Eco-friendly oxyiodination of aromatic compounds using ammonium iodide and hydrogen peroxide

Article abstract of DOI:10.1016/j.tetlet.2007.06.138

A new eco-friendly procedure for the oxyiodination of aromatic compounds with NH₄I as an iodine source and H₂O₂ as an oxidant without any catalyst is presented.

Full text of DOI:10.1016/j.tetlet.2007.06.138

Tetrahedron Letters 48 (2007) 6124–6128
Eco-friendly oxyiodination of aromatic compounds
using ammonium iodide and hydrogen peroxideI
N. Narender,* K. Suresh Kumar Reddy, K. V. V. Krishna Mohan and S. J. Kulkarni
Catalysis Group, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 3 May 2007; revised 20 June 2007; accepted 27 June 2007
Available online 4 July 2007
Abstract—A new eco-friendly procedure for the oxyiodination of aromatic compounds with NH4I as an iodine source and H2O2 as
an oxidant without any catalyst is presented.
Ó 2007 Elsevier Ltd. All rights reserved.
Aryl iodides are important intermediates in organic
synthesis, medicine and biochemistry.1 They are also
valuable and reactive intermediates for various cross-
coupling reactions,2 for example, Heck, Stille and Negi-
shi cross-coupling reactions.
KI-oxoneÒ,17 bis(symcollidine)-iodine(I) hexafluoro-
phosphate,18 KI/H2O2/H2SO4,19 ICl/In(OTf)3,20 HIO4/
Al2O3,21 NIBTS,22 NaI/Chloramine-T,23 KI/H2O2 or
sodium
perborate/sodium
tungstate,24
I2/O2/
H5PV2Mo10O40,25 KI/KIO3/H+,26 I2/UHP27 and NaI/
cerium(IV) trihydroxide/SDS.28 Most of these reagents
are complicated, costly or use toxic heavy metal catalysts
with potential environmental problems due to the gener-
ation of hazardous waste.
The use of molecular halogens for direct halogenation
involves difficulties in handling chlorine and bromine,
while iodine is less reactive. The poor electrophilic
strength of iodine, compared to that of molecular bro-
mine and chlorine, renders direct iodination difficult
and requires the presence of an activating agent in order
to produce a strongly electrophilic IÈ species. Direct
iodination is also hampered by the formation of HI,
which can cause proteolytic cleavage of sensitive com-
pounds. Iodination of aromatic compounds has been
carried out using molecular iodine together with strong
oxidizing agents such as nitric acid, sulfuric acid, iodic
acid, sulfur trioxide and hydrogen peroxide.3 Recently,
iodination methods have been developed using iodonium
donating systems, such as iodine nitrogen dioxide,4
mercury(II) oxide–iodine,5 iodine monochloride,6
bis(pyridine) iodonium(I) tetrafluoroborate–CF3SO3H,7
NaOCl–NaI,8 iodine/Na2S2O8,9 iodine–(NH4)2S2O8–
CuCl2–Ag2SO4,10 I2–tetrabutylammonium peroxydisul-
fate,11 I2–diiodine pentoxide,12 I2–lead acetate,13 I2–thal-
lium acetate,14 I2–F–TEDA–BF4,15 BuLi–F3CCH2I,16
Regarding environmental problems and pollution, clean
organic reaction processes which do not use harmful
organic reagents are encouraged and are in great
demand. The role of enviro-economics in the develop-
ment of new processes for existing and new products
has become important. Hydrogen peroxide has enor-
mous potential as a green oxidant from which the only
waste product is water.29 There are hazards connected
with the use of concentrated solutions but this risk can
be avoided by employing 30% aqueous H2O2. However,
oxidative halogenation of arenes requires the use of a
metal catalyst for activation.30 The non metal-catalyzed
oxidative iodination of aromatic compounds with H2O2
without addition of mineral acid has not been reported
so far. Our aim was to utilize 30% H2O2 for the iodin-
ation of arenes with NH4I without addition of any metal
catalyst or mineral acid.
We have designed an efficient, environmentally benign
procedure for aromatic iodination using NH4I as an
iodine source and commercially available 30% H2O2 as
an oxidant and as a possible alternative to overcome
the disadvantages described in the reported methods
(Scheme 1).
q IICT Communication No. 070222.
*
Corresponding author. Tel.: +91 40 27160123x2704; fax: +91 40
27160387/27160757; e-mail: narendern33@yahoo.co.in
Present address: Instituto de Tecnologia Quimica e Biologica da
Universidade Nova de Lisboa, Apt. 127, Quinta do Marques, EAN,
2781-901 Oeiras, Portugal.
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.06.138

