Regioselective iodination of arenes using iodine/NaBO3· 4H2O system in ionic liquid

Article abstract of DOI:10.1080/00397910801979395

A mild, efficient, and simple protocol was developed for iodination of arenes and heterocyclic compounds with molecular iodine catalyzed by sodium perborate in ionic liquid. The methodology offered iodoarenes in good to excellent yields at room temperature. The protocol proved to be highly selective, as a single isomer was formed exclusively in most of the substrates. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910801979395

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Regioselective Iodination of
Arenes Using Iodine/NaBO ·
3
4
H O System in Ionic Liquid
2
a
b
Sachin V. Bhilare , Amol R. Deorukhkar , Nitin B.
a
b
Darvatkar & Manikrao M. Salunkhe
a
Department of Chemistry, Institute of Science,
Mumbai, India
b
Department of Chemistry, Shivaji University,
Vidyanagar, Kolhapur, India
Published online: 28 Aug 2008.
To cite this article: Sachin V. Bhilare , Amol R. Deorukhkar , Nitin B. Darvatkar &
Manikrao M. Salunkhe (2008) Regioselective Iodination of Arenes Using Iodine/NaBO3
·
4H O System in Ionic Liquid, Synthetic Communications: An International Journal
2
for Rapid Communication of Synthetic Organic Chemistry, 38:17, 2881-2888, DOI:
0.1080/00397910801979395
1
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Synthetic Communications , 38: 2881–2888, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910801979395
Regioselective Iodination of Arenes Using
Iodine/NaBO ꢀ 4H O System in Ionic Liquid
3
2
1
2
1
Sachin V. Bhilare, Amol R. Deorukhkar, Nitin B. Darvatkar, and
2
Manikrao M. Salunkhe
Department of Chemistry, Institute of Science, Mumbai, India
Department of Chemistry, Shivaji University, Vidyanagar, Kolhapur, India
1
2
Abstract: A mild, efficient, and simple protocol was developed for iodination of
arenes and heterocyclic compounds with molecular iodine catalyzed by sodium
perborate in ionic liquid. The methodology offered iodoarenes in good to excel-
lent yields at room temperature. The protocol proved to be highly selective, as
a single isomer was formed exclusively in most of the substrates.
Keywords: Catalysis, iodination, ionic liquid, sodium perborate
INTRODUCTION
Aromatic iodo compounds have been used for more than a century as
[
1]
important chemicals or intermediates in organic synthesis. Iodoarenes
are valuable intermediates in the synthesis of a wide variety of organic
compounds via reactions involving C–C bond formation by transition
[
2]
metals. They have numerous applications in pharmacology, medicine,
and biochemistry.
Because of the low reactivity of molecular iodine, direct iodination of
aromatic compounds is difficult. This problem is overcome by activating
iodine for effective electrophilic substitution; the use of a plethora of cat-
alysts and oxidants in conjunction with iodine is well documented in this
þ
regard. Synthetic methods involving a source of I as the reactive species
seem to be the most convenient procedures for the direct iodination of
Received January 13, 2008.
Address correspondence to Manikrao M. Salunkhe, Department of Chemistry,
Shivaji University, Vidyanagar, Kolhapur 416004, India. E-mail: mmsalunkhe@
hotmail.com
2
881

