Simple preparation of polymer supported IBX esters and amides and their oxidative properties

Article abstract of DOI:10.1016/j.tetlet.2003.10.077

Novel polymer supported IBX esters and amides were prepared in two steps, which were the coupling of 2-iodobenzoic acid to a hydroxy or amino polystyrene followed by activation of the intermediate product. These polymer supported reagents were tested as oxidants by the conversion of a series of alcohols to the corresponding aldehydes or ketones. We found that the polymer supported IBX amides displayed excellent oxidative activity, in that they oxidized benzyl alcohol to benzaldehyde completely within 1 h at an oxidant to alcohol ratio of 2 to 1.

Full text of DOI:10.1016/j.tetlet.2003.10.077

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 9251–9254
Simple preparation of polymer supported IBX esters and amides
and their oxidative properties
Woo-Jae Chung, Duk-Ki Kim and Yoon-Sik Lee*
School of Chemical Engineering, Seoul National University, Kwanak-Ku, Seoul 151-744, Republic of Korea
Received 23 September 2003; accepted 15 October 2003
Abstract—Novel polymer supported IBX esters and amides were prepared in two steps, which were the coupling of 2-iodobenzoic
acid to a hydroxy or amino polystyrene followed by activation of the intermediate product. These polymer supported reagents
were tested as oxidants by the conversion of a series of alcohols to the corresponding aldehydes or ketones. We found that the
polymer supported IBX amides displayed excellent oxidative activity, in that they oxidized benzyl alcohol to benzaldehyde
completely within 1 h at an oxidant to alcohol ratio of 2 to 1.
©
2003 Elsevier Ltd. All rights reserved.
The hypervalent iodine reagent, 2-iodoxybenzoic acid
IBX, 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide)
from 2-amino-5-hydroxybenzoic acid, and then coupled
them onto appropriately-functionalized supports such
as silica gel, gel-type PS-based support, macroporous
(
has gained enormous interest as a highly efficient and
mild oxidant which can be used for the conversion of
5a–c
support, and several other soluble supports.
Subse-
1
alcohols to aldehydes or ketones. However, IBX is
quent to the activation step, the supported IBX
reagents brought about the fast and efficient conversion
of alcohol to aldehyde or ketone. Most recently, Lei et
al. reported an efficient synthesis of a polymer-sup-
ported IBX reagent that differs significantly from the
insoluble in most organic solvents except DMSO, and
this limitation has restricted the practical application of
this reagent. Therefore, several research groups have
tried to solve this problem by using an elevated reaction
2
3
5d
temperature, adding a suitable catalyst, performing
previously reported ones. They prepared a polymer-
4
the reaction in an ionic liquid and water, or using the
solid supported IBX. Recently, Zhdankin et al.
supported IBX reagent through three-step reactions
from macroporous poly(p-methylstyrene) beads, and
then oxidized a range of alcohols to the corresponding
aldehydes successfully using their polymer supported
oxidants. However, the loading level of the oxidant was
as low as 0.2ꢀ0.5 mmol/g, due to the presence of
undesired species generated during the iodination pro-
cess, and the preparation of the polymer supported
oxidants remained time-consuming (>2 days).
5
6
reported on the synthesis of novel IBX amides and
7
IBX esters, which are stable and soluble reagents
having oxidizing properties similar to IBX. They also
reported that the pseudo-cyclic structure of the amides
and esters, which arises from the intramolecular non-
bonding iodine-oxygen interaction, partially replaces
the intermolecular I···O secondary bonds that give rise
to the polymeric structure of the IBX. In recent years,
four research groups have reported on the synthesis of
polymer-supported IBX reagents and their oxidative
Here, for the first time, we propose a very simple
method of preparing polymer supported IBX esters and
amides, in two steps, involving the coupling of 2-
iodobenzoic acid to a hydroxy or amino functionalized
PS bead, followed by subsequent oxidation on the
beads. Also, we proved that these polymer supported
reagents were mild and efficient oxidants by the conver-
sion of a series of alcohols to the corresponding alde-
hydes or ketones.
5
properties, after being inspired by the many advan-
tages of polymer supported reagents, including their
easy work up and simple product isolation, which meet
the industrial needs for environmentally friendly chem-
istry. As a rule, these research groups synthesized IBX
precursors via several elaborate synthetic steps, starting
Keywords: polymer supported IBX ester; polymer supported IBX
amide; oxidant.
Synthesis of polymer supported IBX esters (Scheme 1-I).
8
*
Corresponding author. Tel.: +82-2-880-7080; fax: +82-2-876-9625;
Hydroxyalkyl PS resin (BTCore EM OH bead, 0.91
e-mail: yslee@snu.ac.kr
mmol/g, or 2.1 mmol/g, 1 mol% XL, 100–200 mesh)
0
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.077

