ZnO/CH3COCl: A new and highly efficient catalyst for dehydration of aldoximes into nitriles under solvent-free condition

Article abstract of DOI:10.1055/s-2005-861826

A rapid and efficient synthesis of nitriles via dehydration from the corresponding aldoximes has been carried out in the presence of ZnO/CH ₃COCl as catalyst under solvent free conditions in 83-95% yields. The zinc oxide (ZnO) powder can be re-used upto three times after simple washing with CH₂Cl₂.

Full text of DOI:10.1055/s-2005-861826

PAPER
787
ZnO/CH3COCl: A New and Highly Efficient Catalyst for Dehydration of
Aldoximes into Nitriles Under Solvent-Free Condition
New
a
nd Highly Effici
o
ent Catalyst
for
D
ehydra
t
a
ion of Aldoximes
Hinto Nitriles osseini Sarvari*
Department of Chemistry, Faculty of Science, Shiraz University, Shiraz 71454, Iran
E-mail: hossaini@chem.susc.ac.ir
Received 27 September 2004; revised 29 November 2004
lysts are often comparable to those of enzymes.20 Several
classes of solids have commonly been used for surface or-
ganic chemistry including aluminas, silica gels, and clays.
Zinc oxide (ZnO) is certainly one of the most interesting
of these solids because it has surface properties that sug-
gest that a very rich organic chemistry may occur there.
Abstract: A rapid and efficient synthesis of nitriles via dehydration
from the corresponding aldoximes has been carried out in the pres-
ence of ZnO/CH3COCl as catalyst under solvent free conditions in
83–95% yields. The zinc oxide (ZnO) powder can be re-used upto
three times after simple washing with CH2Cl2.
Keyword: zinc oxide, acetyl chloride, dehydration, aldoximes, ni-
triles
We have recently reported that zinc oxide (ZnO) was an
effective catalyst for Beckmann rearrangement21 and
Friedel–Crafts acylation.22 In this pursuit, and during the
course of our studies aimed at developing solvent-free
procedures,23 we reasoned that use of an immobilized sys-
tem, via the application of solid phase reagents, could lead
to a more efficient and cleaner route to this important
transformation. So, after several trials, we found that com-
bination of ZnO and acetyl chloride accelerated the cata-
lytic dehydration of aldoximes into nitriles dramatically.
The effect of the amounts of ZnO and acetyl chloride in
dehydration of 4-methoxybenzaldoxime is summarized in
Table 1.
The development of new methods for the synthesis of ar-
omatic nitriles is important in organic synthesis, since ni-
triles are useful as intermediates for the preparation of
amines,1 and other functional group moieties.2 There are
many reports on the conversion of oximes,3,4 or oxime
derivatives5–7 to nitriles. Numerous reagents, e.g. Burgess
reagent,8 PPh3/CCl4,9 alkyl cyanoformates,10 AlI3,11
dichlorocarbene/reverse micelle,12 di-2-pyridylsulfite,13
InCl3,14 TiCl3(OTf),15 cytochrome P450,16 silica gel,17 2-
chloro-1-methylpyridinium iodide,18 nickel/zinc,19 etc.
have been developed. Many reagents, however, may have
some limitations, such as low yields, use of strong acids/
or bases or oxidants, harsh reaction conditions, use of ex-
pensive or less readily available reagents, tedious workup
procedure, or limited substrate scope. Therefore there is
still a need to develop a new, mild, general, solvent free
and rapid method for this transformation.
According to Table 1, while no yields were obtained in
the presence of zinc oxide or CH3COCl alone (entries 5
and 6), a 10% yield of 4-methoxybenzonitrile was ob-
tained when combining 1 mmol of ZnO and 1 mmol of
CH3COCl (entry 7). The yield was improved when 3
mmol of ZnO and 3 mmol of CH3COCl were used (entry
10). We also examined the effects of a solvent in this re-
action. Only a trace amount of the product was detected in
CH2Cl2 (entry 11).
Synthetic chemists continue to explore new methods to
carry out chemical transformations. One of these new
methods is to run reactions on the surface of solids. As the
surfaces have properties that are not duplicated in the so-
lution or gas phase, entirely new chemistry may occur.
Even in the absence of new chemistry, a surface reaction
may be more desirable than a solution counterpart, be-
cause the reaction is more convenient to run, or a high
yield of product is attained. For these reasons, synthetic
surface organic chemistry is a rapidly growing field of
study. Experiments using these solid phase catalysts gen-
erally have the following features: i) it is often easy to iso-
late the products and to separate the catalyst; ii)
comparing the reaction conditions with those of related
homogeneous reactions, they are so mild that a high yield
of specific products and suppression of by-product forma-
tion are expected; iii) selectivity and activity of the cata-
Therefore, in order to determine the scope and efficiency
of this procedure, we prepared a number of aldoximes and
treated them with ZnO/CH3COCl (Scheme 1). The prepa-
ration of the aldoximes used as starting materials was car-
ried out by simple condensation between hydroxylamine
hydrochloride and the desired aldehyde in the presence of
zinc oxide (ZnO) as catalyst at 60 °C in an oil bath for a
few min. Elimination of the aldoximes could be signifi-
cantly improved by using ZnO/CH3COCl at 80 °C for 10–
40 min. In a typical experiment, 4-methoxybenzaldoxime
(1 mmol) was added to a mixture of ZnO/CH3COCl (3:3
mmol). The mixture was kept at 80 °C in an oil bath with
occasional shaking for a certain period of time until the re-
action was completed. The product was isolated by simple
extraction of the solid mass by CH2Cl2 followed by usual
workup.
SYNTHESIS 2005, No. 5, pp 0787–0790
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Advanced online publication: 14.02.2005
DOI: 10.1055/s-2005-861826; Art ID: Z18204SS
© Georg Thieme Verlag Stuttgart · New York

