A simple and practical halogenation of activated arenes using potassium halide and oxone in water-acetonitrile medium

Article abstract of DOI:10.1081/SCC-100104419

A simple and practical halogenation of activated arenes using a reagent combination of potassium halide and oxone in water-acetonitrile medium is presented. The halogenated products were obtained with good yields and in high purity.

Full text of DOI:10.1081/SCC-100104419

This article was downloaded by: [Fordham University]
On: 19 November 2012, At: 04:49
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer
House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
A SIMPLE AND PRACTICAL HALOGENATION OF
ACTIVATED ARENES USING POTASSIUM HALIDE AND
OXONE® IN WATER-ACETONITRILE MEDIUM
B. V. Tamhankar a , Uday V. Desai b , R. B. Mane a , P. P. Wadgaonkar c & Ashutosh V.
Bedekar c
a Department of Chemistry, Shivaji University, Kolhapur, 416004, India
b Department of Chemistry, Shivaji University, Kolhapur, 416004, India
c National Chemical Laboratory, Pune, 416008, India
Version of record first published: 09 Nov 2006.
To cite this article: B. V. Tamhankar, Uday V. Desai, R. B. Mane, P. P. Wadgaonkar & Ashutosh V. Bedekar (2001): A SIMPLE
AND PRACTICAL HALOGENATION OF ACTIVATED ARENES USING POTASSIUM HALIDE AND OXONE® IN WATER-ACETONITRILE
MEDIUM, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
31:13, 2021-2027
To link to this article: http://dx.doi.org/10.1081/SCC-100104419
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to
anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the contents
will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses
should be independently verified with primary sources. The publisher shall not be liable for any loss, actions,
claims, proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

SYNTHETIC COMMUNICATIONS, 31(13), 2021–2027 (2001)
A SIMPLE AND PRACTICAL
HALOGENATION OF ACTIVATED ARENES
USING POTASSIUM HALIDE AND OXONEÕ
IN WATER-ACETONITRILE MEDIUM
B. V. Tamhankar,1 Uday V. Desai,1, R. B. Mane,1
*
2
P. P. Wadgaonkar,2 andAshutosh V. Bedekar
1Department of Chemistry, Shivaji University,
Kolhapur-416004, India
2National Chemical Laboratory, Pune-416008, India
ABSTRACT
A simple and practical halogenation of activated arenes using
a reagent combination of potassium halide and oxoneÕ in
water-acetonitrile medium is presented. The halogenated pro-
ducts were obtained with good yields and in high purity.
Halogenated aromatic compounds constitute an important class of
intermediates due to their easy conversion to other functionalities by
simple chemical transformations. Halogenated aromatics, especially bromi-
nated ones, are useful not only as precursors to organometallic reagents1 but
also are of great importance in the pharmaceutical,2 pesticide and agro-
chemical3 industries.
*Corresponding author.
2021
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

ORDER
REPRINTS
2022
TAMHANKAR ET AL.
The direct halogenation with molecular halogen4 has come under
increasing scrutiny due to its potential impact on the environment and
this suffers from the wastage of halogen as hydrohalous acid. This could
be overcome by recycling the same for halogenation in presence of oxidising
agents like H2O2,5 tert-butyl-hypohalite,6 tert-butylhydroperoxide7 and
sodium perborate.8 The hydrohalous acids are highly corrosive and harmful,
as molecular halogen, during large scale preparations, hence the develop-
ment of new methods of halogenation without using molecular halogen
or hydrohalous acid are necessary. The bromination of arenes using organic
ammonium tribromides9 (OATB), KBrO3,10 NBS11 over montmorillonite
k-10 clay and hexamethylene-tetramine tribromide12 have been reported.
However, to the best of our knowledge the chlorination of arenes using
similar reagents has not been reported, although, the chlorination and bro-
mination of arenes have been achieved by alkali metal halides in combination
13
of oxidants like NaClO2 and H2O2.14
OxonesÕ is a stable ternary composite of KHSO5, KHSO4 and K2SO4
in 2:1:1 molar proportions. Its utility as an oxidant has been demonstrated
in the oxidation of sulphides to sulphoxides and sulphones,15 selenides to
selenones,16 s-alcohols to ketones,17 acetals to esters,18 nitriles to alde-
hydes,19 amines to nitro-compounds,20 hydrazides to diacylhydrazines21
and of benzoins to diketones.22 It has also been used for the generation of
carbonyl compounds from oximes,23 hydrazones, semicarbazones, for oxi-
dative Nef reaction24 and in the cleavage of tert-butyl dimethyl silyl ethers.25
The literature reports also revealed the use of metal halide and OxoneÕ for
halogenation of pyrimidines,26 a,b-enones and alkenes27 with alkali halides
but so far, it has not been used for halogenation of arenes. We wish to report
Scheme 1.
herein the halogenation of activated arenes with potassium halide
using oxoneÕ as an oxidant, in water-acetonitrile medium (Scheme 1).
The results of halogenation of arenes are summarised in Table 1.