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W.-J. Chung et al. / Tetrahedron Letters 44 (2003) 9251–9254
Scheme 1. Synthesis of polymer supported IBX esters and amides: (i-a) 2-iodobenzoic acid, DIC, DMAP, DMF, rt, 18 h; (i-b)
2
-iodobenzoic acid, BOP, HOBt, DIEA, DMF, rt, 4 h; (ii) NBu SO H, MeSO H, DCM, rt, 18–20 h.
4 5 3
was pre-swollen with DMF at room temperature for 1
h. 2-Iodobenzoic acid was coupled to the resin by
means of the standard DIC and DMAP coupling
method (rt, 18 h) to afford 2-iodobenzoate resin. The
resulting resin was oxidized successfully by reacting it
with an equimolar mixture of tetrabutylammonium
Evaluation of polymer supported oxidants. Firstly, to
determine the loading levels of the oxidants, excess
benzyl alcohol (>3 equiv.) was oxidized in DCM with
the oxidant beads (100 mg of beads/1 mL) for 18 h at
2
5°C, and the amount of benzaldehyde in the reaction
mixture was measured by GC/MS. The typical loading
levels of the oxidants, in the case of both the polymer
supported IBX esters and amides, were 0.65 mmol/g
9
oxone (5 equiv.) and methylsulfonic acid (DCM, rt,
1
8–20 h). The infrared spectra obtained from 2-
(
3a), 1.08 mmol/g (3b), and 0.98 mmol/g (6). The time
iodobenzoate resin 2, and the oxidant resin 3, revealed
courses of benzyl alcohol oxidation by the polymer
supported oxidants were evaluated in a similar way.
Under different oxidant to benzyl alcohol ratios, the
conversion of benzyl alcohol to benzaldehyde was mea-
sured according to the reaction time (Fig. 1). We found
that the polymer supported IBX amide 6, gave the
fastest oxidation of benzyl alcohol at an oxidant to
benzyl alcohol ratio of 2:1 (100% conversion within 1
that the strong carbonyl absorbance peaks of the ester
−
1
−1
linkage at 1728 cm shifted to 1670 cm after oxida-
tion, which is the characteristic absorbance peak of an
7
IBX ester. The activation of 2-iodobenzoate resin 2,
was terminated when the initial carbonyl peak at 1728
−
1
cm completely disappeared.
Synthesis of polymer supported IBX amides (Scheme
1
2
-II). Aminoalkyl PS resin (BTCore EM NH beads,
.1 mmol/g) was prepared from BTCore EM OH beads
2
(
2.1 mmol/g, 1 mol% XL, 100–200 mesh) by converting
the hydroxy group into an amino group via the Mit-
sunobu reaction followed by the Staudinger reaction.
10
The resin was pre-swollen with DMF solvent at room
temperature for 1 h. 2-Iodobenzoic acid was coupled to
the resin by the standard BOP, HOBt, DIEA (3 equiv.
each) coupling method (rt, 4 h) affording 2-iodobenz-
amide resin. The resin was oxidized successfully by
reacting it with an equimolar mixture of tetra-
butylammonium oxone (5 equiv.) and methylsulfonic
acid (DCM, rt, 18–20 h). The infrared spectra obtained
from the 2-iodobenzamide resins 5, and oxidant resins
6
, indicated that the strong carbonyl absorbance peak
Figure 1. The time courses of benzyl alcohol oxidation by
polymer supported IBX esters and IBX amides: using 2 equiv
of oxidant 3a (ꢀ); 2 equiv of oxidant 3b (ꢁ); 4 equiv of
oxidant 3b (ꢂ); 1.2 equiv of oxidant 6 (ꢃ); 2 equiv of
oxidant 6 (ꢄ). All reactions were performed at 25°C in DCM
(100 mg of bead/1 mL). Conversion (%) was determined by
GC/MS analysis.
−
1
−1
of the amide linkage at 1661 cm shifted to 1618 cm
after oxidation, which is the characteristic absorbance
peak of an IBX amide. The activation of the 2-
iodobenzamide resin was terminated when the
initial carbonyl peak at 1661 cm completely disap-
peared.
6
−
1

