An efficient microwave assisted one-pot conversion of aldehydes into nitriles using silica gel supported NaHSO4 catalyst

Article abstract of DOI:10.1055/s-0029-1216866

The aryl and alkyl aldehydes were rapidly converted to the corresponding nitriles in high yields under microwave irradiation in the presence of silica gel supported NaHSO₄ catalyst.

Full text of DOI:10.1055/s-0029-1216866

LETTER
1569
An Efficient Microwave Assisted One-Pot Conversion of Aldehydes into
Nitriles Using Silica Gel Supported NaHSO4 Catalyst1
Biswanath Das,* P. Madhusudhan, B. Venkataiah
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax: (91) 40-7173387, 7173757; E-mail: jsy@csiict.ren.nic.in
Received 8 July 1999
The catalyst (NaHSO4.SiO2) was previously used11 for de-
hydration and transesterification of alcohols. Several aryl
and alkyl aldehydes have recently been observed to under-
go rapid conversion into the corresponding nitriles in high
yields in the presence of the catalyst under microwave ir-
radiation without any solvent (Table 1). The catalyst can
easily be prepared11d and the experiment procedure is very
simple. The mechanism could be briefly proposed as fol-
lows: the aldehydes were at first converted to aldoximes
by reaction with hydroxylamine. The aldoximes were sub-
sequently underwent rapid dehydration to produce ni-
triles. It has been observed that the aldoximes when
separately irradiated under microwave irradiation in the
presence of NaHSO4.SiO2 catalyst rapidly afforded ni-
triles. The structures of all the nitriles were settled from
their analytical and spectral (1H NMR and MS) data.
Abstract: The aryl and alkyl aldehydes were rapidly converted to
the corresponding nitriles in high yields under microwave irradia-
tion in the presence of silica gel supported NaHSO4 catalyst.
Key words: Aryl and alkyl aldehydes, nitriles, microwave irradia-
tion, NaHSO4.SiO2 catalyst
The conversion of aldehydes into the corresponding ni-
triles constitutes an important functional group transfor-
mation. Nitriles are very useful starting materials for the
synthesis of various bioactive molecules.2 The former can
be converted to amides, carboxylic acids, amines, ketones
and esters.3 Nitriles can be prepared by dehydration of al-
doximes prepared from the corresponding aldehydes.4
Several one-pot conversion of aldehydes into nitriles us-
ing different chemical reagents have also been reported.5,6
However, most of these methods suffer from some draw-
backs which include use of hazardous and expensive or Table 1 Conversion of aldehydes (R-CHO) into nitriles (R-CN)
commerically nonavailable reagents, long reaction time,
low yields, drastic reaction conditions and tedious work-
up procedure. Two methods of the microwave assisted
rapid conversion of aldehydes into nitriles have also re-
cently been reported.7 The first method utilised formic
acid which is corrosive and may also effect the sensitive
aldehydes.8 The other method used potassium peroxy-
monosulfate which being a versatile oxidant may oxidise
the functional groups present in the molecule.9 Therefore
it is necessary to develop a simple, efficient and practical
method for quick one-pot conversion of aldehydes into the
corresponding nitriles.
In continuation of our work10 on the application of micro-
wave irradiation for synthesis of bioactive molecules we
have recently developed a novel microwave promoted
conversion of aldehydes into nitriles in the presence of sil-
ica gel supported sodium hydrgen sulphate
(NaHSO4.SiO2) catalyst (Scheme 1).
In conclusion, we have developed a simple and efficient
methodology with practical applicability for one-pot con-
version of aldehydes into nitriles in high yields. The con-
version occurs in very short time (1-3 min.). The catalyst
(NaHSO4.SiO2) which has been used here for the first
time for such conversion can easily be prepared from
readily available nonexpensive reagents. The experimen-
tal procedure is environmentally benign.
Scheme 1
Synlett 1999, No. 10, 1569–1570 ISSN 0936-5214 © Thieme Stuttgart · New York

