Recent advances in the use of oxone in organic synthesis

Maria Carla Marcotullio, Francesco Epifano and Massimo Curini

Dipartimento di Chimica e Tecnologia del Farmaco-Sez. Chimica Organica, Universit degli Studi, Via del Liceo, 1, 06123 Perugia,
Italy

1.

Abstract
Oxone (potassium monopersulfate) is a cheap,
easy to handle oxidant that can be used either in
homogeneous and in heterogeneous conditions. In these
last years it has been extensively employed in organic
synthesis to perform a variety of transformations such
as protection and deprotection of functional groups,
oxidation of heteroatoms, cleavage of carbon-carbon
double bonds, preparation of useful intermediates for
the synthesis.

Introduction
Persulfuric acid (H2SO5), commonly called Caro s
acid, [1] and its potassium salt are oxidasing agents
known from a long time, but they have been not largely
used in organic synthesis due to their explosive
character. The first report for the preparation of a stable
mixture of potassium persulfate, potassium hydrogen
sulfate and potassium sulfate is a 1957 U.S. Patent. [2]
In these last years there has been a renewed interest,
expecially in potassium monopersulfate (KHSO5), as it
is commercially avalaible as a triple salt
(2KHSO5 KHSO4 K2SO4) with the registered name of
Oxone (Dupont).
Oxone is a white crystallin solid, easy to handle,
not toxic, soluble in water and, above all, cheap and
stable. The commercial triple salt contains only about
50% of active oxidant per mol and in 2002 a new
procedure has been developed to prepare pure
potassium monopersulfate.[3]
In the past twenty years it has been used to
perform a great number of oxidations in water or water
miscible solvents such as methanol or DMF. To
overcome the lack of solubility in common organic
solvents more recently organic salts of Oxone have
been prepared. One of the oldest is tetrabutyl
ammonium persulfate (TBA-OX).[4,5] Recently

Hajipour prepared a new soluble salt: benzyl-triphenyl

phosphonium monopersulfate.[6,7,8]
Another way to use Oxone in organic solvents is
to support it on different solids such as Al2O3.[9]
One of the most common reaction of Oxone is the
interaction with carbonyls, with the formation of
dioxiranes, or with imines, with the formation of
oxaziridines, largely used in organic synthesis.[10]
Beside Oxone itself has been used to perform
several interesting oxidations some of which will be
reviewed herein.

2.

3.

Halide oxidation
In 1960 Kennedy and Stock studied the oxidative
properties of Oxone towards several substrates and
they reported the conversion of toluene into benzyl
halide by interaction of Oxone with metal halides.[11]
Today it is well established that Oxone can easily
oxidise halides to halogens or hypohalite.
3.1 Halogenation of aromatic compounds
Halogenation of aromatic compounds constitutes
an important reaction and usually it is performed using
molecular halogen in the presence of Lewis or mineral
acids. This methodology is not environmetally friendly
as suffers from the production of halogens and
hydroalous acids. To avoid the use and the production
of toxic and corrosive waste several different methods
have been developed, e.g. the use of metal halides in
combination of oxidants such as m-CPBA, H2O2,
NaClO2.
Recently it has been reported that treating 1 mmol
of an activated arene with 1 mmol of potassium or
sodium halides and 1 mmol of Oxone in a 3:1 [12] or
1:1 [13] mixture of acetonitrile-water at room
temperature it is possible to achieve regioselectively psubstitution.

