Solvent-Free Iodination of Arenes at Room Temperature

Article abstract of DOI:10.1055/s-2003-41496

Silica supported bismuth(III)nitrate pentahydrate [BNP-SiO₂] was prepared under simple co-grinding condition. The iodination of aromatic compounds using BNP-SiO₂ and molecular iodine under solvent-free conditions is described. The reaction occurred in the solid state at room temperature, yielding the corresponding mono-iodo derivative in good yields. However, less activated aromatics required longer reaction time with comparatively less yield.

Full text of DOI:10.1055/s-2003-41496

LETTER
1895
Solvent-Free Iodination of Arenes at Room Temperature
S
olvent-Free Iodin
a
ation of
A
r
r
enes at
R
u
oomTempe
g
rature hese M. Alexander, Amit C. Khandekar, Shriniwas D. Samant*
Applied Chemistry Division, Institute of Chemical Technology, University of Mumbai, Nathalal Parekh Marg, Matunga,
Mumbai- 400 019, India
Fax +91(22)24145614; E-mail: mva_sds@yahoo.co.in
Received 18 June 2003
This work is dedicated to the late Dr. B. M. Khadilkar.
of steps performed under controlled temperature condi-
tions. Thus, in general, most reactions described in the
literature are carried out either with excess of the reactant
or by using chlorinated hydrocarbons or acetonitrile as
Abstract: Silica supported bismuth(III)nitrate pentahydrate
[BNP-SiO2] was prepared under simple co-grinding condition. The
iodination of aromatic compounds using BNP-SiO2 and molecular
iodine under solvent-free conditions is described. The reaction
occurred in the solid state at room temperature, yielding the corre- solvent, sometimes at room and often at elevated temper-
sponding mono-iodo derivative in good yields. However, less ac-
atures. In this regard, an efficient construction of this aro-
tivated aromatics required longer reaction time with comparatively
less yield.
matic scaffold employing molecular iodine at room
temperature is always appealing.
Key words: aromatic iodination, solvent-free, bismuth nitrate pen-
Recently, we have reported the iodination of activated
tahydrate, molecular iodine, co-grinding
arenes using silica supported ferric(III)nitrate and molec-
ular iodine, in dichloromethane.6 It should be noted that
Fe+3 functions as a Lewis acid and also can participate in
Halogenated aromatic compounds constitute an important
some redox reactions. Sakae and co-workers have already
class of molecules in synthetic organic chemistry. Io-
demonstrated aromatic iodination and bromination with
doarenes are important intermediates1 with wide practical
antimony(V)chloride and molecular halogens using chlo-
applicability that range from preparation of functionalised
rinated hydrocarbons as solvents.4j Bi(III) salts have
aromatic compounds to aryl organometallic reagents.
gained increasing attention for a variety of organic trans-
Many iodoorganic compounds are biologically active
formations.7 Bismuth(III)nitrate pentahydrate [BNP] i.e.
molecules often used in medicine as drugs or in diagnostic
Bi(NO3)3·5H2O is an inexpensive, commercially available
aids as radioactively labeled markers or contrastors and
reagent and requires no special care during its handling.
thus their related chemistry has attracted broad interest.2
The potentials of this reagent for aromatic nitration,8a
Despite significant improvements for direct bromination
oxidation of alcohols,8b deprotection of oximes8c and con-
and chlorination of aromatics with the respective molecu-
version of thiocarbonyls to the corresponding carbonyl
lar halogens,3 limitations still exist for aromatic iodination
compounds8d have been recently explored.
reaction.
Reactions carried out under solvent-free conditions have
Iodine is a weak electrophile when compared to bromine
received immense popularity in recent years.9 The mild
or chlorine. Moreover, electrophilic iodination often gen-
reaction conditions, low reaction times, sometimes en-
erates hydrogen iodide, which is both a strong reducer as
hanced selectivity and clean products are the salutary
well as a strong acid which can cause protolytic cleavage
features of this approach. On the basis of all the above ra-
of the formed aryl iodide. Iodination of hydrocarbons is
tionale, we thought it would be worthwhile to prepare and
a reversible process and besides requiring electrophilic I+
study the application of this reagent [BNP-SiO2] for direct
species, requires an oxidising agent to oxidise the hy-
iodination of arenes in presence of molecular iodine.
driodic acid formed in the reaction. For this purpose, a va-
Thus, in sharp contrast to the volume of literature,1–4 we
riety of reaction systems involving molecular iodine along
herein disclose the first report for aromatic iodination
with oxidants such as, oleum,4a iodic acid,4b periodic ac-
under solvent-free conditions, using molecular iodine
id,4c peracetic acid,4d mixture of nitric and sulfuric acid,4e
(Scheme 1). This protocol is mild as compared to the
KMnO4,4f MnO2,4f sodium periodate,4g CrO3,4h
existing methods using solvents.
Pb(OAc)4,4i antimony(V)chloride,4j Hg salts,4k nitrogen
dioxide,4l CF3SO3Ag,4m silver sulfate,4n tetrabutylammo-
nium peroxydisulfate,4o diiodine pentoxide,4p etc. were re-
ported. Recent milder modifications employ quaternary
ammonium salts5 prepared either by using the corrosive
and moisture sensitive iodine monochloride or by a series
Our initial experiments focused on the iodination of an ac-
tivated arene like anisole. It was observed that with 0.5
SYNLETT 2003, No. 12, pp 1895–1897
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9
.0
9
.2
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3
Advanced online publication: 19.09.2003
DOI: 10.1055/s-2003-41496; Art ID: G14003ST
© Georg Thieme Verlag Stuttgart · New York
Scheme 1 Solvent-free iodination of aromatics using BNP-SiO2
and molecular iodine, at room temperature

