Conversion of oximes to carbonyl compounds with 2-nitro-4,5- dichloropyridazin-3(2H)-one

Article abstract of DOI:10.1021/jo902356e

(Chemical Equation Presented) Conversion of oximes to the carbonyl compounds has been demonstrated with use of 2-nitro-4,5-dichloropyridazin-3(2H)- one (2) under microwave irradiated conditions. Fourteen aliphatic and aromatic oximes converted to their corresponding aldehydes and ketones in good to excellent yields. It is noteworthy that the reaction is conducted under neutral, mild, and eco-friendly condition.

Full text of DOI:10.1021/jo902356e

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readily form stable anions2 and can act as good leaving
Conversion of Oximes to Carbonyl Compounds with
2-Nitro-4,5-dichloropyridazin-3(2H )-one
groups,1 we explored the application of 2-substitued pyrida-
zin-3(2H )-ones as electrophilic transfer reagents. In our
previous paper,1d we reported the 2-nitro-4,5-dichloropyr-
idazin-3(2H )-one (2) as a nitro group source. According
to the literature,3 Amberlyst 15 supported nitrosonium ion
converts oximes to carbonyl compounds. Therefore, com-
pound 2 may play the role of activating agent in the conver-
sion of oximes into their corresponding carbonyl com-
pounds. Recently, we found the conversion of acetophenone
oxime to the corresponding carbonyl compound by 2-nitro-
4,5-dichloropyridazin-3(2H )-one (2) under neutral condi-
tion in refluxing organic solvents in low yield.
Bo Ram Kim, Hyung-Geun Lee, Eun Jung Kim,
Sang-Gyeong Lee,* and Yong-Jin Yoon*
Department of Chemistry & Environmental Biotechnology
National Core Research Center, Research Institute of Natural
Sciences, Graduate School for Molecular Materials and
Nanochemistry, Gyeongsang National University,
Jinju 660-701, Korea
yjyoon@gnu.ac.kr
Oximes are extensively used for group protecting, purifi-
cation, and characterization of carbonyl compounds.4,5
Thus, there has been increasing interest in the development
of methods for the conversion of oximes into their corre-
sponding carbonyl compounds, and a number of methods
have been explored.6
Received November 3, 2009
However, these methods suffer from one or more draw-
backs such as the use of toxic reagents, strong oxidation
agents, additives and expensive metals, further oxidation in
the case of aldoximes, and difficulty in product isolation.
As a continued interest in developing an efficient, mild,
and greener process, we expected to apply 2-nitro-4,5-di-
chloropyridazin-3(2H )-one (2) as the activating agent. As
expected, oximes were treated with agent 2 under neutral
condition to give their corresponding carbonyl compounds
(Scheme 1).
Conversion of oximes to the carbonyl compounds has been
demonstrated with use of 2-nitro-4,5-dichloropyridazin-
3(2H )-one (2) under microwave irradiated conditions.
Fourteen aliphatic and aromatic oximes converted to their
corresponding aldehydes and ketones in good to excellent
yields. It is noteworthy that the reaction is conducted under
neutral, mild, and eco-friendly condition.
In this paper, we wish to report a new, simple, and
green method for the effective deprotection of oximes under
neutral and microwave irradiation.
(3) Lakouraj, M. M.; Noorian, M.; Mokhtary, M. React. Funct. Polym.
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(4) Yang, Y.; Zhang, D.; Wu, L.-Z.; Chen, B.; Zhang, L.-P.; Tung, C. H.
J. Org. Chem. 2004, 69, 4788 and references cited therein.
(5) Kim, Y. H.; Jung, J. C.; Kim, K. S. Chem. Ind. 1992, 31.
2-Substitued pyridazin-3(2H )-ones as electrophilic agents
are stable and easily prepared compounds whose utility
as synthetic auxiliaries was recently demonstrated by
Yoon et al.1 The ease with which pyridazin-3(2H )-ones
can be removed and/or recycled spurred our interest in their
use for other transformations. Since pyridazin-3(2H )-ones
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484 J. Org. Chem. 2010, 75, 484–486
Published on Web 12/07/2009
DOI: 10.1021/jo902356e
r
2009 American Chemical Society

