An Efficient, Catalytic, Aerobic, Oxidative Iodination of Arenes Using the H5PV2Mo10O40 Polyoxometalate as Catalyst

Article abstract of DOI:10.1021/jo035271h

Iodination of arenes was carried out by reacting 1 equiv of arene substrate with 0.5 equiv of iodine under an oxygen atmosphere with H ₅PV₂Mo₁₀O₄₀ as oxidation catalyst. The synthesis is an inherently waste-free method for the preparation of iodoarenes.

Full text of DOI:10.1021/jo035271h

at least stoichiometric amounts of oxidizing agent are
needed leading to formation of significant amounts of
waste. A slightly less problematic solution is to use
sodium hypochlorite as oxidant to form quaternary
An Efficien t, Ca ta lytic, Aer obic, Oxid a tive
Iod in a tion of Ar en es Usin g th e
H5P V2Mo10O40 P olyoxom eta la te a s Ca ta lyst
-
ammonium ICl2 salts that are effective electrophilic
Olena V. Branytska and Ronny Neumann*
iodination reagents.12 Here, the byproducts are sodium
chloride formed both in the preparation of the ICl2- salts
and the iodination reaction and quaternary ammonium
chlorides that in principle could be recycled.
Department of Organic Chemistry, Weizmann Institute of
Science, Rehovot 76100, Israel
ronny.neumann@weizmann.ac.il
Received August 31, 2003
A preferred iodination technique would espouse the use
of molecular oxygen as the oxidant for formation of the
active iodination species. Such a procedure is possible by
use of a pertinent polyoxometalate, H5PV2Mo10O40, as
catalyst for the aerobic oxidative iodination as presented
in Scheme 1. As is observable from Scheme 1, such a
synthetic method is inherently waste-free. It is notable
that in the past the H5PV2Mo10O40 polyoxometalate has
often been similarly used for aerobic oxidation whereby
the oxidation of the substrate occurs by electron transfer
and the reduced polyoxometalate is reoxidized by oxy-
gen.13
The typical procedure for the catalytic aerobic iodina-
tion of relatively activated arenes involves the reaction
of 1 equiv of the arene substrate with 0.5 equiv of iodine
and a catalytic amount, 1 mol %, of H5PV2Mo10O40 in
acetonitrile under O2. The results are presented in Table
1. First, concerning reactivity one may observe that the
reaction conversions were high with very good to excel-
lent selectivity to the monoiodination product. Second,
the yields in iodine were nearly quantitative in all cases;
therefore, there is very little waste product produced in
these reactions. Third, there was relatively high regiose-
lectivity observed in the iodination reactions. Thus,
anisole, 1,2-dimethoxybenzene, 1-methoxynaphthalene,
and phenol gave almost exclusive iodination at the para
position; aniline also showed relatively high para selec-
tivity. Thiophene and benzothiophene were iodinated
mostly at the 2-position. Notable also is the observation
that V(O)(acac)2 was not an active catalyst; only traces
of product were found in the iodination of anisole.
It would appear from the results above that the
iodination procedure is limited to the more activated
arenes. However, by using nitrobenzene as solvent
instead of acetonitrile, higher temperatures, and some-
what longer reaction times, reactivity for less reactive
arenes significantly increased, Table 2, thus extending
Abstr a ct: Iodination of arenes was carried out by reacting
1 equiv of arene substrate with 0.5 equiv of iodine under an
oxygen atmosphere with H5PV2Mo10O40 as oxidation cata-
lyst. The synthesis is an inherently waste-free method for
the preparation of iodoarenes.
Iodine-substituted aromatic compounds are important
and the most reactive intermediates for various cross-
coupling reactions and especially useful for formation of
carbon-carbon and carbon-heteroatom bonds.1 Iodo-
arenes can be synthesized from bromo- or chloroarenes
using BuLi and then iodine or via the Sandmeyer
reaction from aromatic amines. However, direct iodina-
tion of arenes is logically and therefore a priori more
attractive, but such preparations are not straightforward
since iodination reactions of arenes with molecular iodine
are only weakly catalyzed by Lewis acids as opposed to
the analogous chlorination and bromination reactions.
Thus, direct iodinaton of arenes requires the oxidation
of iodine to the more reactive species with a pronounced
I
+ character. Broadly speaking, many oxidizing reagents
for iodine have been considered for formation of I+ like
species either in situ or as stable isolable intermediates.2
Some examples, mostly postdating a comprehensive
review,2 include nitric acid/sulfuric acid,2 iodic or periodic
acid,3 diiodine pentaoxide,4 silver salts such as silver
trifluoroacetate,5 alumina,6 bis(pyridine)iodonium(I) tet-
rafluoroborate,7 lead(IV) acetate,8 bis(trifluoroacetoxy)-
iodobenzene,9 cerium ammonium nitrate,10 and fluorine
and xenon difluoride.11 All these methods, while syn-
thetically effective, have the obvious disadvantage that
(1) Metal-Catalyzed Cross-coupling Reactions; Diederich, F., Stang,
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P. J .; Asensio, G. J . Org. Chem. 1993, 58, 2058-2060.
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1995, 8, 926-928.
(9) Merkushev, E. B.; Simakhina, N. D.; Koveshnikova, G. M.
Synthesis 1980, 6, 486-487.
(11) (a) Rozen, S.; Zamir, D. J . Org. Chem. 1990, 55, 3552-3555.
(b) Shellhamer, D. F.; J ones, B. C.; Pettus, B. J .; Petts, T. L.; Stringer,
J . M.; Heasley, V. L. J . Fluorine Chem. 1998, 88, 37-39..
(12) (a) Kosynkin, D. V.; Tour, J . M. Org. Lett. 2001, 3, 991-992.
(b) Kajigaeshi, S.; Kakinami, T.; Yamasaki, H.; Fujisaki, S.; Okamoto,
T. Bull. Chem. Soc. J pn. 1988, 61, 600-602. (c) Kajigaeshi, S.;
Kakinami, T.; Yamasaki, H.; Fujisaki, S.; Kondo, M.; Okamoto, T.
Chem. Lett. 1987, 2109-2122. (d) Custelceanu, R.; Vlassa, M.; Silberg,
I. A. Monatsh. Chem. 1997, 128, 919-925. (e) Hajipour, A. R.;
Arbabian, M.; Ruoho, A. E. J . Org. Chem. 2002, 67, 8622-8624. (f)
Wariishi, K.; Morishima, S.-I.; Inagaki, Y. Org. Process Res. Dev. 2003,
7, 98-100.
(13) (a) Kozhevnikov, I. V. Chem. Rev. 1998, 98, 171-198. (b)
Kozhevnikov, I. V. Catalysis by Polyoxometalates; Wiley: Chichester,
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10.1021/jo035271h CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/23/2003
9510
J . Org. Chem. 2003, 68, 9510-9512

