Highly convenient and efficient one-pot conversions of aldehydes into nitriles and ketones into amides using HY-zeolite

Article abstract of DOI:10.1055/s-2002-22701

One-pot conversions of aldehydes into nitriles and ketones into amides have been carried out conveniently and efficiently using HY-zeolite as catalyst. Both microwave irradiation and conventional methods have been studied.

Full text of DOI:10.1055/s-2002-22701

LETTER
625
Highly Convenient and Efficient One-pot Conversions of Aldehydes into
Nitriles and Ketones into Amides Using HY-Zeolite1
Conversions of
Al
.
dehydes into
V
N
itriles and Keton
.
e
s
into
A
mid
N
es . S. Srinivas, E. Bolla Reddy, Biswanath Das*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax +91(40)7173387; E-mail: biswanathdas@yahoo.com
Received 14 January 2002
Abstract: One-pot conversions of aldehydes into nitriles and ke-
tones into amides have been carried out conveniently and efficiently
using HY-zeolite as catalyst. Both microwave irradiation and con-
ventional methods have been studied.
Scheme 1
Key words: aldehydes, ketones, nitriles, amides, HY-zeolite, mi-
crowave irradiation
Several aryl and alkyl aldehydes underwent rapid conver-
sions under microwave irradiation into the corresponding
nitriles in high yields. By the conventional method (by re-
fluxing the reaction mixture) the conversion was complet-
ed within 6–8 hours. The yields of the products were also
high. The mechanism of the reaction is as follows. The re-
action between aldehydes and hydroxylamine hydrochlo-
ride produced first the corresponding aldoximes, which
The conversion of aldehydes into the corresponding ni-
triles is an important transformation which has been ap-
plied to the synthesis of various bioactive molecules.2 The
nitriles are used for the preparation of tetrazole derivatives
as antipicornavirus drugs,2a thiazole analogues as inhibi-
tors of superoxide,2b 1,2-diarylimidazoles as antiinflam-
matory agents,2c and commercially important angiotensin then dehydrated to form the nitriles. The structures of all
1 receptor ligands, losartan and valsartan.2d The transfor-
the products were settled from their analytical and spectral
(IR, 1H NMR and MS) data and by direct comparison with
authentic samples.6d
mations of nitriles to amines, amides, ketones, carboxylic
acids and esters are of considerable importance.3 Nitriles
can be prepared from aldehydes by dehydration of the cor-
responding aldoximes.4 Some one-pot transformations of
aldehydes to nitriles by using various chemical reagents
are also reported.5 However, most of these known meth-
ods suffer from significant draw-backs which include tox-
ic and non-available reagents, harsh reaction conditions,
low yields and long reaction time. A few methods for rap-
id conversion of aldehydes into nitriles are also known.6
One of the methods utilized6a corrosive formic acid which
may affect the sensitive aldehydes7 while the other meth-
od applied6b an oxidant potassium peroxymonosulfate
which may oxidize the functional groups.8 We have also
reported6c,d microwave assisted rapid conversion of alde-
hydes into nitriles using silica gel supported NaHSO4 and
NH4OAc catalysts. However, neither of these catalysts
can be recovered. The first catalyst, which could not be
stored for a long time should be prepared at the time of use
and the second catalyst, which decomposed under micro-
wave irradiation should be used in a larger amount.
The catalyst HY-zeolite was also utilized for one-pot con-
version of ketones into amides which is also an useful
transformation for the synthesis of bioactive compounds9
as well as for the commercial production of polyamides
such as Nylon 6.10 The ketones can be converted into ke-
toximes which can then be transformed to amides by
Beckmann rearrangement.11 Some one-pot conversions of
ketones into amides are also known.12 However, these
methods are associated with some drawbacks such as uses
of corrosive reagents like concentrated H2SO4 and
HCOOH,12a–c low yields12d (< 17% using Mexican Bento-
nite under microwave irradiation) and tedious work up
procedure12e (using hydroxylamine-O-sulfonic acid and
SiO2 in presence of water under microwave irradiation).