The reaction works well for moderately activated

arenes, with greatly activated ones it is possible to have
dibromo substituted compounds, while deactivated
arenes do not react at all.
The influence of the solvent has been studied and
it has been noted that polar solvents, such as acetonitrile
and methanol are better solvents. [14]
The system Oxone/KBr in water has been used
even for the halogenation of nucleic acid bases. [15]
The authors noted that pyrimidines react faster than
purines, and among different pyrimidines cytosine is the
most reactive. [16] The halogenation occurs at the C-5
position and the according the mechanism described in
Scheme 1.
Scheme 1

NH2

NH2

N
O

Br2
N

+ Br
O

N
R

NH2

NH2
Br

N
O

H2O

Br
N

-H2O
N
R

OH

N
R

The halogenation seems to occur with the

intermediancy of a bromohydrin formed by the
interaction of the bromonium ion with water. The
formation of bromine in the reaction media is proposed
because the interaction of KBr and Oxone gives rise to
a bright yellow-orange solution. Neverthless some
authors [14] proposed the formation of hypohalite from
the interaction of halide with Oxone.

by addition to the reaction mixture of a base such as

Et3N or DBU (1,8-diazobiciclo[5.4.0]undec-7-ene).
(Scheme 2)
Scheme 2
Y

Y
Oxone
NaX

Y=H,H or O

3.3 Cohalogenation reactions

The interaction of Oxone with halides has been
even largely used to perform cohalogenation reactions.
Cohalogenations are very important reactions [18]
that allow to create vic-derivatives starting from
alkenes. The first step of these reactions consists in the
interaction of the alkene with a halonium ion with the
formation of a cyclic halonium or a carbocationic
intermediate that then reacts with a nucleophile present
in the reaction medium.
In recent years frequently the formation of a
halonium ion has been achieved by the interaction of a
halide and Oxone.
For example Ryu and coworkers have extensively
used the HCl/DMF/Oxone system to generate Cl+.
By this methodology he has been able to perform
chloroformyloxylation [19] of olefins and cinnamate
esters and nitriles.[20] The reaction seems to occur
through the formation of a chloronium ion that is
opened by the oxygen of the DMF. (Scheme 3)
Scheme 3
+

3.2 Halogenation of double bonds

The formation of halogens has been proposed even
by Dieter and coworkers for the halogenation of , enones and alkenes. [17] According to this author the
interaction between Oxone and NaCl or NaBr is one of
the easiest way to prepare Cl2 and Br2. The formation of
the halogens has been proved by the formation dihalo
compounds.
The formation of elimination products takes place
spontaneusly upon standing neat at room temperature or

Y
X

Cl

Cl

+
OCHNMe 2

Cl
+

Me2NCHO

H3O

Cl

OCHO

When unsimmetrical olefines have been used a

mixture of Markovnikov (major) and anti-Markovnikov

adducts have been obtained. If the reaction is carried out

on cinnamate esters the reaction led to a mixture of
different compounds. (Scheme 4)
Scheme 4

Scheme 6
KBr, Oxone, NaN3

Br
+

CHCl3

N3

8
CO2Et

CO2Et HO

OHCO

CO2Et

+
Ph

Ph

Ph

Cl

1
CO2Et

HO
+

2
Cl

Br

Cl

Br

CO2Et

Br

10

11

+
Ph

Cl

Ph

Cl
5

Compounds such as 2 where in most cases the

major products. The formation of compounds such as 3
and 5 is due to the decomposition during either the
aqueous workup or the silica gel purification.
If the reaction is carried out in the presence of
dimethylacetamide it is possible to achieve the
formation of acetoxychlorinated derivatives. [21]
Another example of cohalogenation reaction
mediated by Oxone oxidation of halides is the
azidoiodination or azidobromination of olefins.[22] In
this case the authors used Oxone supported on wet
alumina. [23] (Scheme 5)

The different chemoselectivity in the two reactions

could be explained by the more nucleophilic character
of the bromide with respect of the iodide and by the
difficulty of obtaining iodohydrines. It is interesting to
note that while the bromoazido derivative 9 shows an
anti-Markovnikov regiochemistry, compounds 10 and
11 have a Markovnikov orientation. This difference is
due to the capability of Oxone to oxidize both halides
to halonium ions and azide ion to azido radical, as
shown in Scheme 7.
Scheme 7
2HSO5- + 2Br- + 2N3- + 4H+
2H2O

