Microwave-assisted chemoselective cleavage of oximes to their corresponding carbonyl compounds using 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) as a new deoximating reagent

Article abstract of DOI:10.1055/s-2005-869901

In the presence of alkene and alcohol, oximes are converted into their parent carbonyl compounds in good yields when treated with 1,3-dichloro-5,5- dimethylhydantoin (DCDMH) (1), under microwave irradiation. The simple work-up minimizes loss of products. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-869901

SHORT PAPER
1929
Microwave-Assisted Chemoselective Cleavage of Oximes to Their
Corresponding Carbonyl Compounds Using 1,3-Dichloro-5,5-dimethyl-
hydantoin (DCDMH) as a New Deoximating Reagent
M
icrowave-Assist
r
e
d
Chem
d
oselective
C
e
leavage of
O
ximes to
h
Carbonyl Co
i
mpoun
r
ds Khazaei,* Abbas Amini Manesh
Department of Chemistry, Faculty of Sciences, Bu-Ali sina University, P.O. Box 65178-4119, Hamadan, Iran
E-mail: khazaei_1326@yahoo.com
Received 14 January 2005; revised 9 March 2005
H
N
Cl
Abstract: In the presence of alkene and alcohol, oximes are con-
O
R1
R2
verted into their parent carbonyl compounds in good yields when
treated with 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) (1),
under microwave irradiation. The simple work-up minimizes loss of
products.
O
+
N
R1
R2
acetone, H2O
MW
O
O
+
O
OH
N
N
H
N
Cl
1
2
Keywords: aldehyde, ketone, microwave, oxime, selective
Scheme 1
Oximes are useful to organic chemists as protecting
groups,1 and as synthetic intermediates en route to
amines2 and nitriles.3 Their synthesis from non-carbonyl
compounds offers an alternative route to aldehyde and ke-
tones.4,5 Regeneration of carbonyl compounds from the
corresponding oximes is a very important reaction. Many
oxidative deoximations have appeared in recent years.6
Each reagent represents a different balance of yield, tox-
icity, expense, selectivity, technique, and convenience.
Various efficient oxidative methods require chromi-
um(VI),6a–6c or aqueous extraction.6d,7 Many reagents are
not selective for oximes in the presence of alkenes,6c or
their selectivity patterns have not yet been explored.6d In
spite of the availability of many reagents there is still
scope for improvement, as the existing oxidative methods
suffer from one or more disadvantages like long reaction
times,8 difficulties in isolation of products,5 and formation
of over-oxidized products leading to low yields. Advan-
tages such as cleaner reactions, very short reaction times,
and easy work-up have kindled a special interest in micro-
wave chemistry.9 During the course of our systematic
study and research on oxidation of organic compounds
with N-halo reagents,10 we discovered a convenient meth-
od for the selective conversion of oximes to their carbonyl
compounds by using 1,3-dichloro-5,5-dimethylhydantoin
(DCDMH) (1), as an effective oxidizing agent, that over-
comes the disadvantages associated with oxidative meth-
ods developed so far.
The results of the conversions of various oximes to their
corresponding carbonyl compounds are presented in
Table 1.
The aldoximes were converted to the corresponding alde-
hydes and no acid was formed due to over-oxidation of the
regenerated aldehyde (Table 1, entries 3,4,7,8, and 11;
Scheme 2).
CH=NOH
CHO
COOH
Cl
Cl
Cl
+ 1, acetone, H2O
+
MW
80%
0%
Scheme 2 Selective formation of aldehyde from aldoxime.
Even the sterically hindered ketone oxime (Table 1, entry
14) was successfully oxidatively cleaved to the corre-
sponding ketone in good yield. This procedure is also use-
ful for the chemoselective oxidative deoximation of
oximes in the presence of alcohols or for oximes that con-
tain a hydroxy group (Table 1, entry 13). Thus, when
equimolar mixtures of camphor oxime and benzyl alcohol
in acetone and water were allowed to react with DCDMH
under microwave irradiation, the ketoxime underwent
chemoselectively oxidative deoximation, giving camphor
(73%), whereas the benzyl alcohol does not get oxidized
to benzaldehyde (Scheme 3; the reaction was monitored
by TLC).
Dissolution of oximes in acetone by the addition of a
small amount of water and subsequent reaction with
DCDMH (1), under microwave irradiation gave the corre-
sponding carbonyl compounds in good yields (Scheme 1).
The unsaturated oxime (Table 1, entry 8) was cleaved to
the corresponding unsaturated aldehyde without affecting
the double bond. So we observed the competitive oxida-
tion of oximes in the presence of alkenes. In a control ex-
periment, when equimolar mixtures of ethyl methyl
ketone oxime and styrene in acetone and water were al-
lowed to react with DCDMH, under microwave irradia-
tion, the ketone oxime underwent chemoselectively
oxidative deoximation giving ethyl methyl ketone (84%),
SYNTHESIS 2005, No. 12, pp 1929–1931
x
x.
x
x
.
2
0
0
5
Advanced online publication: 18.05.2005
DOI: 10.1055/s-2005-869901; Art ID: Z01305SS
© Georg Thieme Verlag Stuttgart · New York