SCHEME 1. Aer obic Iod in a tion of Ar en es Ca ta lyzed by H5P V2Mo10O40
a
TABLE 1. Iod in a tion of Activa ted Ar en es Ca ta lyzed by H5P V2Mo10O40
substrate
product
conversion,b mol %
selectivity,c mol %
anisole
1,2-dimethoxybenzene
1,3-dimethoxybenzene
4-iodoanisole
98
96
86
99.5
98
87, 9
4-iodo-1,2-dimethoxybenzene
4-iodo-1,2-dimethoxybenzene,
2-iodo-1,3-dimethoxybenzene
2-iodo-1,4-dimethoxybenzene
2-iodo-4-methylanisole
4-iodoaniline, 2-iodoaniline
4-iodophenol, 2-iodophenol
2-iodo-1,3,5-trimethylbenzene
2-iodo-1,4-dimethylbenzene
2-iodothiophene
1,4-dimethoxybenzene
4-methylanisole
aniline
97
96
89
100
91
11, 99d
80
92
100
83, 12
98, 2
100
phenol
1,3,5-trimethylbenzene
1,4-dimethylbenzene
thiophene
100
66e
benzothiophene
2-iodo-benzothiophene,
94
85, 3
3-iodo-benzothiophene
1-methoxynaphthalene
2-methoxynaphthalene
4-iodo-1-methoxynaphthalene
1-iodo-2-methoxynaphthalene
99
92
98
100
a
Reaction conditions: 1 mmol of substrate, 0.01 mmol of H5PV2Mo10O40, 0.5 mmol of I2 2 atm of O2, 1 mL of acetonitrile in a 15 mL
glass pressure tube, 80 °C, 8 h. Analysis by GC and GC-MS on a Restek Rtx-5MS column (30 m × 0.32 mm with a 0.25 µm 5% phenyl,
b
95% methysilicone coating) and by 1H NMR carrying out the reactions in CD3CN. mol % of substrate reacted. c mol % of product of all
d
products; the remaining products were diiodinated arenes. Reaction was carried out in nitrobenzene instead of acetonitrile.
e 2,5-Diiodothiophene was the other product.
a
TABLE 2. Iod in a tion of Non a ctiva ted Ar en es Ca ta lyzed by H5P V2Mo10O40
substrate
product
conversion,b mol %
selectivity,c mol %
toluene
biphenyl
naphthalene
bromobenzene
4-iodotoluene, 2-iodotoluene
4-iodobiphenyl, 4,4′-diodobiphenyl
1-iodnaphthalene
1-bromo-4-iodobenzene,
1-bromo-2-iodobenzene
1-chloro-4-iodobenzene,
1-chloro-2-iodobenzene
>99
85
72
85, 15
80, 20
100
91
81, 19
chlorobenzene
92
80, 20
a
1 mmol of substrate, 0.01 mmol of H5PV2Mo10O40, 0.5 mmol of I2 2 atm of O2, 1 mL of nitrobenzene in a 15 mL glass pressure tube,
120 °C, 36 h. Analysis by GC and GC-MS on a Restek Rtx-5MS column (30 m × 0.32 mm with a 0.25 µm 5% phenyl, 95% methysilicone
b
coating) and by 1H NMR carrying out the reactions in C6D5NO2. mol % of substrate reacted. c mol % of product of all products; the
remaining products were diiodinated arenes.
the synthetic utility of the technique. As for the more
activated arenes, also in this case high yields, selectivity
to monoiodoarenes and high regioselectivity were at-
tained.
Since the H5PV2Mo10O40 polyoxometalate is both a
strong Brønsted acid and an oxidizing agent, there are
two possible general explanations for the catalytic activ-
ity of H5PV2Mo10O40. The first explanation is based on
the possible polarizing effect of H5PV2Mo10O40 on molec-
ular iodine leading to a Iδ+-Iδ--type intermediate, which
after reaction with the arene substrate would yield the
iodinated arene and HI. Conceivably, the HI species could
then be oxidized by H5PV2Mo10O40 in a catalytic manner
so as to yield more I2. Alternatively, as presented in
Scheme 1, the molecular iodine is directly oxidized to two
I+-type species that react with the arene substrate. To
differentiate between these two possible generalized
mechanistic pathways, comparative reactions were per-
formed with anisole as model substrate as summarized
in Figure 1. Comparison of the results of the iodination
reaction without catalyst with those using the non-
oxidizing acids, H2SO4 and H3PW12O40 clearly shows that
J . Org. Chem, Vol. 68, No. 24, 2003 9511