2HSO4- + 2N3 + Br2 +

Scheme 5

Br

OH

KX, Oxone, NaN3

CHCl3

R
6

Br

Br

X
R

N3

15

Br-

H2O

The azidoiodination reaction [22a] (KX=KI)

proceeds with high yields and in a completely
regiospecific manner, leading only the antiMarkovnikov adduct.
Using KBr as the source of halonium ion, the
reaction is still regiospecific, but a mixture of haloazido
derivatives, dibromides and bromohydrines where
obtained. (Scheme 6) [22b]

Br
+

Br2

12

13

N3
Br
N3

N3

Br2

16

3.4 Decarboxylation and decarbonylation

Lee and coworkers showed [24] that if cinnamic
acids are used as starting materials and no nucleophiles

are present, the interaction of the olefin with Oxone

generated halonium ion, results in the
halodercarboxylation of the acid. (Scheme 8)

and coworkers were able to obtain , -dichloroketones

in good yields. (Scheme 11)
Scheme 10

Scheme 8
Ar

OH

Oxone, NaX
H2O, MeOH

NaX, Oxone, HCO3A

CH3CN, H2O

A
O

O
17

18

A= CH=CH, S, NH, NHCH3

X
O-

Ar

-CO2

Ar

X= Br, Cl

or

or

A
O

The reaction works well for chloride and bromide,

while iodide reacts only wih activated benzene rings.
The same reaction takes place even on arylpropiolic
acids and it is faster and better yielding. [25]

19

Other oxidants (such as mCPBA) were able to

induce the same reactions, but yields were lower.

Scheme 9

Scheme 11
O

CO2H
R

20

R'

Cl

R
Cl

As it is known that bromine in alcohol is capable

to oxidize aldehydes to esters, [26] Lee and coworkers
were able to obtain methyl and ethyl esters, but not ipropyl esters, starting from electron-deficient aromatic
aldehydes. [27]
3.5 Synthesis of haloketones
The oxidation of halides by Oxone has been used
for the preparation of -halo- and , -dihalo ketone. In
the first case [28] the reaction was carried out using
Oxone, NaX in MeOH and water and gave good
results except with electron-rich aromatics, that gave
preferentially aromatic ring halogenation (eg. 17 and
18). (Scheme 10)
, -dichloroketones are hardly obtained by direct
chlorination of ketones because it is difficult to control
regiospecific dichlorination at the same -position. One
of the best methods is perhaps by reaction of acetylenes
with hypochlorite even if they are obtained in low
yields. [29] Using Oxone/DMF/HCl system [30] Ryu

R'

3.6 Halogenation of oximes

In 1992 Ryu reported the conversion of aldoximes
into hydroxymoyl chlorides, useful precursors for the
preparation of nitrile oxides. [31] (Scheme 12)
Scheme 12

RCH NOH

RC NOH
Cl

Using HCl/DMF/Oxone he was able to transform

oximes into the corresponding chlorides in good yields.
The same results could be obtained using mCPBA, but
the workup is longer and requires the tedious removal of
mCBA.
A plausible mechanism for this conversion is
shown in scheme 13, and involves the partecipation of a
Cl+ formed by Oxone oxidation of HCl.

Scheme 13

RCH NOH

Cl

H
RC NOH

RC N O

Cl

Cl

and carbamates by Oxone and NaCl. (Scheme 16) [34]

Usually N-chloro-N-acyl and N-chloro-N-carbamoyl
aminoacids are precursors of , dehydroaminoacids.[35] The reaction has been carried
out using Oxone supported on wet Al2O3 and CHCl3 as
a solvent.
Scheme 16

It is interesting to note that if the reaction mixture

is diluted with THF and treated with thiourea and NEt3,
it is possible to obtain in short time and in good yields
isothiocyanates. (Scheme 14)

H
R

RCH NOH

Cl+

RC NOH
Cl

thiourea
RN
Et3N/THF

This reaction represents an efficient one-pot

procedure for the synthesis of this moiety.[32]
Curini and coworkers reported the transformation
of ketoximes in gem-halo-nitro derivatives using
Oxone supported on basic wet alumina and potassium
halides (KCl and KBr). [33] The transformation, shown
in Scheme 15, occurs with the initial formation of a
gem-halo nitroso derivative, that is in situ is oxidised to
nitro compound.