W.-J. Chung et al. / Tetrahedron Letters 44 (2003) 9251–9254
9253
h), while the polymer supported IBX esters showed
similar activities to those of the previously reported
insoluble solid supported IBX reagents.
primary alkyl alcohol, 1-decanol, was converted to the
corresponding aldehyde quantitatively after 14 h. These
results demonstrate the very promising activity of the
polymer supported IBX amide 6. Normally, more than
2–5 h would be required to convert benzyl alcohol to
benzaldehyde under similar reaction conditions, and the
oxidation of the primary alkyl alcohol would not have
resulted in more than 60% conversion, even after
To explain the above results, we propose a mechanism
for the oxidation of an alcohol by the supported IBX
amide 6, as shown in Figure 2. Compared with the IBX
ester oxidant, the carbonyl oxygen of the IBX amide
can enter into a stronger intramolecular nonbonding
interaction with iodine. Consequently, this leads to the
formation of a more favorable equilibrium state
between 6, and the cyclic IBX derivative 7, and the
same path of alcohol oxidation as that involving the
common form of IBX is followed (i.e. ligand exchange
5c
extending the reaction time, with the previously
reported polymer supported IBX reagents. With cyclo-
hexanol, the polymer supported IBX amide 6, gave 40%
conversion to cyclohexanone in 1 h. After extending the
reaction time (14 h), it resulted in 81% conversion to
cyclohexanone and an additional 8% conversion to
a,b-unsaturated cyclohexenone, probably via the dehy-
11
and disproportionation), affording an aldehyde and
leaving the iodoso compound on the resins.
5
b,12
drogenation of the first product, cyclohexanone.
These results inspired us to investigate more thoroughly
the oxidative properties of the polymer supported IBX
amide 6, with a series of additional alcohol substrates.
Thus, 4-nitrobenzyl alcohol, 4-methoxybenzyl alcohol,
In summary, we have prepared novel polymer sup-
ported IBX esters and amides in two simple steps. The
oxidant resins were prepared with high loadings of
0.65ꢀ1.08 mmol/g, and were evaluated with a series of
alcohol substrates. The polymer supported IBX amide
6, exhibited particularly fast and efficient oxidative
activities toward a series of alcohols under mild reac-
tion conditions. To the best of our knowledge, our
polymer supported IBX amide 6, resulted in the faster
conversion of alcohols to the corresponding aldehydes
than any other previously reported insoluble polymer
supported IBX reagents.
1
-decanol, and cyclohexanol were oxidized by 2 equiv.
of the polymer supported IBX amide 6, in DCM, and
the reaction mixtures were analyzed by GC/MS to
measure the conversion yields of the alcohols to the
corresponding aldehydes or ketones (Table 1).
The oxidation of the benzyl alcohol derivatives resulted
in nearly complete conversion after only 1 h. Even the
Figure 2. Suggested mechanism of benzyl alcohol oxidation with polymer supported IBX amide.

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W.-J. Chung et al. / Tetrahedron Letters 44 (2003) 9251–9254
Table 1. Results of alcohol oxidation using the polymer
supported IBX amide 6
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of Seoul National University, which is supported by
the Korean Science and Engineering Foundation
KOSEF), and the Brain Korea 21 Program supported
by the Ministry of Education.
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