2,4,6,8-Tetraiodoglycoluril in sulfuric acid as a new powerful reagent for iodination of deactivated arenes

Article abstract of DOI:10.1016/S0040-4039(00)01624-5

Deactivated arenes are iodinated readily at 0°C by the action of 2,4,6,8-tetraiodoglycoluril in sulfuric acid to give the iodoarenes in generally good yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01624-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9101–9104
2,4,6,8-Tetraiodoglycoluril in sulfuric acid as a new powerful
reagent for iodination of deactivated arenes
Vitold K. Chaikovski, Victor D. Filimonov,* Alexander Yu. Yagovkin and
Tatjana S. Kharlova
Department of Organic Chemistry, Tomsk Polytechnic University, Tomsk 634034, Russia
Received 24 June 2000; revised 8 September 2000; accepted 20 September 2000
Abstract
Deactivated arenes are iodinated readily at 0°C by the action of 2,4,6,8-tetraiodoglycoluril in sulfuric
acid to give the iodoarenes in generally good yields. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: arenes; halogenation; N-imides; sulfuric acid.
Iodoarenes are valuable, versatile synthetic intermediates and have found wide applications in
medicine and biochemistry.1 However, the electrophilic nature of iodine is weaker than bromine
and chlorine. For this and other reasons, there are only a limited number of methods for direct
iodination of deactivated aromatics. Some arenes with electron-withdrawing substituents can be
iodinated by I2/HNO3/H2SO4/AcOH,2 I2/Ag2SO4/H2SO4,3 I2/oleum,4 I2/F2,5 or I2/CrO3.6 Nowa-
days, the most potent iodination agents appear to be N-iodosuccinimide in CF3SO3H7 and the
superelectrophilic reagent obtained recently from ICl and Ag2SO4 in sulfuric acid (reagent
‘I+’).8,9 Thus, the former reagent converts nitrobenzene 1a to 3-iodonitrobenzene 2a (86%) within
2 h at room temperature.7 However, this method is limited on a large preparative scale by the
expense of CF3SO3H. On the other hand, while reagent ‘I+’ is capable of iodinating nitrobenzene
1a within 15 min at 20°C or 1.5 h at 0°C very effectively, along with the iodination, a
chlorination process takes place to a small extent.8,9
As an extension of our search for more potent and practical, non-oxidizing iodination
reagents, we have found that 2,4,6,8-tetraiodoglycoluril (2,4,6,8-tetraiodo-2,4,6,8-tetra-
azabicyclo[3.3.0]octane-3,7-dione) (TIG)10 in sulfuric acid has an extremely strong ability for
iodination of various deactivated aromatic compounds at 0°C.
* Corresponding author. Fax: +7(3822)415235; e-mail: filim@org.chtd.tpu.edu.ru
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01624-5

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Table 1
Iodination of aromatics with 2,4,6,8-tetraiodoglycoluril (TIG) at 0°C
Substrate 1
Product 2
Time (min)
90
Yielda (%)
75
Mp (°C) (solvent)
35–36 (EtOH)
Lit. mp (°C)
36–377
70
48
59–60 (EtOH)
55–57 (EtOH)
60–619
60
45
68
52
583a
185–186 (50%
185–1873b
i-PrOH)
60
60
79
82
52–54 (EtOH)
54–556
173–174 (i-PrOH)
174–1765
30
15
65
40
55–56 (EtOH)
91–92 (EtOH)
573a
9211
15
90
45
58
128–129 (EtOH)
249–250 (DMFA)
130–13112
25413
60
60
60
44
205–206 (benzene)
309–310 (toluene)
205–20614
31015
a Yields of pure, isolated products.

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Deactivated arenes 1a–l with electron-withdrawing substituents were shown to react readily
with this reagent giving iodoarenes 2a–l with generally good yields and with complete conver-
sion of the starting materials (Table 1).
Products are obtained according to the rules for aromatic electrophilic substitution. Iodina-
tion of compounds 1b,h,i resulted in addition to the iodarenes 2b,h,i, alternative isomers in
minor quantities. In Table 1 the yields of pure, isolated major products are shown.
For complete conversion of the substrates 1a–i to the corresponding iodoarenes we use 0.5
equivalents of TIG (or double the amount of ‘active iodine’). In the case of the iodination of
compounds 1j–l, one equivalent of TIG per equivalent of the substrate was used.
A representative iodination procedure is as follows: 1.6 g (2.5 mmol) TIG was dissolved in 30
ml 90% concd sulfuric acid at room temperature with stirring. Substrates 1a–i (5 mmol) or 1j–l
(2.5 mmol) were added in one portion to the well-stirred solution at 0°C. The mixture was then
poured into ice-cold water. The products 2c,d,f,j–l were removed by filtration and the products
2a,b,e,g–i were extracted by CHCl3. The solvent was removed in vacuo and the products were
purified by recrystallization from a suitable solvent (Table 1) and identified by comparison of
their melting points and spectroscopic data (IR, NMR) with authentic samples.
The yields, mild experimental conditions, and availability of the reagent are attractive features
of this method. The reaction can be successfully applied to other arenes and heterocycles. Work
is in progress to optimize results, to expand further the scope and applications of this iodination
reagent.
Acknowledgements
We thank Russian Foundation for Fundamental Researches (grant N 00-03-32812a) for the
financial support of this work.
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