Effective 'non-aqueous hydrolysis' of oximes with iodic acid in dichloromethane under mild, heterogeneous conditions

Article abstract of DOI:10.1016/S0040-4039(02)00710-4

Ketoximes and aromatic aldoximes are converted to the corresponding carbonyl compounds in excellent yields (67-97%), upon treatment with a suspension of iodic acid in dry CH₂Cl₂ at room temperature.

Full text of DOI:10.1016/S0040-4039(02)00710-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 4023–4024
Effective ‘non-aqueous hydrolysis’ of oximes with iodic acid in
dichloromethane under mild, heterogeneous conditions
Sosale Chandrasekhar* and Kovuru Gopalaiah
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Received 12 February 2002; revised 23 March 2002; accepted 11 April 2002
Abstract—Ketoximes and aromatic aldoximes are converted to the corresponding carbonyl compounds in excellent yields
(
67–97%), upon treatment with a suspension of iodic acid in dry CH Cl at room temperature. © 2002 Elsevier Science Ltd. All
2 2
rights reserved.
The hydrolysis of oximes to the corresponding carbonyl
compounds has been of considerable interest in recent
years for at least two reasons. Firstly, oxime deriva-
Interestingly, the addition of molecular sieves to the
reaction medium did not prevent the effective hydroly-
sis, indicating that water is not involved. Also, a mini-
mum of three equiv. of iodic acid (2) were found to be
1
tives are often used to purify, characterise and protect
2
aldehydes and ketones, so the regeneration of the
OH
O
parent carbonyl compounds is important. Secondly,
oximes may be accessed by routes not involving the
carbonyl function such as the Barton reaction and the
N
CH2Cl2/RT
+
HIO3
R
R'
R
R'
2
3
3
reduction of nitro compounds, and so subsequent
1
hydrolysis would define a route to the parent carbonyl
compounds. A variety of methods is presently available
for the hydrolytic deblocking of oximes, mostly involv-
ing either aqueous acid or oxidative cleavage; impor-
tantly, it seems necessary to prevent the reversal of the
hydrolysis by either protonation or oxidation of the
derived hydroxylamine.
Scheme 1.
Table 1. The effective hydrolysis of the oximes 1 (Scheme
1) to the carbonyl compounds 3 with iodic acid (2): reac-
tion time and yields of 3
a
1
R
R%
Time (h)
3
Yield (%)
4
In the course of our studies on the Beckmann reaction
a
b
c
d
e
f
Ph
Me
Me
Ph
Ph
p-Tolyl
6
18
11
20
23
13
21
24
a
b
c
d
e
f
92
97
67
90
72
91
94
83
we discovered that a variety of oximes (1) are effectively
hydrolysed by a suspension of iodic acid (2) in dry
dichloromethane at room temperature (Scheme 1). The
corresponding carbonyl derivatives (3) were isolated in
b
a-Tetralone oxime
-(CH ) -
c
2 5
†
1-Naphthaldehyde oxime
p-Anisyl
excellent yields after a simple work-up (Table 1).
g
h
H
g
h
Veratraldehyde oxime
Keywords: hydrolysis; iodic acid; non-aqueous; oximes.
a
The final products in the case of entries d, f and h are also the
corresponding carbonyl compounds; the oximes 1 were prepared by
standard methods and identified by their IR spectra and mp’s; 3
*
Corresponding author. Fax: (+91 80) 3600 529; e-mail:
sosale@orgchem.iisc.ernet.in
Typical procedures: A solution of the oxime (1 mmol) in dry
†
1
were identified spectrally (IR, 300 MHz H NMR and GC–MS: the
CH Cl2 (5 ml) was treated with 2 (3 mmol) and the resulting
2
yields shown have been adjusted for the GC purity, and M+ was
always observed).
suspension stirred at room temperature (with or without 4 A
,
molecular sieves), the reaction being monitored by TLC (SiO2;
eluent: EtOAc/hexane). Upon completion the reaction mixture was
diluted with CH Cl , washed with water and decolourised with
b
c
A by-product, that is most likely 3-iodo-4-methylphenyl methyl
ketone based on the spectral and GC–MS data (M+ 260), was
observed in 22% yield.
7
2
2
activated charcoal at 45°C; filtration to remove the charcoal, fol-
lowed by drying (Na SO ) and distillation of the solvent furnished
GC analysis indicated the formation of high molecular weight
products also (ꢀ20%, as yet unidentified).
2
4
the carbonyl compounds 3.
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00710-4

4
024
S. Chandrasekhar, K. Gopalaiah / Tetrahedron Letters 43 (2002) 4023–4024
required for the reaction to be complete; and further
amounts of 2 speeded up the reaction. These observa-
tions indicate the formal mechanism shown in Scheme
electrophilic substitution, possibly with elemental
iodine formed by the effective reduction of iodic acid
by hydroxylamine. (A combination of iodine and iodic
acid is known to effect the iodination of the aromatic
2, which essentially involves the formation of the cyclic
8
iodate species 4 and its subsequent decomposition. The
formation of 4 effectively involves the addition of the
oxime hydroxyl group in 1 across an IꢀO unit in 2 and
of an hydroxyl group of the iodate moiety across the
oxime CꢀN unit: the simpler, concerted process is
shown although the above additions may be stepwise.
nucleus. ) Also, the formation and subsequent decom-
position of the cyclic adduct 4 may well be catalysed by
2 (as indicated); and the relative insolubility of 2 sug-
gests the reaction occurs either at the solid surface or
via a minuscule form in solution. All these may explain
the observation that an excess of 2 is required for the
reaction to be complete in reasonable time.
(
Another alternative involves the hetero-ene process
represented in I, followed by cyclisation to 4.) The
cyclic iodate 4 decomposes to the carbonyl compound 3
and O-iodylhydroxylamine (5).
Iodic acid (2) is a rather mild inorganic acid (pK 0.80)
a
9
of moderate oxidising power in aqueous acid, and of
low toxicity to humans as it has been used in
10
medicine. It has apparently found only limited use in
Further condensation of the putative 5 with 2 to the
bis-iodylhydroxylamine 6 would render the overall
reaction irreversible (by analogy to the greater stability
of N-acylhydroxylamines relative to the O-
11
organic synthesis so far. Remarkably, the present
method does not involve water although it is effectively
a hydrolysis, and so would be suitable for substrates
that might be sensitive to aqueous acid. The other
advantages are the ready availability of iodic acid, its
low toxicity, the ambient temperatures employed and
the exceedingly simple work-up.
5
acylhydroxylamines; an O- to N-iodyl transfer in 5
would also be effective but may be slow). Although the
final fate of the putative 6 is unclear, the appearance of
a brownish-red colouration towards the end of the
reaction requires mention: this possibly indicates the
presence of products bearing nitrogen in its higher
oxidation states, derived by the effective oxidation of
hydroxylamine. (Although redox potential data indicate
that hydroxylamines are stable to oxidation in aqueous
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In fact, in the case of the methyl tolyl ketone 3c, a
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Scheme 2.