)
70
65
4
5
Cl
C
NOH
Cl
Cl
C
N
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
Cl
Cl
H
C
Cl
NOH
C
C
N
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
Cl
Cl
Cl
Cl
7
134 (136)
80
4
H
Cl
C
NOH
Cl
N
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
H3C
H3C
H C
3
8
9
H
C
72 (71)
82
85
67
77
5
5
5
3
N
NOH
N
C
N
H C
3
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
H
C
C
N
c
NOH
65 (66)
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
1
0
1
190 (192)
C
N
S
C
NOH
S
H
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
c
1
C
H
NOH
C
N
180 (183)
a
b
c
All the products are known.
Isolated yield.
Boiling point.

[()TD$FIG]
818
R. Rezaei, M. Karami / Chinese Chemical Letters 22 (2011) 815–818
NH
N
N
H
N
H
O
N
HN
-
H O
2
HSO4
R
C
N
H
R
N
H
Scheme 1.
1
.1. Preparation of melamine-formaldehyde supported H SO4
2
Commercial sulphuric acid (99%, 5 mL) was stirred with a suspension of melamine-formaldehyde resin (5 g) in
acetone (50 mL) for 20 min. The catalyst obtained after filtration was dried in vaccum oven before use.
1
.2. Typical experimental procedure
The aldoxime (10 mmol) was thoroughly mixed with H SO /melamine-formaldehyde catalyst (5 g) in an agate
4
2
mortar. The resulting fine powder was taken in a pyrex Erlenmeyer flask (25 mL) and irradiated in a microwave oven
conditions, see Table 2). After completion of the reaction dichloromethane 30 mL (2 Â 15) was added to the mixture.
The filtrate was dried (Na SO ) and the crude product obtained after evaporation of solvent was purified by
(
2
4
crystallisation, distillation or column chromatography.
1
Spectral data for selected products: Compound 2: HNMR (500 MHz, CDCl ): d 2.49 (s, 3H, Me), 7.41 (d, 2H,
3
1
J = 10 Hz, H–Ar), 8.07 (d, 2H, J = 5 Hz, H–Ar); CNMR (75 MHz, CDCl ): d 35.56, 103.78, 114.76, 129.27 (2C),
3
3
1
33.94 (2C), 142.85.
References
[
[
[
[
[
[
[
[
[
1] A.J. Fatiadi, in: S. Patai, Z. Rappaport (Eds.), Preparation and Synthetic Applications of Cyano Compounds, Wiley, New York, 1983, p. 1057.
2] K. Friedrick, K. Wallensfels, in: Z. Rappoport (Ed.), Chemistry of the Cyano Group, Wiley-Interscience, New York, 1970, p. 67.
3] C.W. Kuo, J.L. Zhu, J.D. Wu, et al. Chem. Commun. 9 (2007) 301.
4] M. Hosseini Sarvari, Synthesis 5 (2005) 787.
5] N. Mori, H. Togo, Synlett 9 (2005) 1456.
6] J.R. Hwu, F.F. Wong, J. Eur. Org. Chem. (2006) 2513.
7] V.N. Telvekar, R.A. Rane, Tetrahedron Lett. 48 (2007) 6051.
8] S. Lida, H. Togo, Synlett 3 (2007) 407.
9] B. Movassagh, S. Shokri, Synth. Commun. 35 (2005) 887.
[
[
[
[
[
[
[
[
[
10] B. Jose, M.S. Sulatha, P.M. Pillai, et al. Synth. Commun. 30 (2000) 1509.
11] N. Iranpoor, H. Firouzabadi, G. Aghapour, Synth. Commun. 32 (2002) 2535.
12] S.S. Chaudhari, K.G. Akamanchi, Synth. Commun. 29 (1999) 1741.
13] K. Ishihara, Y. Furuya, H. Yamamoto, Angew. Chem. Int. Ed. 41 (2002) 2983.
14] P. Yan, P. Batamack, G.K.S. Prakash, et al. Catal. Lett. (2005) 101.
15] D.C. Barman, A.J. Thakur, D. Prajapati, et al. Chem. Lett. (2000) 1196.
16] N. Iranpoor, B. Zeynizadeh, Synth. Commun. 29 (1999) 274.
17] L. Hu, Y. Wang, B. Li, et al. Tetrahedron 63 (2007) 9387.
18] CRC Handbook of Data on Organic Compounds: CRC Press, Boca Raton, FL 1988, Handbook of Tables for Organic Compounds
Identification, 3rd ed. Chemical Rubber Company, Cleveland, OH, 1978.