A new, environment friendly protocol for iodination of electron-rich aromatic compounds

Article abstract of DOI:10.1016/S0040-4039(03)01144-4

A new environment friendly procedure for effective aromatic iodination is presented. A mixture of potassium iodide and potassium iodate is used in the presence of an acid for in situ iodination of aromatic compounds.

Full text of DOI:10.1016/S0040-4039(03)01144-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5099–5101
A new, environment friendly protocol for iodination of
electron-rich aromatic compounds
Subbarayappa Adimurthy, Gadde Ramachandraiah,* Pushpito K. Ghosh* and
Ashutosh V. Bedekar*
Central Salt and Marine Chemicals Research Institute, G.B. Road, Bhavnagar 364 002, India
Received 8 March 2003; revised 18 April 2003; accepted 2 May 2003
Abstract—A new environment friendly procedure for effective aromatic iodination is presented. A mixture of potassium iodide
and potassium iodate is used in the presence of an acid for in situ iodination of aromatic compounds. © 2003 Elsevier Science
Ltd. All rights reserved.
Aromatic iodo compounds are an important class of
compounds in synthetic organic chemistry. They are
useful for the preparation of organometallic reagents
and some are potential intermediates for the synthesis
of pharmaceutical and bioactive materials. They are
useful in metal catalyzed coupling reactions which are
widely applied in the preparation of complex molecules.
The oxidation of an iodide anion results in the forma-
tion of an electrophilic iodonium species which is
responsible for iodination of the aromatic nucleus. Our
method is based on this concept where a mixture of
0.66 mol equiv. of potassium iodide and 0.33 mol
equiv. of potassium iodate is treated with one mol
equiv. of a mineral acid. This results in the in situ
formation of an iodonium cation which can effect
aromatic iodination, see Eq. (1).
The iodination of organic molecules using elemental
iodine is particularly sluggish compared to chlorination
and bromination and needs activation for effective elec-
trophilic substitution. The reagents reported for iodina-
tion of aromatic substrates include, N-iodosuccinimide
(NIS),1 NIS-CF3SO3H,2 NIS-CF3COOH,3 I2-tetra-
butylammonium peroxydisulfate,4 I2-nitrogen dioxide,5
I2-diiodine pentoxide,6 I2-silver sulphate,7 I2-mercury
salts,8 I2-chromium oxide,9 I2-lead acetate,10 I2-thallium
acetate,11 I2-F-TEDA-BF4,12 iodine monochloride,13
BuLi-F3CCH2I,14 NaOCl-NaI,15 bis(symcollidine)-
+
3ArH+2I−+IO3−3“H 3ArI+3H2O
(1)
The test reaction was carried out on anisole in aqueous
methanol with potassium iodide and potassium iodate
in the presence of hydrochloric acid under ambient
conditions. Careful analysis (TLC and GLC) of the
reaction products confirmed the formation of 4-iodo-
anisole with excellent conversion and isolated yield.
Having established the feasibility of this conversion, we
undertook a systematic study and the results are sum-
marized in Table 1.
iodine(I)
hexafluorophosphate,16
bis(pyridine)-
iodonium(I) tetrafluoroborate-CF3SO3H17 and NaI-
ammonium hexanitrocerate.18 Most of these reagents
are complicated, costly or use toxic heavy metal cata-
lysts with potential environmental problems due to the
generation of hazardous waste. In this note we wish to
report our preliminary studies on an efficient, new
environmentally benign procedure for aromatic iodina-
tion.
Controlled mono iodination of 1,4-dimethoxybenzene
was carried out with one equivalent of the iodinating
reagent and the desired product, 2-iodo-1,4-dimethoxy-
benzene was formed in high yield. Iodination of 2-
naphthol and 2-methoxynaphthalene resulted in 1-iodo
derivatives as the sole products in good, isolable yields.
Diiodination of 4-nitrophenol and 4-chlorophenol was
achieved in excellent yields while triiodination of phe-
nol was effected with three equivalents of the reagent.
Iodination of aniline gave a mixture of para- and
ortho-iodoaniline in the ratio of 90:10 in moderate
yield, while 4-nitroaniline furnished the 2-iodo-com-
pound in good yield. A previously reported procedure15
Keywords: aromatic iodination; potassium iodide; potassium iodate.
* Corresponding authors. E-mail: avbedekar@yahoo.co.in
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01144-4

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S. Adimurthy et al. / Tetrahedron Letters 44 (2003) 5099–5101
Table 1. Iodination for aromatic compounds with KI/
KIO3/H+
Thus, we have reported our findings on the use of a
simple reagent system for an environmentally benign
and efficient procedure for the iodination of aromatic
compounds.
General procedure for the iodination:
4-Iodoanisole: A solution of anisole (1.00 g; 9.26 mmol),
potassium iodide (1.03 g; 6.22 mmol) and potassium
iodate (0.66 g; 3.08 mmol) was prepared in methanol (5
mL) and water (30 mL). This mixture was treated at
room temperature with dilute hydrochloric acid (9.5
mmol) over 40 to 45 minutes and stirred for an addi-
tional 2–3 h, diluted with water (50 mL) and extracted
with dichloromethane (25 mL×3). The combined
organic extract was washed with dilute sodium thiosul-
phate (5%), water, brine, dried over anhydrous sodium
sulphate and concentrated under reduced pressure to
give a thick oil (1.94 g; 90%). Further purification was
carried out by crystallization from cold hexane to
afford a white crystalline product (1.75 g; 81%), mp
52–54°C (Lit.19 53–54°C), which showed satisfactory
analytical and spectroscopic properties.
Acknowledgements
The authors wish to thank CSIR, New Delhi for the
financial assistance to A.V.B. under the Quick Hire
Scheme.
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