IBX-mediated oxidation of primary alcohols and aldehydes to form carboxylic acids

Article abstract of DOI:10.1002/1521-3773(20021104)41:21<4059::AID-ANIE4059>3.0.CO;2-R

Under mild conditions and without the use of toxic metals, the oxidation of primary alcohols and aldehydes to the corresponding carboxylic acids with 1-hydroxy-1,2-benziodoxole-3(1H)-one-1-oxide (IBX) proceeds in the presence of 1-hydroxypyridine or N-hydroxysuccinimide (see scheme). The reaction tolerates a wide variety of functional groups.

Full text of DOI:10.1002/1521-3773(20021104)41:21<4059::AID-ANIE4059>3.0.CO;2-R

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1848 1849.
IBX-Mediated Oxidation of Primary Alcohols
and Aldehydes To Form Carboxylic Acids**
Ralph Mazitschek, Marcel M¸lbaier, and
Athanassios Giannis*
Dedicated to Professor Peter Welzel
on the occasion of his 65th birthday
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During recent years the hypervalent iodine reagent 1-
hydroxy-1,2-benziodoxole-3(1H)-one-1-oxide (IBX) was uti-
lized for numerous novel and synthetically valuable oxidative
transformations, including, among others, the cyclization of
anilides,[1] the preparation of amino desoxy sugars from
glycals,[2] the benzylic oxidation of aromatic compounds,[3] and
the synthesis of a,b-unsaturated aldehydes and ketones from
homologous, saturated precursors.[4]
IBX is safe and easily accessible, and is especially suited to
the oxidation of alcohols in homogenous solution to yield the
corresponding aldehydes and ketones.[5,6] Recently, analogous
reactions using polymer-supported IBX have been report-
ed.[7,8] The transformation of primary alcohols to carboxylic
acids has never been observed using IBX. For the first time,
we report here that primary alcohols are oxidized easily in the
presence of IBX and certain O nucleophiles to give carboxylic
acids at ambient temperature in high yields. Starting from the
hypothesis that the aldehyde II, which is generated from a
primary alcohol I and an excess of IBX, reacts with suited
O nucleophiles (YO-H) to form the intermediate III. This
intermediate can be oxidized to the corresponding active
ester IV, which in turn is hydrolyzed to give the desired
carboxylic acid V (Scheme 1).
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Chem. Int. Ed. 1997, 36, 1494 1496.
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2027; Angew. Chem. Int. Ed. 2002, 41, 1945 1947; b) Suzuki coupling
of alkyl bromides: M. R. Netherton, C. Dai, K. Neusch¸tz, G. C. Fu, J.
Am. Chem. Soc. 2001, 123, 10099 10100.
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Chem. Soc. 2002, 124, 4222 4223.
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organomanganese compounds with alkyl bromides in the presence of
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Tetrahedron 2000, 56, 2733 2737; b) G. Cahiez, S. Marquais, Pure
Appl. Chem. 1996, 68, 53 60.
Scheme 1. Mechanism of the IBX-mediated oxidation of primary alcohols
to give the carboxylic acids.
In our initial attempt 2-hydroxypyridine (1, HYP) was used
as an O nucleophile. We were pleased to find that, in the
presence of 2equivalents of IBX and 4 equivalents of 2-
hydroxypyridine, 1-decanol was oxidized to form decanoic
acid in 48 h in 92% yield. A series of other aliphatic alcohols
(and aldehydes) was oxidized under the same reaction
conditions in high yields to give the carboxylic acid analogues
(Table 1). That only catalytic amounts of hydroxypyridine are
[*] Prof. Dr. A. Giannis, Dipl.-Chem. R. Mazitschek,
Dipl.-Chem. M. M¸lbaier
Institut f¸r Organische Chemie
Universit‰t Leipzig
Johannisallee 29, 04103 Leipzig (Germany)
Fax : (þ 49)341-97-36-599
E-mail: giannis@chemie.uni-leipzig.de
[**] IBX ¼ 1-hydroxy-1,2-benziodoxole-3(1H)-one-1-oxide.
Angew. Chem. Int. Ed. 2002, 41, No. 21
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required for the transformation is consistent with the pro-
posed mechanism, however the reaction times also increase
dramatically. Benzaldehyde (and benzylic alcohol) was not
oxidized under these conditions. Also the oxidation of 2-
decenal (and of 2-decen-1-ol) was not observed. We suppose
that 2-hydroxypyridine is insufficiently nucleophilic to form
Table 1. Oxidation of primary alcohols and aldehydes to form carboxylic acids.
Entry
1
Substrate
Method
Product
Ratio A:AE[a]
Yield[b] of A [%]
HYP
NHS
91
80
2
3
1:10
1:10
HYP
NHS
91
40
4
5
6
HYP
HYP
NHS
85
74
67
1:10
0:1
7
8
NHS
64
HYP
NHS
90
40
1:10
9
HYP
79[c]
85[c]
79
10
HYP
11
12
NHS
NHS
2:3
1:293
13
14
15
NHS
NHS
NHS
1:4
76
1:290
1:1
68
16
17
NHS
NHS
1:0
1:0
64
95
[a] A: acid, AE: active ester. [b] Yield of product isolated. [c] The enantiomeric purity was determined by chiral HPLC.[10]
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To isolate the active esters, semisaturated NaHCO3 solution (50 mL) was
added. After stirring for 5 min the reaction mixture was extracted (3 î
50 mL) with diethyl ether. The iodosocarboxylic acid, which precipitated as
an off-white amorphous solid, was removed by filtration. The organic phase
was washed once more with 10% NaHCO3 solution (50 mL) and dried over
Na2SO4. The solvent was removed under reduced pressure. Analytically
pure product was obtained by column chromatography on silica gel.
