Mild oxidation of alcohols with o-iodoxybenzoic acid (IBX) in a water/CH2CL2 mixture in the presence of phase-transfer catalyst

Article abstract of DOI:10.1080/00397910600770821

A mild oxidation of alcohols to the respective carbonyl compounds with o-iodoxybenzoic acid (IBX) catalyzed by n-Bu₄NBr in a water/dichloromethane (1:1) mixture is described. The method offers the advantage of a simple, inexpensive catalyst and the diminution of organic solvent employed in the reaction. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600770821

Synthetic Communicationsw, 36: 2887–2892, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600770821
Mild Oxidation of Alcohols
with o-Iodoxybenzoic Acid (IBX) in a
Water/CH2Cl2 Mixture in the Presence
of Phase-Transfer Catalyst
Chutima Kuhakarn, Krisada Kittigowittana,
Pattama Ghabkham, Manat Pohmakotr,
and Vichai Reutrakul
Department of Chemistry, Faculty of Science, Mahidol University,
Bangkok, Thailand
Abstract: A mild oxidation of alcohols to the respective carbonyl compounds with
o-iodoxybenzoic acid (IBX) catalyzed by n-Bu4NBr in a water/dichloromethane
(1:1) mixture is described. The method offers the advantage of a simple, inexpensive
catalyst and the diminution of organic solvent employed in the reaction.
Keywords: Alcohols, IBX, oxidation, phase-transfer catalyst
INTRODUCTION
Hypervalent iodine reagents have gained much attention because of their mild,
selective, and environmentally friendly properties as oxidizing agents in
organic synthesis.[1] Among this class of compounds, the Dess–Martin perio-
dinane (DMP) and its precursor, o-iodoxybenzoic acid (IBX), have gained
popularity as the reagents of choice for conversion of alcohols to aldehydes
or ketones and other synthetically useful oxidative transformations.[2–4]
Reported since 1893,[5] IBX has been rarely used because of its virtual inso-
lubility in most common organic solvents. The first practical applications of
IBX have been conducted in DMSO.[3] Even though not entirely inconvenient,
Received in India February 28, 2006
Address correspondence to Chutima Kuhakarn, Department of Chemistry, Faculty
of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand. E-mail:
scckk@mahidol.ac.th
2887

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C. Kuhakarn et al.
the limitations of using the high-boiling dimethyl sulfoxide (DMSO) as a
solvent are apparent and have led to many variations.
In recent years, there are several syntheses of solid-supported IBX.[6] In
each work, the authors demonstrated that these solid-supported analogues of
IBX have found use as oxidant particularly suitable for converting alcohols to
the respective carbonyl compounds, in good to excellent yields. Efforts
toward the synthesis of modified IBX reagents that allow better solubility in
other solvents besides DMSO have also been reported.[7] Recently, it was
demonstrated that IBX is an effective heterogeneous oxidant in most organic
solvents at elevated temperature[8] or in the presence of a suitable catalyst.[9]
Most recently, the oxidation of a diverse collection of alcohols using IBX
was carried out in a mixture of an ionic liquid and water as the solvent.[10]
The authors noted that this methodology represents mild and homogeneous
reaction conditions, simplifies separation of oxidation by-products, and facilitates
the recovery and reuse of the oxidant. Quite remarkably, IBX has recently been
demonstrated to be employed as an oxidant under solvent-free conditions,[11] as
well as a catalytic oxidant in the presence of a co-oxidizing reagent.[12]
RESULTS AND DISCUSSION
As a part of our research program to develop IBX oxidation under various
conditions and novel applications of IBX, we have previously reported a
selective oxidation of secondary alcohols by IBX.[13] We now describe a
simple and mild method for the oxidation of benzylic, allylic, and aliphatic
alcohols with IBX catalyzed by n-Bu4NBr in a water/CH2Cl2 mixture as
the solvent. This allows the oxidation reaction to proceed at room temperature
in an aqueous/organic medium.
Typical reaction conditions employed 1.5 equivalents of IBX and 0.5
equivalent of n-Bu4NBr in 1:1 v/v mixture of water/CH2Cl2 as a solvent.
The reaction was maintained at room temperature for 4 h. A variety of
alcohols underwent oxidation to give the corresponding carbonyl compounds
in variable yields. Among the alcohols investigated, benzylic alcohols gave
moderate to excellent yields of the corresponding carbonyl compounds. The
oxidation efficiency is seemingly dependent on the electronic environment on
the phenyl ring. Initially, the study began with the oxidation of benyl alcohol
and substituted benzyl alcohols containing substituents on phenyl ring
(entries 1–6, Table 1). Benzyl alcohol was oxidized to benzaldehyde in good
yield (81%, entry 1). The reactions show a dramatic substituent effect on the
oxidative process. Electron-releasing substituents such as the methoxy group
improved the yield (92%, entry 2). In contrast, the presence of the electron-with-
drawing groups resulted in low yields of the aldehyde products as a function of
electron-attracting power. The reaction of p-nitro- and m-nitrobenzyl alcohols
sluggishly proceeded to give the corresponding aldehydes in low yields
(entries 3 and 4). p-Chlorobenzyl alcohol gave p-chlorobenzaldehyde in

