Pyridinium fluorochromate supported on wet alumina: A mild convenient reagent for the facile deprotection of aldoximes

Article abstract of DOI:10.1081/SCC-120001501

A simple mild method of oxidative deoximation based on pyridinium fluorochromate (PFC) on wet alumina support is described. This method is particularly effective for rapid deprotection of aldoximes and aliphatic ketoximes. Sterically hindered ketoximes are resistant to the reagent.

Full text of DOI:10.1081/SCC-120001501

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PYRIDINIUM FLUOROCHROMATE SUPPORTED ON WET
ALUMINA: A MILD CONVENIENT REAGENT FOR THE
FACILE DEPROTECTION OF ALDOXIMES
Nemai C. Ganguly a , Prithwiraj De a , Arun K. Sukai a & Sripada De a
a Department of Chemistry, University of Kalyani , Kalyani, 741235, India
Published online: 21 Aug 2006.
To cite this article: Nemai C. Ganguly , Prithwiraj De , Arun K. Sukai & Sripada De (2002) PYRIDINIUM FLUOROCHROMATE
SUPPORTED ON WET ALUMINA: A MILD CONVENIENT REAGENT FOR THE FACILE DEPROTECTION OF ALDOXIMES, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:1, 1-7, DOI:
10.1081/SCC-120001501
To link to this article: http://dx.doi.org/10.1081/SCC-120001501
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SYNTHETIC COMMUNICATIONS, 32(1), 1–7 (2002)
PYRIDINIUM FLUOROCHROMATE
SUPPORTED ON WET ALUMINA:
A MILD CONVENIENT REAGENT
FOR THE FACILE DEPROTECTION
OF ALDOXIMES
Nemai C. Ganguly,* Prithwiraj De,
Arun K. Sukai, and Sripada De
Department of Chemistry, University of Kalyani,
Kalyani-741 235, India
ABSTRACT
A simple mild method of oxidative deoximation based on
pyridinium fluorochromate (PFC) on wet alumina support is
described. This method is particularly effective for rapid
deprotection of aldoximes and aliphatic ketoximes. Sterically
hindered ketoximes are resistant to the reagent.
The conversion of oximes to parent carbonyl compounds constitutes an
important synthetic transformation and the host of reagents1 employed for
this purpose over the years directly attest to its importance. Several
reagents1h,1j,1m are selective in deprotecting ketoximes in preference to aldo-
ximes, while some others demask aldoximes with concomitant overoxidation.
*Corresponding author.
1
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

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GANGULY ET AL.
The differential deprotection in the opposite sense i.e. selective removal of
aldoximes in the presence of ketoximes has not been adequately explored.
Our interest in developing new selective oxidation procedures based on pyri-
dinium fluorochromate (PFC)2 which combines reactivity of pyridinium
chlorochromate (PCC) with relatively mild acidic character2b prompted us
to address the issue. Recently, we reported3 a method of deprotective oxida-
tion of oximes using pyridinium fluorochromate in combination of 30%
hydrogen peroxide. In that communication we noted that although generality
of the method was an advantage, oxidation of aldoximes was attended with
considerable overoxidation. To circumvent this problem and the environ-
mental consideration that halogenochromates have potential genotoxicity4
related to cellular reductants such as ascorbic acid, glutathione and cysteine,
we chose to use this versatile oxidant on wet alumina support. We envisaged
that this oxidant system, in addition to its mildness, would have the
additional advantage of trapping the toxic reduced chromium species in the
alumina matrixmaking isolation of products of oixdation easier. We
present herein a milder variation of our earlier method of deoximation and
summarize the results of oxidation of a variety of oximes with pyridinium
fluorochromate adsorbed on wet alumina (Table 1).
The facile cleavage of aldoximes and aliphatic ketoximes is amply
demonstrated (entries 1–7, 10–11) and, importantly, the generation of alde-
hydes occurred without overoxidation, even for aldoximes substituted with
electron-releasing groups in ortho/para positions (entries 2–5). The presence
of electron-withdrawing group (entry 8) definitely retarded the cleavage pro-
cess. The reagent system is compatible with carbon–carbon double bonds,
unconjugated as well as conjugated (entries 7, 9) and methylenedioxy func-
tions (entry 5). Exposure of oximes of acid-sensitive molecules e.g. citral,
2-furfural led to rapid demasking without overoxidation or further reaction
(e.g. acid-induced ring closure as observed in pyridinum chlorochromate5
oxidation of citronellol). However, benzoin oxime was completely oxidized
to the corresponding 1,2-diketone, benzil (30 min) and no benzoin could be
isolated. Interestingly, attempts at similar oxidation of aryl aldoximes with
pyridinium fluorochromate under homogeneous conditions (in acetone
solution) led to some overoxidation to carboxylic acids and consequently
gave lower yields. Short reaction time and non-aqueous work-up presumably
allowed acid-labile molecules to be handled more efficiently when surface-
mediated protocol is used. The method also compares favourably in
respect of reaction times and yields with other oxochromium (VI) reagents
employed for this purpose. For example, benzaldoxime afforded benz-
aldehyde in 56% yield (15 h) with pyridinium chlorochromate,1b in 35%
yield with pyridinium chlorochromate and 30% hydrogen peroxide,1c in 72%
yield (10 min) with trimethylsilylchlorochromate1g and in 45% yield (2 h)

