Efficient iodination of aromatic compounds using potassium ferrate supported on montmorillonite

Article abstract of DOI:10.1016/j.cclet.2011.06.001

Potassium ferrate impregnated on montmorillonite is a mild, cheap, and non-toxic reagent for the iodination of phenols, including naphthol, aromatic amines, and heterocyclic substrates in fair to excellent yields by a simple isolation procedure.

Full text of DOI:10.1016/j.cclet.2011.06.001

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 1427–1430
www.elsevier.com/locate/cclet
Efficient iodination of aromatic compounds using potassium
ferrate supported on montmorillonite
a
Hoda Keipour , Mohammad A. Khalilzadeh , Bita Mohtat ,
b,*
a
b
Abolfazl Hosseini , Daryoush Zareyee
b
a
Department of Chemistry, Islamic Azad University, Karaj Branch, Karaj, Iran
b
Department of Chemistry, Qaemshahr Branch, Islamic Azad University, Qaemshahr, Iran
Received 9 May 2011
Available online 28 July 2011
Abstract
Potassium ferrate impregnated on montmorillonite is a mild, cheap, and non-toxic reagent for the iodination of phenols,
including naphthol, aromatic amines, and heterocyclic substrates in fair to excellent yields by a simple isolation procedure.
#
2011 Mohammad A. Khalilzadeh. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Iodination; Heterocyclic and aromatic compounds; Potassium ferrate
Aromatic iodo compounds are widely employed as important chemicals or intermediates in organic synthesis [1].
Iodoarenes are useful intermediates for pharmaceuticals [2] natural products [3] and in carbon–carbon and carbon–
heteroatom bond formation via cross-coupling reactions [4].
Because of the low reactivity of molecular iodine toward electrophilic reactions, direct iodination of aromatic
compounds is more difficult than other halogens. This problem is overcome by activating iodine for electrophilic
+
substitution by the use of iodonium equivalents (I ) or catalysts and oxidants in conjunction with iodine that generate
electrophilic iodine (I) species [5].
Many methods have been reported for efficient nuclear iodination of aromatic compounds, however, most of them
involve the use of toxic elements such as, I /CrO [6], I /Hg(NO ) [7], I /Pb(OAc) [8] and I /Ce(OTf) [9].
2
3
2
3 2
2
4
2
4
It has been reported that efficiency of potassium ferrate could be increased when it was supported on clay mineral or
silica gel [10,11]. The solid-supported reagent was used for variety of organic transformation in an effective manner
[
11]. Due to the attributes described above for the use of supported potassium ferrate and our current interest in
developing new iodination procedures we reveal herein for the first time, using potassium ferrate impregnated on
montmorillonite, as a safe, inexpensive, easy to handle, and convenient oxidative source. In this note we wish to report
that K FeO supported on montmorillonite (K-10) allows the iodination reaction of several activated aromatics,
2
4
including anilines, alkyl benzenes and phenols to yield the corresponding iodinated products in good to excellent
yields. Our results are summarized in Table 2. The reagent is prepared by simple mixing of commercially available
montmorillonite and potassium ferrate in a weight ratio of 1:2 by mortar.
*
Corresponding author.
E-mail address: m.khalilzadeh@hotmail.com (M.A. Khalilzadeh).
1001-8417/$ – see front matter # 2011 Mohammad A. Khalilzadeh. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.06.001

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H. Keipour et al. / Chinese Chemical Letters 22 (2011) 1427–1430
Table 1
Optimization of anisole iodination using 1 mmol K
2
FeO
4
2
and different ratio of K-10/I under various conditions at reflux temperature.
a
GC yield (%)
Entry
Solvent
K-10 (g)
Time (h)
1
2
3
4
5
6
7
8
9
dichloromethane
chloroform
diethyl ether
acetonitrile
benzene
0.4
0.4
0.4
0.4
0.4
0.4
0.2
0.4
0.6
3
15
20
–
3
3
3
–
b
3
60
n-pentane
n-hexane
3
93
36
95
93
8
n-hexane
3
n-hexane
2.5
a
Isolated yields.
b
Iodobenzene was monitored.
In initial studies, we examined anisole as a model substrate (Table 1). For establishing the best reaction conditions,
an optimization study was performed using the reaction of anisole in the presence of varying amounts of potassium
ferrate and K-10. Along this line, potassium ferrate (1 mmol) and montmorillonite (0.4 g) in hexane gave the best yield
of the desired product within 3 h (GC analysis). Workup of the reaction mixture resulted in the corresponding 4-
iodoanisole with excellent regioselectivity and in excellent isolated yield (95%).
The amount of potassium ferrate can greatly affect the yield of 4-iodoanisole, and improves by increasing the
equivalents of potassium ferrate, and reaches to the maximum level on 0.5 mmol. Study about the effect of K FeO to
the K-10 weight ratio, the iodination reaction was carried out with increasing amounts of K FeO , however, a 1:2
2
4
2
4
potassium ferrate: K-10 weight ratio was required in order to achieve a quantitative conversion of anisole within a few
hours. It is noteworthy that with increasing the K-10 to K FeO weight ratio, the yield of 4-iodoanisole was not
2
4
significantly affected. The effects of solvents were examined and further improved rates of conversion were achieved
when the reactions were carried out in pentane or hexane.
The generality of this approach was established on a series of activated aromatics along with some heterocyclic
compounds as presented in Table 2. It is important to notice that trace amounts of water accelerates the transformation
Table 2
Iodination of various aromatic compounds with K
2
FeO
4
/K-10/I
2
in n-hexane.
Time (min)
110
Entry
1
Substrate
Product
Yield (%)
95
mp (litre) (8C)
OMe
OMe
48–49 (53–54) [12a]
I
a
2
3
OH
OH
OH
140
120
85
40–41 (43–44) [12b]
Oil (oil) [12c]
I
OH
95
I
H C
3
H C
3
4
5
OH
OH
I
120
110
77
92
88–90 (91–92) [12d]
OH
OH
61–62 (63.5–64.5) [12e]
I
MeO
O2N
MeO
6
7
OH
OH
150
90
81
88
85–87 (90–91.5) [12f]
62–63 (64–65) [12g]
I
O2
N
NH 2
NH2
I

