A facile route to a polymer-supported IBX reagent

Article abstract of DOI:10.1016/S0040-4039(03)00041-8

A three-step preparation of a polymer-supported IBX reagent from poly(p-methylstyrene) is reported. This reagent has been used successfully for the efficient oxidation of a series of alcohols to the corresponding aldehydes.

Full text of DOI:10.1016/S0040-4039(03)00041-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 1635–1637
A facile route to a polymer-supported IBX reagent
Z. Lei,a C. Denecker,b S. Jegasothy,c D. C. Sherrington,b N. K. H. Slaterc and A. J. Sutherlanda,*
aChemical Engineering & Applied Chemistry, Aston University, Aston Triangle, Birmingham B4 7ET, UK
bDepartment of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK
cDepartment of Chemical Engineering, University of Cambridge, New Museums Site, Pembroke Street,
Cambridge CB2 3RA, UK
Received 25 November 2002; revised 9 December 2002; accepted 20 December 2002
Abstract—A three-step preparation of a polymer-supported IBX reagent from poly(p-methylstyrene) is reported. This reagent has
been used successfully for the efficient oxidation of a series of alcohols to the corresponding aldehydes. © 2003 Elsevier Science
Ltd. All rights reserved.
In 1983 Dess and Martin first introduced the use of
hypervalent compounds to facilitate the oxidation of
alcohols.1 They demonstrated successfully that periodi-
nane (DMP) 1, prepared in two steps from o-iodoben-
zoic acid, could be used to oxidise primary and
secondary alcohols to the corresponding aldehydes and
ketones. Subsequently, this reagent found widespread
use in synthetic organic chemistry and is renowned for
its mild reactivity and chemoselectivity. Unfortunately,
however, periodinane 1 is unstable to prolonged storage
and is thus best synthesised immediately prior to use. In
1994 Frigero and Santagostino reported that the pre-
cursor to DMP 1, 1-hydroxy-1,2-benziodoxole-3(1H)-
one-1-oxide (IBX) 2 could also be utilised in the
oxidation of alcohols.2 The mildness of this reagent was
further demonstrated by the finding that IBX could
also be employed in the oxidation of 1,2-diols to 1,2-
diketones without the unwanted cleavage of the CꢀC
bond associated with the use of DMP 1,3 tetra-
propylammonium perruthenate4 (TPAP) or pyridinium
chlorochromate5 (PCC) reagents. IBX 2 is still continu-
ing to find new and varied applications in organic
synthesis.6
Polymer-supported reagents have found widespread
utility in organic synthesis.7 Their use is especially
relevant in automated high through-put applications
since attachment of a chemical reagent to an insoluble
polymer matrix enables easy reaction work-up. A sim-
ple filtration process allows the product to be recovered
and moreover recovery of the spent reagent enables it
to be recycled, thus meeting the requirements of envi-
ronmentally friendly chemistry. Three syntheses of
solid-supported IBX have been published recently.8
Each of these routes commenced with a solution phase
synthesis employing 2-amino-5-hydroxybenzoic acid as
a starting material. In each case, after elaboration, this
molecule was coupled to an appropriately-function-
alised solid support, either an aminopropyl silica gel,8a
or a polystyrene based support8b,c or else to soluble
non-crosslinked polystyrene or PEG-based supports.8c
However, difficulties were encountered in isolating the
supported reagent when attached to non-crosslinked
supports and, in every case, attachment to non-soluble
supports involved the formation of potentially labile
amide and benzyl ether bonds.
We wished to develop a synthesis of a solid-supported
IBX reagent that did not require a late stage linkage
step and thus the incorporation of potentially labile
covalent bonds into the supported reagent. We there-
fore elected to carry out a synthesis of IBX that was
totally solid support-based. Moreover, by using a
crosslinked support, this strategy would also avoid the
difficulties encountered in handling non-crosslinked sol-
uble supports Reported herein is the synthesis of the
reagent and an evaluation of its utility for the oxidation
of a series of alcohols.
Keywords: polymer-supported reagents; iodoxybenzoic acid (IBX);
oxidation; alcohols.
* Corresponding author. Tel.: +44-121-359-3611; fax: +44-121-359-
4094; e-mail: a.j.sutherland@aston.ac.uk
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(03)00041-8

