Efficient and Rapid One-pot Conversions of Aldehydes into Nitriles and Ketones into Amides Using Silica Chloride under Microwave Irradiation

Article abstract of DOI:10.1246/cl.2003.738

Under solvent free conditions, several aldehydes and ketones were efficiently and rapidly converted into the corresponding nitriles and amides respectively by treatment with hydroxylamine hydrochloride under microwave irradiation using silica chloride as catalyst. The yields of the products were very high and the time required for their preparation was very short compared to conventional heating experiments.

Full text of DOI:10.1246/cl.2003.738

738
Chemistry Letters Vol.32, No.8 (2003)
Efficient and Rapid One-pot Conversions
of Aldehydes into Nitriles and Ketones into Amides
Using Silica Chloride under Microwave Irradiation1
K. V. N. S. Srinivas, I. Mahender, and Biswanath Dasꢀ
Organic Chemistry Division-I,
Indian Institute of Chemical Technology, Hyderabad 500 007, India
(Received April 16, 2003; CL-030326)
Under solvent free conditions, several aldehydes and ke-
give high yield (65%) of benzonitrile. Thus there is a need to
develop improved methods for rapid one-pot conversions of al-
dehydes into nitriles and ketones into amides using easily avail-
able catalysts. Here we describe our recent work on such con-
versions in the presence of silica chloride (silica gel treated18
with thionyl chloride) under microwave irradiation.
tones were efficiently and rapidly converted into the corre-
sponding nitriles and amides respectively by treatment with hy-
droxylamine hydrochloride under microwave irradiation using
silica chloride as catalyst. The yields of the products were very
high and the time required for their preparation was very short
compared to conventional heating experiments.
In continuation of our research19 on eco-friendly reactions
we have observed that aldehydes and ketones can rapidly be
converted into nitriles and amides respectively by treatment
with hydroxylamine hydrochloride under microwave irradiation
in the presence of silica chloride as catalyst.
Various aldehydes were readily converted into the corre-
sponding nitriles (Table 1), and ketones into amides (Table 2).
Cyclohexanone was transformed to the industrially important
compound, caprolactam (Table 2, Entry 8). The structures of
all the products were established from their analytical and spec-
tral data. The products were formed in very high yields within a
very short period of time. The experimental procedure is very
simple and the conversions occurred under solvent free condi-
tions.20 The catalyst, silica chloride, can easily be prepared18
from the readily available inexpensive reagents, thionyl chlo-
ride and silica gel (100-200 mesh). As it is a heterogenous cat-
alyst it can easily be removed by filtration from the reaction
mixture.
The transformations of aldehydes to nitriles,2 and ketones
to amides3 are highly useful for the synthesis of bioactive as
well as commercially important compounds. Nitriles are em-
ployed for the preparations of anti-picornavirous and anti-in-
flammatory drugs2a,b and angiotension receptor ligands like los-
artan and valsartan.2c Amides are also used in medicine as
febrifuge4 and the cyclic derivatives for the preparation of in-
dustrially useful polymeric compounds like Nylon 6.3b Nitriles
can be converted into amines, amides, ketones, acids and esters
while amides into nitriles, acids, esters, and amines.4,5 These
conversions are of considerable importance in synthetic organic
chemistry. Nitriles and amides can be prepared from the corre-
sponding aldehydes and ketones respectively. The aldehydes
can be converted6 into aldoximes which undergo dehydration
to form nitriles. The ketones, on the other hand, can be convert-
ed7 into ketoximes which under Beckmann rearrangement can
produce amides. A limited numbers of microwave assisted rapid
one-pot conversions of aldehydes into nitriles, and ketones into
amides are also known but most of these methods are associated
with certain drawbacks. As for example, for conversion of alde-
hydes into nitriles under microwave irradiation reagents like
corrosive formic acid8 (which may affect the sensitive alde-
hydes)9 oxidant potassium peroxymonosulfate10 (which may
oxidise the functional groups)11 and hygroscopic ammonium
acetate12 (which may itself decompose under microwaves) have
been used. Mexican Bentonite13 which was applied for micro-
wave assisted conversion of ketones into amides afforded very
low yields of the products while hydroxylamine-o-sulfonic
acid14 required tedious work up procedure. Silica-supported so-
dium hydrogen sulfate (NaHSO4ꢁSiO2)15 and HY-Zeolite16
have also recently been employed for both the conversions of
aldehydes into nitriles, and ketones into amides under micro-
wave irradiation. However, the first catalyst should be freshly
prepared at the time of its use and properly activated keeping
in oven to make the conversions efficient while the second cat-
alyst is not a common desk reagent in the laboratory of organic
chemist. An another microwave assisted method17 for direct
conversion of aldehydes into nitriles used N-methyl pyrrolidone
as a solvent without any catalyst but benzaldehye itself did not
.
NH2OH HCl
Silica chloride
R-CN
R-CHO
R1
M. W. (1-2 min)
(87-96%)
.
NH2OH HCl
Silica chloride
R1-NHCO-R2
(86-93%)
C=O
M. W. (2-3.5 min)
R2
The mechanism of the formation of nitriles from aldehydes
may be proposed as follows. The reaction between aldehydes
and hydroxylamine hydrochloride produced first the corre-
sponding aldoximes which then underwent dehydration to af-
ford the nitriles. Similarly, for the conversion of ketones into
amides the former first reacted with hydroxylamine hydrochlo-
ride to form ketoximes which subsequently under Beckmann re-
arrangement yielded the amides.
In conclusion, we have developed a novel, simple and effi-
cient method for one-pot conversions of aldehydes into nitriles,
and ketones into amides using inexpensive silica chloride as cat-
alyst under microwave irradiation. The yields of the products
are very high and the time required for their preparation is very
short. The process is environmentally benign.
Copyright ꢀ 2003The Chemical Society of Japan

