Mild and regioselective iodination of aromatic compounds with N,N′-diiodo-N,N′-1,2-ethanediylbis(p-toluenesulphonamide)

Article abstract of DOI:10.1016/j.tetlet.2003.08.019

N,N′-Diiodo-N,N′-1,2-ethanediylbis(p-tolouenesulphonamide) [NIBTS] and catalytic trifluoroacetic acid can be used for the regioselective iodination of aromatic compounds in acetonitrile under mild conditions in excellent yields.

Full text of DOI:10.1016/j.tetlet.2003.08.019

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7529–7532
Mild and regioselective iodination of aromatic compounds with
N,N%-diiodo-N,N%-1,2-ethanediylbis(p-toluenesulphonamide)
Ramin Ghorbani-Vaghei*
Department of Chemistry, Faculty of Science, Bu-Ali Sina University, Hamadan, Iran
Received 7 July 2003; revised 31 July 2003; accepted 8 August 2003
Abstract—N,N%-Diiodo-N,N%-1,2-ethanediylbis(p-tolouenesulphonamide) [NIBTS] and catalytic trifluoroacetic acid can be used
for the regioselective iodination of aromatic compounds in acetonitrile under mild conditions in excellent yields.
©
2003 Elsevier Ltd. All rights reserved.
Aromatic iodides have long been used in organic syn-
thesis as versatile intermediates that can be transformed
to a variety of functional groups. They can be easily
The advantages of NIBTS are as follows:
1
1. The preparation of NIBTS is easy.
2. NIBTS is stable for six months under atmospheric
conditions.
3. After the reaction of NIBTS with a substrate, the
sulphonamide is recovered and can be reused many
times without decreasing the yield.
functionalized through metal catalyzed cross-coupling
2
reactions. These derivatives have been used in the
3
synthesis of many interesting natural products and also
4
bioactive materials. The moderate reactivity of iodine
with aromatic substrates requires the addition of acti-
vating agents for its utilization and recently direct
iodination methods have been developed by using the
following iodonium donating reagents: iodine-tetra-
The reaction of aromatic compounds with NIBTS in
refluxing acetonitrile afforded iodo-compounds without
side products (Scheme 2).
5
6
9
butylammonium peroxydisulfate,
BuLi-F CCH I,
3 2
8
7
iodine-nitrogen dioxide, iodine-F-TEDA-BF , NIS,
iodine-diiodine pentoxide, bis(sym-collidine)iodine(I)
12
4
1
0
However, this reaction does not proceed in the absence
of trifluoroacetic acid and it is probable that the active
species for this iodination is probably the ‘in situ’
formed iodine trifluoroacetate which can act as a very
reactive electrophile. The following mechanism for the
reaction (Scheme 3) is suggested.
11
hexafluorophosphate,
iodine
monochloride,
13
bis(pyridineiodonium(I)tetrafluoroborate - CF SO H,
NIS-CF SO H, iodine-silver sulfate, iodine-mercury
3
3
1
4
15
3
3
1
6
17
18
salts, NaOCl-NaI and NIS-CF CO H. However,
3
2
most of these methods require hazardous or toxic
9
reagents or long reaction times.
The results of the iodination of representative aromatic
compounds are presented in Table 1.
Herein, a convenient method for iodination of aromatic
compounds using a new reagent [NIBTS] 1 (Scheme 1)
that is prepared from N,N%-1,2-ethanediylbis(p-toluene-
1
9
sulphonamide) and catalytic trifluoroacetic acid is
reported.
*
0
Corresponding author. Fax: (+98) 811 8272404; e-mail: ghorbani@
basu.ac.ir
Scheme 1.
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.08.019

7
530
R. Ghorbani-Vaghei / Tetrahedron Letters 44 (2003) 7529–7532
Scheme 2.
Scheme 3.
The products of reaction with NIBTS were isolated
simply by filtering off the sulfonimide 2 and evapo-
rating the solvent from the filtrate. The method has
advantages in terms of yields, simplicity of reaction
conditions, short reaction times and lack of side
products. The recovered starting material 2, was re-
iodinated and used many times without reducing the
yield.
dried in a vacuum desicator at room temperature for
6 h. The reaction gives 1 in (0.9 g, 90%). IR (KBr): w
−
1
1
6
1600, 1460, 1340, 1150 cm . H NMR (DMSO-d ): l
1
3
2.40 (s, 6H), 2.70 (s, 4H), 7.50–7.76 (m, 8H).
C
NMR (DMSO): l 20.2 (CH ), 45.1 (CH ), 126.20–
3
2
141.19 (4 peaks for the aromatic carbons).
General procedure for iodination of aromatic com-
pounds with NIBTS: To a solution of 1 mmol of
Procedure for the preparation of N,N%-diiodo-N,N%-1,2-
the aromatic compound in 5 ml of CH CN, 0.5
3
ethanediylbis(p-toluenesulphonamide)
1:
N,N%-1,2-
mmol of NIBTS and five drops of trifluoroacetic acid
were added, then the mixture was refluxed for the
specified time (Table 1). After completion of the reac-
tion, the insoluble sulfonamide 2 was removed by
filtration and washed with cold acetonitrile (10 ml).
The solvent was then evaporated and ether was
added. The ethereal phase was washed with aqueous
ethanediylbis(p-toluenesulphonamide) (1 g, 0.006 mol)
was dissolved in a slight molar excess of sodium
hydroxide solution (6 M) at room temperature and
was transferred to a beaker. Iodine (10 g) dissolved in
carbon tetrachloride (15 ml) was added to the solu-
tion with vigorous stirring at −10°C and immediately
a yellow precipitate was formed. The product (yellow
precipitate) was collected on a Buchner funnel and
washed with distilled cold water (10 ml) and then
NaHSO3 and water. After work-up, the crude
1
iodoaromatic was obtained pure as shown by
NMR.
H