The processess using concentrated acids may also affect
the acid sensitive functionalities. Previously we used12f
sodium hydrogen sulfate adsorbed on silica gel as catalyst
for one-pot conversion of ketones into amides but the cat-
alyst has to be prepared at the time of use. The recovery of
catalyst is also a problem in the reported methods.
Recently we have developed a highly convenient and ef-
ficient practical method for one-pot conversion of alde-
hydes into nitriles by treatment with hydroxylamine
hydrochloride using HY-zeolite as catalyst. Both the mi-
crowave irradiation and conventional methods have been
studied (Scheme 1, Table 1).
Recently we have observed that HY-zeolite can efficient-
ly catalyze the reaction of ketones with hydroxylamine
hydrochloride to form amides (Scheme 2, Table 2).
Synlett 2002, No. 4, 29 03 2002. Article Identifier:
1437-2096,E;2002,0,04,0625,0627,ftx,en;D00902ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214
Scheme 2

626
K. V. N. S. Srinivas et al.
LETTER
Table 1 Conversion of Aldehydes (R-CHO) into Nitriles (R-CN)
Time
Isolated Yield (%) of Nitriles
Entry
1
R
M.W. Irradiation (min)
Conventional (h)
M.W. Irradiation
Conventional
C6H5
1
1
1
1
1
1
1
1
1
2
2
2
7
8
8
8
7
7
7
8
6
8
7
8
94
92
95
96
95
94
92
90
95
84
86
87
74
70
77
79
78
72
71
70
79
68
67
69
2
3-(MeO)C6H4
4-(HO)C6H4
4-(NO2)C6H4
3-(MeO), 4(HO)C6H3
3,4-(MeO)2C6H3
3,4-(CH2O2)C6H3
2,4,6-(MeO)3C6H2
3,4,5-(MeO)3C6H2
C6H5CH=CH
C7H15
3
4
5
6
7
8
9
10
11
12
C9H19
Table 2 Conversion of Ketones (R1COR2) into Amides (R1NHCOR2)
Time
Isolated Yield (%) of Amides
Entry
R1
R2
M.W. Irradiation Conventional
M.W. Irradiation Conventional
(min)
(h)
1
2
3
4
5
6
7
8
C6H5
CH3
C6H5
CH3
CH3
CH3
CH3
CH3
2
9
94
95
82
95
92
86
94
95
62
65
56
67
61
58
60
64
C6H5
2.5
3
10
11
9
4-(HO)C6H4
4-(MeO)C6H4
4-(Cl)C6H4
4-(Br)C6H4
4-(Me)C6H4
-(CH2)5-
2
2.5
2.5
2
10
11
9
2
9
Several ketones were readily converted into amides by In conclusion, we have developed a novel and highly con-
microwave irradiation as well as by refluxing the reaction venient method for one-pot conversions of aldehydes into
mixture. Cyclohexanone was converted into caprolactam nitriles and ketones into amides using HY-zeolite as cata-
(Table 2, entry 8), an industrially important product. The lyst. The catalyst can efficiently be utilized for both the
mechanism of the reaction is as follows. The ketones first microwave irradiation and conventional methods. The
reacted with hydroxylamine hydrochloride to form ke- yields of the products produced by microwave irradiation
toximes, which then underwent Beckmann rearrangement are very high and the time required for conversions is very
to form the amides. The major products were produced by short. The great advantage of the present method is that
migration of the aryl groups (except entry 8) of the inter- the catalyst is commercially available and can easily be
mediate ketoximes during rearrangement but the amides recovered and reused.
