5
46
Published on the web April 24, 2010
Selective Oxidation of Hydrazides Using o-Iodoxybenzoic Acid
to Carboxylic Acids, Esters, and Aldehydes
Balaram S. Takale and Vikas N. Telvekar*
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology,
Matunga, Mumbai 400 019, India
(
Received March 11, 2010; CL-100228; E-mail: vn.telvekar@ictmumbai.edu.in)
A selective method for conversion of hydrazide to
CHO
CHCl , catalytical base
3
corresponding aldehydes, acids, and esters by using hypervalent
iodine reagent o-iodoxybenzoic acid (IBX) has been developed
under different reaction conditions. The developed method is
mild and gives moderate to good yields for both aliphatic and
aromatic substrates.
O
NH-NH2
15 min, 94%
COOH
COOCH3
IBX
rt
CHCl3,H2O
15 min, 90%
CHCl , CH OH
3
3
30 min, 80%
Hydrazides are important intermediates required in protec-
tion and deprotection of carboxylic acids in peptide chemistry.
1
Scheme 1. Conversion of benzohydrazide into benzaldehyde, benzoic
acid, and methyl benzoate using IBX at room temperature.
However, potential utility and applicability as a protecting group
are diminished considerably owing to high hydrolytic stability.
Hence, much less work has been done for deprotection of
hydrazide and thus deprotection of hydrazide to the correspond-
ing acid using mild conditions is of great interest. Similarly there
are few methods reported for the conversion of aldehydes and
esters from corresponding hydrazides. Previous methods for all
Table 1. Effect of different base on formation of benzaldehyde from
benzohydrazide
a
b
Entry
Base
Yield /%
1
2
3
4
5
Ammonia
Pyridine
Triethylamine
NaOH
94
80
90
50
35
2
these conversions included use of acidic resin, benzeneseleninic
3
4
5
acid anhydride, copper(II) catalyst, enzymatic cleavage, lead
NaOMe
6
7
8
tetraacetate, oxone, cerric ammonium nitrate, NaBH /copper
4
a
9
10
Reaction conditions: benzohydrazide (1 equiv), IBX (1 equiv),
chloride, and thallium(III) in acidic medium, however, all
these methods require either toxic metals or tedious work up
procedure. Hypervalent iodine reagents have found widespread
applications in organic synthesis because of their selectivity and
b
and base (0.1 equiv); 15 min. Isolated yield by column
chromatography.
11
simplicity in use. Ever since the innovative work by Dess and
the presence of neat methanol as a solvent reaction does not take
place, due to the insolubility of IBX, thus combination of
methanol and chloroform is required. In the third case,
combination of chloroform and water (1:1) gives benzoic acid
as a product. All these reactions give quantitative yield in short
reaction time. We also observed that higher esters are possible
when higher alcohols are used. Chloroform can be replaced by
dichloromethane and acetonitrile without affecting the results.
In order to explore the reaction scope, a variety of
hydrazides were prepared by standard reported procedures and
were selectively converted to corresponding aldehydes, carbox-
1
2
Martin, explorations into the chemistry of pentavalent iodine
compounds have become the subject of growing interest due to
their mild nature. Our group has been working extensively on
the development of novel methodologies under mild reaction
conditions using various hypervalent iodine reagents like o-
iodoxybenzoic acid (IBX).13 Recently efficient cleavage of
N¤,N¤-dimethylhydrazide has been reported by using PhI(OH)Ts
to corresponding acids, however, no attempts have been made
to prepare aldehydes and esters from corresponding N¤,N¤-
1
4
dimethylhydrazides.
1
5
Herein we report for the first time a new application of IBX
for oxidative conversion of hydrazides into corresponding
aldehydes, acids, and esters. During our reaction study we
found that hydrazides can be converted selectively into
corresponding carboxylic acids, esters, and aldehydes under
different reaction conditions using IBX at room temperature in
short reaction time. We carried out reactions using benzohy-
drazide as a model substrate (Scheme 1). In the first case,
benzohydrazide was converted into benzaldehyde by using
different organic and inorganic bases in chloroform (Table 1).
The reactions were carried out by using 0.1 equivalent base in
ylic acid, and esters in moderate to good yields.
It was clearly indicated that hydrazides substituted with
electron-donating groups like hydroxy or methoxy undergo very
fast transformation giving desired aldehydes (Table 2, Entries 2
and 3), carboxylic acid (Table 3, Entries 2 and 3), and esters
(Table 4, Entries 2 and 3) in a short reaction time and good
yields. On the other hand electron-withdrawing groups such as
nitro, comparatively lower yields and slower reaction rate were
observed (Table 2, Entry 4; Table 3, Entry 4; and Table 4,
Entry 4).
With the same reagent system heterocyclic hydrazides also
gave good yields of the corresponding aldehydes, carboxylic
acid, and esters, with lower reaction rate (Table 2, Entry 5;
Table 3, Entry 5; and Table 4, Entry 5). These reaction systems
are also suitable for conversion of aliphatic hydrazides to
15 min at room temperature and it was observed that liquor
ammonia is suitable base for this conversion.
In the second case, the presence of a methanol and
chloroform mixture (1:1) reaction gave methyl benzoate. In
Chem. Lett. 2010, 39, 546547
© 2010 The Chemical Society of Japan
Takale, Balaram S.