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3
Table 1. Oxidative Deoximation with Pyridinium Fluorochromate (PFC) on Wet
Alumina Support
Yielda of
Carbonyl
Compound (%)
Entry
Substrate
Reaction Time
1
2
syn-Benzaldehyde oxime
2-Methoxybenzaldehyde
oxime
20 min (20 minb)
10 min (10 minb)
90 (80b)
88 (76b)
3
4
5
2,4-Dimethoxybenzaldehyde
oxime
4-Dimethylaminobenzaldehyde
oxime
3,4-Methylenedioxybenzaldehyde
oxime
2-Furfuraldehyde oxime
Citral oxime
4-Nitrobenzaldehyde oxime
Cinnamaldehyde oxime
Ethyl methyl ketone oxime
Isobutyl methyl ketone oxime
Acetophenone oxime
Benzophenone oxime
(a) Z-Benzil monoxime
(b) E-Benzil monoxime
Cyclohexanone oxime
Cyclopentanone oxime
Camphor oxime
10 min (15 minb)
10 min (15 minb)
15 min (15 minb)
84 (70b)
86 (70b)
90 (72b)
6
7
8
30 min (45 min)
30 min (45 min)
8 h
5 h
1 h
1.5 h
6 h
7 h
9 h
7 h
10 h
10 h
36 h
36 h
36 h
96 (82b)
98 (78b)
76
90
98
94
92
80
78
82
84
9
10
11
12
13
14
15
16
17
18
19
80
No reaction
No reaction
No reaction
1-Tetralone oxime
4-Carbethoxy-3-methyl-
2-cyclohexen-1-one oxime
(Hagemann’s ester oxime)
aYields refer to products isolated by column chromatography; the products are fully
characterized by their physical properties (mp and bp), spectral characteristics (IR,
1H NMR) and comparison with authentic samples (mixed mp, co-TLC and super-
imposable IR).
bValues in parenthesis indicate reaction time and yield when the reaction was carried
out with pyridinium fluorochromate under homogeneous conditions.

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GANGULY ET AL.
with dimethyldichlorosilane and chromium trioxide.1g Oxidative cleavage of
aryl ketoximes was comparatively much slower and the rate differential was
large enough to allow selective cleavage of aldoximes in the presence of
ketoximes. Exposure of an equimolar mixture of benzaldoxime and benzo-
phenone oxime to 2 mol equivalents of the reagent led, after 20 min, to almost
quantitative recovery of unreacted benzophenone oxime along with benzal-
dehyde in 90% yield. Use of 2 mol equivalents of pyridinium
fluorochromate (1 mmol absorbed on 1 g of alumina) was found to be the
optimized reaction condition that gave excellent yields and use of a higher
excess of the reagent and longer reaction time gave lower yields due to
overoxidation. This reagent, however, did not work for sterically hindered
oximes (entries 17, 18) and one with vinylogous ester moiety (entry 19).
Methyl ether of acetophenone oxime was inert to the reagent even on
prolonged exposure (36 h) suggesting that the presence of free oxime group
is essential for successful cleavage.
Mechanistically, the cleavage process is initiated by nucleophilic attack
of oxime hydroxy group on the fluorochromate anion to form the chromate
ester intermediate (1a) (Scheme 1). The enhanced nucleophilicity observed
for oxime or oximate anion due to a-effect6 favours this process. Unlike
similar chromate ester formations in cases of primary and secondary
alcohols,7 this step is subject to electronic control due to conjugation of
oxygen lone pair with the aromatic moiety. Subsequent mode of cleavage
of the chromate ester (1a) presumably also depends on degree of electron
release by the aromatic system. The intermediacy of a stabilized carbocation
intermediate (1b) followed by nucleophilic attack of water as such or hydro-
xide ion attached to solid support8 seems to be a plausible route of cleavage
Scheme 1.