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Z. Lei et al. / Tetrahedron Letters 44 (2003) 1635–1637
Table 2. Evaluation of time course for the oxidation of
benzyl alcohol by polymer-supported oxidant 6
Entry
Time / h
Conversiona (%) Selectivitya (%)
1
2
3
4
5
6
1
2
3
4
5
7
44
66
72
81
86
98
100
100
100
100
98
97
All reactions were carried out at 25°C. aPercentage conversion and
reaction selectivity were determined by GC analysis.
from polymer 6 had three strong absorbances at 1555,
1603 and 1657 cm−1 which are characteristic of IBX13
and polymer-supported IBX.8a,b
Evaluation of polymer-supported IBX 6. Initially, the
loading of polymer-supported oxidant 6 was deter-
mined by oxidising benzyl alcohol to benzaldehyde in
CH2Cl2 and analysing the reaction mixture by GC. In
this way the loadings of two separate batches of poly-
mer-supported oxidant 6 were determined to be 0.2 and
0.5 mmol/g. The higher of these values is in good
agreement with loadings obtained previously for poly-
mer-supported IBX.8 We next set out to determine the
optimum solvent in which to study the reaction and
also to investigate the effect of differing oxidant:alcohol
ratios. The results obtained from this study are sum-
marised in Table 1.
Scheme 1. Synthesis of polymer-supported IBX reagent 6.
Reagents and conditions: (i) suspension polymerisation,
AIBN, PVA (87–89% hydrolysed), 2-ethyl-1-hexanol, D; (ii)
I2, NaIO4, H2SO4, Ac2O, CH3COOH, CH2Cl2, rt, 24 h; (iii)
KMnO4, methyltri-n-octylammonium chloride, H2O, CH2Cl2,
D, 24 h; (iv) NBu4SO5H, MeSO3H, CH2Cl2, rt, 5 h.
Synthesis of polymer-supported IBX. Macroporous
poly(p-methylstyrene) resin beads 3 were prepared from
p-methylstyrene and divinylbenzene (8 mol%) using
standard suspension polymerisation techniques with 2-
ethyl-1-hexanol being used as the porogen (Scheme 1).
The poly(p-methylstyrene) resin was then iodinated by
treatment with sodium periodate and iodine in a mix-
ture of acetic acid, sulfuric acid, acetic anhydride and
dichloromethane to give iodinated poly(p-methyl-
styrene) 4.9 On the basis of steric grounds and literature
precedence,10 we believe that iodinated product 4 con-
sists of a major component, the desired ortho-iodinated
species (ortho to the methyl group) and a minor compo-
nent the undesired meta-iodinated species (meta to the
methyl group). Iodinated polymer 4 was then oxidised
successfully by reaction with potassium permanganate
in the presence of methyltri-n-octylammonium chloride
(Aliquat®) in a mixed solvent system of water and
dichloromethane to give polymer 5.11 Polymer-sup-
ported oxidant 6, of which the major component is
polymer-supported IBX, was obtained by the oxidation
of 5 by treatment with tetrabutylammonium oxone12 in
Similarly, the time course of benzyl alcohol oxidation
by polymer-supported IBX 6 was evaluated. Table 2
shows the effect upon yield and purity of benzaldehyde
production at various time intervals. These results led
to all subsequent work adopting a 5 h reaction protocol
employing CH2Cl2 as the solvent and a ratio of oxi-
dant:alcohol of 2:1.
Having established an effective oxidation protocol a
series of alcohols were treated with polymer-supported
IBX 6. Benzyl alcohol, 4-methoxybenzyl alcohol, 4-
nitrobenzyl alcohol, octanol and 3,4-(methylene-
dioxy)benzyl alcohol were all oxidised to the
corresponding aldehydes in 5 h by treatment with
reagent 6 at room temperature in dichloromethane. The
results obtained from this study are shown in Table 3
and indicate that polymer-supported IBX 6 oxidises
effectively both electron rich and electron deficient ben-
zyl alcohols to the corresponding benzaldehydes in
dichloromethane containing
a
small amount of
methanesulfonic acid.8b The infrared spectrum obtained
Table 1. Evaluation of reaction conditions for the oxidation of benzyl alcohol by polymer-supported oxidant 6
Entry
Oxidant:alcohol (mmol:mmol)
Solvent
Conversiona (%)
Selectivitya (%)
1
2
3
4
5
1:1
2:1
2:1
2:1
2:1
CH2Cl2
CH2Cl2
DMSO
THF
66
86
44
50
75
100
98
100
96
CHCl3
100
All reactions were carried out at 25°C. aPercentage conversion and reaction selectivity were determined by GC analysis.

Z. Lei et al. / Tetrahedron Letters 44 (2003) 1635–1637
1637
Table 3. Oxidation of a series of alcohols using polymer-
supported IBX reagent 6
this work through the provision of grants GR/N38183/
01, GR/N34611/01 and GR/N34253/01.
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excellent yields and purity. However, oxidation of a
primary alkyl alcohol proved to be more difficult and a
lower yield was obtained. This finding is again in
agreement with previous studies.8b,c
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11. The oxidative conditions used for this step were based
upon those used to perform a similar transformation in
the gernation of a series of alkylated IBX oxidants. See:
Panetta, C. A.; Garlick, S. M.; Durst, H. D.; Longo, F.
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In summary a short efficient synthesis of a polymer-
supported IBX reagent that differs significantly from
previously reported syntheses8 has been developed. This
reagent has been used successfully for the oxidation of
a range of alcohols under very mild conditions to
furnish the corresponding aldehydes. Currently, we are
evaluating the use of reagent 6 in a flow through
reactor system and will report our findings in this area
in due course.
13. An infrared spectrum obtained from a sample of IBX
synthesised according to the published procedure (see
Acknowledgements
Ref. 2c) gave absorbances at 1561, 1599 and 1637 cm−1
.
We gratefully acknowledge the EPSRC for supporting