788
M. Hosseini Sarvari
PAPER
NOH
H
Table 1 Dehydration of 4-Methoxybenzaldoxime (1 mmol) into 4-
Methoxybenzonitrile under Various Reaction Conditions
O
ZnO
ZnO/CH3COCl
80 °C
R
N
R
R
H
NH2OH⋅HCl
60 °C
CH=NOH
CN
MeO
MeO
Scheme 1
Entry Conditions
Time Yielda
(min) (%)
The results of dehydration of aldoximes into nitriles are
collected in Table 2. Both aromatic and aliphatic al-
doximes reacted very rapidly within 10–40 min. The reac-
tions are remarkably clean, and no chromatographic
separation is necessary to get the spectra-pure com-
pounds. This procedure is good enough for the dehydra-
tion of heterocyclic aldoximes such as thiophene-2-
carbaldehyde oxime (entry 14) producing the correspond-
ing thiophene-2-carbonitrile in excellent yield.
1
2
H2SO4/SiO2/MW
3
8924a
24 6025
6626
t-BuMe2SiCl/imidazol/DMF/140 °C
DBU/MW
3
6
4
Envirocat EPZG/100 °C
1440 923
60 Trace
60 70b
60 10
5
CH3COCl (3 mmol), 80 °C
6
ZnO (3 mmol)21
Furthermore, catalytic activity of the recovered catalyst
(ZnO) was examined. As shown in Table 3, the yields of
4-methoxybenzonitrile in second and third uses of the cat-
alyst were almost same as that in the first use. In every
case almost > 85% of the ZnO was easily recovered from
reaction mixture by simple washing with CH2Cl2.
7
ZnO (1 mmol):CH3COCl (1 mmol), 80 °C
ZnO (1 mmol):CH3COCl (3 mmol), 80 °C
ZnO (3 mmol):CH3COCl (1 mmol), 80 °C
ZnO (3 mmol):CH3COCl (3 mmol), 80 °C
8
60 10
9
40 63
10
11
15 95
No attempt has been made to probe the mechanism of the
reaction. Mechanistically, the aldoximes 1 undergo its re-
action with CH3COCl in the presence of ZnO to generate
compound 2, as the key intermediate. Then, compound 2
subsequently undergoes elimination thermally to produce
nitrile 3 with the liberation of CH3CO2H (Scheme 2).
ZnO (3 mmol):CH3COCl (3 mmol), CH2Cl2,
reflux
60 Trace
a Isolated yields.
b The corresponding amide (4-methoxybenzamide) was prepared (see
ref.21).
Table 2 ZnO/CH3COCl Catalyzed Nitriles Preparation from Aldoximes
Entry
1
Substrate
Product
Time (min)
20
Yieldsa (%)
92
Mp or bp (°C)/Torr (lit.)
187/637 (190/760)24b
CN
CHNOH
2
30
95
96 (97)27
CHNOH
OH
CN
OH
3
4
30
20
93
90
80 (83)28
HO
HO
CHNOH
HO
CN
CN
112 (112)27
CHNOH
CHNOH
HO
5
15
95
60 (61)24b
CN
MeO
Me
MeO
Me
6
7
20
20
93
95
210/637 (213/760)28
216/637 (218/760)24b
CHNOH
CHNOH
CN
CN
Me
Me
8
CN
CN
35
87
148 (147)24b
CHNOH
CHNOH
O2N
O2N
O2N
O2N
9
40
15
84
90
117 (117)28
42 (42)27
10
CHNOH
Cl
CN
Cl
11
12
15
10
92
95
90 (91)24b
CHNOH
CN
Cl
Cl
Cl
140 (145)24b
Cl
CHNOH
Cl
CN
Cl
Synthesis 2005, No. 5, 787–790 © Thieme Stuttgart · New York