formed by alkyl migration also were the minor products
(yield < 5%) in each case. The structures of the products
1
were derived from their analytical and spectral (IR, H
NMR and MS) data and by comparison with authentic
samples.12f
A) Conversion of Aldehydes into Nitriles
1) Microwave Irradiation: 3,4,5-Trimethoxybenzaldehyde (196
mg, 1 mmol) and NH2OH HCl (91 mg, 1.3 mmol) were mixed thor-
oughly with HY-zeolite (PQ Corporation, USA) (25 mg). The mix-
Synlett 2002, No. 4, 625–627 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Conversions of Aldehydes into Nitriles and Ketones into Amides
627
ture was taken in a test tube, placed in an alumina bath inside a
microwave oven (BPL, BMO, 700T, 466 watt) and irradiated for 1
min. This was removed from the oven, cooled and shaken with
EtOAc (10 mL). After filtration the filtrate was concentrated and the
residue was purified by column chromatography over silica gel us-
ing EtOAc as eluent to afford 3,4,5-trimethoxybenzonitrile (185
mg, 96%).
Acknowledgement
The authors thank CSIR, New Delhi for financial assistance.
References
(1) (a) Part 13 in the series, „Studies on Novel Synthetic
Methodologies“, for part 12 see: Ravindranath, N.; Ramesh,
C.; Das, B. Synlett 2002, submitted. (b) IICT
Communication No. 4325.
Using the recovered zeolite a separate experiment with the similar
quantities of 3,4,5-trimethoxybenzaldehyde and NH2OH HCl was
carried out under the similar conditions. The product, 3,4,5-tri-
methoxybenzonitrile was obtained in similar yield.
(2) (a) Diana, G. D.; Cutcliffe, D.; Volkots, D. L.; Mallamo, J.
P.; Bailey, T. R.; Vescio, N.; Oglesley, R. C.; Nitz, T. J.;
Wetzel, J.; Girandu, V.; Pevear, D. C.; Dutko, F. J. J. Med.
Chem. 1993, 36, 3240. (b) Chihiro, M.; Nagamoto, H.;
Takemura, I.; Kitano, K.; Komatsu, H.; Sekiguchi, K.;
Tabusa, F.; Mori, T.; Tominnaga, M.; Yabuuchi, Y. J. Med.
Chem. 1995, 38, 353. (c) Fabiani, M. E. Drug News
Perspect. 1999, 12, 207. (d) Khanna, I. K.; Weier, R. M.;
Yu, Y.; Xu, X. D.; Koszyk, F. J.; Callins, P. W.; Kobaldt, 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.
2) Conventional Method: 3,4,5-Trimethoxybenzaldehyde (588
mg, 3 mmol) and NH2OH HCl (365 mg, 4 mmol) were taken in tol-
uene (25 mL). HY-zeolite (60 mg) was added. The mixture was re-
fluxed for 6 h under N2 atmosphere and filtered. The concentrated
filtrate was subjected to column chromatography over silica gel us-
ing EtOAc as eluent to give 3,4,5-trimethoxybenzonitrile (457 mg,
79%).
The recovered zeolite was again used to get the product in similar
yield.
B) Conversion of Ketones into Amides
(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 and
Sons: New York, 1992, 1038; and references cited therein.
(5) Wang, E. C.; Lin, G.-J. Tetrahedron Lett. 1998, 36, 4047;
and references cited therein.
1) Microwave Irradiation: Benzophenone (182 mg, 1 mmol) and
NH2OH HCl (104 mg, 1.5 mmol) were mixed with HY-zeolite (25
mg). The mixture was taken in a test tube, kept in an alumina bath
inside the microwave oven and irradiated for 2 min. The mixture
was cooled, shaken with EtOAc (10 mL) and filtered. The filtrate
was purified over silica gel using hexane–EtOAc (1:1) as eluent to
afford benzanilide (187 mg, 95%).
The recovered zeolite when reused to conduct the conversion of
benzophenone into benzanilide under similar reaction conditions
the yield of the product was same.
(6) (a) Feng, J.-C.; Lin, G.; Dia, L.; Bian, N.-S. Synth. Commun.
1998, 28, 3765. (b) Bose, D. S.; Narsaiah, A. V.
Tetrahedron Lett. 1998, 39, 6533. (c) Das, B.;
2) Conventional Method: Benzophenone (546 mg, 3 mmol) and
NH2OH HCl (312 mg, 4.5 mmol) were taken in toluene (25 mL).