R. Ghorbani-Vaghei / Tetrahedron Letters 44 (2003) 7529–7532
Table 1. Iodination of aromatic compounds with NIBTS and CF CO H
7531
3
2
a
Products were characterized by their physical properties, comparison with authentic samples and by spectroscopic methods.
References
6. Blackmore, I. J.; Boa, A. N.; Murray, E. J.; Dennis, M.;
Woodward, S. Tetrahedron Lett. 1999, 40, 6671.
7. Noda, Y.; Kashima, M. Tetrahedron Lett. 1997, 38, 6225.
8. Zupan, M.; Iskra, J.; Stavber, S. Tetrahedron Lett. 1997,
38, 6305.
9. Carreno, M. C.; Ruano, J. L. G.; Sanz, G.; Toledo, M.
A.; Urbano, A. Tetrahedron Lett. 1996, 37, 4081.
10. Bradzil, L. C.; Cutler, C. J. J. Org. Chem. 1994, 59, 6233.
11. Brunel, Y.; Rousseau, G. Tetrahedron Lett. 1995, 45,
8217.
1
. Farina, V. In Comprehensive Organometallic Chemistry
II; AbeI, E. W.; Stone, F. G.-A.; Wilkinson, G., Eds.;
Pergamon Press: Oxford, 1995; Vol. 12, pp. 161–240.
. Diederich, F.; Stang, P. J. Metal-Catalyzed Cross-Cou-
pling Reactions; Wiley-VCH: Weinheim, Germany, 1998.
. (a) Larock, R. C.; Lee, N. H. J. Org. Chem. 1991, 56,
2
3
6
1
253; (b) Larock, R. C.; Yum, E. K. J. Am. Chem. Soc.
991, 113, 6689; (c) Busacca, C. A.; Johnson, R. E.
Tetrahedron Lett. 1992, 33, 165; (d) Swenton, J. S.;
Callinan, A.; Wang, S. J. Org. Chem. 1992, 57, 78.
. (a) Seevers, R. H.; Counsell, R. E. Chem. Rev. 1982, 82,
12. Hubig, S. M.; Jung, W.; Kochi, J. K. J. Org. Chem. 1994,
59, 6233.
13. Barluenga, J.; Gonzalez, J. M.; Garcia-Martin, M. A.;
Campos, P. J.; Asensio, G. J. Org. Chem. 1993, 58, 2058.
14. Olah, G. A.; Qi, W.; Sandford, G.; Prakash, G. K. S. J.
Org. Chem. 1993, 58, 3194.
4
5
5
74; (b) Nicolaou, K. C. Angew. Chem., Int. Ed. Engl.
1
993, 32, 1377.
. Yang, S. G.; Kim, Y. H. Tetrahedron Lett. 1999, 40,
051.
6
15. Sy, W.-W. Tetrahedron Lett. 1993, 34, 6223.

7
532
R. Ghorbani-Vaghei / Tetrahedron Letters 44 (2003) 7529–7532
16. Bachky, A.; Foubelo, F.; Yus, M. Tetrahedron 1994, 50,
4975.
5
139.
21. (a) Weast, R. C.; Grasselli, J. G. Handbook of Data on
Organic Compounds, 2nd ed.; CRC Press, Inc: Boca Raton,
1989; Vol. 1, p. 46; (b) Weast, R. C.; Grasselli, J. G.
Handbook of Data on Organic Compounds, 2nd ed.; CRC
Press, Inc: Boca Raton, 1989; Vol. 2, p. 606.
1
1
7. Edgar, K. J.; Falling, S. N. J. Org. Chem. 1990, 55, 5287.
8. Castanet, A.-S.; Colobert, F.; Broutin, P.-E. Tetrahedron
Lett. 2002, 43, 5047.
1
9. Khazaei, A.; Vaghei, R. G.; Tajbakhsh, M. Tetrahedron
Lett. 2001, 42, 5099.
0. Keefer, R. M.; Andrews, L. J. J. Am. Chem. Soc. 1956, 78,
22. Cambie, R. C.; Rutledge, P. S.; Smith-Palmer, T.;
Woodgate, P. D. J. Chem. Soc., Perkin Trans. 1 1976, 1161.
2