A facile deprotection of oximes using glyoxylic acid in an aqueous medium

Article abstract of DOI:10.1016/j.tetlet.2004.02.049

Oximes of ketones and aldehydes are efficiently deprotected with glyoxylic acid in an aqueous medium at room temperature. Oximes can be cleaved selectively in the presence of a TBDMS group. This method is high yielding, fast, clean, safe, cost effective, and therefore very suitable for practical organic synthesis.

Full text of DOI:10.1016/j.tetlet.2004.02.049

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 3161–3162
A facile deprotection of oximes using glyoxylic
acid in an aqueous medium
Subhash P. Chavan* and Priti Soni
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune 411008, India
Received 16 December 2003; revised 28 January 2004; accepted 5 February 2004
Abstract—Oximes of ketones and aldehydes are efficiently deprotected with glyoxylic acid in an aqueous medium at room tem-
perature. Oximes can be cleaved selectively in the presence of a TBDMS group. This method is high yielding, fast, clean, safe, cost
effective, and therefore very suitable for practical organic synthesis.
Ó 2004Elsevier Ltd. All rights reserved.
Oximes are frequently used to protect carbonyl com-
pounds in the course of total syntheses and hence a
plethora of reagents and methods1 have been devised for
the deprotection of oximes. Methods so far developed to
regenerate carbonyl compounds from oximes consist of
oxidative2–6 or acid catalyzed7 or reductive reactions.8
Most of the methods involve reagents that are often
hazardous or very toxic, expensive or not readily avail-
able.9–18 These reagents often need to be freshly pre-
pared or the reaction requires drastic conditions, long
reaction times, and tedious work up. With increasing
environmental concerns, it is imperative that new envi-
ronmentally friendly reagents be developed.
anticipated that both functionalities could be utilized
and exploited for functional group transformations of
carbonyl compounds. Encouraged by the ability of gly-
oxylic acid to effect deprotection of oxathiolanes21 we
wanted to explore the potential of the activated aldehyde
in glyoxylic acid as an acceptor of oxime. We postulated
that the activated aldehyde would serve as an excellent
acceptor, in the presence of the internal acid, and would
be able to transform oximes into the corresponding
carbonyl compounds. We now report that glyoxylic acid
is an efficient reagent for the selective deprotection of
oximes derived from ketones and aldehydes (Scheme 1).
The experimental procedure is very simple and involves
stirring the oxime with 50% aq glyoxylic acid at room
temperature. The reaction is fast and the product can be
isolated by simple aqueous work up. The reaction is
monitored by TLC. After completion of the reaction,
reaction mixture is extracted with ether. The ether layer
is separated, washed with 10 mL aq NaHCO3, (10%)
dried over anhydrous Na2SO4, filtered, and solvent is
removed under reduced pressure to furnish carbonyl
compound in pure form. Glyoxylic acid is commercially
available as a 50% aqueous solution and requires no
special handling. The reactions are performed in aqueous
medium without any additional organic solvent. The
carbonyl compounds thus obtained were sufficiently pure
The identification of aqueous glyoxylic acid as a mild
and chemoselective reagent for the deprotection of oxi-
mes under solvent-free conditions formed the basis of
this investigation. Organic reactions in water, without
the use of any harmful organic solvents, are of great
current interest, because water is an easily available,
economical, safe, and environmentally benign solvent.
Levulinic acid19 and pyruvic acid20 have been reported
for trans-oximation, but the former procedure uses 1 N
HCl, and the latter method acetic acid at reflux. This is
not a very desirable situation when other acid-sensitive
groups are present in the molecule.
Intrigued by the presence of two functional groups, viz
acid as well as reactive aldehyde in glyoxylic acid, it was
OH
N
O
CHOCOOH
RT
R
R'
R
R'
Keywords: Ketone; Aldehyde; Oxime.
* Corresponding author. Tel./fax: +91-20-5893614; e-mail: spchavan@
dalton.ncl.res.in
R, R' = alkyl, aryl, H
Scheme 1.
0040-4039/$ - see front matter Ó 2004Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.049

3162
S. P. Chavan, P. Soni / Tetrahedron Letters 45 (2004) 3161–3162
Table 1. Deprotection of oximes
of reactivity was observed with phenolic t-butyl dimethyl
silyl ether. To demonstrate the chemoselectivity of this
reagent we prepared the TBDMS ether (entry 1). We
were able to selectively deprotect the oxime group
without affecting the TBDMS group in an excellent yield.
Entry
Substrate
Product
Time (h)
Yield (%)
NOH
CHO
1
1
96
OMe
Thus this method could be used to selectively deprotect
oximes in the presence of a TBDMS ether in a multi-
functional compound.
OMe
OTBDMS
OTBDMS
O
NOH
In conclusion, this paper describes the use of glyoxylic
acid for the chemoselective deprotection of oximes in an
aqueous medium. The advantages of this method are the
ease of work up, the observed selectivity and the use of
environmentally benign reagent that is easy to handle
and is inexpensive.
2
3
4
1
94
94
95
OH
OH
NOH
CHO
1.2
NO2
NO2
Acknowledgements
NOH
CHO
One of the authors P.B.S. thanks CSIR, New Delhi for
financial support. Funding from CSIR, New Delhi un-
der YSA (SPC) scheme is gratefully acknowledged.
1
OMe
O
OMe
NOH
5
6
1
1
94
94
References and notes
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NOH
O
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NOH
NOH
O
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9
1.5
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NOH
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1
O
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No reaction
1.5
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OTBDMS
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Oximes derived from aromatic as well as simple ketones
were smoothly deprotected at room temperature. Lack