2-Methyl-2-propanol as solvent for o-iodoxybenzoic acid (IBX) oxidation of 1? alcohols to aldehydes

Article abstract of DOI:10.1016/j.tetlet.2009.06.045

2-Methyl-2-propanol has been demonstrated to be an effective solvent for IBX oxidation of 1? alcohols to the corresponding aldehydes. IBX has a measurable, but low, solubility in 2-methyl-2-propanol and thus partially avoids the drawbacks inherent in the solubility problems associated with IBX without resorting to less desirable solvents. This may be particularly useful where solubility of the alcohol is also at issue.

Full text of DOI:10.1016/j.tetlet.2009.06.045

Tetrahedron Letters 50 (2009) 4693–4695
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
2-Methyl-2-propanol as solvent for o-iodoxybenzoic acid (IBX) oxidation
of 1ꢀalcohols to aldehydes
*
Scott A. Van Arman
Department of Chemistry, Franklin and Marshall College, PO Box 3003, Lancaster, PA 17604-3003, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
2-Methyl-2-propanol has been demonstrated to be an effective solvent for IBX oxidation of 1ꢀalcohols to
the corresponding aldehydes. IBX has a measurable, but low, solubility in 2-methyl-2-propanol and thus
partially avoids the drawbacks inherent in the solubility problems associated with IBX without resorting
to less desirable solvents. This may be particularly useful where solubility of the alcohol is also at issue.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 26 May 2009
Revised 5 June 2009
Accepted 8 June 2009
Available online 12 June 2009
Aldehydes are extremely important targets and intermediates
in organic synthesis but their preparation by selective oxidation
from primary alcohols can be difficult relative to the full oxidation
to carboxylic acids. As such the development of methods for this
simple transformation has a long and varied history. However,
some of the more historically prominent methods have significant
drawbacks. Cr(VI) reagents1 (Jones,2 Collins/Sarrett,3 PCC4) are
toxic and often their use involves a difficult workup. Swern5 re-
quires low temperature, a solvent that can be difficult to remove,
and generates stench. TEMPO6/oxidant lacks tolerance for many
functional groups. As such, there is growing interest in the use of
hypervalent iodine compounds such as the Dess–Martin period-
inane7 and o-iodoxybenzoic acid (IBX)8 as mild, selective reagents
for this transformation that also have relatively low toxicity.9 In-
deed, IBX is the synthetic precursor to the Dess–Martin reagent
and where possible and applicable its use may be preferred.
One remaining drawback10 to the use of IBX for this purpose
had been the need to use the high boiling solvent DMSO for the
procedure because it was the only solvent in which IBX was solu-
ble. This barrier has recently been removed as a result of More and
Finney’s observation that a variety of solvents may be suitable for
the reaction despite the lack of (or low) IBX solubility.11 They argue
that the IBX in these alternative solvents serves as a (de facto) solid
phase reagent that, along with its similarly insoluble byproducts,
can be removed from the reaction mixture by simple filtration.
Additional efforts to ameliorate the solubility problem include
application in DMF12 (in which IBX has been found to be soluble),
ionic liquids,13 mixed solvent/phase transport,14 structural modifi-
cation,15 polymer support,16 and use of IBX as a catalyst.17 All these
efforts speak to the utility of IBX but also point out that its solubil-
ity in common solvents remains a problem for which new solu-
tions are still sought. Solubility continues to be cited explicitly as
an ongoing barrier to the simple utility of IBX.
In our work toward the synthesis of fluorescent chemosensors
we had the occasion to need 1,3,5-triformylbenzene. Two recently
reported syntheses were effected with IBX in DMSO (modest
yields).18 In order to avoid that solvent we deferred to More and
Finney’s methodology but were met with mild disappointment be-
cause the precursor, 1,3,5-tris-(hydroxymethyl)benzene, is insolu-
ble in any of the solvents reported. The low solubility (or
insolubility) of IBX and the substrate led to unsatisfactory yield
over a few hours. 1,3,5-Tris-(hydroxymethyl)benzene is, however,
highly soluble in hydroxylic or protic solvents. As such we at-
tempted the oxidation (Scheme 1) in tert-butanol (often over-
looked as a possible solvent for such transformations).
The quantitative isolated yield of the desired trialdehyde
prompted us to briefly explore the general applicability of
2-methyl-2-propanol as solvent for IBX oxidations of primary alco-
hols. Perhaps as important as the solubility of the alcohol in the sol-
vent, we found that IBX has a measurable solubility in tert-butanol of
0.8 mg/mL at 20 °C and 4.9 mg/mL in refluxing tert-butanol.
In general for the oxidation reaction19 approximately 200 mg of
alcohol was dissolved in 25 mL of tert-butanol and IBX (2 equiv)
was added. The mixture was stirred and heated to reflux for about
1 h. Although the IBX did not completely dissolve in the solvent, as
O
I
HO
H
O
OH
O
O
O
H
HO
tert-butanol, 82 ºC
H
O
OH
* Tel.: +1 717 291 4355; fax: +1 717 291 4343.
E-mail address: scott.vanarman@fandm.edu
Scheme 1. A representative transformation.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.045

