Solvent free permanganate oxidations

Article abstract of DOI:10.1016/S0040-4039(01)01129-7

The oxidations of organic compounds by permanganate under solvent free conditions have been studied. Thiols and primary aromatic amines undergo oxidative coupling reactions to give disulfides and diazenes, respectively, sulfides are oxidized to sulfones, primary and secondary alcohols are converted to aldehydes and ketones, 1,4-diols and cyclic ethers give lactones and arenes are oxidized to the corresponding α-ketones. The experimental procedure is simple and the products are easily isolated in good yields.

Full text of DOI:10.1016/S0040-4039(01)01129-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5833–5836
Solvent free permanganate oxidations
Ahmad Shaabani† and Donald G. Lee*
Department of Chemistry and Biochemistry, University of Regina, Regina, SK, Canada S4S 0A2
Received 12 March 2001; revised 5 June 2001; accepted 18 June 2001
Abstract—The oxidations of organic compounds by permanganate under solvent free conditions have been studied. Thiols and
primary aromatic amines undergo oxidative coupling reactions to give disulfides and diazenes, respectively, sulfides are oxidized
to sulfones, primary and secondary alcohols are converted to aldehydes and ketones, 1,4-diols and cyclic ethers give lactones and
arenes are oxidized to the corresponding a-ketones. The experimental procedure is simple and the products are easily isolated in
good yields. © 2001 Elsevier Science Ltd. All rights reserved.
Although solvent free reactions are of general interest
because of their potential applications in combinatorial
chemistry, only a limited number of useful oxidation
procedures have been reported.1–12 In this paper we
wish to describe a simple and general procedure that
can be used for the oxidative transformation of many
organic functional groups using an inexpensive and
environmentally friendly oxidant, potassium per-
manganate.13
drate in a mortar until homogeneous or by adding a
concentrated aqueous solution of potassium permanga-
nate to alumina, giving a paste which is then ground
with an equal amount of copper sulfate pentahydrate.
Reductant (2 mmol) is added to a portion of the
oxidant (ꢀ4 g) in a 25 mL round bottomed flask and
stirred magnetically until TLC analysis indicates a com-
pleted reaction. The residue is then washed with a
minimum amount of solvent (methylene chloride, hex-
ane and/or ether). Distillation of the solvent gives a
product that is of acceptable purity for most purposes.
If greater purity is required, the product can be distilled
or recrystallized.
Best results are obtained when KMnO4 is first mixed
with copper sulfate pentahydrate (or a 20/80 mixture of
copper sulfate pentahydrate and alumina) to give a
reagent that has previously been used extensively as a
heterogeneous oxidant in inert solvents. The reductant
is then added dropwise while the solid oxidant is tum-
bled using a magnetic stirrer. Most reactions can be
carried out at room temperature; however, improved
yields for solid reductants are obtained when the reac-
tion temperature is near or above their melting points.
Some reactions benefit from the application of addi-
tional energy in the form of microwaves.8,9 Product
isolation can be achieved by washing the spent oxidant
with an organic solvent, which can subsequently be
recovered by simple distillation. Many of the reactions
are nearly quantitative giving products of relatively
high purity.
As can be seen from the first three reactions in Table 1,
thiols are converted into the corresponding disulfides in
good yields under very mild conditions (Scheme 1). The
times required compare favorably with those for sol-
vent free oxidations of thiols using other oxidants.1–3
Addition of alumina to the solid support did not
improve the yields of these reactions.
Primary aromatic amines are also oxidatively coupled
under these conditions (Scheme 2). As indicated by
reactions 4–6 in Table 1, the presence of electron with-
drawing substituents such as chloro decreases the reac-
tion rate, but not the yield of diazene. The reaction
times are shorter than those reported for the corre-
sponding heterogeneous reactions, but the yields appear
to be slightly lower.14 Cleaner products were obtained
from these reactions when alumina was added to the
solid support.
The oxidant is prepared by grinding equal amounts of
potassium permanganate and copper sulfate pentahy-
Keywords: oxidation; permanganate; solvent free; thiols; sulfides;
alcohols; diols; ethers; arenes.
Aryl and alkyl sulfides are converted into the corre-
sponding sulfones in good yields (reactions 7–13, Table
* Corresponding author. E-mail: dglee@uregina.ca
† Permanent Address: Shahid Beheshti University, Tehran, Iran.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01129-7

