Regioselective iodination of activated arenes using phenyl trimethylammonium dichloroiodate in ionic liquid under microwave irradiation

Article abstract of DOI:10.1081/SCC-200057244

The regioselective iodination of activated arenes has been achieved in the presence of phenyltrimethylammonium dichloroiodate and ionic liquid. The reaction has been carried out by both conventional heating as well as by microwave irradiation. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200057244

Synthetic Communicationsw, 35: 1313–1318, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200057244
Regioselective Iodination of Activated
Arenes Using Phenyl Trimethylammonium
Dichloroiodate in Ionic Liquid Under
Microwave Irradiation
Rutuja D. Tilve and Vinod R. Kanetkar
Dyestuff Technology Division, Institute of Chemical Technology,
University of Mumbai, Matunga, Mumbai, India
Abstract: The regioselective iodination of activated arenes has been achieved in the
presence of phenyltrimethylammonium dichloroiodate and ionic liquid. The reaction
has been carried out by both conventional heating as well as by microwave irradiation.
Keywords: Ionic liquid, microwave, phenyltrimethylammonium dichloroiodate, regio-
selective iodination
INTRODUCTION
Iodoarenes are biologically active molecules used as drugs or in diagnostic
aids and as radioactive-labeled markers or contractors in radioimmunoassay
studies and in nuclear magnetic imaging. Synthetic methods involving a
source of positive iodine (Iþ) as the reactive species seem to be the most con-
venient procedure for the direct iodination of arenes. A wide array of reagents
and methods involving molecular iodine has been documented.[1]
With an ever-increasing quest for exploration of newer reactions in ionic
liquids and our interest in the iodination of arenes,[2,3] we report herein the use
of ionic liquids and ionic liquids in conjunction with microwave heating as
promoters and a recyclable system for the synthesis of iodoarenes using
Received in India January 18, 2005
Address correspondence to Vinod R. Kanetkar, Dyestuff Technology Division,
Institute of Chemical Technology, University of Mumbai, Matunga, Mumbai 400
019, India. E-mail: rutujatilve@yahoo.co.in
1313

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R. D. Tilve and V. R. Kanetkar
phenyl trimethyl ammonium dichloroiodate (PTMA ICl2) (Scheme 1). Phenyl
trimethyl ammonium chloride was prepared as follows: To the black solution
of ICl (0.1 mol) in dichloromethane (MDC) (200 ml) was added dropwise a
solution of phenyltrimethylammonium chloride (0.1 mol) in 100 ml of water
under stirring at room temperature. After the mixture was stirred for 30 min,
the MDC layer was separated, dried with sodium sulphate, and evaporated
in vacuo to give a residue that, on recrystallization, afforded PTMA ICl2 as
stable orange yellow needles.
RESULTS AND DISCUSSION
For our optimization studies, the reaction between anisole and PTMA ICl2 in
[bmim]PF6 (molar ratio 1 : 1.1 respectively) was chosen as a model. Among
several reactions attempted, we observed that the conversion of anisole to the
desired p-iodoanisole was highest at 1008C. We therefore screened a range of
arenes and the results are presented in Table 1. This practically simple protocol
avoids the use of any additives or acidic promoters. The products obtained
after the reaction resulted from the regioselective iodination of the aromatic
ring. The observed regioselectivity can be explained from the result
that iodination occurs at more electron-rich and less sterically hindered
positions.
In this reaction, the efficiency of ionic liquid (IL) was strongly influenced
by the nature of the anion. Among the hydrophilic [bmim]BF4 and hydro-
phobic [bmim]PF6, [bmim]PF6 was found to be superior in terms of yields
and reaction rates (Table 1, entries 1 and 2). In further reactions, the efficiency
of other quaternary ammonium salts was studied. The reaction was not suc-
cessful in molten salts such as Bu4N Cl or [bmim] Cl. To determine whether
the IL influences reaction rate and yields, the same reaction was carried out in
acetonitrile and toluene under reflux. Under this condition, longer reaction
times and lower yields were observed.
Scheme 1. Iodination of activated arenes using phenyltrimethyl ammonium dichloro-
iodate in [bmim]PF6.

Table 1. Iodination of activated arenes using PTMA ICl2 in [bmim]PF6 at 1008C by conventional heating and microwave heatinga
Conventional heating Microwave heating Melting point (8C)
Reported[4,5]
No.
1
Substrate
Product
Time (h)
3
Yieldc (%)
95
Time (min)
20
Yieldc (%)
92
Observed
52–53
51–52
2
3
5
76b
91
—
27
—
92
52–53
28–29
51–52
28–29
2.5
4
5
6
4
4
5
89
82
85
27
30
25
85
79
86
29–30
78–80
88–89
29–30
77–78
87–88
(continued)

Table 1. Continued
Conventional heating
Microwave heating
Time (min)
Yieldc (%)
22 70
Melting point (8C)
No.
7
Substrate
Product
Time (h)
4
Yieldc (%)
75
Observed
Reported[4,5]
178–180
180–181
8
3
87
35
81
53–54
—
9
3
4
89
85
25
35
90
82
75–76
30–31
74–76
30–31
10
aReactions were performed at 60 W.
bReaction was performed in [bmim]BF4, at 1008C.
cIsolated yields.