ORDER
REPRINTS
HALOGENATION OF ACTIVATED ARENES
2023
OxoneÕ though soluble in water, is insoluble in most of the common
organic solvents. Hence halogenations were performed in a solvent mixture
of water-acetonitrile (3:1, v/v) in which both, the substrates and OxoneÕ,
are freely soluble. This constitutes a single phase and halogenation proceeds
smoothly at room temperature within 2–3 h. The use of one equivalent
of each, OxoneÕ and alkali metal halide, yields monohalogenated product
while two equivalents of same furnishes dihalogenated products. The halo-
Table 1. Halogenation of Arenes Using KX/Oxone
(continued )

ORDER
REPRINTS
2024
TAMHANKAR ET AL.
Table 1. Continued
genation studies with various arenes revealed that, only activated arenes
undergo halogenation smoothly to yield para halogenated products and if
para position is blocked, ortho halogenation results. In case of the
deactivated arenes, halogenation was not observed even after prolonged
reaction time (10 h). Further, when halogenation of toluene was carried
out, nuclear halogenation took place instead of side chain halogenation
which is indicative of electrophilic substitution mechanism rather than the
radical pathway.
In conclusion, the present procedure is simple, convenient and less
expensive. In addition the reagent used is non toxic and easy to handle.

ORDER
REPRINTS
HALOGENATION OF ACTIVATED ARENES
EXPERIMENTAL
2025
OxoneÕ (Lancaster), KX (E. Merck), Acetanilide, Toluene,
p-Hydroxy benzoic acid & Cresols (Sd fine chem) were used. Cresyl
methyl ethers, 1,4-Dimethoxybenzene and 4-Methoxymethylbenzoate were
prepared from the corresponding hydroxy derivatives by standard methods
reported in the literature.31
Typical Procedure for Bromination of 1,4-Dimethoxybenzene
a) Monobromination: To a stirred solution of OxoneÕ (2.5 m mol)
in 30 ml water: acetonitrile (3:1, v/v) was added the solution
of 1,4-dimethoxy benzene (2.5 m mol) in acetonitrile (3 ml).
Potassium bromide (2.5 m mol) was added and stirring was con-
tinued at room temperature till the completion of reaction (tlc).
Water (20 ml) was then added and the reaction mixture was
extracted with ether (2 ꢀ 30 ml). The ether extract was washed
with water, dried over Na2SO4 and ether removed to yield
2-bromo-1,4-dimethoxy benzene. It was chromatographed over
silica gel and elution with light petroleum afforded pure com-
pound, (Table 1, Entry 5) (0.44 g, 80%), b.p. 258–260ꢁC (lit.28
262ꢁC). PMR (CDCl3): d 3.76 (3H, s, Ar-OCH3), 3.83 (3H, s,
OCH3 ortho to-Br), 6.83 (2H, d, Ar-H ortho to–OCH3) and 7.11
(1H, bs, ArH ortho to–Br).
b) Dibromination: It was carried out as above except the quantities
of potassium bromide and OxoneÕ were doubled. The workup
afforded 2,5-dibromo 1,4-dimethoxybenzene, (Table 1, entry 7)
which was purified by crystallisation (CHCl3 þ light petroleum),
yield (0.640 g, 84%), m.p. 142ꢁC (Lit.7 142ꢁC). PMR (CDCl3):
d 3.85 (6H, s, 2 ꢀ Ar OCH3), 7.11 (2H, s, ArH ortho to–OCH3).
REFERENCES
1. a) Normant, A. Advan. Org. Chem. 1960, 2:1. b) Wakefield, B.J.
The Chemistry of Organolithium compounds: Pergamon: Oxford, 1976.
c) Davies, S.G. In Organotransition Metal Chemistry: Applications
to Organic Synthesis: Pergamon: Oxford, 1882. d) Cannon, K.C.; Krow,
G.R. In Handbook of Grignard reagents: Ed. Silverman, G.S. Rakita, P.E.;
Dekker, M. New York, 1996, Chap. 25, p. 497. e) Rieke, R.D.; Sell, M.S.
In Hand book of Grignard reagents: Ed. Silverman, G.S., Rakita, P.E.,
Dekker, M. New York, 1996, Chap. 26, p. 527.