R'

R'

4.

Protection and deprotection of functional

groups
The selective introduction and removal of
protecting groups is very important in the synthetic
organic chemistry. A great variety of protecting groups
for different moieties has been developed, but still is
always very interesting to find milder and more
selective processes for their preparation. While a lot of
new procedures utilising Oxone have been proposed
for the deprotection of protecting groups, as far as we
know, only one methology has been described for the
protection of a functional group, namely the carboxylic
acid.
The authors [36] have been able to protect several
carboxylic acid moieties as diphenylmethyl esters, using
Oxone oxidation of benzophenone hydrazone.
(Scheme 17)
Scheme 17

Scheme 15
R'

Cl

Scheme 14

RC NOH

X+

R'
RC NO
X

R'
RC NO2
X

The overoxidation of the nitroso intermediate

obtained by Curini respect to Ryu could be ascribed to
the larger excess of Oxone used in this case (5 eq. vs
2.6 eq.). The reaction proceeds with good yields, it is
never accompanied by the formation of the
corresponding ketones (excepts for acetophenone
oxime) and is fast and simple.
Another example of synthetically useful oxidation
of halides is represented by N-chlorination of amides

RCO2H

PhC(NNH2)Ph
Oxone, wet Al2O3
0 C

RCO2Dpm

Diphenylmethyl esters (Dpm, benzhydril) are

important protecting groups expecially for -amino
acids, [37] penicillins and cephalosporins. [38] The
reaction is carried out using Oxone (1.5 eq) supported
on wet Al2O3 in methylene chloride at 0 C. This
procedure is of particular importance looking at the
previously reported ones, that used diphenylmethyl
phosphates, [39] and diphenyldiazomethane generated
by oxidation of benzophenone hydrazone. [38,40]

4.1 Deprotection of silyl, tetrahydropyranil ethers

and ketals and acetals
Deprotection of protecting groups by Oxone has
been extensively studied. Among different groups that
can be removed there are silyl and tetrahydropyranyl
ethers, ethylene acetals and ketals, oximes and
thioketals.
The protection of alcoholic function by conversion
to silyl and tetrahydropyranyl ethers is a common
practice. Baltork [41] reported that the treatment of
TMS- and THP-ethers with Oxone (1:1 molar ratio) in
refluxing acetonitrile gave deprotection in short times
and excellent yields (80-99%). (Scheme 18)
It is interesting to note that this procedure
transform allylic ethers into the corresponding allylic
alcohols without epoxidation of the carbon-carbon
double bond.
Scheme 18
OH

OR
Oxone, CH3CN
reflux, 0.1-1.5h
R= THP, TMS

The same condition were applied to the

deprotection of ethylene acetals and ketals (Scheme 19).
These moieties were cleaved in good yields. The
deprotection of conjugated enal system occurred
without exploiting the double bond.
Scheme 19

O
O

Oxone, CH3CN
reflux, 1-2.5h
72-99%

Scheme 20
OR

BnPPh3HSO5/BiCl3
MW, CH2Cl2
R= THP, TMS

O
BnPPh3HSO5/BiCl3
MW, CH2Cl2

Several different Lewis acids were tested, but only

BiCl3 was an effective catalyst for these reaction and the
optimum molar ratio was of 0.4 molar ratio.
It is interesting that primary ethers were converted
to the corresponding carbonyl compounds without
further overoxidation.
Among different silyl ethers used as protecting
groups tert-butyldimethylsilyl ones are perhaps the most
difficult to remove. Several methodologies have been
developed for their cleavage, most of these use basic
[43] or strong oxidasing [44,45] or reducing
systems.[46]
In 1999 Sabitha reported a new mild and selective
methods for primary TBDMS-ethers deprotection using
Oxone in 50% aqueous methanol. [47] The reactions
of primary TBDMS-ethers were complete in 2.5-3.0 h
and in these times phenolic TBDMS-ethers and other
functional groups such as secondary TBDMS-ethers,
ketals, esters and amides were unaffected. With
prolonged times (20-24 h) the cleavage of phenolic
TBDMS-ethers was observed. (Scheme 21)
Schem 21
OH

