Clean and highly selective oxidation of alcohols in an ionic liquid by using an ion-supported hypervalent iodine(III) reagent

Article abstract of DOI:10.1002/anie.200461889

Alcohol consumption: The Phl(OAc)₂-derived hypervalent iodine reagent 1 acts as an oxidant in the conversion of primary and secondary alcohols 2 into carbonyl compounds 3 with good to excellent yields (see scheme). The bromide ion remaining from the preparation of [emim]⁺[BF ₄]-(emim = 1-ethyl-3-methylimidazolium tetrafluoroborate) acts as a catalyst in the reaction. Primary alcohols are oxidized without any detectable overoxidation.

Full text of DOI:10.1002/anie.200461889

Communications
Oxidation Reagents
Clean and Highly Selective Oxidation of Alcohols
in an Ionic Liquid by Using an Ion-Supported
Hypervalent Iodine(iii) Reagent
Weixing Qian, Erlei Jin, Weiliang Bao, and
Yongmin Zhang*
The oxidation of alcohols to carbonyl compounds plays an
important role in organic synthesis, not only in the laboratory
but also at the industrial level. Numerous methods are
available to accomplish this conversion under various reac-
tion conditions.[1] The demands in recent years for environ-
mentally benign and eco-conscious chemical processes are
encouraging chemists to search for clean, high-yielding, highly
selective, and economical oxidation methods.[2] In the last
decade, in particular, there has been increasing interest in the
oxidizing properties of organohypervalent iodine reagents.[3]
The extensively studied pentavalent iodine reagents, for
example, Dess–Martin periodane (DMP)[4] and its direct
precursor o-iodoxybenzoic acid (IBX),[5] oxidize alcohols
efficiently to carbonyl compounds in organic solvents such as
DMSO, CH2Cl2, and acetone. Despite their utility and
popularity, these iodine(v) oxidants are potentially explosi-
ve.[2e] Thus, the readily available and stable iodine(iii)
oxidants such as iodosobenzene PhIO and diacetoxyiodoben-
zene PhI(OAc)2 attract much attention. An effective and
convenient polymer-supported PhI(OAc)2 reagent was dem-
onstrated by Tohma et al. for the oxidation of alcohols in
aqueous media with a potassium bromide catalyst, but
primary alcohols were further oxidized to carboxylic
acids.[2e] Adam et al. employed CrIII–salen complexes
(salen = N,N’-bis[(2-hydroxyphenyl)methylene]-1,2-ethane-
diimine) for the selective catalytic oxidation of allylic alcohols
to enones by PhIO and PhI(OAc)2 in dichloromethane.[6]
However, in view of the carcinogenicity of chromium com-
pounds, environmental and health concerns greatly limit their
use. Although the dehydrogenating properties of PhIO and
PhI(OAc)2 have been demonstrated in a few cases, only a
limited number of clean and selective catalytic oxidations of
alcohols to carbonyl compounds have been reported.[7]
Recently, much attention has been focused on the use of
ionic liquids as environmentally benign reaction media.
Various chemical reactions can be performed in ionic
liquids.[8] This fact is attributed to some intriguing properties
of ionic liquids, such as high thermal stability, negligible vapor
pressure, high loading capacity, and tunable polarity. In view
of these distinct advantages, ionic liquids have become an
[*] Prof. W. Qian, E. Jin, Prof. W. Bao, Prof. Y. Zhang
Department of Chemistry
Zhejiang University, Xi Xi Campus
Hangzhou, Zhejiang 310028 (P. R. China)
Fax : (+86)571-8880-7077
E-mail: yminzhang@mail.hz.zj.cn
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200461889
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Angewandte
Chemie
exciting area of research. More recently, ionic liquid formu-
lations have been expanded to include ions with structurally
and functionally complex side chains—the so-called “task-
specific ionic liquids”.[9] Miao and Chan employed ionic
liquids as soluble supports for a Suzuki coupling reaction.[10]
In comparison with traditional polymer supports or soluble
polyethylene glycol (PEG), which has some limitations in
loading capacity and solubility,[11] these low-molecular-weight
ionic liquids have larger loading capacity and tunable
solubility. Herein we report the preparation of 1-(4-diacetoxy-
iodobenzyl)-3-methylimidazolium tetrafluoroborate ([dib-
mim]+[BF4]À; 1) and its application in the oxidation of
alcohols.
