Tetrahedron Letters 48 (2007) 81–83
A mild and simple regioselective iodination of activated
aromatics with iodine and catalytic ceric ammonium nitrateI
Biswanath Das,* Maddeboina Krishnaiah, Katta Venkateswarlu and V. Saidi Reddy
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 28 August 2006; revised 23 October 2006; accepted 1 November 2006
Available online 21 November 2006
Abstract—Molecular iodine in the presence of a catalytic amount of CAN has been utilized efficiently for regioselective iodination of
activated aromatic compounds under mild reaction conditions.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Aromatic iodo compounds are important intermediates
for the synthesis of various pharmaceutical and bio-
active compounds.1 They are also useful in metal-cata-
lyzed cross coupling reactions, such as Heck, Stille and
Negishi reactions which are utilized in C–C and C–N
bond formation.2 However, direct iodination of aro-
matic compounds is difficult due to the low electrophilic-
ity of molecular iodine compared to that of molecular
chlorine and bromine. Generally, arenes are iodinated
by iodine in the presence of a Lewis acid or an oxidizing
agent. Direct iodination methods have been reported
using various iodonium donating systems, such as
NIS–CF3SO3H,3a iodine–Ag2SO4,3b iodine–HgO,3c
NIS,3d iodine–tetrabutylammonium peroxydisulfate,3e
n-BuLi–CF3CH2I,3f and ICl.3g However, most of these
methods require toxic and costly reagents, high temper-
atures and long reaction times. Thus it is desirable to
apply a simple, inexpensive and non-toxic reagent sys-
tem for iodination of aromatic compounds.
have been iodinated using iodine–CAN at room
temperature to form the corresponding iodo compounds
(Table 1). The I+ electrophile generated in situ by the
reaction of iodine and CAN causes nuclear iodination
of the electron rich aromatic compounds and Ce(III) is
re-oxidized to Ce(IV) in the presence of aerial oxygen.
Under nitrogen, the yields of aryl iodides were very
low. Electron deficient aromatic compounds, such as
nitrobenzene and benzoic acid, did not undergo iodin-
ation. Though CAN is acidic, aniline (Table 1, entry e)
could be iodinated smoothly. The phenolic hydroxyl
groups (entries g–k) were not affected.
The iodination of the substrates took place with high
regioselectivity and only mono-iodination was found
to occur. When an alkoxy or an amine group was pres-
ent on the aromatic ring (entries a, e and n), iodination
proceeded with high para-selectivity while ortho-iodin-
ation occurred when the para-position was blocked with
a substituent other than a hydroxyl group (entries m and
o). However, with the phenolic compounds (entries d
and j) the ortho-iodo compounds were the major prod-
ucts. The structures of the aryl iodides were established
In continuation of our work4 on the development of
useful synthetic methodologies, we have observed that
iodine in the presence of a catalytic amount of ceric
ammonium nitrate (CAN) is an effective reagent system
for iodination of activated aromatic compounds. CAN
is a valuable reagent for various chemical transforma-
tions.5 Here, a series of activated aromatic compounds
1
from their H NMR and mass spectral data.
In conclusion, we have developed a very simple, mild
and regioselective method for nuclear iodination of
activated aromatic compounds using the iodine–CAN
reagent system which is readily available, inexpensive
and non-toxic.
Keywords: Activated aromatic; Aryl iodide; Iodine; CAN;
Regioselectivity.
q Part 113 in the series, ‘Studies on novel synthetic methodologies.’
General experimental procedure: To a mixture of an
activated arene (0.5 mmol) and molecular iodine
(0.5 mmol), CAN (10 mol %) was added. The mixture
IICT Communication No. 061022.
Corresponding author. Tel./fax: +91 40 7160512; e-mail:
*
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.11.009
Das, Biswanath