1896
V. M. Alexander et al.
LETTER
Table 1 Solvent-Free Iodination of Aromatics Using BNP-SiO2 and
Molecular Iodine, at Room Temperature
equivalents of this oxidant 95% of the p-iodoanisole was
isolated within 5 minutes under the reaction condition.10
On decreasing the amount of the oxidant to 0.3 equiva-
lents, 92% of the iodo product was isolated in the same pe-
riod. These exciting results prompted us to carry out all
further studies using 0.3 equivalents of the oxidant with
respect to the substrate used.
Entry Substrate
Product
Time
Yielda
(%)
1
2
5 min
5 min
92
91
Nitration of aromatic compounds using BNP/K10 clay
has been reported.8a However, in the present protocol the
formation of nitro derivatives was not observed in spite of
increasing the amount of BNP-SiO2. Subsequently, sup-
ported reagents like BNP/K10 and BNP/KSF were pre-
pared following the co-grinding procedure. The reagents
were mixed with anisole and allowed to stand. The forma-
tion of the nitro derivative was not observed even after
half an hour. To see the implication of reactivity of aro-
matic compounds in the interplay of iodination and nitra-
tion, 1,4-dimethoxybenzene was co-grinded with the
BNP-SiO2 and molecular iodine. However, in this case ni-
tration was observed within few minutes. Thus, it is ap-
parent that the method can be extended for the nitration of
highly activated arenes.
3
4
10 min
5 min
84
89
5
6
5 min
5 min
82
84
7
10 min
84
To demonstrate the scope of the solvent-free iodination
reaction, we subjected a range of substituted aromatic
ethers to the present conditions. Most of the substituted ar-
omatic ethers were rapidly converted to the corresponding
iodo derivatives in good yields. To further generalise this
methodology, arenes like benzene, some of its alkyl deriv-
atives and a few heterocycles were subjected to the reac-
tion conditions. Xylenes, mesitylene and durene were
readily converted to the corresponding mono-iodo prod-
ucts, in a relatively short reaction time. In an unoptimised
reaction, iodination of benzene led to the formation of
iodobenzene with 37% yield after 3 days. Also, few het-
erocycles like pyrazole and thiophene were iodinated,
though some optimisation is required. The unoptimised
results are summarised in Table 1.
8
9
12 h
2 h
69
76
70
10
11
5 h
3 days 37
5 min 90
12
13
14
5 min 87
As anticipated, the products obtained after the reaction re-
sulted from the regioselective iodination of the aromatic
ring. The observed regioselectivity was in accordance
with the electronic consideration and steric factor.
However, in case of activated arenes like naphthalene,
methoxy naphthalenes and acetanilide, formation of trace
amounts of the corresponding nitro product was observed
under the present reaction conditions (TLC analysis).
10 min 58
15
10 min 52
In conclusion, a highly novel, mild, inexpensive and
solvent-free protocol for iodination of activated arenes is
described. This practically simple method led to the cor-
responding iodo derivatives in short reaction times under
extremely mild conditions. The ease of this protocol is of
general interest as these iodo derivatives have wide poten-
tial applications in synthetic and combinatorial chemistry.
Attempts to exploit the catalytic performance of this
oxidant and few other metallic nitrates in polar solvents
like ionic liquids have been accomplished and will be
published in due course.
a Isolated yields after chromatographic separation.
Acknowledgment
The authors are thankful to DAE/BRNS (99/37/39/BRNS/1749)
and AICTE for financial assistance.
Synlett 2003, No. 12, 1895–1897 © Thieme Stuttgart · New York

LETTER
Solvent-Free Iodination of Arenes at Room Temperature
1897
(8) (a) Samajdar, S.; Becker, F. F.; Banik, B. K. Tetrahedron
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(d) Baltork, I. M.; Khodaei, M. M.; Nikoofar, K.
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Synlett 2003, No. 12, 1895–1897 © Thieme Stuttgart · New York