2882
S. V. Bhilare et al.
arenes. The reagents reported for iodination of arenes include
HNO =H SO , HIO or HIO =H SO , NIS-CF SO H, NIS-CF COOH,
3
2
4
3
4
2
4
3
3
3
I –tetra butylammonium peroxydisulfate, I –nitrogen dioxide, I –
2
2
2
diiodine pentoxide, I –chromium oxide, I –silver sulphate, I –mercury
2
2
2
salts, I –lead acetate, I –thallium acetate, I –F-TEDA-BF , bis(pyri-
2
2
2
4
dine)–iodonium(I) tetrafluoroborate–CF SO H, iodine monochloride,
3
3
BuLi-F CCH I, NaOCl-NaI, bis(symcollidine)–iodine(I) hexafluoropho-
2
3
[
3–6]
sphate, and NaI–ammonium hexanitrocerate.
However, most of these
methods suffer from major drawbacks such as use of harsh conditions,
toxic heavy-metal catalysts, and longer reaction times. Thus, there is a
need to develop a simple, cost-effective, and convenient method for the
iodination of arenes under mild reaction conditions.
Sodium perborate (NaBO ꢀ 4H O) (SPB) is a cheap, stable, nontoxic,
3
2
easily handled, crystalline, easily available peroxygen compound that has
[7]
industrial applications. SPB is a convenient source of H O , and the
2
2
borate helps somewhat to buffer, stabilize against decomposition, and
activate toward nucleophilic oxidations through associated species such
–
as [B(OH) (OOH)] .
[8]
3
To realize the potential of mild and efficient catalysis under environ-
mentally benign conditions, we chose ionic liquids (ILs) as the reaction
medium. Ionic liquid technology, when used in place of conventional
organic solvents, offers an environmentally benign approach toward
[9]
organic synthesis. The union of reagents with ionic liquid is a viable
alternative approach toward modern synthetic chemistry, especially when
considering the growing environmental demands being placed on chemical
processes. When a catalyst is employed, the ionic liquid phase containing
the catalyst can be separated and reused after product isolation. For the
past few years, we have been actively engaged in the field of ionic liquids
and employed these neoteric solvents for a number of organic transforma-
[10]
tions of high synthetic importance. We report here the first iodination
of arenes in ionic liquids in the presence of a catalytic amount of SPB.
RESULTS AND DISCUSSION
To decipher the effect of these designer solvents on the outcome of the
reaction, we investigated a model reaction of iodination of anisole.
Initially, the reaction of anisole with stoichiometric amounts of molecular
iodine in the presence of SPB was carried out in 1-butyl-3-methylimida-
zolium tetrafluoroborate, [bmim]BF . As expected for an oxidative
4
þ
aromatic iodination involving transient iodine (I) species I , para-iodina-
tion of the activated monosubstituted benzene substrate (i.e., anisole) was
observed, and no trace of the potentional ortho-isomer was detected in

Regioselective Iodination of Arenes
2883
Scheme 1. Sodium perborate–catalyzed aromatic iodination in ionic liquid.
the purified product. The reaction proceeded well at ambient temperature
and afforded p-iodoanisole with 90% yield in 4 h (see Scheme 1).
Considering that ionic liquid is beneficial for the reaction, we planned a
study wherein various ionic liquids (namely 1-butyl-3-methylimidazolium
hexafluorophosphate, [bmim]PF ; 1-butyl-3-methylimidazolium chloride,
6
[
BF ) were selected for the reaction.With all these ionic liquids, the reaction
bmim]Cl; and 1-hexyl-3-methylimidazolium tetrafluoroborate, [hmim]
4
proceeded smoothly with SPB (Table 1), with [bmim]BF giving the highest
4
yields. Hence, [bmim]BF was employed for further study. A higher
4
amount of SPB did not affect the yield of the reaction and no diiodinated
product was obtained.
To envisage the synthetic potential of the methodology, several acti-
vated and unactivated arenes along with heterocyclic compounds were
iodinated under optimized reaction conditions. We observed that the
reaction conversions were high, as iodinated products were obtained in
high yields. Thus, phenol (Table 2, entry 7) and 1-naphthol (Table 2,
entry 12) gave exclusive iodination at the 4-position; however, 2-naphthol
(
Table 2, entry 13) gave 1-iodo-2-naphthol in good yield. In the case of
3
4
-methylphenol, iodination occurred at the sterically less hindered
-position. 1,3-Dimethoxybenzene (Table 2, entry 2) gave exclusively
the mono-iodinated product.
The deactivating substrates such as 4-chloroaniline, 4-chlorophenol,
and 4-bromophenol (Table 2, entries 6, 8, and 9) gave 2-iodo products
exclusively. Activated arenes such as aniline and N,N-dimethylaniline
(
Table 2, entry 4, 5) responded well to the reaction conditions, as the
Table 1. Comparison of different ionic liquids as solvent for
the iodination of anisole using sodium perborate as oxident
Sr. no.
Ionic liquid
[bmim]BF
Time (h)
Yield (%)
1
2
3
4
5
6
7
4
4.0
5.0
5.0
5.0
5.0
5.0
5.0
90
86
85
83
74
56
48
[bmim]PF
[bmim]Cl
6
[hmim]BF
DMSO
THF
4
CHCl
3