place of I2 with H5PV2Mo10O40 as catalyst did not yield
significant iodination also argues strongly against the
formation and then oxidation of I-. This indicates that
the formation of an active electrophilic iodine species is
very sluggish from HI and H5PV2Mo10O40. In fact, the
limited activity of HI is somewhat surprising since more
difficult to oxidize HBr has been used as a brominating
agent in the presence of H5PV2Mo10O40 and oxygen.14
Clearly, strongly oxidizing H5PV2Mo10O40 is the most
active catalyst; H3PMo12O40 is also oxidizing but the well-
known slower reoxidation of the reduced species limits
the reaction.13
Ack n ow led gm en t. This research was supported by
the Basic Research Foundation administered by the
Israeli Academy of Science and Humanities and the
Helen and Martin Kimmel Center for Molecular Design.
R.N. is the Rebecca and Israel Sieff Professor of Organic
Chemistry.
Su p p or tin g In for m a tion Ava ila ble: A detailed Experi-
mental Section. This material is available free of charge via
the Internet at http://pubs.acs.org.
F IGURE 1. Iodination of anisole under different reactions
conditions: 1 mmol of anisole, 0.01 mmol of catalyst, 0.5 mmol
of I2, 2 atm of O2, 1 mL of acetonitrile, 80 °C, 8 h. For entry
HI/ H5PV2Mo10O40, 1 mmol of HI was used instead of I2.
J O035271H
there is no significant acid catalysis for the iodination
with I2. Furthermore, the finding that the use of HI in
(14) Neumann, R.; Assael, I. J . Chem. Soc., Chem. Commun. 1988,
1285-1287.
9512 J . Org. Chem., Vol. 68, No. 24, 2003