oxidant was conducted in the ionic liquid [emim]+[BF4]À (1-
ethyl-3-methylimidazolium tetrafluoroborate; Scheme 1) in
the presence of a low concentration of bromide ions under
mild conditions (308C, a 1:1.4 ratio of substrate 2:oxidant 1;
(Table 1).
Compound 1 was readily synthesized by reaction of 1-
methylimidazole with 4-bromomethyliodobenzene and then
oxidation with peracetic acid (30% H2O2 and acetic anhy-
dride). The oxidation of alcohols using [dibmim]+[BF4]À as an
Scheme 1. Selective oxidation by [dibmim]+[BF4]À (1) in [emim]+[BF4]À
of alcohol substrates (2) to give carbonyl compounds (3).
Table 1: Oxidation of alcohols with [dibmim]+[BF4]À in [emim]+[BF4]À.
Entry
Substrate
Product
t [h]
3
Yield [%][a]
1
2
3
2a
2b
2c
3a
3b
3c
92[b]
95
3
3
91
4
5
2d
2e
3d
3e
3
3
89
57
6
7
2 f
3 f
3
4
94[b]
2g
3g
<5
3g’
3h
3i
93
8
9
2h
2i
16
18
95
75[c]
10
11
12
2j
2k
2l
3j
3k
3l
4
5
5
90[b]
94
96
13
14
2m
2n
3m
3n
2
9
93
98[c]
15
2o
3o
12
98[c]
[a] Yields of isolated product after chromatographic purification unless otherwise noted. [b] Yields were determined by 1H NMR spectrometry. [c] Ten
drops of acetonitrile were added to increase the solubility of substrates.
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Communications
A variety of primary and secondary alcohols were
concentration from 0 to 10% (w/w). The reaction was
oxidized to carbonyl compounds in moderate to excellent
yields at room temperature. The reactions were performed in
a flask without any particular precautions. Under these
conditions primary alcohols (Table 1, entries 1–6) were oxi-
dized in less than four hours to the corresponding aldehydes
in 57–95% yields without any noticeable overoxidation to the
carboxylic acids. Secondary alcohols (Table 1, entries 8–15)
were oxidized to the corresponding ketones over longer
reaction times except for entry 13. The oxidation was
relatively sluggish (16–18 h) and needed two equivalents of
oxidant for the unactivated, alicyclic substrates (Table 1,
entries 8 and 9). Notably, cinnamyl alcohol (Table 1, entry 7)
was mainly converted into the double-bond addition product.
It has been suggested that the oxidation of alcohols is
catalyzed by a small amount of bromide ion remaining in the
[emim]+[BF4]À.[12] A possible mechanism for the oxidation of
alcohols with [dibmim]+[BF4]À is described in Scheme 2. The
performed in
a
mixture of purified ionic liquid
[emim]+[BF4]À (1.50 g), alcohol (0.5 mmol), and oxidant
(0.7 mmol). We were pleased to find that alcohol 2c was
oxidized to aldehyde 3c in 72–93% yield (Table 2). A low
Table 2: The influence of the bromide ion concentration on oxidation.