By this procedure TMS-ethers were deprotected in

the presence of THP-ethers and acetals or ketals with
high selectivity.
If the reaction on THP-, TMS-ethers and ketals is
carried out using benzyltriphenylphosphonium Oxone
[6] in the presence of BiCl3 under microwave irradiation
it is possible to achieve deprotection of these protecting
groups. [42] (Scheme 20)
Times of the reactions were really short (3-5 min.)
and yields were in the range 80-99%.

OTBDMS

3h

Oxone
50% aq MeOH

TBDMSO
OH

TBDMSO

24h
HO

At the same pH condition HF and HCl were less

selective.
4.2 Deprotection of oximes and hydrazones
Oximes and hydrazones are largely used as
protecting groups for carbonyls. Bose and coworkers
have extensively studied the oxidative deprotection of
such functional groups using Oxone. In 1997 they
reported the carbonyl regeneration from oximes by
Oxone in the presence of acetic acid. [48] (Scheme 22)
Scheme 22
R
N OH
R'

Oxone
AcOH

R
O
R'

The reactions were over in 1-5 h and the yield

range was 70-88 %. Ketoxime were cleaved faster and
in better yields than aldoximes. Later Bose [49] reported
a solvent free procedure using silica gel to support
Oxone and microwave. This methodology was
successful for a variety of oximes and hydrazones
giving better yields than the previous described.
4.3 Deprotection of thioketals
Oxone is able to oxidise several heteroatoms such
as sulfur. This ease has been used to cleave 1,3dithiolanes and 1,3-dithianes to give back carbonyl
groups.[50] (Scheme 23)
Scheme 23
R S ( )n
R'

Scheme 24
R
Oxone, Al2O3
CHCl3, reflux

OH

O
R'

The reaction worked better to regenerate ketones

than aldehydes and for the cleavage of dithiane better
than dithiolanes (shorter times and higher yields, 8499%). This last feature represents an improvement as
trimethylene dithioketals are usually more stable to the
action of other reagents. [51]
5.

the possibility to use Oxone for the conversion of

alcohols to carbonyl compounds. One of the first
examples has been reported by Morimoto in 1991. [52]
He found that, treating secondary alcohols with Oxone
supported on wet alumina in dichlorometane or
acetonitrile, ketones were obtained in good yields and
methylene chloride showed to be the best solvent.
As a matter of fact the author observed the
influence of the solvent on the distribution of products
and on the yields. Using acetonitrile, Oxone showed a
higher reactivity than in dichloromethane, but the
formation of byproducts was observed for the oxidation
of cyclohexanols. Prolonged reaction times and higher
concentration (more 2.5 times moles of the alcohol) led
to the formation of unknown products. The oxidation in
hexane was considerably slow affording only poor yield
of ketones.
Bolm and coworkers afforded catalytic synthesis
of aldehydes and ketones using TEMPO/Oxone
system.[53]
TEMPO (2,2,6,6,-tetramethylpiperidinyl-1-oxy)
has emerged to be the catalyst of choice in metal-free
alcohol oxidation. [54] A lot of terminal oxidant have
been used such as aqueous bleach, [55] and mCPBA.
[56] In 1999 Rychnovsky [57] showed the dipendence
of the catalyst on the presence of different halide ions,
tetrabutylammonium bromide being the best.
Bolm in his work showed that Oxone in
combination with TEMPO provides an efficient system
for the mild oxidation of primary and secondary
alcohols to the corresponding aldehydes or ketones.
(Scheme 24)

Oxidation of functional groups

5.1 Oxidation of alcohols

The behaviour of Oxone to very often act as a
peracid has prompted many researchers to investigate

R'

1%mol TEMPO
4%mol nBu4NBr
2.2 eq Oxone, r.t

O
R

R'