HY-zeolite (60 mg) was added. The mixture was refluxed under N2
atmosphere for 10 h. After filtration the filtrate was purified by col-
umn chromatography over silica gel using hexane–EtOAc (1:1) as
eluent to give benzanilide, 384 mg, 65%).
Madhusudhan, P.; Venkataiah, B. Synlett 1999, 1569.
(d) Das, B.; Ramesh, C.; Madhusudhan, P. Synlett 2000,
1599.
(7) Sosnovsky, G.; Krogh, J. A.; Umhoefer, S. G. Synthesis
1979, 722.
(8) Webb, K. S.; Levy, D. Tetrahedron Lett. 1995, 36, 5117.
(9) Marouka, K.; Yamamoto, H. In Comprehensive Organic
Synthesis, Vol. 6; Trost, B. M., Ed.; Pergamon Press:
Oxford, 1991, 763.
The recovered zeolite was reused to get the similar yield of the prod-
uct.
(10) (a) Olah, G. A.; Fung, A. P. Synthesis 1979, 537.
(b) Gawly, R. E. Org. React. 1988, 35, 1.
(11) Meshram, H. M. Synth. Commun. 1990, 20, 3253; and
references cited therein.
Spectroscopic Data of some Nitriles and Amides are given be-
low:
3,4,5-Trimethoxybenzonitrile: IR (KBr): 2227, 1592, 1483, 1464,
1134 cm–1; 1H NMR (CDCl3): = 6.89 (2 H, s, H-2, H-6), 3.86 (3
H, s, OMe), 3.82 (6 H, m, 2 OMe); MS: m/z (%) = 193 (100) [M+],
178 (62), 150 (46), 132 (24).
(12) (a) Novotny, A. U.S. Patent 2569114, 1951; Chem. Abstr.
1952, 46, 5078. (b) Novotny, A. U.S. Patent 2579851, 1951;
Chem. Abstr. 1952, 46, 6668. (c) Barnett, C.; Cohn, I. M.;
Lincoln, J. U.S. Patent 2754298, 1956; Chem. Abstr. 1957,
51, 2853. (d) Delgado, F.; Cano, A. C.; Garcia, O.;
Alvarado, J.; Velasco, L.; Alvarez, C.; Rudler, H. Synth.
Commun. 1992, 22, 2125. (e) Lavrent, A.; Jacquault, P.; Di
Martino, J.-L.; Hamelin, J. J. Chem. Soc., Chem. Commun.
1995, 1101. (f) Das, B.; Ravindranath, N.; Venkataiah, B.;
Madhusudhan, P. J. Chem. Res., Synop. 2000, 482.
1
Octanenitrile: IR (KBr): 2232, 1446, 1362, 1224 cm–1; H NMR
(CDCl3): = 2.36 (2 H, t, J = 7.0 Hz, H2-2), 1.76–1.57 (2 H, m, H2-
3), 1.43–1.12 (8 H, m, H2-4 to H2-7), 0.94 (3 H, t, J = 7.0 Hz, Me);
MS: m/z (%) = 125 (25) [M+], 79 (6), 51 (4).
1
Benzanilide: IR (KBr): 3362, 1658, 1630, 1494, 1408 cm–1; H
NMR (CD3OD): = 8.04 (1 H, brs, -NH-), 7.84–7.12 (10 H, m, Ar-
H); MS: m/z (%) = 197 (32) [M+], 105 (100), 77 (48).
1
Caprolactum: IR (KBr): 3477, 1643, 1592, 1439, 1366 cm–1; H
NMR (CDCl3): = 3.21 (1 H, m, one of H2-6), 2.44–2.39 (2 H, m,
one of H2-2, one of H2-6), 2.19 (1 H, m, one of H2-2), 1.78–1.58 (6
H, m, 3 -CH2); MS: m/z (%) = 113 (95), 98 (24), 80 (26), 72 (26).
Synlett 2002, No. 4, 625–627 ISSN 0936-5214 © Thieme Stuttgart · New York