Bismuth compounds in organic synthesis. Deprotection of ketoximes using bismuth bromide-bismuth triflate

Article abstract of DOI:10.1016/j.tetlet.2003.10.031

Ketoximes undergo deprotection in CH3CN/acetone/H2O (3:6:1) in the presence of 20-40 mol percent BiBr3/5 mol percent Bi(OTf)3. Bismuth(III) salts are relatively non-toxic, insensitive to air and inexpensive. These features coupled with the use of a relatively non-toxic solvent system make this method an attractive alternative to existing routes for deprotection of ketoximes.

Full text of DOI:10.1016/j.tetlet.2003.10.031

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 9173–9175
Bismuth compounds in organic synthesis. Deprotection of
ketoximes using bismuth bromide-bismuth triflate
Joshua N. Arnold, Patrick D. Hayes, Robert L. Kohaus and Ram S. Mohan*
Laboratory for Environment Friendly Organic Synthesis, Department of Chemistry, Illinois Wesleyan University,
Bloomington, IL 61701, USA
Received 17 September 2003; revised 5 October 2003; accepted 6 October 2003
Abstract—Ketoximes undergo deprotection in CH3CN/acetone/H2O (3:6:1) in the presence of 20–40 mol% BiBr3/5 mol%
Bi(OTf)3. Bismuth(III) salts are relatively non-toxic, insensitive to air and inexpensive. These features coupled with the use of a
relatively non-toxic solvent system make this method an attractive alternative to existing routes for deprotection of ketoximes.
© 2003 Elsevier Ltd. All rights reserved.
Oximes are frequently used to protect carbonyl com-
pounds and hence considerable attention has been
given to develop methods for their deprotection.1
Oximes can also be synthesized from non-carbonyl
compounds and thus their conversion to carbonyl com-
pounds constitutes a useful synthesis of the latter.2 The
classical method for deprotection of oximes viz.
hydrolytic cleavage requires the use of strong mineral
acids and often results in low yields due to the forma-
tion of polymeric by-products. Hence a number of
oxidative methods have been developed for the cleavage
of oximes. Some examples include Dess–Martin period-
inane,3 PCC,4 TBHP,5 I2/CH3CN,6 manganese acetate/
benzene,7 and potassium peroxymonopersulfate.8
However, many of these reagents or the solvents used
are toxic, corrosive or difficult to handle, especially on
a large scale. With increasing environmental concerns,
it is imperative that new ‘environment friendly’ reagents
be developed.9 One example of a mild method for
deprotection of oximes uses DOWEX-50 resin.10
Recently, bismuth compounds have become attractive
candidates for use as reagents in organic synthesis
because most bismuth compounds are relatively non-
toxic, readily available at low cost and are fairly insen-
sitive to small amounts of water.11 Bismuth has an
electron configuration of [Xe]4f 145d106s26p3. Due to
the weak shielding of the 4f electrons (Lanthanide
contraction), bismuth(III) compounds exhibit Lewis
acidity. BiCl3/microwave,12 BiCl3 in the presence of
benzyltriphenylphosphonium peroxymonosulfate13 and
Bi(NO3)3·5H2O14 have been used for the deprotection
of oximes. We now report the use of a new bismuth-
based catalyst system (bismuth bromide/bismuth trifl-
ate) for the deprotection of ketoximes.
Our continued work with bismuth(III) reagents has led
to the development of bismuth bromide/bismuth triflate
as an efficient reagent for the conversion of ketoximes
to ketones (Scheme 1, Table 1).
The reaction is carried out using 20–40 mol% BiBr3 and
5 mol% Bi(OTf)3·4H2O as a co-catalyst. The use of an
inert atmosphere is not required for these reactions.
Several solvents were investigated during the course of
this study. The best results were achieved using
CH3CN/acetone/H2O (3:6:1, v/v/v). The results of this
study are summarized in Table 1.
While detailed mechanistic studies were not carried out,
a few points merit comment. While BiBr3 alone was
effective in catalyzing the deprotection, the addition of
Bi(OTf)3 accelerated the reaction considerably. The use
of 5 mol% Bi(OTf)3 alone (no BiBr3) was almost inef-
fective in catalyzing the deprotection. However, when
40 mol% Bi(OTf)3 was used alone, the deprotection did
Scheme 1.
Keywords: bismuth and compounds; oximes; deprotection; environ-
ment-friendly chemistry.
* Corresponding author. Tel.: +1-309-556-3829; fax: +1-309-556-3864;
e-mail: rmohan@iwu.edu
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.031