4694
S. A. Van Arman / Tetrahedron Letters 50 (2009) 4693–4695
Table 1
Representative reactants and products
Entry
Alcohol
Product
Reaction time (h)
Yield (%)
>95
OH
H
O
1
1
HO
O
H
OH
H
O
H
OH
2
3
4
5
6
1
>95
95
O
H
1
OH
O
OH
O
H
2
80
H
OH
2
90
O
H
H
1.5
1.5
95
OH
OH
O
O
7
50a
a
Product likely lost in rotary evaporation.
the reaction proceeded the visible appearance of the mixture chan-
ged from a clear solution with granular IBX to a suspension of very
fine solid. Because this occurs without stirring, it provides some
evidence for dissolution equilibria for IBX and its reaction byprod-
uct(s). The reaction was found (by tlc) to occur at room tempera-
ture, although reaction times were much greater than 10 h. After
the reaction was complete the t-butanol was removed by rotary
evaporation. Taking advantage of the insolubility of IBX and its
byproducts in most other solvents, the residue could be dissolved
in dichloromethane/hexane and filtered giving a clean solution of
the aldehyde. When traces of IBX byproducts persisted they could
be removed by filtration through a plug of silica. The applicability
of the method for aliphatic, allylic, and benzylic alcohols is demon-
strated in Table 1 including for 2-phenylethanol which is some-
times overlooked in such series perhaps because homobenzylic
alcohols sometimes undergo C–C bond cleavage or other further
reaction.20
Acknowledgments
Acknowledgement is made to the donors of The Petroleum Re-
search Fund for partial support of this research. We also thank the
William M. and Lucille M. Hackman Scholars Program at Franklin
and Marshall College and the Franklin and Marshall College com-
mittee on grants for their generous support of this research. We
are also grateful for the assistance of Beth Buckwalter, Lisa Mertz-
man, and Carol Strausser.
Supplementary data
Copies of 1H and 13C NMR spectra are available for verification
of purity. Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2009.06.045.
IBX and other hypervalent iodine reagents remain an active area
of exploration for organic oxidation reactions. Insolubility of IBX in
most common organic solvents has resulted in many efforts to
broaden the scope of IBX application. We have found tert-butanol
to be a suitable solvent for the oxidation of primary alcohols to
aldehydes particularly where a hydroxylic solvent is necessary
for dissolution of the substrate. The relative low toxicity and low
cost of tert-butanol may make this a desirable alternative for many
such applications.
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0.95 mmol) was dissolved with stirring in 25 mL 2-methyl-2-propanol. To this
was added IBX (0.535 g, 1.96 mmol). The mixture was stirred and heated to
reflux for 1 h. The mixture was quickly filtered by vacuum and the filtrant was
washed with a 20 mL portion of CH2Cl2. The filtrate was rotary evaporated to
an off-white solid. This residue was taken up in 25 mL CH2Cl2/hexane (1:1) and
vacuum filtered. Solvent was removed from filtrate by rotary evaporation to
give an off-white solid (0.15 g, 0.96 mmol, 100%). 1H NMR (CDCl3, 500 MHz) d
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