The author showed an interesting effect of the

solvent on the yield of the reaction. While primary
alcohols react better in methylene chloride, secondary
ones give better yields using toluene. By this procedure
phenolic TBDMS-ethers were unaffected.
The oxidation of organic compounds by hypohalite
salts or halogen is well known and the capability of
Oxone to oxidise halide to halogens or hypohalite
prompted Koo and coworkers to examine the possibility
to oxidise benzyl alcohols using Oxone and NaBr.[58]
Using 1eq. of Oxone, 2 eq of NaBr in a 1:1 mixture of

CH3CN/H2O they were able to transform a range of

primary and secondary benzylic alcohols in good yields.
It is important to note that the reaction did not proceed
at all without NaBr. A plausible mechanism is shown in
Scheme 25.
The application of 4-AcNHTEMPO/Oxone/NaBr system has been successfully
applied by Bragd to the selective oxidation of the
primary hydroxyl function of carbohydrates to
carboxylic function. [59] Using Oxone instead
common peracids (e.g. peracetic acid) he was able to
perform the reaction in half time (5-10 vs. 10-12 h). The
optimal pH value was 8.2 obtained by the addition of
0.5 M NaOH. Higher pH (>9) led to the instability of
the nitrosonium salt.
Scheme 25
-

SO42-

HSO5 + Br

OH
R

R'

Scheme 26
O

O
ODNs

HDNIB
( )n

Oxone, PTSA
MeOH-H2O

( )n

O
OMe

( )n

MeO

Oxone in DMF. [63]

The reaction worked well both for aromatic and
aliphatic aldehydes.
For aromatic aldehydes (scheme 27) the electron
nature of aromatic ring substituent is important.

+ HOBr

OBr
HOBr

Very recently Borhan and coworkers reported a

facile oxidation of aldehydes to acids and esters using

O
-HBr

R'

R'

5.2 Oxidation of carbonyl compounds

As we said in the introduction Oxone is able to
interact with ketones to afford dioxiranes which in turn
act as powerful oxidants. In 1991 Morimoto reported a
useful Baeyer-Villiger oxidation of cyclic ketones to
lactones using Oxone supported on wet alumina. [60]
The reactions were carried out in dichlomethane at
reflux. The reaction showed to be effective for the
oxidation of cyclopentanones and cyclohexanones (8085% yield), while it was not good yielding in the
oxidation of cycloheptanones (23%). The only
drawback of this procedure is the long reaction time
(20-24 h).
Treatment of cycloalkanones with [hydroxy-(2,4dinitrobenzensulfonyloxy) iodo] benzene (HDNIB) and
subsequently with Oxone and PTSA in aqueous
methanol provides , -dicarboxylic acid dimethyl
esters. [61] This methodology (Scheme 26) represents
an improving respect to the previously used for the
conversion for the synthesis of dicarboxylic acids. [62]
The oxidation of aldehydes to carboxylic acids is
one of the easiest reaction in organic chemistry, but in
most of the cases utilized Cr, Mn, Ru or other transition
metal oxides with the result of a not environmentally
friend procedures.

Scheme 27
CHO
Oxone
DMF

CO2H

Electron-withdrawing and electron-neutral

benzaldehydes were oxidized efficiently (90-97%
yield), electron-rich substrates gave poor yields in
oxidated products (19-31%) while major product was
Dakin product via Baeyer-Villiger ester. (Scheme 28)
Scheme 28
CHO

OCHO

OH

X=OH, OMe

The same results were observed with aliphatic

aldehydes.

Very few solvents provided the desired acids even

after 36 h of reaction. Testing different solvents the
authors descovered that performing the reaction in
alcohol it was possible to obtain directly from the
aldehyde the corresponding esters. (Scheme 29)

Scheme 31
O ( )n
R

Oxone, wet Al2O3

CHCl3, 50 C

Scheme 29
O
R

O
R

( )n

OH

n= 1,2

Oxone
H R'OH

O
R

Using dioxane at 80 C the ester was obtained

almost as the sole product.

