A facile, catalytic deoximation method using potassium bromide and ammonium heptamolybdate in the presence of hydrogen peroxide in an aqueous medium

Article abstract of DOI:10.1055/s-2008-1032035

A simple, mild and efficient procedure for the cleavage of a wide range of ketoximes and aldoximes to the corresponding carbonyl compounds in an aqueous medium using catalytic amounts of potassium bromide and ammonium heptamolybdate tetrahydrate in combination with 30% hydrogen peroxide is described. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1032035

PAPER
425
A Facile, Catalytic Deoximation Method Using Potassium Bromide and
Ammonium Heptamolybdate in the Presence of Hydrogen Peroxide in an
Aqueous Medium
Facile,
Catalytic
D
e
eoximation
m
Method ai C. Ganguly,* Sujoy Kumar Barik
Department of Chemistry, University of Kalyani, Kalyani 741235, India
Fax +91(33)25828282; E-mail: nemai_g@yahoo.co.in
Received 15 October 2007
oxidant, oxidations of organic compounds with hydrogen
peroxide are usually kinetically slow and require catalytic
activation. A wide array of catalysts involving early tran-
sition metals (Ti, V, Mo, W) that form peroxo complexes
Abstract: A simple, mild and efficient procedure for the cleavage
of a wide range of ketoximes and aldoximes to the corresponding
carbonyl compounds in an aqueous medium using catalytic
amounts of potassium bromide and ammonium heptamolybdate tet-
rahydrate in combination with 30% hydrogen peroxide is described. are well documented.19 We identified ammonium hepta-
molybdate tetrahydrate for electrophilic activation of hy-
drogen peroxide in view of its ready availability and low
cost, and particularly because oxidations employing mo-
lybdenum(VI) and hydrogen peroxide such as epoxida-
tion, oxybromination and the Hunsdiecker reaction have
been previously effectively carried out at higher pH (5–7)
compared to similar vanadium(V)-catalyzed reactions in
aqueous media.20,21 Herein, we delineate a mild, simple
and convenient method of regeneration of aldehydes and
ketones from their oximes employing catalytic amounts of
potassium bromide and ammonium heptamolybdate tet-
rahydrate in combination with 30% hydrogen peroxide
and a trace of perchloric acid in aqueous solution
(Scheme 1).
Key words: oximes, potassium bromide, ammonium heptamolyb-
date tetrahydrate, hydrogen peroxide
Oximes are extensively used for protection, characteriza-
tion and purification of carbonyl compounds.1 Apart from
their usefulness as latent protected forms of aldehydes and
ketones, oximes occupy a key position in the chemical
space that correlates carbonyl compounds with nitroal-
kanes, amines and carboxamides.2,3 Thus, the synthesis of
oximes from non-carbonyl sources and subsequent cleav-
age to carbonyl compounds constitutes a number of useful
entries to carbonyl compounds. Development of a pletho-
ra of deoximation methods by way of oxidative, hydrolyt-
ic and reductive cleavage of the C=N bond over the
years4,5 attests to its synthetic importance. Currently, a
fervent search for newer protocols addressing green
chemistry issues, such as utilization of nontoxic reagents
and photosensitizers, use of water as the reaction medium
avoiding volatile organic solvents and replacement of sto-
ichiometric by catalytic methods, is continuing. Thus,
platinum(II) terpyridyl acetylide complex,6 chloranil/hn,7
a catalytic amount of iodine/surfactant/water,8 silicon
bromide on wet silica gel,9 iodic acid for ‘nonaqueous’
hydrolysis,10 2,2¢-dipyridyl diselenide with triphenyl-
phosphine,11 2-iodylbenzoic acid in the presence of b-cy-
clodextrin catalyst,12 glyoxylic acid,13 functional ionic
liquids physically confined in silica gel,14 and chloramine
T15 have been employed for this purpose.
KBr (20 mol%),
(NH4)6Mo7O24·4H2O (20 mol%),
R1
R2
R1
R2
NOH
O
30% H2O2,
HClO4 (trace), r.t.
R1, R2 = alkyl, aryl, H
Scheme 1
To this end, we initially set out to investigate the efficacy
of a catalytic combination of ammonium heptamolybdate
tetrahydrate and 30% hydrogen peroxide.22 Oximes of ar-
omatic aldehydes and ketones were found to be resistant
to cleavage with a reagent system comprising 30% hydro-
gen peroxide (1 mL/mmol substrate) and 20 mol% ammo-
nium heptamolybdate tetrahydrate in aqueous solution.
Addition of anionic surfactant (SDS) to the reaction mix-
ture was also of no avail. However, benzaldehyde oxime
and acetophenone oxime were cleaved to the parent car-
bonyl compounds in 70% and 75% yield in tetrahydrofu-
ran/water (4:1 v/v) in 24 and 18 hours, respectively. The
disappointingly slow reaction rates and, very importantly,
failure to regenerate carbonyl compounds in aqueous so-
lution without an organic solvent compelled us to explore
an alternative oxidant system.
Our interest in developing deprotection protocols utilizing
hydrogen peroxide and related compounds16 prompted us
to explore a catalytic deoximation method in an aqueous
medium17 based on hydrogen peroxide as the terminal ox-
idant. The low cost, high active oxygen content and for-
mation of water as the only byproduct are the key
advantageous features18 of this environment-friendly oxi-
dant. However, although a thermodynamically powerful
SYNTHESIS 2008, No. 3, pp 0425–0428
x
x
.
x
x
.2
0
0
8
At this stage, we observed a dramatic increase in cleavage
rate and yield upon addition of a catalytic amount of po-
Advanced online publication: 10.01.2008
DOI: 10.1055/s-2008-1032035; Art ID: Z24107SS
© Georg Thieme Verlag Stuttgart · New York