ORDER
REPRINTS
2026
TAMHANKAR ET AL.
2. Butler, A.; Walker, J.V. Chem. Rev. 1993, 93, 1937.
3. McLane, S.R.; Dean, E.W.; Brown, J.W.; Connell, C.R.; Howard,
W.H.; Minarik, C.E. Weeds 1953, 2, 288.
4. Norman, R.O.C.; Taylor, R. Electrophilic Substitution in Benzenoid
Compounds, Elsevier: New York, 1965, 130.
5. a) Jihad, D.; Yoel, S.J. Chem. Soc. Chem. Commun. 1987, 19, 1421. b)
Balaram Gupta, B.G.; Olah, G.A. Synthesis 1977.
6. a) Ravindranath, B.; Srinivas, P. Ind. J. Chem. 1985, 24B, 163. b)
Peake, C.J.; Stickland, J.H. Synth. Commun. 1986, 16, 763 and refs.
therein.
7. Barhate, N.B.; Gajare, A.S.; Wakharkar, R.D.; Bedekar, A.V.
Tetrahedron 1999, 55, 11127.
8. Deshmukh, A.P.; Padiya, K.J.; Jadhav, V.K.; Salunkhe, M.M. J. Chem.
Research (S) 1998.
9. Chaudhari, M.K.; Khan, Abu, T.; Patel, B.K. Tetrahedron Lett. 1998,
39, 8163.
10. Groweiss, Amiram. Org. Pro. Res. Dev. 2000, 4, 30.
11. Perumal, S.; Vijayabaskar, V.; Gomathi, V.; Selvaraj, S. Ind. J. Chem.
1999, 38B, 603.
12. Bisarya, S.C.; Rao, R. Synth. Commun. 1993, 23, 779.
13. Hirano, M.; Monobe, H.; Yakabe, S.; Morimoto, T. J. Chem.
Research (S) 1998, 662.
14. Srinivasu, P.; Narender, N.; Kulkarni, S.J.; Raghavan, K.V.
P8 National Workshop on Catalysis, IICT Hyderabad, January 2000.
15. a) Greenhalgh, R.P. Synlett 1992, 235 b) Hirano, M.; Tomaru, J.;
Morimoto, T. Chem. Lett. 1991, 523.
16. Ceccherelli, P.; Curini, M.; Epifano, F.; Macrotullio, M.C. Rosati, O.
J. Org. Chem. 1995, 60, 8412.
17. Hirano, M.; Oose, M.; Morimoto, T. Bull., Chem. Soc. Jpn. 1991, 64,
1046.
18. Curini, M.; Epifano, F.; Marcotullio, M.C.; Rosati, O. Synlett. 1999, 777.
19. Bose, D.S.; Baquer, S.M. Synth. Comm. 1997, 27 (18), 3119.
20. Webb, K.S.; Seneveratne, V. Tet. Lett. 1995, 36, 2377.
21. Kulkarni, P.P.; Kadam, A.J.; Desai Uday, V.; Mane, R.B.;
Wadgaonkar, P.P. J. Chem. Res. (S) 2000, 4, 184.
22. Varma, Rajender, S.; Dahiya, Rajender, Kumar Dalip, Molecules
Online 1998, 2, 82–85.
23. Bose, D.S.; Srinivas, P. Synth. Comm. 1997, 27 (22), 3835.
24. Curini, M.; Ceccherelli, P.; Marcotullio, M.C.; Epifano, F.; Rosati, O.
Synth. Comm. 1998, 28 (16), 3057.
25. Gowravaram, Sabitha, Mandali, Syamala, Yadav, J.S. Org. Lett. 1999,
1 (11), 1701–1703.

ORDER
REPRINTS
HALOGENATION OF ACTIVATED ARENES
2027
26. Steven, A.; Ross, Cynthia, Burrows, J. Tetrahedron Lett. 1997, 38 (16),
2805–2808.
27. Dieter, R.; Karl, Nice, Lois, E.; Velu, Sadanandan, E. Tetrahedron
Lett. 1996, 37, 2377.
28. a) Buckingham, J. Dictionary of Organic Compounds, Chapmann and
Hall, England. b) Catalogue Handbook of Fine Chemicals, Aldrich,
Gillingham, 1999.
29. Oberhauser, Thomas, J. Org. Chem. 1997, 62, 4504.
30. Riggs, R.M.; Nichols, D.E.; Foreman, M.M.; Truex, L.L. J. Med.
Chem. 1987, 30, 1889.
31. Vogel, A.I. A Text Book of Practical Organic Chemistry, ELBS, 1975.
Received in the UK June 13, 2000

Request Permission or Order Reprints Instantly!
Interested in copying and sharing this article? In most cases, U.S. Copyright
Law requires that you get permission from the article’s rightsholder before
using copyrighted content.
All information and materials found in this article, including but not limited
to text, trademarks, patents, logos, graphics and images (the "Materials"), are
the copyrighted works and other forms of intellectual property of Marcel
Dekker, Inc., or its licensors. All rights not expressly granted are reserved.
Get permission to lawfully reproduce and distribute the Materials or order
reprints quickly and painlessly. Simply click on the "Request
Permission/Reprints Here" link below and follow the instructions. Visit the
U.S. Copyright Office for information on Fair Use limitations of U.S.
copyright law. Please refer to The Association of American Publishers’
(AAP) website for guidelines on Fair Use in the Classroom.
The Materials are for your personal use only and cannot be reformatted,
reposted, resold or distributed by electronic means or otherwise without
permission from Marcel Dekker, Inc. Marcel Dekker, Inc. grants you the
limited right to display the Materials only on your personal computer or
personal wireless device, and to copy and download single copies of such
Materials provided that any copyright, trademark or other notice appearing
on such Materials is also retained by, displayed, copied or downloaded as
part of the Materials and is not removed or obscured, and provided you do
not edit, modify, alter or enhance the Materials. Please refer to our Website
User Agreement for more details.
Order now!
Reprints of this article can also be ordered at
http://www.dekker.com/servlet/product/DOI/101081SCC100104419