Simple and regioselective oxyiodination of aromatic compounds with ammonium iodide and Oxone

Article abstract of DOI:10.1016/j.tetlet.2004.09.010

Oxyiodination of aromatic compounds using NH₄I and Oxone gives high yields and selectivity. A simple method for the iodination of aromatic compounds using NH₄I as the iodine source and Oxone as the oxidant is described.

Full text of DOI:10.1016/j.tetlet.2004.09.010

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8015–8018
Simple and regioselective oxyiodination of aromatic
compounds with ammonium iodide and OxoneÒq
K. V. V. Krishna Mohan, N. Narender* and S. J. Kulkarni
Catalysis Group, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 17 May 2004; revised 24 August 2004; accepted 2 September 2004
Available online 18 September 2004
Abstract—Asimple method for the iodination of aromatic compounds using NH 4I as the iodine source and OxoneÒ as the oxidant
is described.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
R
I
R
NH4I, Oxone®
MeOH, RT
In the 1960s the homolytic cleavage of the carbon–
iodine bonds of iodoarenes was found to proceed with
ease under the influence of UV radiation. This reaction
immediately found wide application in organic synthe-
sis.1 In recent years, direct iodination methods have
been intensively developed by using iodonium donating
systems, such as iodine–mercury(II) oxides,2 iodine–tetra-
butylammonium peroxydisulfate,3 BuLi–F3CCH2I,4
NIS–CF3SO3H,5 iodine–F–TEDA–BF4,6 NIS,7 bis-
(syn-collidine)iodine(I) hexafluorophosphate,8 iodine
monochloride,9 bis(pyridine)iodonium(I) tetra fluorobo-
rate–CF3SO3H,10 iodine–(NH4)2S2O8–CuCl2–Ag2SO4,11
iodine–silver sulfate12 and iodine–mercury salts.13 How-
ever, most of these methods require hazardous or toxic
reagents or high reaction temperature for a long reac-
tion time. Organometallic reagents are convenient pre-
cursors for the preparation of aryl iodides but their
use is somewhat restricted due to the high reactivity
and toxic properties of many reagents.14–16 We have
designed a practical and regioselective method for direct
aromatic iodination. Our method is based on generation
of electrophilic iodine in situ from NH4I as the iodine
source and OxoneÒ as the oxidant (Scheme 1). OxoneÒ
is a stable ternary composite of KHSO5ÆKHSO4 and
K2SO4 in 2:1:1 molar ratio and its use has been demon-
strated for a variety of organic reactions.17–22
Scheme 1.
Our results are summarized in Table 1. As can be seen,
this iodination generally proceeds well with high yields
and regioselectivity. Iodination of methoxy aromatic
derivatives takes place in high yields at room tempera-
ture. Surprisingly, iodinations of mesitylene, 1,2,4-tri-
methylbenzene and m-xylene proceed at room
temperature in 24h in high yields whereas o-xylene only
gave a lower yield after 48h. 2-Methoxynaphthalene
gave 1-iodo-2-methoxynaphthalene. Nitrobenzene and
benzoic acid were not iodinated even under severe con-
ditions and were recovered without change. Iodination
was para-directed whenever possible, otherwise it
occurred in the ortho-position. O-Iodination occurred
when the p-position was blocked with a substituent
(Table 1, entries 3 and 4). The regioselectivity was
deduced from the observation that iodination occurred
at the more electron rich and less sterically hindered
positions. The iodination proceeded highly para-selec-
tively to a substituent, especially an alkoxy group and
for m-xylene, even though in the cases of phenols and
o-xylene the selectivities were only moderate. All prod-
ucts were characterized by NMR and mass spectra.
Keywords: Iodination; Ammonium iodide; OxoneÒ; Aromatic com-
pounds; Regioselectivity.
q IICT Communication No: 030806.
*
We have also checked the influence of solvent on the
reactivity. When this reaction was performed using
Corresponding author. Tel.: +91 40 27160123x2704; fax: +91 40
27160387/27160757; e-mail: nama@ins.iictnet.com
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.010

8016
K.V.V.Krishna Mohan et al./ Tetrahedron Letters 45 (2004) 8015–8018
Table 1. Regioselective oxyiodination of aromatics with NH4I and OxoneÒa
Entry
Substrate
T/h
Conversion (%)
Selectivityb (%)
Di-iodination
ortho
para
Other products
––
OCH
3
1
2
8
99
88
5
95
––
––
OCH
3
Br
48
––
99
99
––
––
––
OCH
3
3
4
20
99
98
––
––
CH
3
OH
8
––
99
––
OCH
3
OCH
3
OCH
3
3
5
6
8
97
73
––
––
99
99
––
––
––
––
OCH
O
24
O
3
OCH
7
24
36
99
––
––
––
Br
OCH
3
8
9
24
24
93
99
2
94
––
4
––
4
OCH
3
96
––
OH
OH
OH
10
11
12
8
6
88
97
48
42
20
7
51
70
93
7
10
––
––
––
––
CH
Cl
3
24
OH
NO
2
13
14
24
24
70
99
14
––
53
99
33
––
––
––
CH
3
CH
3