the semiacetals of type III with these compounds. Therefore
we decided to test 1-hydroxybenzotriazole (2, HOBT), as its
hydroxy group shows an increased nucleophilic character,
caused by the a effect. Actually, using benzaldehyde, IBX,
and HOBT (1:1:1) we were able to detect the formation of
benzoic acid within a few minutes. However, the yield was
only 20%. The reason for this is the decomposition of 2 under
the reaction conditions. To circumvent this problem, we
decided to substitute HOBT with N-hydroxysuccinimide
(NHS) 3, because this compound is stable to IBX. Indeed,
we could oxidize aromatic aldehydes as well as a,b-unsatu-
rated aldehydes to the corresponding carboxylic acids.
Identical products were obtained from benzyl and allyl
alcohols. Aliphatic aldehydes were also oxidized to form
carboxylic acids. Interestingly, the NHS-mediated oxidation
yielded the preparatively valuable active esters (O-succini-
midyl) in most cases.[9] This observation endorses the mech-
anism postulated in Scheme 1. The addition of water (ap-
proximately 10 vol%) did not influence the reaction. The
hydroxypyridine and the NHS-mediated methods both toler-
ate a wide variety of functional groups, such as isolated and
conjugated double bonds, alkyl halogenides, urethanes, and
electron-rich and -poor aromatic compounds. Starting from
N-protected a-amino alcohols, the corresponding amino acids
can be generated without racemization.[10]
For isolation of the carboxylic acid, 1n NaOH (50 mL) was added to the
reaction mixture and stirring was continued until a clear solution was
obtained. This solution was washed with diethyl ether (1 î 50 mL) and
acidified with 2n hydrochloric acid to pH 1. The aqueous phase was
extracted with diethyl ether (3 î 50 mL). The combined organic extracts
were washed once with 5% KHSO4 solution and dried over Na2SO4. The
solvent was removed under reduced pressure. Analytically pure product
was obtained by column chromatography on silica gel.
Received: April 26, 2002 [Z19182]
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[7] M. M¸lbaier, A. Giannis, Angew. Chem. 2001, 113, 4530 4532;
Angew. Chem. Int. Ed. 2001, 40, 4393 4394.
In the past, various highly efficient methods for oxidizing
alcohols to give carboxylic acids have been developed.
However, all of these methods have inherent disadvantag-
14]
es.[11
For example, using the TEMPO/NaOCl/NaOCl2
[8] G. Sorg, A. Mengel, G. Jung, J. Rademann, Angew. Chem. 2001, 113,
4395 4397; Angew. Chem. Int. Ed. 2001, 40, 4532 4535.
method, electron-rich aromatic alcohols are scarcely oxidized
and the chlorination of the aryl ring is often a side reaction.
Double bonds require special reaction conditions. Similar is
true for the Sharpless-Katsuki-method as well as for the
recently reported Pd-mediated oxidation of alcohol groups to
give carboxylic acids.
Our method is mild, efficient, and avoids the use of toxic
metals. It is compatible with various functional groups and the
iodosobenzoic acid can be separated from the reaction
mixture and easily reoxidized to form IBX.
1
[9] The active esters were identified by means of H NMR spectroscopy
and HRMS.
[10] The optical purity of the a-amino acids was determined by chiral
HPLC (stationary phase: Chirobiotic T (250 î 4.6 mm) Astec/ict,
eluent: 30% EtOH, 70% doubly distilled H2O, flow: 0.4 mLminꢀ1
after removal of the protecting groups.
)
[11] M. Zhao, J. Li, E. Mano, Z. Song, D. M. Tschaen, E. J. J. Grabowski,
P. J. Reider, J. Org. Chem. 1999, 64, 2564 2566.
[12] P. H. J. Carlsen, T. Katsuki, V. S. Martin, K. B. Sharpless, J. Org. Chem.
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[14] H. Tohma, S. Takizawa, T. Maegawa, Y. Kita, Angew. Chem. 2000, 112,
1362 1364; Angew. Chem. Int. Ed. 2000, 39, 1306 1308.
Experimental Section
HYP method: IBX (2.6 equiv, 13 mmol; 1.6 equiv of IBX or 8 mmol, when
starting from the aldehyde) were dissolved in DMSO (10 mL). The alcohol/
aldehyde (5 mmol) was added in a single portion at room temperature.
After oxidation of the alcohol (in most cases after 10 20 min) of HYP
(5 equiv, 25 mmol) was added and the reaction mixture was stirred for an
additional 72h. It is not necessary to exclude moisture and oxygen. For the
workup semisaturated NaHCO3 solution (50 mL) was added and the
reaction mixture extracted with diethyl ether (2î 30mL). The iodosocar-
boxylic acid, which precipitated as an off-white amorphous solid, was
removed by filtration. After acidification to pH 1 with 10% sulfuric acid,
the aqueous phase was extracted (3 î 50 mL) with diethyl ether. The
combined organic phases were washed once with a 5% KHSO4 solution
and dried over Na2SO4. The solvent was removed under reduced pressure,
to leave the acid containing traces of iodobenzoic acid. Analytically pure
product was obtained by column chromatography on silica gel.
NHS method: IBX (2.6 equiv, 13 mmol; 1.6 equiv of IBX or 8 mmol
starting from the aldehyde) were dissolved in DMSO (15 mL). The alcohol/
aldehyde (5 mmol) was added in a single portion at room temperature.
After oxidation of the alcohol to the aldehyde, N-hydroxysuccinimide
(5 equiv, 25 mmol) was added slowly so that the temperature did not
exceed 308C. The reaction mixture was stirred over 16 h.
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