PAPER
New and Highly Efficient Catalyst for Dehydration of Aldoximes into Nitriles
789
Table 2 ZnO/CH3COCl Catalyzed Nitriles Preparation from Aldoximes (continued)
Entry
13
Substrate
Product
Time (min)
20
Yieldsa (%)
90
Mp or bp (°C)/Torr (lit.)
48 (53)28
H2N
CHNOH
H2N
CN
14
15
30
25
83
84
190/637 (192/760)24b
47 (50)28
CHNOH
CHNOH
CN
S
S
CN
N
N
16
17
30
20
87
91
160 (162)28
34 (35)27
HONHC
CHNOH
NC
CN
CHNOH
CN
Me
18
19
30
35
90
90
210 (210)23d
Me
CHNOH
CN
CN
260/637 (263.8/760)28
CHNOH
20
21
CH3CH2CH2CHNOH
CH2(CH2)3CHNOH
CH3CH2CH2CN
CH2(CH2)3CN
30
30
85
85
110/637 (118/760)28
138 (141)28
a Yields of the isolated compounds.
Table 3 Reuse of ZnO
200 stationary phase and N2 as the carrier gas. IR spectra were re-
corded on a Perkins Elmer 781 and on Impact 400 D Nickolet FTIR
spectrophotometers. NMR spectra were recorded on a Bruker DPX
250 MHz instrument.
CH=NOH
ZnO/CH3COCl
CN
MeO
80 °C
Yield (%)
95
MeO
Number of use
Recovery of ZnO
Conversion of Aldoximes into Nitriles (Table 2); General Proce-
dure
1
2
3
94
87
85
To a mixture of CH3COCl (3 mmol, 0.08 mL) and ZnO (3 mmol,
0.24 g) an aldoxime (1 mmol) was added and then the reaction mix-
ture was heated in an oil bath at 80 °C and stirred with a magnetic
stirrer. The progress of the reaction was monitored by TLC. After
the reaction was complete, CH2Cl2 was added to the reaction mix-
ture and zinc oxide (ZnO) was removed by filtration. It was then
washed with water (2 × 10 mL), saturated solution of NaHCO3, and
dried over anhyd Na2SO4. After removal of the solvent, the pure
product was obtained. This was further purified by recrystallization
with suitable solvent (Et2O or CHCl3). The structure of the products
was confirmed by 1H NMR, IR and comparison with authentic sam-
ples obtained commercially or prepared by reported methods.
90
87
R
N
R
O
ZnO
ZnO/CH3COCl
NOH
RCN + CH3CO2H
H
O
H
3
1
2
Scheme 2
Preparation of Aldoximes in the Presence of Zinc Oxide (ZnO);
General Procedure
Hydroxylamine hydrochloride (0.3 g, 4.3 mmol) was added to a
In conclusion, we have described a novel and highly effi-
cient solvent-free protocol for dehydration of aldoximes stirred mixture of ZnO (1 mmol, 0.08 g) and aldehydes (1 mmol) in
an oil bath at 60 °C. The progress of the reaction was monitored by
into nitriles using non-toxic and inexpensive ZnO powder.
TLC. The reaction mixture was washed with CH2Cl2 (2 × 10 mL)
and water (2 × 50 mL). The organic layer was dried over Na2SO4
and evaporated to give the pure aldoximes. This was further purified
by recrystallization with suitable solvent (Et2O or CHCl3). The
products were identified by comparison of their physical data with
those prepared in accordance with the literature procedures.
The advantages of this environmentally benign and safe
protocol include a simple reaction set-up not requiring
specialized equipment, very mild reaction conditions,
high product yields, very short reaction times, reusable
catalyst, and the limitation of solvents.
Chemicals were purchased from Fluka, Merck, B. D. H. and Aldrich
Chemical Companies. Progress of the reactions was followed by
TLC using silica gel polygrams SIL G/UV 254 plates or by GC us-
ing a Shimadzu gas chromatograph GC-14A, equipped with a flame
ionization detector and a 3 m length glass column packed with DC-
Acknowledgment
We gratefully acknowledge the support of this work by the Shiraz
University Research Council.
Synthesis 2005, No. 5, 787–790 © Thieme Stuttgart · New York