426
N. C. Ganguly, S. K. Barik
PAPER
tassium bromide to the above reaction mixture in aqueous carbonyl compounds containing hydroxy/methoxy groups
solution. Optimization experiments with benzaldehyde is another remarkable feature of this method. This meth-
oxime as the model substrate revealed that 30% hydrogen odology is compatible with common functional groups
peroxide (1 mL/mmol substrate) in the presence of 20 such as hydroxy, methoxy, benzyloxy, ester, nitro, amino
mol% each of ammonium heptamolybdate tetrahydrate and methylenedioxy, and with conjugated as well as iso-
and potassium bromide, and a trace of perchloric acid, lated double bonds.
yielded benzaldehyde, unaccompanied by any byproduct
arising out of its further oxidation, in reasonable time (3
h) and excellent yield (95%) (Table 1, entry 3).
Table 2 Deoximation with 30% Hydrogen Peroxide and Catalytic
Amounts of Potassium Bromide and Ammonium Heptamolybdate
Tetrahydrate in Water
Table 1 Cleavage of Benzaldehyde Oxime to Benzaldehyde with
30% Hydrogen Peroxide, Catalyzed by Potassium Bromide and
Ammonium Heptamolybdate Tetrahydrate, in Aqueous Solution
Entry Substrate
1
Timea (h) Yieldb (%)
NOH
3
4
95
92
Entry H2O
(mL)
KBr
(mol%) 4H2O (mol%) (mL) (h)
(NH4)6Mo7O24· HClO4 Timea Yieldb
(%)
60
75
95
92
94
68
85
NOH
NOH
2
1
2
3
4
5
6
7
1
1
1
1
2
2
1
20
20
20
30
20
10
20
10
20
20
20
20
10
–
–
10
7
HO
–
0.1
0.1
0.1
0.1
0.1
3
3
5
90
HO
3
OMe
3
NOH
O
O
4
5
3
5
95
98
8
NOH
6
a Reactions were conducted on 1 mmol of substrate at r.t.
b Isolated yield upon column chromatography.
OH
NOH
6
7
5
85
95
NO2
The fact that deoximation takes place with the potassium
bromide/hydrogen peroxide combination, albeit slowly,
even without ammonium heptamolybdate tetrahydrate is
compatible with a cleavage process that is mediated by
Br2 or a Br+ equivalent. Ammonium heptamolybdate tet-
rahydrate catalyzes the oxybromination process, particu-
larly in the presence of traces of perchloric acid. It has
been demonstrated23 that a proton source is required for
oxyhalogenation and perchloric acid in trace amounts pre-
cisely fulfills this requirement thereby facilitating deoxi-
mation. The optimized reaction conditions24 worked well
for a wide range of substrates25 including oximes of aro-
matic aldehydes and ketones, cyclic ketones with different
levels of steric congestion, and a,b-unsaturated aldehydes
1.5
NOH
8
9
2
3
3
80
85
90
NOH
H2N
NOH
NO2
NOH
and ketones, as shown in Table 2. It was gratifying to ob- 10
serve that oxidation-prone aryl aldoximes as well as cin-
namaldehyde oxime (entry 16) underwent cleavage
without further oxidation to the corresponding carboxylic
acids. Remarkably, citral oxime (entry 20), which is often
NOH
11
7
78
88
susceptible to acid-catalyzed rearrangement,26 yielded ci-
tral cleanly. Sterically hindered oximes, such as camphor
oxime (entry 18) and a 1-tetralone oxime derivative (entry
17), were cleaved with ease. No fragmentation product,
such as a nitrile, was formed from camphor oxime, which
NO2
NO2
NOH
O
12
2.5
often characterizes such highly branched ketoximes with
a quaternary a-carbon atom facilitating formation of ter-
tiary carbenic ion-mediated fragmentations.11 The ab-
sence of byproducts with bromine substitution in the side
chain of acetophenone or the aromatic ring of activated
(Z-isomer)
Synthesis 2008, No. 3, 425–428 © Thieme Stuttgart · New York