Chemistry Letters Vol.32, No.8 (2003)
739
Table 1. Conversion of Aldehydes (R-CHO) into Nitriles (R-CN)
Entry
R
M.W.
Conven-
tional
Isolated Yield/%
Conven-
Time/min
Time/h
M.W.
tional
72
73
70
76
78
72
73
78
1.
2.
3.
4.
5.
6.
7.
8.
9.
C6H5
4-(OH)C6H4
1
8
9
9
8
8.5
7
8
7.5
7.5
8.5
7
92
94
91
94
96
95
92
94
9376
90
87
89
1.5
1.5
1
1.5
1
1
1
1
2
4-(NO2)C6H4
3-(MeO)C6H4
3-(MeO), 4-(OH)C6H3
3,4-(MeO)2C6H3
3,4-(CH2O2)C6H3
3,4,5-(MeO)3C6H2
2,4,6-(MeO)3C6H2
C6H5CH=CH
C7H15
10.
11.
12.
68
64
67
2
2
C9H19
8
Table 2. Conversion of Ketones (R1COR2) into Amides
13F. Delgado, A. C. Cano, O. Garcia, J. Alvarado, L. Velasco, C. Alvarez,
and H. Rudler, Synth. Commun., 22, 2125 (1992).
14 A. Lavrent, P. Jacquault, J.-L. Di Martino, and J. Hamelin, J. Chem.
Soc., Chem. Commun., 1995, 1101.
15 B. Das, P. Madhusudhan, and B. Venkataiah, Synlett, 1999, 1569.
16 K. V. N. S. Srinivas, E. B. Reddy, and B. Das, Synlett, 2002, 625.
17 H. Kashima, M. Hamada, M. Tani, S. Iwasaki, and F. Sato, Heterocyles,
57, 2145 (2002).
18 H. Firouzabadi, N. Iranpoor, B. Karimi, and H. Hazarkhani, Synlett,
2000, 263.
19 a) B. Das, A. Kashinatham, and P. Madhusudhan, Tetrahedron Lett., 38,
7457 (1997). b) B. Das, P. Madhusudhan, and A. Kashinatham, Tetrahe-
dron Lett., 39, 431 (1998). c) B. Das and P. Madhusudhan, Tetrahedron,
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(R1NHCOR2)
Entry R1
R2
M.W. Conven- Isolated Yield/%
tional
Time/min Time/h M.W. Conven-
tional
1. C6H5
2. C6H5
3. 4-(Cl)C6H4
4. 4-(Br)C6H4
5. 4-(MeO)C6H4 CH3
6. 4-(Me)C6H4 CH3
7. 4-(OH)C6H4 CH3
8. -(CH2)5-
CH3
C6H5
CH3
CH3
39.5
310
310.5
311
2
2
3.5
2.5
90
9637
89
86
10
10.5
11
9
63
62
64
93
91
92
91
66
60
59
62
20 a) Typical procedure for conversion of aldehydes into nitriles:
i) Microwave irradiation: 3,4-Dimethoxybenzaldehyde (166 mg,
1 mmol) and NH2OHꢁHCl (91 mg, 1.3mmol) were mixed thoroughly
with silica chloride (100 mg). The mixture was taken in a test tube, kept
in an alumina bath inside a microwave oven (BPL, BMO, 700 T, 466
watt) and irradiated for 1 min at 105 ꢂC maintaining 70% efficiency of
the oven. The mixture was removed from the oven, cooled, shaken with
EtOAc (10 mL) and filtered. The filtrate was concentrated and purified
by column chromatography over silica gel using hexane–EtOAc (1:1)
as eluent to produce 3,4-dimethoxybenzonitrile (155 mg, 95%), mp 63-
The authors thank CSIR, New Delhi, for financial assis-
tance and Dr. J. S. Yadav for encouragement.
References and Notes
1
2
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65 ꢂC, IR: nmax (KBr) 2931, 2223, 2026 cmꢃ1
