Triiodoisocyanuric acid: a new and convenient reagent for regioselective coiodination of alkenes and enolethers with oxygenated nucleophiles

Article abstract of DOI:10.1016/j.tetlet.2007.10.011

The reaction of triiodoisocyanuric acid (prepared from I₂ and trichloroisocyanuric acid in 90% yield) with alkenes in the presence of oxygenated nucleophilic solvents (alcohols, AcOH and H₂O) led to the corresponding β-iodoethers, β-iodoacetates and iodohydrins, in 66-98% isolated yield. Enolethers reacted with triiodoisocyanuric acid in MeOH to produce dialkylacetals (70-83%).

Full text of DOI:10.1016/j.tetlet.2007.10.011

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Tetrahedron Letters 48 (2007) 8747–8751
Triiodoisocyanuric acid: a new and convenient reagent for
regioselective coiodination of alkenes and enolethers
with oxygenated nucleophiles
Rodrigo da S. Ribeiro, Pierre M. Esteves* and Marcio C. S. de Mattos*
ˆ
Instituto de Quı´mica, Departamento de Quı´mica Organica, Universidade Federal do Rio de Janeiro, Cx. Postal 68545,
21945-970 Rio de Janeiro, Brazil
Received 17 April 2007; revised 1 October 2007; accepted 2 October 2007
Available online 6 October 2007
Abstract—The reaction of triiodoisocyanuric acid (prepared from I2 and trichloroisocyanuric acid in 90% yield) with alkenes in the
presence of oxygenated nucleophilic solvents (alcohols, AcOH and H2O) led to the corresponding b-iodoethers, b-iodoacetates and
iodohydrins, in 66–98% isolated yield. Enolethers reacted with triiodoisocyanuric acid in MeOH to produce dialkylacetals (70–83%).
ꢀ 2007 Elsevier Ltd. All rights reserved.
The regioselective functionalization of alkenes is an
important process in organic chemistry. Among the
several methodologies, the so-called ‘cohalogenation’
(halogenation of an alkene in the presence of a nucleo-
philic solvent) provides vicinal halo-functionalized
products regioselectively, which are useful intermedi-
ates for diverse synthetic applications.1 Besides the
large applicability in organic synthesis, the recent dis-
covery of the bioactivity of naturally occurring organo-
halogen compounds has attracted the interest in such
compounds.2
N-Haloimides13 and N-halosaccharins14 are mild elec-
trophilic halogenating agents, which can be used under
neutral conditions. The halogen in those of compounds
has a greater electrophilic character than in X2 and the
representative iodination reagents are N-iodosuccin-
imide (NIS)15 and N-iodosaccharin (NISac).15c,16
Recent papers have demonstrated that trihaloisocyanu-
ric acids (Fig. 1), such as trichloroisocyanuric17 (TCCA)
and tribromoisocyanuric acids18 (TBCA), are efficient
halogenating agents, due to their capability of halenium
(‘X+’) atoms transfer to unsaturated substrates. These
trihaloisocyanuric acids are also very interesting from
the green chemistry point of view,19 as they can intro-
duce halogen atoms in organic compounds without
using toxic and corrosive X2 and also present good atom
economy.
In contrast to other halogens, the simple iodination of
an alkene is very slow and hence, the coiodination of
alkenes is only effective using alternate sources of elec-
trophilic iodine.3 Traditional methodologies for the regio-
selective 1,2-alkoxy, -acetoxy and -hydroxy iodination
of alkenes include the reaction of I2 with an alkene in
the presence of alcohols, acetic acid and water, respec-
tively, mediated by diverse heavy metal salts4 or oxidiz-
ing reagents.5 Alternative methodologies are the
reactions of alkenes with excess iodine,6 I2/clays,7 diac-
etoxyiodine(I) complexes,8 in situ generated acyl hypoio-
dite,9 IPy2BF4,10 I2/ultrasound11 or iodide/H2O212 in the
presence of the nucleophilic solvent, to name a few.
Triiodoisocyanuric acid (TICA), an analogue of TCCA
and TBCA, synthesized by Gottardi more than 35 years
ago,20 has not yet been reported as an iodination reagent
X
O
X
N
O
X
X = Cl (TCCA)
Br (TBCA)
I (TICA)
N
N
Keywords: Triiodoisocyanuric acid; Alkenes; Cohalogenation; Enol-
ethers; Iodohydrins.
O
*
Corresponding authors. Fax: +55 21 25627133 (M.C.S.M.); e-mail
addresses: pesteves@iq.ufrj.br; mmattos@iq.ufrj.br
Figure 1. The trihaloisocyanuric acids.
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.011