K.V.V.Krishna Mohan et al./ Tetrahedron Letters 45 (2004) 8015–8018
8017
Table 1 (continued)
Entry
Substrate
T/h
Conversion (%)
Selectivityb (%)
Di-iodination
ortho
para
Other products
CH
3
CH
3
15
16
48
24
63
99
––
88
––
––
12
––
CH
3
––
––
99
99
H C
CH
3
3
CH
3
CH
3
17
24
90
––
––
CH
Br
3
18
19
24
24
––
––
––
––
––
––
––
––
––
––
COOH
NO
2
20
24
––
––
––
––
––
a Substrate (2mmol), NH4I (2.2mmol), OxoneÒ (2.2mmol), methanol (10mL), rt.
b The products were characterized by NMR, mass spectra and yields were quantified by GC.
carbon tetrachloride, hexane, dichloromethane or aceto-
nitrile, the reactivity observed was lower than in MeOH.
Acknowledgements
K. V. V. Krishna Mohan thanks CSIR, New Delhi for
the award of a Senior Research Fellowship.
Atypical oxyiodination of aromatic compounds in the
presence of OxoneÒ proceeded according to the stoichio-
metry of Eq. 1.
References and notes
ArH+NH4I+2KHSO5ꢀKHSO4ꢀK2SO4!ArI+NH4OH
1. (a) Farina, V. In Comprehensive Organometallic Chemistry
II; Abel, E. W., Stone, F. G.-A, Wilkinson, G., Eds.;
Pergamon: Oxford, 1995; Vol. 12, p 161; (b) Negishi, E.;
Coperet, C.; Ma, S.; Liou, S.; Liu, F. Chem.Rev. 1996, 96,
365.
+K2S2O8ꢀKHSO4ꢀK2SO4+H2O
ð1Þ
In conclusion, the regiospecific nuclear iodination of
aromatic compounds can be achieved efficiently with
NH4I–OxoneÒ in MeOH.
2. Orito, K.; Hatakeyama, T.; Takeo, M.; Suginome, H.
Synthesis 1995, 1273–1277.
3. Yang, S. G.; Kim, Y. H. Tetrahedron Lett. 1999, 40, 6051.
4. Blackmore, I. J.; Boa, A. N.; Murray, E. J.; Dennis, M.;
Woodward, S. Tetrahedron Lett. 1999, 40, 6671.
5. Olah, G. A.; Wang, Q.; Sandford, G.; Prakash, G. K. S. J.
Org.Chem. 1993, 58, 3194–3195.
2. General procedure for the iodination of aromatic
compounds
OxoneÒ (2.2mmol) was added to a well-stirred solution
of NH4I (2.2mmol) and substrate (2.0mmol) in metha-
nol (10mL) and the reaction mixture was allowed to stir
at room temperature. The reaction was monitored by
thin layer chromatography (TLC). After completion of
the reaction, the reaction mixture was filtered and sol-
vent evaporated under reduced pressure. The products
were purified by column chromatography over silica
gel (finer than 200mesh) with 5–30% ethyl acetate in
hexane as eluent. All the structures of the products were
confirmed by NMR and mass spectra.13,23–28
6. Zupon, M.; Iskra, J.; Stavber, S. Tetrahedron Lett. 1997,
38, 6305.
7. Carreno, M. C.; Ruano, J. L. G.; Sanz, G.; Toledo, M. A.;
Urbano, A. Tetrahedron Lett. 1996, 37, 4081–4084.
8. Brunel, Y.; Rousseau, G. Tetrahedron Lett. 1995, 45, 8217.
9. Hubig, S. M.; Jung, W.; Kochi, J. K. J.Org.Chem. 1994,
59, 6233–6244.
10. Barluenga, J.; Gonzalez, J. M.; Garcia-Martin, M. A.;
Campos, P. J.; Ascnsio, G. J.Org.Chem. 1993, 58, 2058–
2060.
11. Marko, D. M.; Belyaev, Y. A. Khim.Referat.Zhur. 1941,
4, 49–50.

8018
K.V.V.Krishna Mohan et al./ Tetrahedron Letters 45 (2004) 8015–8018
12. Sy, W. W. Tetrahedron Lett. 1993, 34, 6223–6224.
13. Bachki, A.; Foubelo, F.; Yus, M. Tetrahedron 1994, 50,
5139–5146.
21. Ceccherelli, P.; Curini, M.; Epifano, F.; Marcotullio, M.
1998, 28, 3057–
C.; Rosati, O. Synth.Commun.
3064.
14. Larock, R. C. Tetrahedron 1982, 38, 1713.
15. Burnett, D. A.; Caplen, M. A.; Domalski, M. S.; Browne,
M. E.; Davis, H. R.; Clader, J. W. Bioorg.Med.Chem.
Lett. 2002, 12, 311.
16. Pomilio, A. B.; Barolli, M. G. J.Labelled Compd.
Radiopharm. 1997, 39, 927.
22. Kim, E. H.; Koo, B. S.; Song, C. E.; Lee, K. J. Synth.
Commun. 2001, 31(23), 3627–3632.
23. Pouchert, C. J. The Aldrich Library of NMR Spectra;
Aldrich Chemical Company: Wisconsin.
24. Cambie, R. C.; Rutledge, P. S.; Palmer, T. S.; Woodgate,
P. D. J.Chem.Soc,. Perkin Trans.1
1976, 9, 1161.
17. Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.
Tetrahedron Lett. 2002, 43, 1201–1203.
25. Radner, F. J.Org.Chem. 1988, 53, 3548.
26. Tribble, T. M.; Traynham, J. G. J.Am.Chem.Soc. 1969,
91, 379.
18. You, H. W.; Lee, K. J. Synlett 2001, 105–107.
19. Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.;
Rosi, M. Tetrahedron 1999, 55, 6211–6218.
20. Ross, S. A.; Burrows, C. J. Tetrahedron Lett. 1997, 9,
2805–2808.
27. Lindberg, J. G.; Leong, A. J.Magn.Reson.
89.
1975, 20,
28. Edgar, K. J.; Falling, S. N. J.Org.Chem. 1990, 55, 5287–
5291.