Oxidation of Alcohols with IBX in Water/CH2Cl2 Mixture
2889
Table 1. Oxidation of alcohols with IBX using catalytic n-Bu4NBr in
1:1 v/v water/CH2Cl2 mixture
Entry
1
Substrate
Product
Yield (%)a
81
2
3
92
12
4
5
19
72
6
7
37
71
8
9
62
66
10
11
94
72
12
52
(continued)

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C. Kuhakarn et al.
Table 1. Continued
Entry
Substrate
Product
Yield (%)a
b
13
14
H3C(H2C)4–CH2OH
H3C(H2C)6–CH2OH
H3C(H2C)4–CHO
H3C(H2C)6–CHO
—
b
—
15
19
16
80
aYield of product isolated after column chromatography.
bLess than1% conversion to aldehyde was observed by 1H NMR (300 MHz).
moderate yield (72%, entry 5). To our surprise, 3,4-(methylenedioxy)benzyl
alcohol afforded piperonal in low yield (37%, entry 6). Secondary benzylic
oxidation also gave satisfactory results. 1-Phenylethanol smoothly underwent
the oxidation to afford acetophenone in moderate yield (71%, entry 7). The
yields were decreased when steric demanding of the alkyl groups increased
(entries 8 and 9). Interestingly, when highly hindered mesityl methyl carbinol
was employed as a substrate (entry 10), the corresponding ketone was
obtained in excellent yield (94%). Oxidation of primary allylic alcohols was
also investigated to result in the formation of a,b-unsaturated aldehydes in
moderate to good yields (entries 11 and 12). It should be noted that primary
aliphatic alcohol was sluggish to undergo oxidation under the reaction con-
ditions (entries 13 and 14). On the contrary, even though menthol was not a
good substrate under the reaction conditions employed, a simple aliphatic
secondary alcohol (i.e., cyclohexanol) was oxidized to cyclohexanone in
good yield (entries 15 and 16). All of the carbonyl compounds were character-
ized by 1H NMR, IR, and comparison with the known compounds.
In conclusion, we have demonstrated a mild, convenient, and easy
procedure for the oxidation of alcohols to carbonyl compounds using
IBX at ambient temperature in the presence of a phase-transfer catalyst
(n-Bu4NBr) under a biphasic system (aqueous/dichloromethane mixture).
EXPERIMENTAL
General Procedure for the Oxidation of Alcohols with IBX
Catalyzed by n-Bu4NBr
To a suspension of IBX (1.5 equiv) in 1:1 v/v mixture of water/CH2Cl2
(0.25 M based on starting alcohol), n-Bu4NBr (0.5 equiv) was added

Oxidation of Alcohols with IBX in Water/CH2Cl2 Mixture
2891
followed by alcohol (1.0 mmol). The resulting mixture was stirred at room
temperature for an additional 4 h. The residual solids were filtered through
filter paper and washed thoroughly with diethyl ether. The filtrate was
washed successively with 8% aqueous sodium thiosulfate (15 mL), water
(2 Â 15 mL) and brine (1 Â 15 mL). The organic layer was dried (anh.
Na2SO4), filtered, and evaporated (aspirator) to give a crude product, which
was purified by column chromatography on silica gel. All products were
1
identified by H NMR spectroscopy.
ACKNOWLEDGMENT
We acknowledge the financial support by the Thailand Research Fund (TRF)
for the post doctoral research fellowship awarded to C. K. The support
provided by the Postgraduate Education and Research Program in
Chemistry (PERCH) and the facilities at the Department of Chemistry,
Mahidol University, are also gratefully acknowledged.
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