790
M. Hosseini Sarvari
PAPER
(16) Yang, S. H.; Chang, S. Org. Lett. 2001, 3, 4209.
References
(17) Dewan, S. K.; Singh, R. Synth. Commun. 2003, 3085.
(18) Lee, K.; Han, S. B.; Yoo, E. M.; Chung, S. R.; Oh, H.; Hong,
S. Synth. Commun. 2004, 34, 1775.
(19) Maeyama, K.; Kobayashi, M.; Kato, H.; Yonezawa, N.
Synth. Commun. 2002, 32, 2519.
(20) Pagni, R. M.; Kobalka, G. W.; Boothe, R.; Gaetano, K.;
Stewart, L. J.; Conawaya, R. J. Org. Chem. 1998, 53, 4477.
(21) Sharghi, H.; Hosseini Sarvari, M. Synthesis 2002, 1057.
(22) Hosseini Sarvari, M.; Sharghi, H. J. Org. Chem. 2004, 69,
6953.
(23) (a) Sharghi, H.; Hosseini Sarvari, M. Synlett 2001, 99.
(b) Sharghi, H.; Hosseini Sarvari, M. Tetrahedron 2002, 58,
10323. (c) Sharghi, H.; Hosseini Sarvari, M. J. Chem. Res.,
Synop. 2001, 446. (d) Sharghi, H.; Hosseini Sarvari, M.
Synthesis 2003, 243.
(1) March, J. In Advanced Organic Chemistry: Reactions,
Mechanism, and Structure, 4th ed.; John Wiley & Sons, Inc.:
New York, 1992, 907.
(2) Larock, R. G. Comprehensive Organic Transformation, A
Guide to Functional Groups; VCH Publisher, Inc: New
York, 1989.
(3) Bandgar, B. P.; Nikat, S. M.; Wadganoker, P. P. Synth.
Commun. 1995, 25, 863.
(4) Meshram, H. M. Synthesis 1992, 943.
(5) Grundmann, C. Methoden der Organischen Chemie,
Houben-Weyl, Vol. E5; Thieme: Stuttgart, 1985, 1322.
(6) Hegarty, A.; Tuohey, P. J. J. Chem. Soc., Perkin Trans. 2
1980, 1313.
(7) Cho, B. R.; Je, T. J. Org. Chem. 1993, 58, 6190.
(8) Miller, C. P.; Kaufman, D. H. Synlett 2000, 1169.
(9) Kim, J. N.; Chung, K. H.; Ryu, E. K. Synth. Commun. 1990,
20, 2785.
(10) Thomas, H. G.; Greyn, H. D. Synthesis 1983, 472.
(11) Konwar, D.; Boruah, R. C.; Sandhu, J. S. Tetrahedron Lett.
1990, 31, 1063.
(12) Jurisic, B. Synth. Commun. 1989, 19, 689.
(13) Kim, S.; Yi, K. Y. Tetrahedron Lett. 1986, 27, 1925.
(14) Barman, D. C.; Thakut, A. J.; Prajaptai, D.; Sandhu, J. S.
Chem. Lett. 2000, 10, 1196.
(24) (a) Sampath Kumar, H. M.; Mohanty, P. K.; Suresh Kumar,
M.; Yadav, J. S. Synth. Commun. 1997, 27, 1327.
(b) Sampath Kumar, H. M.; Subba Reddy, B. V.; Tirupathi
Reddy, P.; Yadav, J. S. Synthesis 1999, 586.
(25) Ortiz-Marciales, M.; Pinero, L.; Ufret, L.; Algarin, W.;
Morales, J. Synth. Commun. 1998, 28, 2807.
(26) Sabitha, G.; Syamala, M. Synth. Commun. 1998, 28, 4577.
(27) Ali, S. L.; Nikalje, M. D.; Dewkar, G. K.; Paraskar, A. S.;
Nikalje, M. D.; Sudalai, A. J. Chem. Res., Synop. 2000, 30.
(28) CRC, Handbook of Tables for Organic Compound
Identification, 3rd & 54th ed.
(15) Iranpoor, N.; Zeynizadeh, B. Synth. Commun. 1999, 29,
2747.
Synthesis 2005, No. 5, 787–790 © Thieme Stuttgart · New York