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5
for aryl aldoximes particularly for those with electron-releasing substituents
in ortho/para positions in the aromatic ring. However, this mechanism is
unlikely for p-nitrobenzaldehyde oxime where electron depletion destabilizes
the carbocation (1b) and also diminishes the electrophilicity of carbon–
nitrogen double bond. We propose that the decomposition of (1a) to the
carbonyl compound, in this case, occurs by 2,3-sigmatropic shift to (1c)
followed by nucleophilic attack on chromium (IV) species in a manner
analogous to the mechanistic pathway proposed in deoximation with
benzeneseleninic anhydride.1d This step involves conversion of the sp2-carbon
of carbon–nitrogen bond to more sterically congested sp3 state and is, there-
fore, also subject to steric retardation.
In conclusion, a mild convenient method of oxidative deprotection
based on the inexpensive reagent, pyridinium fluorochromate on wet
alumina support is reported. The great advantage of this method is that it
provides for rapid and efficient demasking of aldoximes without overoxida-
tion. Aryl ketoximes are less readily cleaved which may be utilized for
selective cleavage of aldoximes in the presence of former. Sterically hindered
oximes do not respond to cleavage by this reagent.
EXPERIMENTAL
Typical Procedure for the Deoximation with Pyridinium
Fluorochromate (PFC) on Wet Alumina Support
Alumina (20 g, neutral Brockman Grade 1) activated at 100ꢀC for 4 h
prior to use was thoroughly mixed with a solution of pyridinium fluoro-
chromate (4 g, 20 mmol) in water (6 ml) for 30 min at room temperature. It
was then evaporated to dryness in vacuo and the orange powder so obtained
was used as the reagent for deoximation. Benzaldehyde oxime (1.2 g,
ꢁ10 mmol) in dichloromethane (40 ml) was stirred with the reagent for
20 min (TLC-monitored). The solid material was then filtered, washed with
ether (3 Â 20 ml). The filtrate combined with washings was evaporated to give
the crude product which upon chromatography over silica gel (60–120 mesh)
and distillation under reduced pressure gave benzaldehyde (950 mg, 90%).
Oxidative Cleavage of Syn-benzaldehyde Oxime
Under Homogeneous Conditions
To a solution of pyridinium fluorochromate (1.2 g, 6 mmol) in acetone
(15 ml) cooled to 0ꢀC was added dropwise a solution of syn-benzaldehyde

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GANGULY ET AL.
oxime (320 mg, 3 mmol) in acetone (5 ml) with stirring. The reaction was
stirred at room temperature for 20 min and then acetone was removed under
water suction. The crude mass was extracted repeatedly with ether
(5 Â 20 ml) and the combined ethereal extract was washed successively
with 5% sodium sulphite solution (10 ml), 1 (N) hydrochloric acid (10 ml),
water (10ml) and then dried over anhydrous sodium sulphate. The crude
product showed, in addition to the TLC spot identical with that of benzal-
dehyde, a minor polar spot corresponding to benzoic acid. Removal of
solvent, chromatography over silica gel (60–120 mesh, BDH) and distillation
under reduced pressure afforded benzaldehyde (225 mg, 80%).
ACKNOWLEDGMENT
One of the authors (PD) is thankful to CSIR, New Delhi for a research
fellowship.
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Received in Japan October 6, 2000

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