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Facile, Catalytic Deoximation Method
427
Table 2 Deoximation with 30% Hydrogen Peroxide and Catalytic
Amounts of Potassium Bromide and Ammonium Heptamolybdate
Tetrahydrate in Water (continued)
Acknowledgment
S.K.B. thanks the University of Kalyani for financial assistance by
way of a research fellowship. Facilities provided by a DST-FIST
Grant, Government of India are also acknowledged.
Entry Substrate
Timea (h) Yieldb (%)
NOH
References
13
4
85
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NOH
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CO2Et
NOH
a Reaction conditions: KBr (20 mol%), (NH4)6Mo7O24·4H2O (20
mol%), 30% H2O2 (1 mL), HClO4 (0.1 mL), r.t.
b Refers to chromatographically pure products; all products were
identified by IR and 1H NMR spectra, and comparison with authentic
samples.
In conclusion, a simple, mild and clean catalytic method
of deoximation in aqueous solution utilizing inexpensive,
commercially available potassium bromide and ammoni-
um heptamolybdate tetrahydrate as catalysts and 30% hy-
drogen peroxide has been developed. The absence of
overoxidation and other byproducts of released carbonyl
compounds, operational simplicity, good balance of yield
and reaction time, and avoidance of organic solvents as
the reaction medium are the key advantageous features of
this protocol.
173.
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(24) Typical Deoximation Procedure: To a thoroughly stirred
soln of (NH4)6Mo7O24·4H2O (296 mg, 0.24 mmol) in H2O
(0.5 mL) was added 30% H2O2 soln (1.2 mL). After stirring
for 10 min, a soln of KBr (29 mg, 0.24 mmol) in H2O (0.5
mL) was added followed by a drop of HClO4 (0.1 mL)
Synthesis 2008, No. 3, 425–428 © Thieme Stuttgart · New York

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N. C. Ganguly, S. K. Barik
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whereupon the reaction mixture assumed a yellow
benzaldehyde (120 mg, 95%). Its identity was confirmed by
co-TLC (and superimposable IR spectrum) with an authentic
sample.
coloration. Benzaldehyde oxime (145 mg, 1.2 mmol) was
slowly added and the resulting mixture was stirred for 3 h
(monitored by TLC); the mixture turned almost colorless.
The reaction mixture was washed successively with 5%
NaHSO3 soln (2 × 2 mL) and H2O (2 mL), and was then
extracted with EtOAc (2 × 10 mL) and dried (Na2SO4). The
concentrated extract was subjected to column chromato-
graphy (silica gel, 60–120 mesh; light petroleum) to yield
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otherwise stated (entry 12).
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Synthesis 2008, No. 3, 425–428 © Thieme Stuttgart · New York