Entry
Conc. of BrÀ [%(w/w)]
0.0
t [h]
Yield [%]
1
2
3
4
5
6
7
24
3
3
3
3
84
91
72
92
93
91
83
ca. 1.9
0.5
1.0
2.0
5.0
10.0
3
3
concentration of bromide ions (Table 2, entry 3, 0.5%) was
unfavorable since it slowed down the reaction rate; the
reaction was very slow in the absence of bromide ions
(Table 2, entry 1). However, when 10% of bromide ion (equal
to 0.193 g NaBr) was added to 1.50 g of purified
[emim]+[BF4]À, the solid could not dissolve in the ionic
liquid completely, which made the solution too thick to stir
efficiently and resulted in a decreased yield. No further
oxidation of 4-chlorobenzaldehyde to the corresponding
carboxylic acid was observed even after the reaction times
were prolonged to 24 hours. We think that in this system the
ionic liquid [emim]+[BF4]À plays a very important role in
preventing aldehydes from overoxidation to carboxylic
acids.[15]
Scheme 2. A possible mechanism for the oxidation of substrates by
[dibmim]+[BF4]À.
bromide ion present in the [emim]+[BF4]À seems to be
oxidized by [dibmim]+[BF4]À to form a highly active inter-
mediate Br+ ion, probably in the form of acetyl hypobromite
or the bromate(i) complex reported by Kirschning and co-
workers,[13] which reacts with alcohols to produce the
To evaluate the performance of [dibmim]+[BF4]À we
compared it with the widely used oxidant PhI(OAc)2 in
[emim]+[BF4]À. The results (Table 3) show that the yields of
alcohols using [dibmim]+[BF4]À are higher than those with
PhI(OAc)2 in the same reaction time. For the primary
alcohols (Table 3, entries 1 and 2) with PhI(OAc)2 as the
oxidant, an electron-donating group on the aryl ring gives
satisfactory yields, but an electron-withdrawing group greatly
decreases the yields. Poor yields are obtained in the oxidation
of secondary alcohols, which means not only electronic effects
corresponding carbonyl compounds with regeneration of the
+
bromide ion.[14] The Br ion attacks a C C bond of a substrate
=
preferentially, so the main product from the oxidation of
cinnamyl alcohol is 2,3-dibromo-3-phenylpropanol.
The ionic liquid [emim]+[BF4]À used in the above
reactions was prepared by the metathesis of 1-ethyl-3-
methylimidazolium bromide with sodium tetrafluoroborate
in acetone. However, this method did not remove the bromide
ion completely if no further purification procedure was
applied. Although the oxidation reaction proceeded in high
yield, we were concerned about whether the change in
concentration of the bromide ion would lead to overoxida-
tion. Therefore, we investigated the influence of bromide ion
concentration on the oxidation result. First, the concentration
of bromide ion in [emim]+[BF4]À was measured by Volhardꢀs
procedure (Table 2, entry 2) to be 1.82–1.94% (w/w). The
ionic liquid [emim]+[BF4]À was then thoroughly purified
through method B reported by Park and Kazlauskas.[12] In the
following experiment sodium bromide was taken as the
source of the bromide ion.
Table 3: Comparison of [dibmim]+[BF4]À with PhI(OAc)2 in
[emim]+[BF4]À.
Entry Substrate Product t [h] Yield with
PhI(OAc)2 [%]
Yield with
[dibmim]+[BF4]À [%]
1
2
3
4
5
2b
2c
2k
2l
3b
3c
3k
3l
3
3
5
5
9
73
37
32
95
91
94
22
96
2n
3n
11[a]
98[a]
The oxidation of 4-chlorobenzyl alcohol (2c) was exam-
ined as a standard substrate while varying the bromide ion
[a] Ten drops of acetonitrile were added to increase the solubility of the
substrates.
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In conclusion, we have demonstrated that the dehydro-
genating properties of [dibmim]+[BF4]À can be used for the
oxidation of alcohols to carbonyl compounds. The main
features of this process are: 1) a high degree of selectivity for
the oxidation of primary alcohols to carbonyl compounds in
an ionic liquid; 2) easy workup and environmentally benign—
the ion-supported hypervalent iodine(iii) reagent can be
recovered and reused after oxidation with peracetic acid; and
3) notably, the aldehydes do not undergo further oxidation to
carboxylic acids even at longer reaction times. Studies on
applications of [dibmim]+[BF4]À in other reactions are in
progress.
Received: September 3, 2004
Published online: January 3, 2005
Keywords: alcohols · hypervalent compounds · iodine ·
.
ionic liquids · oxidation
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