OR'

According the authors the esters are not obtained

by a Fischer-type oxidation, but through dialkyl acetals
formation. (Scheme 30)

Scheme 32
ROH +

Scheme 30

RO

O
HO
R

O OSO3K

OH

+ KHSO4

O
KHSO5

RO
O
R

R'O
R

KHSO5

HO

R'OH

OR' KHSO5

O OSO3K
R

OH

OR'

+ KHSO4

5.3 Oxidation of acetals

As we have already seen acetals are one of the
most used protecting group for carbonyl and usually
they are removed by acid hydrolysis. Oxone has shown
to be effective for the deprotection of this group. [41]
(Scheme 19)
Marcotullio et al. found that Oxone on wet
alumina in chloroform at 50 C is able to afford the
transformation of acetals to - or -hydroxy esters.
(Scheme 31) [64]
The yields were good (90%) with R=alkyl, and
lower with R=Ar (60-79%).
In the same conditions THP-ethers (a) gave
oxidation to alkyl 5-hydroxy-pentanoate (b) and
oxidative deprotection of the ether (c and d). (Scheme
32)

Ketals in the same conditions did not react at all.

The solvent and the presence of wet alumina play a
fundamental role.
As a matter of fact Shereshovets and coworkers reported
[65] that using the above conditions without Al2O3 no
reaction was observed. Much lower yields are obtained
by these authors changing the order of the addition. [66]
Performing the reaction in the presence of catalytic
amount (0.001 mmol) of 2,2,5,5-tetramethyl-4-phenyl3-imidazoline-3-oxide-1-oxyl and KBr (1 mmol)
Oxone was able to convert in quantitative yields
acetals into glycol monoesters.
5.4 Oxidation of nitrogen containing groups
In organic synthesis nitrogen containing groups
play a fundamental role both as protecing groups
(oximes, hydrazones, hydrazides) and as intermediates
for the preparation of different moieties.
Oxone ha shown to be able to interact with these
group to perform a variety of synthetic useful
transformations.

5.4.1 Oxidation of hydrazides

Hydrazides are versatile intermediates in organic
synthesis expecially as synthons for the construction of
heterocycles. [67] A variety of oxidants have been used
for the conversion of hydrazides into the corresponding
acids, but the reaction always led to side products.
Treatment of hydrazides with Oxone at room
temperature in water affords in short times (20-30 min.)
and good yields (84-93%) N,N -diacyl-hydrazines. [68]
Although all hydrazides are practically isoluble in
water, when added to the solution of Oxone in water,
they dissolve allowing a single phase oxidation. The
resultant N,N -diacyl-hydrazines are insoluble in water
and separate out during the reaction allowing the
recovering of the reaction products by simple filtration.
(Scheme 33)
Scheme 33
O
R

Oxone
NH NH2

Oxone

N NH

O
HO N N

5.4.2 Oxidation of hydrazones

The conversion of aldehydes into nitriles is an
important process in organic synthesis. Several
procedures are available [70] among these the oxidative
conversion of N,N-dimethylhydrazones to nitriles is
very important. [71]
In 2000 Ramalingam reported an efficient
conversion of N,N-dimethylhydrazones into nitriles
using Oxone supported on wet Al2O3 and microwaves.
[72] The reaction showed to be general as aliphatic,
aromatic, heterocyclic and , -unsaturated hydrazones
gave good results. (Scheme 35) Without using
microwaves the reaction times resulted much longer and
the yields low. The author studied different solid
supports for Oxone (SiO2, KSF) but alumina gave best
results.
Scheme 35

O
R

It is interesting to note that while the conversion to

esters is simply obtained perfoming the reaction in dry
alcohol, the oxidation into acids requires more complex
reaction conditions (acetone, NaHCO3, EDTA).
Probably these conditions are required to avoid the
formation of acyl hydrazines.

