PAPER
1195
Oxidative Iodination of Deactivated Arenes in Concentrated Sulfuric Acid
with I2/NaIO4 and KI/NaIO4 Iodinating Systems1
O
xidative Iodin
u
ation of Dea
c
tivate
d
A
ren
a
es sz Kraszkiewicz, Maciej Sosnowski, Lech Skulski*
Chair and Laboratory of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw,
1 Banacha Street, 02-097 Warsaw, Poland
Fax +48(22)5720643; E-mail: lechskulski@yahoo.com
Received 17 October 2005
5 ArH + 2 I2 + NaIO3 + H2SO4 → 5 ArI + NaHSO4 + 3
Abstract: Deactivated arenes were mono- or diiodinated with
strong electrophilic I+ reagents, which were prepared from NaIO4
and either I2 or KI in concentrated H2SO4 (minimum 95% by
weight). In general a small excess of the dark brown iodinating so-
lution was used (1.1/1.5 equivalents, for nitrobenzene two equiva-
lents was required). The iodinations were conducted at 25–30 °C
with a reaction time of 1–2 hours using either a ‘direct’ or an ‘in-
verse’ method of aromatic iodination to give mono- or diiodinated
pure products in 31–91% optimized yields.
H2O (monoiodination)
2.5 H-Ar-H + 2 I2 + NaIO3 + H2SO4 → 2.5 I-Ar-I +
NaHSO4 + 3 H2O (diiodination)
Generally, the arenes reacted with the previously prepared
iodinating solution at 25–30 °C for 1–2 hours giving the
desired products in 33–85% yield, by two different meth-
ods.7 For nitrobenzene, benzoic acid and other deactivated
arenes, which can be partly diiodinated only by a large ex-
cess of iodinating solution, a ‘direct’ method of aromatic
monoiodination was applied: the arenes were added in one
portion to the iodinating solution and stirred at 25–30 °C
for one hour. However, some mildly deactivated arenes
readily formed mixtures of mono- and diiodinated prod-
ucts, which were difficult to separate, for example, meth-
oxy or methyl para-substituted benzoic acids and
nitrobenzenes. An ‘inverse’ method of monoiodination
was preferred to obtain pure monoiodinated crude prod-
ucts: the mildly deactivated arenes were suspended in
90% H2SO4, the iodinating solution was added very slow-
ly (45 min) at 25–30 °C, and stirring was continued at the
same temperature for a further 15 minutes to complete the
reactions. The simpler ‘direct’ method of aromatic iodina-
tion was preferable for the diiodination of arenes.7
Key words: iodoarenes, deactivated arenes, iodine, potassium io-
dide, sodium periodate, direct oxidative iodination
Aromatic iodides are generally more reactive, albeit more
costly, than their respective bromides and chlorides.
There are many different methods, direct and indirect, for
their synthesis;2 they are widely used in laboratory scale
organic synthesis and to a lesser extent in industry. More-
over, they are able to form a variety of aromatic hyperva-
lent iodine derivatives, which have found increasing
application in modern organic synthesis.3 Our two
reviews4,5 relate and explain a variety of aromatic iodina-
tion methods suitable for both activated and deactivated
aromatics, devised in our laboratory since 1990, as well as
our novel methods for preparing several classes of aro-
matic hypervalent iodine compounds, easily synthesized
from aromatic iodides; our most recent work is in relation
to the oxidative iodination of various aromatics.6,7
In our previous work,7 two ‘model’ deactivated arenes,
benzoic acid and nitrobenzene, dissolved in concentrated
H2SO4 (90%) were monoiodinated with strongly electro-
philic I+ reagents prepared from diiodine and various oxi-
dants (CrO3, KMnO4, active MnO2, HIO3, NaIO3, or
NaIO4) in concentrated H2SO4 (90%, 30 min at 25–
30 °C), to give a stable dark brown iodinating solution
containing I+ (i.e. IOSO3H) intermediates; 1.1 equivalents
were required for the monoiodination of benzoic acid,
while two equivalents were required for the monoiodina-
tion of nitrobenzene. Only the I2/NaIO3/H2SO4 liquid sys-
tem was next used to effectively mono- or diiodinate a
considerable number of more or less deactivated arenes,
according to the following stoichiometries:
In order to further extend and improve our iodination pro-
cedures,7 herein we describe numerous oxidative iodina-
tion reactions, employing I2/NaIO4/H2SO4 and, for the
sake of comparison, KI/NaIO4/H2SO4, with a variety of
more or less deactivated arenes, including nitrobenzene
(Tables 1– 3). It was convenient to change the concentra-
tion of H2SO4 from 90% to the commercially available
95% to avoid the hazardous dilution of 95% H2SO4. In-
creasing the concentration of H2SO4 to 95%, has resulted
in a greater oxidizing ability at 25–30 °C, however, in
only a few cases it has had some negative consequences
(vide infra). According to Merkushev,2 the replacement of
elemental iodine, usually requiring careful grinding be-
fore use, by readily accessible and cheap alkali iodides, is
often convenient, although larger quantities of the oxi-
dants are required in such oxidative iodination reactions.
However, in the application of periodic acid, iodic acid, or
their alkali salts as the oxidants in the oxidative aromatic
iodination reactions8 nearly all the iodine atoms present in
the oxidant are incorporated into the iodinated final prod-
ucts (an eco-friendly factor);8 hence, the said disadvan-
SYNTHESIS 2006, No. 7, pp 1195–1199
x
x
.
x
x
.2
0
0
6
Advanced online publication: 08.03.2006
DOI: 10.1055/s-2006-926374; Art ID: Z20305SS
© Georg Thieme Verlag Stuttgart · New York