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J. N. Arnold et al. / Tetrahedron Letters 44 (2003) 9173–9175
Table 1. Deprotection of ketoximes using BiBr3-Bi(OTf)3·4H2O in CH3CN/acetone/H2O
proceed smoothly. Since BiBr3 is commercially avail-
able, we found it more practical to use BiBr3 with
Bi(OTf)3 as a co-catalyst.15 A suspension of the catalyst
system in water is acidic (pH 2). Hence it is possible
that the true catalyst is HBr and/or TfOH, released
from hydrolysis of BiBr3 and Bi(OTf)3. Indeed, the
deprotection of 1-indanone oxime using 1.2 equivalents
of HBr and 15 mol% TfOH proceeded smoothly, but
the highly corrosive nature of HBr and TfOH detract
from their use. The attempted deprotection of 1-
indanone oxime using BiBr3 and Bi(OTf)3 in the pres-
ence of proton-sponge®(N,N,N%,N%-tetramethyl-1,8-
naphthalenediamine)16 was unsuccessful suggesting that
the main role of the catalysts is to provide an acidic
reaction medium.
been synthesized from aldehydes and ketones by acid
catalyzed transoximations using acetone oxime.17 This
suggests that the role of acetone is to drive the equi-
librium towards product formation. The deprotection
of 1-indanone oxime in acetonitrile/water (6:4) was only
78% complete after 5 h, suggesting that acetone plays a
crucial role in driving the reaction. Water is also neces-
sary for the deprotection since the reaction was signifi-
cantly slower in CH3CN/acetone as the solvent.
The deprotection works well with
a variety of
ketoximes. Aldoximes on the other hand proved much
more resistant to the deprotection conditions. With
benzaldehyde oxime, the reaction reached a 1:1 equi-
librium mixture of benzaldehyde and the starting oxime
within an hour. When the reaction was carried out with
40 mol% BiBr3/20 mol% Bi(OTf)3, the reaction reached
a 3.5:1 equilibrium mixture of benzaldehyde and the
starting oxime in 1 h.
The choice of solvents also merits comments. Acetone/
H2O was found to be effective but the rate of deprotec-
tion was considerably slower in this solvent system. For
example, the deprotection of 1-indanone oxime in ace-
tone/H2O took over 12 h, while the addition of the
polar coordinating solvent CH3CN accelerated the
reaction considerably (reaction time=3 h). Acetone
oxime was found to be a product of the reaction. This
is not surprising in light of the fact that oximes have
A representative procedure is given here: A solution
1-indanone oxime (0.500 g, 3.40 mmol) in CH3CN/ace-
tone/H2O (3:6:1, v/v/v) (5.00 mL) was stirred as BiBr3
(0.609 g, 1.36 mmol), and Bi(OTf)3·4H2O (0.111 g,

J. N. Arnold et al. / Tetrahedron Letters 44 (2003) 9173–9175
9175
0.170 mmol) were added. The mixture was stirred and
heated at reflux. Reaction progress was followed by GC
analysis. After 3 h, 10% aqueous acetic acid was added
and the mixture was suction filtered and the solids were
rinsed with ether (20 mL). The combined filtrates were
concentrated on a rotary evaporator to remove the
organic solvents. The residue was extracted with ether
(2×40 mL). The organic layer was washed successively
with 2 M NaOH (15 mL), H2O (3×15 mL), saturated
aqueous NaCl (20 mL), dried (Na2SO4) and concen-
trated on a rotary evaporator to yield 0.356 g (79%) of
1-indanone that was determined to be at least 96% pure
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Chemical Society Symposium Series 640: Washington,
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1
by H and 13C NMR spectroscopy and GC analysis.
In summary, this work demonstrates a new and useful
method for deprotection of ketoximes. The advantages
of this method include (1) the use of relatively non-
toxic reagents that are insensitive to air and small
amounts of moisture and (2) the use of a relatively
non-toxic solvent system.
Acknowledgements
12. Boruah, A.; Baruah, B.; Prajapati, D.; Sandhu, J. S.
Tetrahedron Lett. 1997, 38, 4267.
We gratefully acknowledge financial support from The
National Science Foundation (NSF-RUI grant,
CHE0078881). R.M. would also like to acknowledge
The Camille and Henry Dreyfus foundation for a
Henry Teacher Scholar Award.
13. (a) Hajipour, A. R.; Mallakpour, S. E.; Mohammadpoor-
Baltork, I.; Adibi, H. Monatshefte fuer Chemie 2003, 134,
45; (b) Hajipour, A. R.; Mallakpour, S. E.; Baltork, I.
M.; Adibi, H. Synth. Commun. 2001, 31, 3401.
14. Nattier, B. A.; Eash, K. J.; Mohan, R. S. Synthesis 2001,
1010.
15. Preparation of bismuth triflate: Labrouille`re, M.; Le
Roux, C.; Gaspard, H.; Laporterie, A.; Dubac, J.; Des-
murs, J. R. Tetrahedron Lett. 1999, 40, 285. Bismuth
triflate synthesized by this procedure is reported to be
mainly the tetrahydrate. Recently, another procedure for
the synthesis of bismuth triflate has been reported.
Re´pichet, S.; Zwick, A.; Vendier, L.; Le Roux, C.;
Dubac, J. Tetrahedron Lett. 2002, 43, 993.
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