Regioselective Iodination of Activated Arenes
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A model reaction composed of anisole and PTMA ICl2 (in molar ratio
1 : 1.1) in [bmim]PF6 was irradiated at power levels 30 W, 60 W, and 90 W
respectively. The optimum power was found to be 60 W, wherein high
yields were obtained; a low yield was obtained at 30 W whereas at 90 W
decomposition was noted.
CONCLUSION
In conclusion, we were successful in using ionic liquid in conjunction with
microwave heating as a convenient reaction medium and promoter for the
iodination of arenes. The notable features of this protocol are the absence of
any additives/acidic promoters, rate enhancement, cleaner reaction profiles,
and recyclability of the ionic liquid.
EXPERIMENTAL
The microwave oven used for performing the reaction was MARS 5
microwave oven (CEM Corp. Mathews, North Carolina). Products were
characterized by comparison of their spectral data (1H-NMR, IR) and
physical data with those reported in the literature.
General Procedure for Iodination Reactions of Activated Arenes
using Phenyl Trimethyl Ammonium Dichloroiodate in Ionic Liquids
By conventional heating: In a representative procedure, the reaction mixture
of substrate (5 mmol), PTMA ICl2 (5.5 mmol), and 1.5 ml of [bmim]PF6
was stirred at 1008C for the specified time. The reaction mixture was
extracted with diethyl ether, washed with sodium thiosulphate solution,
dried over anhydrous sodium sulphate, and evaporated under reduced
pressure to obtain the crude products. The crude products were chromato-
graphed using silica gel chromatography to afford pure products wherever
necessary and characterized by their physical constants and spectral analysis.
By microwave heating: The reaction mixture of substrate (5 mmol),
PTMA ICl2 (5.5 mmol), and 1.5 ml of [bmim]PF6 was irradiated in a
microwave at 60 W for the time as specified in Table 1. After completion of
the reaction, workup was carried out as described and the desired product
was isolated.
ACKNOWLEDGMENT
This work is dedicated to the late Bhushan Khadilkar. We thank S. D. Samant
from MUICT for valuable suggestions with this manuscript. We gratefully

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R. D. Tilve and V. R. Kanetkar
acknowledge BRNS (99/37/39/BRNS/1749) for financial assistance and
G. D. Gokhale Trust for awarding a fellowship to one of the authors.
REFERENCES
1. (a) Galli, C. Aromatic iodination: Evidence of reaction intermediate and of the
s-complex of the transition state. J. Org. Chem. 1991, 56, 3238;
(b) Alexander, M. V.; Khandekar, A. C.; Samant, S. D. Synlett 2003, 12, 1895,
and references cited therein.
2. (a) Tilve, R. D.; Alexander, M. V.; Khandekar, A. C.; Samant, S. D.; Kanetkar, V. R.
Synthesis of 2,3-unsaturated glycopyranosides by Ferrier rearrangement in FeCl3
based ionic liquid. J. Mol. Cat. (A) 2004, 223, 237; (b) Alexander, M. V.;
Khandekar, A. C.; Samant, S. D. Sulphonylation of aromatics using FeCl3 based
ionic liquids. J. Mol. Cat. (A) 2004, 223, 75; (c) Paul, A. M.; Khandekar, A. C.;
Khadilkar, B. M. Baeyer condensation in chloroaluminate ionic liquid. J. Chem.
Res, Synop. 2003, 3, 168; (d) Rebeiro, G. L.; Khadilkar, B. M. Chloroaluminate
ionic liquid for Fischer indole synthesis. Org. Pro. Res. Dev. 2002, 6, 826;
(e) Khandekar, A. C.; Khadilkar, B. M. Pechmann condensation in chloroaluminate
ionic liquids. Synlett 2002, 1, 152; (f) Rebeiro, G. L.; Khadilkar, B. M. Microwave
assisted synthesis of room temperature ionic liquid precursors in closed vessel.
Synthesis 2001, 3, 370.
3. Tilve, R. D.; Alexander, M. V.; Khadilkar, B. M. Iodination of activated arenes
using silfen: An improved protocol. Tetrahedron Lett. 2000, 43, 9457.
4. Krassowska-Swiebocka, B.; Lulinski, P.; Skulski, L. Aromatic iodination
of activated arenes and heterocycles with lead tetracetate as oxidant. Synthesis
1995, 926.
5. Orito, K.; Hatakeyama, T.; Takeo, M.; Suginome, H. Iodination of alkyl aryl ethers
by mercury (II) oxide–iodine reagent in dichloromethane. Synthesis 1995, 1273.