Deprotection of Ketoximes Using Bismuth(II) Nitrate Pentahydrate

Article abstract of DOI:10.1055/s-2001-14568

Ketoximes undergo facile deprotection in acetone-H2O (9:1) in the presence of 0.5 equivalents of Bi(NO3)*5H2O. Bismuth(III) nitrate is 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:10.1055/s-2001-14568

1
010
SHORT PAPER
Deprotection of Ketoximes Using Bismuth(III) Nitrate Pentahydrate1
D
B
eprotection of
K
r
etoxime
y
s
ce A. Nattier, Kyle J. Eash, Ram S. Mohan*
Department of Chemistry, Illinois Wesleyan University, Bloomington, IL 61701, U.S.A.
Fax +1(309)5563864; E-mail: rmohan@titan.iwu.edu
Received 12 January 2001; revised 25 January 2001
We wish to report that Bi(NO ) ·5H O is an efficient re-
3
3
2
Abstract: Ketoximes undergo facile deprotection in acetone–H O
2
agent for the conversion of ketoximes to ketones
Scheme, Table). The reaction is carried out using 0.5
equivalent of Bi(NO ) ·5H O and 0.1 equivalent of
(
9:1) in the presence of 0.5 equivalents of Bi(NO ) ·5H O. Bis-
3 3 2
(
muth(III) nitrate is relatively non-toxic, insensitive to air and inex-
pensive. These features coupled with the use of a relatively non-
3 3
2
toxic solvent system make this method an attractive alternative to Cu(AcO) ·×H O. The best yields were obtained when bis-
2
2
existing routes for deprotection of ketoximes.
muth nitrate was mixed with Montmorillonite K 10. Bis-
Key words: bismuth and compounds, oximes, deprotection, pro- muth nitrate pentahydrate is commercially available and
tecting groups, ketones
requires no special handling. The use of an inert atmo-
sphere is not required for these reactions. Several solvents
including acetone–H O, acetonitrile, dichloromethane
2
Oximes are frequently used to protect carbonyl com- and tetrahydrofuran were investigated during the course
pounds and hence considerable attention has been given to of this study. The best results were achieved using ace-
2
develop methods for their deprotection. Oximes can also tone–H
O (9:1, v/v). Deprotection was also observed in
good yield in dichloromethane. However, some oximes
acetophenone oxime and cyclohexanone oxime) under-
went a very exothermic reaction in dichloromethane. No
2
be synthesized from non-carbonyl compounds and thus
their conversion to carbonyl compounds constitutes a use-
ful synthesis of the latter. The classical method for depro-
tection of oximes viz. hydrolytic cleavage requires the use
of strong mineral acids and often results in low yields.
Hence a number of oxidative methods have been devel-
oped for cleavage of oximes. Some examples include
Dess−Martin periodinane, PCC, TBHP, I /CH CN,
manganese acetate/benzene, and potassium peroxy-
monopersulfate. However, many of these reagents or the
(
3
such exothermic reaction was observed with acetone–H O
as the solvent system.
2
4
5
6
7
2
3
8
9
solvent systems used are toxic, corrosive or difficult to
handle, especially on a large scale. With increasing envi-
ronmental concerns, it is imperative that new “environ-
Scheme
While detailed mechanistic studies were not carried out, a
few points merit comment. The use of Montmorillonite K
1
0
ment friendly” reagents be developed. One example of
such an environment friendly, mild method for deprotec-
1
0 gave a better yield of product though deprotection was
1
1
tion of oximes uses DOWEX®50W. Recently, bismuth
compounds have become attractive candidates for use as
reagents in organic synthesis because most bismuth com-
pounds are relatively non-toxic, readily available at low
cost and are fairly insensitive to small amounts of water.12
also observed in its absence. Presumably, Montmorillo-
nite K 10 acts as a carrier to increase the surface area in
this heterogeneous reaction. In the absence of copper(II)
acetate, the crude product was found to contain up to 10%
acetone oxime. The formation of acetone oxime is not sur-
prising in light of the fact that oximes have been synthe-
sized from aldehydes and ketones using acid catalyzed
transoximations by acetone oxime. No deprotection was
observed when cyclohexanone oxime or acetophenone
oxime was heated in acetone–H O in the absence of bis-
Bismuth
has
an
electron
configuration
of
1
4
10
2
3
[
Xe]4f 5d 6s 6p . Due to the weak shielding of the 4f
electrons (Lanthanide contraction), bismuth(III) com-
pounds exhibit Lewis acidity. Bismuth in the +5 state is an
oxidizing agent. Recently zinc bismuthate has been re-
ported as a reagent for conversion of allylic and benzylic
oximes to the corresponding aldehyde or ketone in high
15
2
muth nitrate, suggesting that the presence of this reagent
is necessary for deprotection.
A
suspension of
1
3
yields. Zn(BiO ) is however not commercially avail-
3
2
Bi(NO ) ·5H O in water is acidic. The aqueous layer from
3
3
2
able and must be synthesized prior to use. The deprotec-
the work up was also found to be very acidic (pH 2). Thus
it appears that the reagent, when suspended in the solvent,
releases small amounts of nitric acid which presumably
promotes the deprotection. It is also possible that the co-
ordination of bismuth to the oxime nitrogen increases the
susceptibility of the oxime carbon to nucleophilic attack
by water.
tion of oximes using BiCl under microwave irradiation
3
1
4
conditions has also been reported.
Synthesis 2001, No. 7, 01 06 2001. Article Identifier:
437-210X,E;2001,0,07,1010,1012,ftx,en;M00201SS.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
1
©