1570
B. Das et al.
LETTER
(3) a) Cohen, M.A.; Sawden, J.; Turner, N.J. Tetrahedron Lett.
1990, 31, 7223. b) Yamada, H. Chimia. 1993, 47, 69.
c) Crossby J.; Moiller, J.; Parratt, J.S.; Turner, N.J. J. Chem.
Soc. Perkin Trans 1. 1994, 1679. d) Luo, F.-T.; Jeevanandam,
A. Tetrahedron Lett. 1998, 39, 9455.
(4) March, J. Advanced Organic Chemistry, John Wiley & Sons,
New York, 1992, pp. 1038-1039 and reference cited therein.
(5) Wang, E.-C.; Lin, G.-J. Tetrahedron Lett. 1998, 36, 4047 and
reference cited therein.
(6) Kamal, A.; Arifuddin, M.; Rao, N.V. Syn. Commun. 1998, 28,
4507 and references cited therein.
(7) a) Feng, J.-C.; Lin, B.; Dai, L.; Bian, N.-S. Syn. Commun.
1998, 28, 3765. b) Bose, D.S.; Narsaiah, A.V. Tetrahedron
Lett. 1998, 39, 6533.
Typical Experimental Procedure
3,4-Dimethoxybenzaldehyde (166 mg, 1 mmol) and
NH2OH.HCl (91 mg, 1.3 mmol) were mixed thoroughly
with NaHSO4-SiO2 catalyst (100 mg, prepared by the re-
ported method11d). The mixture was kept inside a micro-
wave oven (BPL, BMO, 700T, 466 watt) and irradiated
for 1 min. This was removed from the oven, cooled and
shaken with CHCl3 (10 ml). The mixture was filtered and
concentrated. The residue was purified by column chro-
matography over silica gel using EtOAc as eluent to pro-
duce 3,4-dimethoxybenzonitrile (158 mg, 97%).
(8) Sosnovsky, G.; Krogh, J.A.; Umhoefer, S.G. Synthesis 1979,
722.
Acknowledgement
(9) Webb, K.S.; Levy, D. Tetrahedron Lett. 1995, 36, 5117.
(10) a) Das, B.; Madhusudhan, P.; Kashinatham, A. Tetrahedron
Lett. 1998, 39, 431; Bioorg. Med. Chem. Lett. 1998, 8, 1403.
b) Das, B.; Madhusudhan, P.; Venkataiah, B. J. Ind. Chem.
Soc. 1998, 75, 662. c) Das, B.; Venkataiah, B. Syn. Commun.
1999, 29, 863.
(11) a) Nishiguchi, T.; Kamio, C. J. Chem. Soc. Perkin Trans 1.
1989, 707. b) Nishiguchi, T.; Taya, H. J. Chem. Soc. Perkin
Trans 1. 1990, 172. c) Nishiguchi, T.; Kawamine, K.;
Ohtsuka, T. J. Org. Chem. 1992, 57, 312. d) Breton, G.W. J.
Org. Chem. 1997, 62, 8952.
The authors thank CSIR, New Delhi for financial assistance.
References and Notes
(1) Part 4 in the series "Studies on Novel Synthetic
Methodologies", for part 3 see Das, B.; Venkataiah, B.;
Madhusudhan, P. Tetrahedron Lett. 1999 (submitted). IICT
communication No. 4330.
(2) a) Medwid, J.B.; Paul, R.; Baker, J.S.; Brockman, J.A.; Du,
M.T.; Hallett, W.A.; Hanifin, J.W.; Hardy, R.A.; Tarrant,
M.E.; Torley, I.W.; Wrenn, S. J. Med. Chem. 1990, 33, 1230.
b) Diana, G.D.; Cutcliffe, D.; Volkots, D.L.; Mallamo, J.P.;
Bailey, T.R.; Vescio, N.; Oglesby, R.C.; Nitz, T.J.; Wetzel, J.;
Girandu, V.; Pevear, D.C.; Dutko, F.J. J. Med. Chem. 1993,
36, 3240. c) Judkins, B.D.; Allen, D.G.; Cook, T.A.; Evans,
B.; Sardharwala, T.E. Syn. Commun. 1996, 26, 4351. d)
Khanna, I.K.; Weier, R.M.; Yu, Y.; Xu, X.D.; Koszyk, F.J.;
Callins, P.W.; Koboldt, C.M.; Veenhuizen, A.W.; Perkins,
W.E.; Casler, J.J.; Masferrer, J.L.; Zhung, Y.Y.; Gregory,
S.A.; Seibert, K.; Isakson, P.C. J. Med. Chem. 1997, 40, 1634.
Article Identifier:
1437-2096,E;1999,0,10,1569,1570,ftx,en;L11899ST.pdf
Synlett 1999, No. 10, 1569–1570 ISSN 0936-5214 © Thieme Stuttgart · New York