NH NH2

O
R

O
NH NH

Ramalingam reported an efficient and selective

conversion of hydrazides into esters and acids. [69] The
reaction, as shown in Scheme 34 proceeds through the
formation of an acyldiazene that, in the presence of a
nucleophile such as water or alcohol, gives in good
yields (70-90%) acids or esters respectively.

NN(CH3)2

Oxone, Al2O3
M.W.

5.4.3 Oxidation of nitro groups

Aliphatic nitrocompounds are important
intermediates in organic synthesis, particularly in
carbon-carbon bond formation. [73] The conversion of
nitro group into carbonyl (Nef reaction) [74] has been
performed both by hydrolytic and oxidative
methods.[75] Oxone in buffered aqueous methanol
showed, in the presence of NaOH, to be capable of
effecting Nef reaction. [76]
Secondary nitro groups were transformed in good
yields into the corresponding ketones (Scheme 36)
while primary ones into carboxylic acids.

Scheme 34
Scheme 36
R'

O
R

Oxone
NH NH2

YOH
N NH

R'

O
R

NO2

OY
OH

Y=H, R'

NO2

A variety of different moieties (acetates, silyl

ethers, alcohols, acetales) were unaffected by this
reaction.
The same methodology applied to nitrocycloalkanones gave , -dicarboxylic acid
monoesters (Scheme 37) or, if performed in water, , dicarboxylic acids. [77]

were dramatically shortened to 40s with microwave

irradiation.
Scheme 39
H
R

R'

[O]

Oxone, buffer
NaOH 1M
MeOH-H2O

( )n

MeO

OH

( )n
O

5.4.4 Oxidation of amines

Different examples of oxidation of primary [78]
and secondary [79] by dimethyldioxiranes have been
reported, while only one example is referred to Oxone
[80] The authors using supported Oxone were able to
oxidise primary and secondary amines to
hydroxylamines either in the presence or absence of a
solvent. (Scheme 38)
Scheme 38

N:

R
[O]

[O]

R'

OH

5.5

[O]

Oxone
NaOH 1M
H2O

HO

OH

( )n

[O]

R'

OH

O
NO2

[O]

OH

Scheme 37

OH
[O]

N+

O-

N OH

[O]

(R=H)

Kropp studied the influence of the supporting agent

on the selectivity of the reaction. Using the most
common Al2O3-Oxone system he was able to perform
the oxidation of primary and secondary amines to
hydroxylamines, but the chemoselectivity was low, as
different side products (such as imine oxide, oxime or
nitroso) were recovered (Scheme 39)
Better results have been obtained using SiO2 as a
support. Using these conditions tertiary amines were
transformed into N-oxides.
The use of solvent free conditions at 80 C afforded
the same products at rate comparable, but reaction times

Oxidation of selenides
While the oxidation of sulfides to sulfones using
Oxone is largely described, [81] few example of the
oxidation of selenides to selenoxides and selenones are
reported.
One of the first is the preparation of selenones using
Oxone in methanolic, aqueous buffered solution has
been described in 1995.[82] (Scheme 40)
Scheme 40
O
R

Se

R'

Oxone, MeOH
H2O, pH 8

Se

R'

The protocol was applied to the oxidation of three

classes of substrates: alkylaryl selenides, methoxyalkyl selenides, and -hydroxyalkyl selenides.
Selenones were obtained in good yields, bettere than the
already described, in short times and milder conditions
in the oxidation of alkyaryl selenides and methoxyalkyl selenides. In the oxidation of hydroxyalkyl selenides only the corresponding epoxides
were obtained. (Scheme 41)
Scheme 41
OH
R

OH
SePh

O
R

SeO2Ph

It is interesting to note that using this procedure it is

possible to avoid skeletal rearrangements always
observed during selenone formation of -hydroxy and
-methoxy selenides (Scheme 42).[83]
Scheme 42
OR

OR
SePh

SeO2Ph

OR
OR

6.

Conclusions
Oxone showed to be a convenient and efficient
oxidant in organic chemistry allowing a great variety of
reaction by fast, good yielding and simple procedures.
The low cost and the stability of this reagent make it an
important tool in organic synthesis.
8.

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