SHORT PAPER
Deprotection of Ketoximes
1011
Table Deprotection of Ketoximes using Bi(NO ) ·5H O in Ace-
much more resistant to the deprotection conditions. Ben-
zaldehyde oxime (entry 9) and anthraldehyde oxime (en-
try 10) were recovered unchanged when subjected to the
reaction conditions for 4 hours. Only partial deprotection
3
3
2
tone–H O
2
Entry Oxime
Time (h)Product
Yield
%)a
(
(
approx. 25%) was observed when heptanal oxime (entry
11) or cinnamaldehyde oxime (entry 12) was heated for
2 hours under the same conditions. This is in contrast to
1
2
2
3
88b
1
80c
results obtained with zinc bismuthate, which works well
for deprotection of aldoximes but fails to give good yields
of ketone with aliphatic ketoximes or dioximes.13
3
4
3
2
76c
A representative procedure is given here: A solution of
2
-heptanone oxime (2.00 g, 15.5 mmol) in acetone–H O
80d
2
(
9:1, v/v) (50 mL) was stirred as Bi(NO ) ·5H O (3.75 g,
3 3 2
7
.74 mmol), Cu(AcO) ·×H O (0.28 g, 1.55 mmol) and
2 2
Montmorillonite K 10 (3.0 g) were added. The mixture
was stirred and heated at reflux. After 5 h, the mixture was
suction filtered and the solids were rinsed with acetone.
The combined filtrates were concentrated on a rotary
evaporator to remove most of the acetone. The residue
512
2
5
90d
80d
62,d
was partitioned between sat. NaCl and Et O. The organic
68c
65c
2
7
8
9
12
21
layer was washed with sat. NaHCO , sat. NaCl, dried
3
(
Na SO ), and the solvents were removed on a rotary
2 4
evaporator to yield 1.42 g (80%) of 2-heptanone that was
1
13
determined to be > 98% pure by H and C NMR spec-
troscopy.
In summary, this work demonstrates a new and useful
method for deprotection of ketoximes. The advantages in-
clude (1) the use of a relatively non-toxic reagent that is
insensitive to air and moisture and (2) the use of a relative-
ly non-toxic solvent system.
4
4
NRf
NRf
1
0
e
e
Acknowledgement
1
1
1
2
12
12
We gratefully acknowledge financial support from The National
Science Foundation (NSF-RUI grant, CHE0078881).
a
b
c
d
Refers to yield of isolated product.
Purified by Kugelrohr distillation.
Purified by flash chromatography.
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(
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1
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e
NMR analysis of the crude product showed that only partial depro-
(
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f
NR = No reaction.
(
1
995.
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went hydrolysis at a much slower rate and hence it was
possible to isolate benzil monooxime from this reaction.
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SHORT PAPER
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Synthesis 2001, No. 7, 1010–1012 ISSN 0039-7881 © Thieme Stuttgart · New York