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H.-S. Jang et al. / Tetrahedron Letters 48 (2007) 3731–3734
H
H
II
I
MPS
MPS
N
MPS
N
NH2
O
I
O
I
O
O
Scheme 1. Synthesis of MPS supported IBX amides. Reagents and conditions: (i) 2-iodobenzoic acid, DIC, HOBT, DIEA, DMF, rt, 6 h; (ii)
NBu4SO5H, MeSO3H, DCM, rt, 10–12 h.
1
mixture was measured by 300 MHz H NMR spectro-
scopy. The loading level of the MPS-IBX amide was
100
a
determined to be in the range of 0.44–0.54 mmol/g (see
Scheme 1).
80
60
The oxidation reaction was also performed in various
solvents such as acetonitrile (ACN), THF, acetone,
40
20
0
and diethyl ether (100 mg of bead/1 mL) at 25 °C. As
was expected, the MPS-IBX amides were compatible
with all the solvents since the solvents could easily dif-
fuse into the MPS resin. However, GC/MS analysis
indicated that lactol and lacton were formed with the
MPS-IBX amide when THF was used as the solvent.
This was probably due to the oxidation reaction of
THF by the MPS-IBX amide, and for this reason it
could not be used as a solvent. We employed 300 MHz
1H NMR spectroscopy to determine the conversions.
The profiles of benzyl alcohol oxidation reaction in sev-
eral solvents were compared between on the gel type PS-
IBX amide resin and on the MPS-IBX amide resin. Both
resins in DCM were shown similar oxidative properties
(Fig. 1). However, in acetone, diethyl ether, and THF,
only the MPS-IBX amide resin revealed strong oxidative
properties toward benzyl alcohols. The reduced MPS-
IBX amide resin was regenerated by oxidation with
tetrabutylammonium oxone, and we observed no loss
of activity after five regenerations.
0
20
40
60
Time (min)
100
80
60
40
20
0
b
0
20
40
60
These results inspired us to investigate further the MPS-
IBX amide’s oxidative properties using an additional
series of alcohols. As shown in Table 1, the alcohols
were oxidized in DCM, ACN, acetone, and diethyl
ether. The reaction mixtures were analyzed by
300 MHz 1H NMR spectroscopy to measure the conver-
sion of the alcohols to the corresponding aldehydes or
ketones (Table 1).
Time (min)
Figure 1. The time course for the oxidation of alcohol to aldehyde
using MPS-IBX amide (a) and gel type polystyrene-supported IBX
amide (b) in different solvents: using 2 equiv of oxidant at rt and
methoxybenzyl alcohol as the substrate; DCM (h), ACN (Ç), THF
(j), acetone (m) and diethyl ether (+). Conversion (%) was determined
by 300 MHz 1H NMR spectroscopy.
In our previous studies with the gel type PS-IBX amide,
we noticed that the oxidation of both the primary and
long chain alkyl alcohols took at least 12 h at rt for more
than a 98% conversion toward the quantitative alde-
hydes.5e The PS-IBX amide in particular gave a conver-
sion of only 40% for cyclohexanol to cyclohexanone in
1 h. After extending the reaction time to 14 h, we ob-
tained an 81% conversion to cyclohexanone and an
additional 8% conversion to a,b-unsaturated cyclohexe-
none, probably via the dehydration of cyclohexa-
none.5e,8 However as shown in Table 1, the MPS-IBX
amide resin offered good conversion rates in DCM
(4 h) for the oxidizations of long chain alkyl alcohols
and cyclohexanol to the corresponding aldehydes and
ketones. We also found that MPS-IBX amide resin
had excellent properties for oxidizing benzyl alcohols
to the corresponding aldehydes in acetone and diethyl
ether. Based on these results, we can confirm that the
diffusion of alcohols may be an important factor in
determining the oxidation power of the IBX resin. When
the gel type PS-IBX resin is not fully solvated, the alco-
hols may experience diffusion resistance and, therefore,
slowly diffuse into the inner reactive sites of the resin.
Moreover, in a poor solvent system the polymer matrix
of the gel type PS-supports could collapse and block the
internal reactive sites. In the case of the MPS-IBX resin,
however, high levels of internal crosslinking can create a
rigid porous structure, which may neither collapse nor
swell in various solvents.9 In addition, the internal reac-
tive sites of macroporous resins are freely accessible
across a broad spectrum of solvent polarities,10 and
the alcohols are free to move into the resin reaction sites.
Therefore, the MPS-IBX amide resin can be used for
oxidizing alcohols in a variety of solvents, as long as
the solvents themselves are not oxidized.