H. Keipour et al. / Chinese Chemical Letters 22 (2011) 1427–1430
1429
Table 2 (Continued )
Entry
8
Substrate
Product
Time (min)
100
Yield (%)
82
mp (litre) (8C)
NMe2
CH3
Cl
NMe2
77–78 (76.5–78.5) [12d]
I
9
CH3
140
95
Oil (oil) [12h]
I
1
0
1
Cl
190
150
76
85
52–53 (53) [12i]
Oil (oil) [12j]
I
1
CH3
CH3
CH3
I
CH3
12
CH3
CH3
180
95
30–31 (30–31) [12k]
H3C
CH3
Cl
H3C
I
CH3
Cl
1
3
4
600
600
25
40
54–55 (54.5) [12l]
90–91 (90) [12l]
I
Br
Br
1
I
1
5
6
360
520
73
50
bp 180–182 (bp 180–182) [12m]
190–191 (191–192) [12n]
I
I
S
S
H
N
H
N
1
N
I
N
I
17
150
85
133–135 (134–136) [12o]
N
N
N
N
a
The ratio of ortho: para is about 90:10.
and improves its efficiency and in some cases iodination was not occurred in the absence of water (Table 2, entries 4, 8,
4 and 15). These results are consistent with Laszlo’s and Caddick’s observations that the presence of water is
1
important [10,11]. In all cases the reaction proceeds to completion in a short period affording good to excellent yield
with a higher preference for monosubstitution, which occurs mainly on the para position. Interestingly, regioselective
iodination was observed in the case of phenol to give 2-iodophenol in 85% yield (Table 2, entry 2). Other phenolic
compounds were also iodinated under similar conditions (entries 3–6). The reagent was also successful in converting
4
-nitrophenol to the corresponding iodo derivative (entry 6). In the case of p-methoxyphenol (entry 5) where this para
substitution is prohibited, it is worth noticing that the regioselectivity is governed by the hydroxy group.
Iodinations of aniline, N, N-dimethylaniline were also completed in a short reaction time (90 and 100 min,
respectively) and the mono-iodinated para isomers were obtained in 88 and 82% isolated yields plus their
corresponding ortho isomers, which were isolated in 10–15% yields (entries 7–8). The present method can be
applicable to alkylbenzenes, and the corresponding monoiodination product was obtained in good yield (entries 9 and
1
0). Di- or tri-substituted benzenes such as 1,3-dimethylbenzene (entry 11) and 1,3,5-trimethylbenzene (entry 12) also
reacted to give the corresponding monoiodination products. Iodinations of chlorobenzene and bromobenzene as less
reactive arenes were also studied. Progress of the reactions was monitored by GC analysis whereby, after 10 h only 25
and 40% yields were observed, respectively (entries 13 and 14).
Also, monoiodination of an activated heterocycle, thiophene (entry 15) was obtained, while, imidazole was mostly
diiodinated by this system (entry 16). The iodination of 3,5-dimethylpyrazole produced 4-iodo-3,5-dimethylpyrazole
in 85% isolated yield as the sole product after 2.5 h together with unreacted starting material (entry 17). Attempted

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H. Keipour et al. / Chinese Chemical Letters 22 (2011) 1427–1430
iodination of nitrobenzene with K FeO /K-10 under similar reaction conditions failed and the starting material was
2
4
isolated intact after 12 h.
The other unusual results were observed when 1-naphthol and 2-naphthol used as substrates. Surprisingly, 1-
naphthol was remained almost unchanged under same protocol while 2-naphthol converted to desired product 1-iodo-
2
-naphthol in good yield. These results encouraged us to carry out a competition experiment and we found that
iodination of a mixture of 1-naphthol and 2-naphthol led to almost exclusive formation of 1-iodo-2-naphthol (70%)
with very little 4-iodo-1-naphthol formed (5%).
In conclusion, we have established potassium ferrate impregnated on K-10 as an efficient and eco-friendly oxidant
for regioselective monoiodination under mild conditions. The ease of this present protocol is expected to make this
methodology a good alternative to well-known methods, since the iodination proceeds in high yields. To develop the
synthetic utility of this method, its applications to other heterocycles are being pursued.
Typical procedure for iodination of anisole: To a mixture of Iodine (0.127 g, 0.5 mmol) and K-10 (0.4 g) in n-
hexane (10 mL), K FeO (0.5 mmol), anisole (0.108 g, 1 mmol) was added and the mixture was heated to reflux
2
4
temperature for the time specified in Table 2. The progress of the reaction was monitored by GC or TLC. The reaction
mixture was filtered and treated with 10% aqueous sodium thiosulfate solution (10 mL). The resulting mixture was
dried over anhydrous MgSO and filtered. Evaporation of the solvent resulted in the crude product was further purified
4
by column chromatography to afford 4-iodoanisole in 95% yield (Table 2, entry 1). Then similar reaction conditions
were applied for the iodination at reflux temperature.
Acknowledgment
The authors are grateful to the Islamic Azad University of Qaemshahr for financial support.
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