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A. Shaabani, D. G. Lee / Tetrahedron Letters 42 (2001) 5833–5836
Table 1. Solvent free permanganate oxidations
Reaction
Reductant
Timea
Product (% yield)b
1
2
3
4
5
6
7
8
Thiophenol
Butanethiol
Cyclopentanethiol
Aniline
2,4,6-Trimethylaniline
4-Chloroaniline
Benzyl phenyl sulfide
Methoxymethyl phenyl sulfide
Dibutyl sulfide
Dibenzyl sulfide
Dibenzyl sulfide
Dioctyl sulfide
Dioctyl sulfide
4-Methoxybenzyl alcohol
1-Pentanol
2-Cyclohexylethanol
Cinnamyl alcohol
2-Octanol
2,6-Dimethylcyclohexanol
1,4-Butanediol
7 min
15 min
15 min
5 hc
Diphenyl disulfide (100)
Dibutyl disulfide (95)
Dicyclopentyl disulfide (95)
Azobenzene (75)
1,2-Bis(2,4,6-trimethylphenyl)diazene (70)
1,2-Bis(4-chlorophenyl)diazene (85)
Benzyl phenyl sulfone (85)
Methoxymethyl phenyl sulfone (90)
Dibutyl sulfone (90)
Dibenzyl sulfone (98)
Dibenzyl sulfone (99)
Dioctyl sulfone (90)
Dioctyl sulfone (100)
4-Anisaldehyde (95)
Pentanal (80)
2-Cyclohexylethanal (85)
Cinnamaldehyde (95)
2-Octanone (90)
2,6-Dimethylcyclohexanone (70)
g-Butyrolactone (95)
a-Methyl-g-butyrolactone (70)
4-Oxo-1-pentanol (30)
g-Butyrolactone (70)
a-methyl-g-butyrolactone (90)
d-Valerolactone (65)
2,5-Hexanedione (60)
1-Indanone (90)
Phthalide (95)
No reaction
Xanthone (95)
Xanthone (98)
5 hc
20 hc
12 h
8 h
9
5 h
10
11
12
13
14
15
16
17
18
19
20
21
10 hd
10 mine
15 h
2 mine
45 minf
4 hf
4 hf
8 hc
1.5 h
6 h
14 hc
36 hc
1,4-Pentanediol
22
23
24
25
26
27
28
29
30
31
32
33
Tetrahydrofuran
2-Methyltetrahydrofuran
Tetrahydropyran
2,5-Dimethyltetrahydrofuran
Indane
Phthalan
Dihydrobenzofuran
Xanthene
Xanthene
Fluorene
Fluorene
2-Ethylthiophene
6 hc
36 hc
6 hc
8 hc
1.3 h
5 min
24 h
5 h
10 mine
1.3 hg
10 mine
6 h
9-Fluorenone (95)
9-Fluorenone (98)
2-Acetylthiophene (90)
a Unless otherwise indicated all reactions were completed at room temperature using KMnO4/CuSO4·5H2O as the oxidant.
b Products were identified from comparison of physical and spectroscopic properties with authentic compounds.
c The oxidant was KMnO4/Al2O3/CuSO4·5H2O.
d Temperature was increased to 50°C.
e Assisted by microwave irradiation.
f The oxidant was KMnO4/Al2O3.
g Temperature increased to 120°C.
tions of sulfides result in the formation of sulfoxides;4–6
however, sulfoxides were not produced under these
conditions. Addition of alumina to the solid support
increased the rates of these reactions, but not the yields.
Scheme 1.
Scheme 2.
As indicated in Scheme 4, secondary alcohols are con-
verted into the corresponding ketones in good yields
(reactions 18 and 19, Table 1) and aldehydes are
obtained in comparable yields from the oxidation of
primary alcohols (reactions 14–17, Table 1). The prepa-
ration of both aliphatic and aromatic aldehydes from
the corresponding primary alcohols has not previously
been easily achieved using permanganate or other
strong oxidants because aldehydes are so readily con-
verted to carboxylic acids under oxidizing conditions.
1). This is a highly useful reaction for the preparation
of sulfones (Scheme 3) which are important intermedi-
ates in the synthesis of many organic compounds.15 The
observation that benzyl phenyl sulfide is oxidized to the
corresponding sulfone indicates that the reaction pro-
ceeds by way of an oxygen transfer mechanism. If the
reaction involved electron transfer instead of oxygen
transfer, substantial amounts of benzaldehyde would
have been formed.16,17 Most other solvent free oxida-
Scheme 3.

A. Shaabani, D. G. Lee / Tetrahedron Letters 42 (2001) 5833–5836
5835
Cyclic ethers are also converted into lactones under
these conditions (reactions 22–24, Table 1). Although
these transformations can also be achieved using other
oxidants such as ruthenium tetroxide18 or chromi-
um(VI),18 the experimental simplicity of this procedure
may make it the approach of choice. When the a-car-
bons are tertiary, the product is a dione, formed pre-
sumably by dehydration of the corresponding diol as in
Scheme 6. Addition of alumina to the solid support did
not improve the yields of these reactions.
Scheme 4.
The use of alumina as the solid support is necessary in
order to obtain good yields of aldehydes. Its use causes
the rates of alcohol oxidation to be greater than those
for the corresponding aldehydes. Under conditions
where alcohols and aldehydes are oxidized at compara-
ble rates, the product is necessarily a mixture of alde-
hyde and the corresponding carboxylic acid. Since
ketones are resistant to further oxidation, the use of
alumina with secondary alcohols provides little or no
advantage.
Arenes are converted into the corresponding a-ketones
under these conditions (reactions 26, 31–33, Table 1).
The products are identical to those obtained under
heterogeneous conditions where the reductant is dis-
solved in an inert solvent;19 however, the reaction times
are reduced from a few days to a few hours at room
temperature. Addition of alumina to the solid support
decreased the yields of these reactions. As indicated in
Scheme 7, the reaction displays an interesting selectivity
for compounds containing oxygen as part of a cyclic
side chain. When oxygen is in the b-position, lactones
are obtained in good yields; when it is in the a-position
the reaction is completely inhibited. The unique selec-
tivity demonstrated by the reactions in Scheme 7 may
find application in the synthesis of dihydroisocoumarins
and similar compounds.20
Of particular interest is the observation that 1,4-diols
are easily and completely converted into lactones under
these conditions, as in Scheme 5. Although the proce-
dure works well for the preparation of butyrolactones
(reactions 20 and 21, Table 1), attempts to obtain
lactones from 1,3- or 1,5-diols failed.
Attempts to use this reaction for the oxidative cleavage
of alkenes were largely unsuccessful. Yields of 20% or
less were realized when stilbene and styrene were oxi-
dized to benzaldehyde.
Scheme 5.
Acknowledgements
The authors are pleased to acknowledge financial sup-
port from the Natural Sciences and Engineering
Research Council of Canada.
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