Selective oxidation of methylarenes with pyridinium chlorochromate

Article abstract of DOI:10.1055/s-2005-917118

A simple and selective method for oxidation of methylarenes, using pyridinium chlorochromate (PCC) is described. This reagent can efficiently oxidize methylarenes to the corresponding aldehydes under mild aprotic conditions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-917118

LETTER
2769
Selective Oxidation of Methylarenes with Pyridinium Chlorochromate
Selective
Oxidati
a
on of Meth
h
ylarenes man Hosseinzadeh,* Mahmood Tajbakhsh,* Hossein Vahedi
Department of Chemistry, Mazandaran University, Babolsar, Iran
Fax +98(11252)42002; E-mail: r.hosseinzadeh@umz.ac.ir
Received 15 July 2005
Abstract: A simple and selective method for oxidation of methyl-
arenes, using pyridinium chlorochromate (PCC) is described. This
reagent can efficiently oxidize methylarenes to the corresponding
aldehydes under mild aprotic conditions.
Scheme 1 Oxidation of methylarenes using PCC
Key words: methylarenes, PCC, benzylic oxidations, aldehydes
ratio of oxidant to substrate and solvent to obtain the opti-
mum conditions. Our observations revealed that, amongst
the various solvents used, acetonitrile was the most effec-
tive and gave high yields with a molar ratio of 1:1 sub-
strate:reagent under reflux condition. Under the optimum
conditions, different methyl-substituted aromatic com-
pounds were oxidized to the corresponding aldehydes.
The results are presented in the Table 1.
Oxidation of methyl groups on aromatic rings is a fre-
quently used procedure in organic synthesis.1–6 Most com-
monly used are transition metal oxidants. In these cases,
the initial oxidation products are often more susceptible to
oxidation than the starting material. Once a methyl group
is attacked, it is likely to be oxidized to the carboxylic
acid.7 While such reactions readily give benzoic acids in
high yields, they are rather difficult to stop at the aldehyde
stage. Several special procedures have been developed to
suppress further oxidation of the aldehyde to the corre-
sponding acid. Basically, there are two approaches: first,
the use of special oxidants that oxidize the aromatic meth-
yl group to the aldehyde, but not further,1 and second, the
application of specific reagents that trap the aldehyde
formed.8 The reagents reported for oxidation of benzylic
hydrocarbons include benzeneseleninic anhydride,1 2,3-
dichloro-5,6-dicyanobenzoquinone (DDQ),2 Co/Mn/Br–,3
Ag(Py)4S2O8,4 Ce(NH4)2(NO3)6,5 O2/NBS,6 Ce(IV)/meth-
anesulfonic acid,9 RhCl(PPh3),10 KMnO4/Al2O3,11 O2/
As indicated in Table 1, o-, m-, p-xylenes are oxidized to
their corresponding aldehydes in relatively high yields
when treated with PCC in refluxing acetonitrile. Under
these reactions only one methyl group is oxidized and fur-
ther oxidation to the corresponding carboxylic acid and
also the oxidation of other methyl group did not occur,
even using higher molar ratios of PCC and longer reaction
times. This indicates the selective oxidation nature of
PCC in these reactions. To confirm further, we have ex-
amined 1,3,5-trimethylbenzene and durene and observed
that, similar to xylenes, only one methyl group was trans-
formed to the aldehyde group. Similarly, toluene and p-
methoxytoluene under these reaction conditions gave
high yields of benzaldehyde and p-methoxybenzalde-
hyde, respectively. Introduction of electron-withdrawing
groups, such as bromine and nitro groups, on the aromatic
ring retards the oxidation reaction.
12
Laccase/ABTS–(NH4)2 and CrO3/Me3SiCl.13 However,
all of these procedures exhibit some disadvantages, such
as the need for drastic reaction conditions, rather poor
yields and long reaction times.
Pyridinium chlorochromate (PCC), a readily available
and stable reagent, can oxidize a wide variety of organic
substrates such as primary and secondary alcohols with
high efficiency.14 It has also been used for the oxidation of
active methylenes (benzylic and allylic) to their corre-
sponding ketones.15 In our best knowledge there is no
report concerning oxidation of methylarenes to their cor-
responding aldehydes using PCC. We now wish to report
here another use of PCC in organic synthesis: the selective
oxidation of methylarenes to the corresponding aldehydes
under very mild conditions (Scheme 1).
In order to investigate the applicability of this procedure
in industry, we have carried out the oxidation of p-xylene
under our optimum reaction conditions on large scale (15–
20 mmol) and obtained almost the same yields as in the
small-scale reaction. It is also noteworthy that, unlike
other oxidative methods, the major drawback of over-
oxidation of the aldehyde to the carboxylic acid was not
observed.
In conclusion we have introduced another efficient use of
PCC as a readily available reagent in organic oxidation
reactions.
To gain some preliminary information on this synthetical-
ly useful reaction, p-xylene was chosen as a model sub-
strate. We have studied the influence of temperature, mole
General Procedure for Oxidation of Methylarenes with PCC
To a solution of 1 mmol of PCC in 10 mL of dried MeCN, 1 mmol
of the aromatic compound was added, and then the mixture was re-
fluxed for the specified time. After completion of the reaction, the
reagent (PCC) was removed by filtration and washed with CH2Cl2.
SYNLETT 2005, No. 18, pp 2769–2770
Advanced online publication: 10.10.2005
DOI: 10.1055/s-2005-917118; Art ID: D19905ST
© Georg Thieme Verlag Stuttgart · New York
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R. Hosseinzadeh et al.
LETTER
The CH2Cl2 phase was washed with H2O. The combined extracts
were dried with MgSO4. Evaporation of the solvent gave the corre-
sponding aldehyde derivatives. Further purification of products was
carried out by column chromatography and then the products were
characterized by 1H NMR, GC and comparison with authentic
samples.
Table 1 Oxidation of Methylarenes Using PCC
Entry
1
Substrate
Producta
Time Yield
(h)
(%)b
2
78
Acknowledgment
2
3
3.5
67
79
Financial support of this work from the Research Council of
Mazandaran University is gratefully acknowledged.
3
3
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Synlett 2005, No. 18, 2769–2770 © Thieme Stuttgart · New York