Kim et al.
JOCNote
SCHEME 1
TABLE 2. Conversion of Oximes to Carbonyls with 2
TABLE 1. Optimization of Conditions
entry
solvents
conditions
25 °C
reflux
25 °C
reflux
reflux
time
72 h
yielda (%)
1
2
water
water
80b
64c
53 b
60 c
50 c
1 h
3
MeOH (1 mL H2O)
MeOH
MeOH/H2O (1:1, v/v)
72 h
24 h
24 h
4
5
6
MeOH/H2O (1.5:1, v/v) 150 °C, microwave 10 min 88
7
MeOH/H2O (1:1, v/v)
MeOH/H2O (1:1, v/v)
25 °C, microwave
150 °C, microwave 10 min 92
10 min 80 b
8
9
10
MeOH/H2O (1:1.5, v/v) 150 °C, microwave 10 min 88
MeOH/H2O (1:9, v/v)
150 °C, microwave 10 min decom
aIsolated yield. bOxime was not converted completely into the
corresponding carbonyl compound. cOxime was not converted comple-
tely into the corresponding carbonyl compound and also detected
unknown byproduct.
Direct N-nitration of 4,5-dichloropyridazin-3(2H )-one
(2) was performed by the literature method.1d
With use of a model reaction based on acetophenone oxime
(1a), some different conditions have been screened. The results
are shown in Table 1. On the basis of the observation, this
reaction is more favorable under microwave irradiation. Finally,
the following systems proved to be best: 1a (1 equiv)/2 (1 equiv)/
H2O-MeOH (1:1, v/v) at 150 °C under microwave irradiation.
Four ketoximes 1b-e were treated with 2 under the
optimized conditions at 130 °C (for 1e) or 150 °C to give
the corresponding ketones 3b-e in good to excellent yields
(entries 1-4 in Table 2). Similarly, aldoximes 1f-o were also
reacted with 2 under the same conditions at 130 °C (for
1k-o) or 150 °C (for 1f-j) to afford the corresponding
aldehydes 3f-o in good to excellent yields (entries 5-14 in
Table 2). In the conversion of all aldoximes under our
conditions, we obtained only the corresponding aldehydes,
and did not detect the overoxidation to the carboxylic acids.
All oximes involving the electron-withdrawing and the elec-
tron-donating groups on the phenyl ring were also easily
converted to the corresponding carbonyl compounds. In
addition, reusable 4,5-dichloropyridazin-3(2H )-one was iso-
lated quantitatively. The product structures were established
by IR and NMR, and the spectral data and Rf values of TLC
are also identical with the data of their authentic samples.
A plausible mechanism of carbon-nitrogen double bond
cleavage of oximes may be represented as Scheme 2. Finally,
oximes react with compound 2 as an activating agent to
convert the corresponding carbonyl compounds through the
N-hydroxynitramide intermediate (I) and/or 1,2,3-oxadiaze-
tidin-2-ium (II).
aIsolated yield. bMicrowave irradiation, 200 W, 1378 kPa, 150 °C.
cMicrowave irradiation, 200 W, 1378 kPa, 130 °C.
In summary, we have reported the oxidative conversion of
oximes with compound 2 as an activating agent into the
corresponding carbonyl compounds in good to excellent
J. Org. Chem. Vol. 75, No. 2, 2010 485

Kim et al.
JOCNote
SCHEME 2. Plausible Mechanism for Conversion of Oximes to
Carbonyls
(2, 0.73 mmol) were dissolved in MeOH (4 mL) at room
temperature in a vial. After adding H2O (4 mL) into the solution,
the resulting mixture was irradiated in a microwave oven (200 W
output, 1378 kPa) at 130 °C (for 1e and 1k-o) or 150 °C (for
1a-d and 1f-j) for 10 min in a capped vial. The reaction was
monitored by TLC. After completion of the reaction, product
was extracted with dichloromethane (40 mL). After separating
the organic layer, the organic solution was then dried over
anhydrous MgSO4. After evaporating the solvent under reduced
pressure, the resulting residue was then further purified by
column chromatography with dichloromethane to give the
corresponding carbonyl compounds 3.
yields. The conversion was accompanied by no formation of
byproduct. In the case of aldoximes, overoxidation products
also were not detected under our condition. Compound 2 is a
stable, efficient and eco-friendly agent, and easily prepared
from commercially available 4,5-dichloropyridazin-3(2H )-
one. In addition, 4,5-dichloropyridazin-3(2H )-one can be
reusable and easily separated from the reaction mixture.
Acknowledgment. This work was supported by a grant
from the Korea Science and Engineering Foundation
(KOSEF) to the Environmental Biotechnology National
Core Research Center (grant no. R15-2003-012-02001-0).
Supporting Information Available: Complete experimental
procedures, 1H and 13C NMR spectral data, and melting points
for compounds 3b-d, 3k-m, and 3o. This material is available
free of charge via the Internet at http://pubs.acs.org.
Experimental Section
General Procedure for the Conversion of Oxime to Carbonyl.
Oxime (1a-o, 0.73 mmol) and 4,5-dichloro-2-nitropyridazinone
486 J. Org. Chem. Vol. 75, No. 2, 2010