2884
S. V. Bhilare et al.
Table 2. Iodination of arenes and heterocycles catalyzed by NaBO
liquid
3
ꢀ4H
2
O in ionic
a
b
Yield (%)
Sr. no.
1
Substrate
Time (h)
4
Product
90
2
3
4
5
3.5
3
89
88
c
4
90 (11:89)
c
4.5
89 (08:92)
6
7
8
9
4.5
4
85
90
82
78
86
4.5
4.5
4
10
(
Continued)

Regioselective Iodination of Arenes
2885
Table 2. Continued
a
b
Yield (%)
Sr. no.
Substrate
Time (h)
4
Product
1
1
2
86
1
5
75
13
14
15
16
17
5
8
80
54
46
—
—
8
24
24
No reaction
No reaction
a 1
The product were characterized by H NMR, IR, MS, and comparison with
authentic samples.
b
Isolated yields.
The ortho-para ratio was determined by GC-MS.
c
percentage conversions were good to high. However, the reactions offered
a mixture of isomers with a preference for para product as confirmed by
1
gas chromatography-mass spectroscopy (GC-MS) and H NMR spectral
data. A point worth mentioning here is that easily oxidizable groups such
as hydroxyl and amino groups are not affected. The deactivated arenes
such as 4-nitroaniline and 4-nitrophenol did not react under these reaction
conditions even after stirring for 24 h. Heterocyclic compounds such as
imidazole and thiophene gave monoiodo compounds, albeit in lower
yields, and the reactions took longer times.

2886
S. V. Bhilare et al.
Table 3. Recyclability of ionic liquid in iodination of anisole
Run
Yield (%)
1
2
3
90
86
84
Taking into consideration environmental legislation, it is of high
importance that ionic liquid is reused for the maximum number of times.
Hence, after the reaction was completed and the crude product isolated,
the remaining system of the ionic liquid and the catalyst was washed with
ether to remove of any organic impurities. Four consecutive runs were
carried out with the same lot of ionic liquid. Diminution was observed
in the yield of the reactions. The results are summarized in Table 3.
In conclusion, we have developed a simple methodology for the iodina-
tion of aromatic compounds and heterocyclic compounds using I =sodium
2
perborate as a mild, inexpensive, and selective iodinating agent in ionic
liquid. The protocol provided high yields of the products at ambient tem-
perature. The highlighted feature of the present study is regioselectivity.
General Procedure for Iodination of Anisole in Ionic Liquid
I (227 mg, 1 mmol) and NaBO ꢀ4H O (310 mg, 1 mmol) were taken in a
2
3
2
mortar and ground well. This powdered mixture was then added to a
mixture of anisole (214 mg, 2 mmol) and 2 ml of [bmim]BF . The resulting
4
reaction mixture was stirred at room temperature for the time specified in
Table 2. After the reaction reached maximum conversion (as indicated by
GC), the crude product was isolated by extracting it with ether. The
extracts were washed successively with saturated sodium thiosulphate
solution, brine, and water, and passed through anhydrous Na SO .
2
4
The crude product was purified on silica-gel column chromatography
using hexane–ethyl acetate as eluent.
After the crude product was extracted from the reaction mixture with
diethyl ether, the ionic liquid was reused for subsequent runs, and the
previously mentioned procedure was followed.
ACKNOWLEDGMENTS
S. V. B., A. R. D., and N. B. D. are thankful to the Council of Scientific
and Industrial Research New Delhi for the award of senior research
fellowships and financial support.

Regioselective Iodination of Arenes
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