;
1H NMR
(CDCl3+DMSO-d6): d 7.25 (1H, dd, J ¼ 9:0, 1.5 Hz, H-6), 7.06 (1H,
d, J ¼ 1:6 Hz, H-2), 6.87 (1H, d, J ¼ 9:0 Hz, H-5), 3.93, 3.89 (3H each,
s, 2x-OMe); MS: m=z 163(M þ), 148, 120, 102. ii) Conventional meth-
od: 3,4-Dimethoxybenzaldehyde (166 mg, 1 mmol) and NH2OHꢁHCl
(91 mg, 1.3mmol) were taken in acetonitrile (15 mL). Silica chloride
(100 mg) was added. The mixture was refluxed under N2 atmosphere
for 7 h. After filtration the filtrate was purified by column chromatogra-
phy over silica gel using hexane–EtOAc (1:1) as eluent to give 3,4-dime-
thoxybenzonitrile. (117 mg, 72%). b) Typical procedure for conversion
of ketones into amides: i) Microwave irradiation: 4-Hydroxyaceto-
phenone (136 mg, 1 mmol) and NH2OHꢁHCl (104 mg, 1.5 mmol) were
mixed with silica chloride (100 mg). The mixture was taken in a test
tube, placed in an alumina bath inside the microwave oven and irradiated
for 3.5 min at 160 ꢂC maintaining 70% efficiency of the oven. The mix-
ture was cooled and shaken with EtOAc (10 mL). After filtration the fil-
trate was concentrated and the residue was purified by column chroma-
tography over silica gel using hexane-EtOAc (1:1) as eluent to afford 4-
hydroxyacetanilide (139 mg, 92%), m.p. 167-168 ꢂC, IR: nmax (KBr)
3a) K. Marouka and H. Yamamoto, in ‘‘Comprehensive Organic Synthe-
sis,’’ B. M. Trost, Pergamon Press, Oxford (1991), Vol. 6, p 763. b) G. A.
Olah and A. P. Fung, Synthesis, 1979, 537.
4
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York (1992), p 1038, and references cited therein.
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therein.
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(1998).
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5
6
7
8
9
3325, 1655, 1600, 1562 cmꢃ1 1H NMR (CDCl3+DMSO-d6): d 7.34
;
(2H, d, J ¼ 8:0 Hz, H-2, H-6), 6.62 (2H, d, J ¼ 8:0 Hz, H-3, H-5),
2.03(3H, s, -Me); MS: m=z 151 (Mþ), 136, 108. ii) Conventional meth-
od: 4-Hydroxyacetophenone (136 mg, 1 mmol) and NH2OHꢁHCl
(104 mg, 1.5 mmol) were taken in acetonitrile (15 mL). Silica chloride
(100 mg) was added. The mixture was refluxed under N2 atmosphere
for 11 h. After filtration the filtrate was purified by column chromatogra-
phy over silica gel using hexane–EtOAc (1:1) as eluent to give 4-hydrox-
yacetanilide (89 mg, 59%).
10 D. S. Bose and A. V. Narsaiah, Tetrahedron Lett., 39, 6533 (1998).
11 K. S. Webb and D. Levy, Tetrahedron Lett., 6, 5117 (1995).
12 B. Das, C. Ramesh, and P. Madhusudhan, Synlett, 2000, 1599.
Published on the web (Advance View) July 21, 2003; DOI 10.1246/cl.2003.738