N. Narender et al. / Tetrahedron Letters 48 (2007) 6124–6128
6125
treated with sodium thiosulfate and extracted with ethyl
acetate. The organic extract was dried over anhydrous
sodium sulfate and the solvent was evaporated under re-
duced pressure. The products were purified by column
R
R
NH4I, H2O2
AcOH, RT
1
chromatography and their structures confirmed by H
NMR and mass spectroscopy.
I
Scheme 1.
The results of the iodination of a wide range of aromatic
compounds are given in Table 1. The reaction of aro-
matic compounds with NH4I and 30% H2O2 in acetic
acid at room temperature afforded iodo compounds
with high regioselectivity and in excellent yields.
General procedure for the iodination of aromatic com-
pounds: a 30% aqueous solution of H2O2 (2.2 mmol)
was added dropwise to a well stirred solution of NH4I
(2.2 mmol) and aromatic substrate (2 mmol) in acetic
acid (4 ml) and the reaction mixture was allowed to stir
at room temperature. The reaction was monitored by
thin layer chromatography (TLC). After completion,
the reaction mixture was filtered and the filtrate was
Deactivated and weakly activated compounds failed
to undergo iodination, whereas more activated com-
pounds, that is, anilines, substituted anilines, phenols,
substituted phenols and methoxynaphthalenes were
Table 1. Oxyiodination of aromatic compounds with NH4I and H2O2 in acetic acida
Entry
Substrate
Time (h)
Conversion (%)
Selectivityb (%)
para
ortho
Di
Others
—
NH2
1
8
82
97
3
—
NH2
CH3
2
3
8
8
88
69
77
99
23
—
—
—
—
—
NH2
C2H5
NH2
C2H5
CN
4
5
24
8
93
38
99
61
—
39
—
—
—
—
NH2
Cl
NH2
Cl
Cl
6
7
24
42
99
99
—
—
85
—
—
10
NH2
8
5
Cl
NH2
8
8
99
—
75
5
20
F
(continued on next page)

6126
N. Narender et al. / Tetrahedron Letters 48 (2007) 6124–6128
Table 1 (continued)
Entry
Substrate
Time (h)
Conversion (%)
Selectivityb (%)
para
ortho
Di
Others
—
NH2
NO2
9
24
—
—
—
—
NO2
OH
10
11
6
6
78
70
53
55
47
40
—
5
—
—
OH
OH
CH3
12
13
6
6
73
72
56
66
42
34
2
—
—
CH3
OH
—
H3C
CH3
OH
14
15
16
6
6
6
84
73
70
—
—
—
93
99
95
4
3
CH3
OH
—
—
—
Br
OH
5
Cl
OH
CH3
17
18
6
87
—
—
—
99
—
—
—
—
—
OH
NO2
24

N. Narender et al. / Tetrahedron Letters 48 (2007) 6124–6128
6127
Table 1 (continued)
Entry Substrate
Time (h)
Conversion (%)
Selectivityb (%)
para
ortho
Di
Others
—
OMe
19
6
6
98
82
99
—
—
OMe
20
—
—
99c
—
—
—
—
OMe
OMe
21
24
—
—
OMe
22
23
24
24
—
—
—
—
—
—
—
—
—
—
CH3
CH3
24
24
—
—
—
—
—
H3C
Br
CH3
25
26
24
24
—
—
—
—
—
—
—
—
—
—
OCOCH3
a Substrate (2 mmol), NH4I (2.2 mmol), 30% H2O2 (2.2 mmol), acetic acid (4 ml), rt.
b The products were characterized by 1H NMR and mass spectroscopy and quantified by GC.
c 1-Iodo-2-methoxynaphthalene.
converted into the corresponding iodinated products.
Surprisingly, methoxybenzene derivatives, despite their
marked activity in electrophilic reactions, were not
iodinated.
also formed. The para substituted aromatics were iodin-
ated at the ortho-position (Table 1, entries 7, 8 and 14–17).
We have also studied the influence of a wide-range of
solvents including carbon tetrachloride, hexane, dichlo-
romethane, chloroform, methanol, acetonitrile and ace-
tic acid on the reactivity. Our observations revealed
that, among the various solvents, acetic acid was the
most effective, giving high yields in short reaction times.
The rate of the reaction was increased by using acetic
acid. It was assumed that acetic acid forms an interme-
diate species CH3COOÉIÈ (Scheme 2), which facilitates
easy generation of IÈ. The role of hydrogen peroxide
was confirmed by conducting a blank experiment where
formation of the iodo compound was not observed.
The results also indicate that activated aromatic com-
pounds are more selective for nuclear iodination and no
side-chain iodination was observed in the case of alkyl
substituted aromatics (Table 1, entries 2, 3, 11–14 and
17). Introduction of an electron-withdrawing group on
the aromatic ring substantially decreased the rate of ring
iodination (Table 1, entry 4). Unless the para-position is
substituted, this reaction system yields, selectively, para-
iodinated aromatics with anilines, while with phenols,
substantial amounts of ortho substituted aromatics were

6128
N. Narender et al. / Tetrahedron Letters 48 (2007) 6124–6128
NH4OH + HOI
NH4I + H2O2
+
-
HOI + CH3COOH
H2O + CH3COO I
R
R
I
R
-
CH3COO
- +
+
CH3COO I
CH3COOH
+
+
I
H
Scheme 2.
9. Elbs, K.; Jaroslawzee, A. J. Proki. Chem. 1913, 88, 92–94.
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11. Yang, S. G.; Kim, Y. H. Tetrahedron Lett. 1999, 40, 6051–
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A plausible mechanism for the iodination of aromatic
compounds is shown in Scheme 2. It is assumed that
hydrogen peroxide oxidizes the IÉ (NH4I) to IÈ (HOI),
which further reacts in the presence of acetic acid
(Brønsted acid) with the organic substrate to give the
corresponding iodinated product.
12. Bradzil, L. C.; Cutler, C. J. J. Org. Chem. 1994, 59, 6233–
6244.
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gate, P. D. J. Chem. Soc., Perkin Trans. 1 1976, 1161–
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In conclusion, we have reported a practical, efficient,
relatively inexpensive and eco-friendly method for iodin-
ation of aromatic compounds using commercially avail-
able NH4I and H2O2. This method can be applied to a
wide range of aromatic compounds with moderate to
high regioselectivity.
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Acknowledgement
K.S.K.R. thanks the CSIR, New Delhi, for the award of
a Senior Research Fellowship.
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