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L. Bailey, S. T. Handy / Tetrahedron Letters 52 (2011) 2413–2414
Table 1
Iodination results
O
N
I
S
O2
Arene
Iodoarene
BMIM BF4
RT, 6-12 h
n
Arene
Producta
Isolated yieldb
1
2
3
4
5
6
7
8
9
Anisole
Mesitylene
Thiophene
1,2-Dimethoxybenzene
1,2,3-Trimethoxybenzene
3,4,5-Trimethoxybenzaldehyde
o-Xylene
m-Xylene
p-Xylene
4-Iodoanisole
92 (91)
97
92 (88)
68
2-Iodo-1,3,5-trimethylbenzene8
2-Iodothiophene
4-Iodo-1,2-dimethoxybenzene
5-Iodo-1,2,3-trimethoxybenzene
2-Iodo-3,4,5-trimethoxybenzaldehyde9
4-Iodo-1,2-dimethylbenzene7
1-Iodo-2,4-dimethylbenzene8
2-Iodo-1,4-dimethylbenzene7
54
68
94
95
91
MeO
OH
MeO
OH
10
52
MeO
MeO
I
10
11
12
13
14
Toluene
Anthracene
Pyrene
4-Iodotoluene
None
None
89 (92)
0
0
0
Naphthalene
None
a
The structure of the product was confirmed by comparison (spectral and/or melting point) with commercially available samples or with the data reported in the
literature.
b
The numbers in parentheses are for the corresponding reaction performed in BMIM NTf2.
It is worth noting that the use of ionic liquids as the solvent ap-
3. Conclusion
pears to enhance the reactivity of N-iodosaccharin, just as was the
case with N-iodosuccinimide. For example, the reaction of N-iodo-
saccharin with toluene in acetonitrile is reported to afford a 53%
yield of the iodinated product after 5 h at reflux. The same reaction
in BMIM BF4 affords the iodotoluene product in 89% yield after 12 h
at room temperature and avoids the formation of a regioisomeric
mixture of products.
Although the ionic liquid could be readily separated at the end
of the reaction, removal of the saccharin by-product was not
straightforward as both it and the BMIM BF4 were water soluble.
Fortunately, simply switching the solvent to BMIM NTf2 resulted
in equally efficient iodination (Table 1, entries 1, 3 and 11), but
now the saccharin by-product could also be readily removed by
washing the ionic liquid layer with water. The recovered BMIM
NTf2 could then be recycled in subsequent iodination reactions
(the same 1 mL sample of BMIM NTf2 was used for all three of
these reactions, with the recovered material being used in entry
3 and then recovered and reused again in entry 11).
Finally, it is worth noting that N-iodosaccharin is easily pre-
pared starting from saccharin according to the literature proce-
dure.5 In our hands, this method works very well and the crude
product was pure enough for the iodination reactions. It is also rea-
sonably stable over the period of 2–6 months, although we did
store it in the dark in a refrigerator. One practical note of caution
is that the reaction time for the conversion of the silver salt of sac-
charin to N-iodosaccharin is of importance. Attempts to let the
reaction run overnight resulted in decomposition of the N-iodosac-
charin via reaction with the acetone solvent to afford 1-iodoace-
tone. Although this reactivity maybe of synthetic interest, for the
preparation of N-iodosaccharin, it means that reaction times must
be kept in the range of 5–6 h.
In summary, we have developed a convenient method for the
synthesis of aryl iodides from a range of arenes, including only
modestly activated ones. The more hydrophobic RTIL BMIM NTf2
has the added advantage that the saccharin by-product can be re-
moved from the RTIL layer by extraction with water, thereby en-
abling more effective recycling of the RTIL. Attempts to iodinate
even less reactive arenes are underway and will be reported in
due course as is the application of this iodination to further one-
pot halogenation/cross-coupling reactions.
References and notes
1. Stavber, S.; Jereb, M.; Zupan, M. Synthesis 2008, 1487–1513.
2. Hanson, J. R. J. Chem. Res. S 2006, 277–280.
3. Firouzabadi, H.; Iranpoor, N.; Kazemi, S. Can. J. Chem. 2009, 87, 1675–1681.
4. Handy, S. T. Synlett 2006, 3176–3178.
5. Dolenc, D. Synlett 2000, 544–546.
6. General procedure: To a solution of 54 mg (0.5 mmol) of anisole in 1 mL of
BMIM BF4 was added 158 mg (0.51 mmol) of N-iodosaccharin. The reaction
was stirred at room temperature protected from light for 8–12 h. The product
was then isolated by extraction with ether (3 Â 3 mL), followed by evaporation
of the solvent to afford the desired iodinated product. In some cases, the
product was contaminated with small amounts of BMIM BF4. This could be
removed via filtration with ether through a short plug of silica. Alternatively, it
could be avoided entirely by extraction of the product from the reaction using
1:1 ether/hexanes in place of pure ether. The identity of all products were
confirmed by comparison (spectral and mp) with either commercially available
samples or data reported in the literature as indicated in Table 1.
7. Kataoka, K.; Hagiwara, Y.; Midorikawa, K.; Suga, S.; Yoshida, J. Org. Process Res.
Dev. 2008, 12, 1130–1136.
8. Wan, S.; Wang, S. R.; Lu, W. J. Org. Chem. 2005, 71, 4349–4352.
9. Nicolaus, N.; Strauss, S.; Neudoerfl, J.-M.; Prokop, A.; Schmalz, H.-G. Org. Lett.
2009, 11, 341–344.
10. Ruiz, J.; Ardeo, A.; Ignasio, R.; Sotomayor, N.; Lete, E. Tetrahedron 2005, 61,
3311–3324.