1930
A. Khazaei, A. A. Manesh
SHORT PAPER
Table 1 Deoximation with DCDMH under MW Irradiation
Entry
1
Substrate
Product
Time (s)
110
120
120
120
140
140
150
100
150
150
180
150
180
180
180
Yield (%)a,b
Cyclohexanone oxime
Acetophenone oxime
Benzaldehyde oxime
Cyclohexanone
Acetophenone
89
87
86
86
84
85
83c
70
84
82
80
84c
74
73
78
2
3
Benzaldehyde
4
4-Chlorobenzaldehyde oxime
Benzophenone oxime
4-Methyl acetophenone oxime
Isobutyraldehyde oxime
Cinnamaldehyde oxime
Isobutyl methyl ketone oxime
Diisopropyl ketone oxime
2-Chlorobenzaldehyde oxime
Ethyl methyl ketone oxime
Benzoin oxime
4-Chlorobenzaldehyde
Benzophenone
5
6
4-Methyl acetophenone
Isobutyraldehyde
Cinnamaldehyde
Isobutyl methyl ketone
Diisopropyl ketone
2-Chlorobenzaldehyde
Ethyl methyl ketone
Benzoin
7
8
9
10
11
12
13
14
15
Camphor oxime
Camphor
Cyclopentanone oxime
Cyclopentanone
a Products were characterized by their physical constants, comparison with authentic samples, and melting points of 2,4-dinitrophenyl hydra-
zone derivatives, as well as by their IR and NMR spectra.
b Isolated yields.
c CH2Cl2–H2O was used as reaction solvent.
Scheme 3 Chemoselective deoximation in the presence of benzyl alcohol.
CH=CH2
CHO
DCDMH, easy work-up procedure, and good yields. The
OH and C=C functional groups in the oxime structure are
not oxidized to other functional groups, and finally, the
dechlorinated product 2 can be converted to 1 and reused
several times.
H3C
H3C
DCDMH , acetone
H2O, MW
N
+
+
O
OH
H5C2
H5C2
Oxidized
Alkene
Ketone
84%
The proposed mechanism for deoximation by DCDMH is
shown in Scheme 5.
0%
Scheme 4 Chemoselective deoximation in the presence of styrene.
Deoximation; General Procedure
whereas the styrene does not get oxidized to benzaldehyde
(Scheme 4; the reaction was monitored by TLC).
A mixture of the oxime (3 mmol) and DCDMH (1), (3 mmol,
591.07 mg), in acetone (10 mL) and water (0.1 mL), was introduced
into a two-necked flask and refluxed under microwave irradiated in
a domestic microwave oven at a power output of 300 W for the ap-
propriate times as indicated in Table 1. After the reaction was com-
plete (every 30 s the microwave oven was turned off and the
In all of the reactions, DCDMH was converted to 5,5-di-
methylhydantoin (2), which can be isolated, chlorinated
and reused many times as a deoximating reagent.
In conclusion, the striking features of our method are: progress of the reaction was monitored by TLC), the solvent was re-
moved under reduced pressure, and CCl4 (20 mL) was added to the
mixture, then it was stirred for 10 min; 5,5-dimethyl hydantoin (2)
very short reaction times, no formation of over-oxidation
products due to high chemoselectivity, the mild nature of
Synthesis 2005, No. 12, 1929–1931 © Thieme Stuttgart · New York

SHORT PAPER
Microwave-Assisted Chemoselective Cleavage of Oximes to Carbonyl Compounds
1931
R1
R2
..
N
OH
Cl
O–
R1
R2
Cl
N
N
O
N
+
O–
O
N
+
2
1 )
N
OH
Cl
R1
R2
..
N
OH
O–
Cl
R1
Cl
R1
R2
+
R2
+OH2
N
N
..
H2O
2 )
OH
OH
H
H
Cl
O+
R2
R1
N
OH
H
Cl
O–
OH
O
N
N
N
O–
R2
R1
N
O
+
2
3 )
N
H
OH
H
H
Cl
O
+
R2
R1
N
OH
H
Cl
R1
O
R2
R1
4 )
N
2
O
+
NHOHCl
2
2
OH
R2
Scheme 5
was removed by filtration and the product was purified by column
chromatography (hexane–Et2O; CH2Cl2 was used for isobutyralde-
hyde, and ethyl methyl ketone).
(5) Drabowicz, J. Synthesis 1980, 125.
(6) (a) Zhang, G.; Yang, D.; Chem, M.; Cai, K. Synth. Commun.
1998, 28, 2221. (b) Bendale, P. M.; Khadilkar, B. M.
Tetrahedron Lett. 1998, 39, 5867. (c) Zhang, G.; Yang, D.;
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Tetrahedron Lett. 1997, 38, 4267. (e) Chrisman, W.;
Blankinship, M. J.; Taylor, B.; Harris, C. E. Tetrahedron
Lett. 2001, 42, 4775.
For benzoin oxime, benzophenone oxime, 4-chloro benzaldoxime
and camphor oxime, after the reaction was complete, the solvent
was removed under reduced pressure, H2O (15 mL) was added to
the mixture, and it was stirred for 10 min, then the aldehyde or ke-
tone was removed by filtration, evaporation of H2O from the filtrate
resulted in 5,5-dimethyl hydantoin (2).
(7) Hajipour, A. R.; Mahboubhgah, N. Org. Prep. Proced. Int.
1999, 31, 112.
(8) Barhate, N. B.; Gajare, A. S.; Wakharkar, R. D.; Sudalai, A.
Tetrahedron Lett. 1997, 38, 653.
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Synthesis 2005, No. 12, 1929–1931 © Thieme Stuttgart · New York