8748
R. S. Ribeiro et al. / Tetrahedron Letters 48 (2007) 8747–8751
1) I2 (3.3 mol equiv.), sealed tube, 180 oC, 24 h
2) distillation of ICl
Cl
N
I
O
O
O
I
N
O
I
90 %
3) 230 oC, 48 h
4) distillation of ICl
N
N
N
N
Cl
Cl
O
O
Scheme 1. Preparation of TICA.
Table 1. Coiodination of alkenes with TICA and oxygenated nucleophiles
O
OR
C
I
I
ROH
r.t.
N
N
C
C
+
C
I
O
N
I
O
Entry
1
Alkene
Product
Reaction condition
MeOH, 15 min
Yielda (%)
90
Ref. to Product
24
OMe
I
OEt
I
I
2
3
EtOH, 30 min
84
90
25
25
Oi-Pr
i-PrOH, 60 min
OH
I
4
5
6
7
8
Me2CO–H2O (2:1), 60 min
AcOH–Ac2O (1:1), 40 min
Me2CO–H2O (2:1), 20 min
MeOH, 5 min
88
73
98
89
74
25
4
OAc
I
I
26
27
28
OH
OMe
I
Oi-Pr
i-PrOH, 20 min
I
Ot-Bu
9
t-BuOH, 150 min
66
77
28
24
I
OH
10
Me2CO–H2O (2:1), 5 min
I
OAc
I
11
12
AcOH–Ac2O (1:1), 30 min
Me2CO–H2O (2:1), 10 min
79
93
4
6
OH
I

R. S. Ribeiro et al. / Tetrahedron Letters 48 (2007) 8747–8751
8749
Table 1 (continued)
Entry
Alkene
Product
Reaction condition
Yielda (%)
88
Ref. to Product
OH
I
I
+
I
OH
13
Me2CO–H2O (2:1), 10 min
26
29
Hex
Hex
Hex
Hex
(75 : 25)b
OMe
+
I
OMe
14
MeOH, 90 min
88
Hex
Hex
(80 : 20)b
a Isolated yield, based on alkene.
b Determined by HRGC–MS.
and this motivated us to use it in our studies of iodin-
ation reactions. Furthermore, TICA has also the advan-
tage of transferring 3 equiv of iodine atom to the
substrate, representing an atom economy of 75%. In
the present work, we studied the regioselective coiodi-
nation of alkenes and enolethers using TICA as the
source of I+ in the presence of oxygenated nucleophiles
(water, alcohols and acetic acid).
In this study, alkenes (cyclohexene, 1-methylcyclo-
hexene, styrene, a-methylstyrene and 1-octene) and acti-
vated alkenes that possess an enolethers moiety (butyl
vinyl ether, dihydropyran and 1-methoxycyclohexene)
were used as substrates and acetic acid, alcohols and
acetone/water system as nucleophilic solvents. The
scope of the coiodination reactions using TICA is indi-
cated by the examples listed in Tables 1 (alkenes) and
2 (enolethers).
In a previous study, Gottardi demonstrated that the
reaction between dichloroisocyanuric acid and I2 for
three days at 180–230 ꢁC produces a mixture of triio-
doisocyanuric acid and ICl, which can be separated
through evaporation of ICl under reduced pressure.20
Herein, we have prepared TICA substituting dichloro-
isocyanuric acid by the readily available and inexpensive
trichloroisocyanuric acid employing 3.3 mol equiv of I2.
The product, a brown solid, was obtained in 90% yield
after 24 h at 180 ꢁC followed by 48 h at 230 ꢁC in a
sealed tube and distillation of ICl under reduced pres-
sure (Scheme 1).21
The reactions were carried out with 2 mmol of alkene
and 0.67 mmol of TICA at room temperature (Table
1).22 Iodohydrins were rapidly obtained in good yields
using a mixture of acetone/water (2:1). The iodination
of alkenes with TICA in the presence of alcohols
(MeOH, EtOH, i-PrOH, t-BuOH) and acetic acid/acetic
anhydride resulted in the respective b-iodoethers and b-
iodoacetates, in good yields. The reactions with styrene,
a-methylstyrene and 1-methylcyclohexene were highly
regioselective, following Markovnikoff fashion (Table
1, entries 1–6 and 12) and no regioisomers were detected
Table 2. Coiodination of enolethers with TICA and oxygenated nucleophiles
O
R1O
I
I
R2OH
N
N
C
C
+
O
N
I
O
2 min / r.t.
Entry
1
Enolether
Product
R2OH
Yielda (%)
83
Ref. to Product
5c
I
MeOH
MeOH
O
O
OMe
OMe
OBu
2
3
83
70
—
31
OBu
OMe
I
MeO OMe
I
MeOH
H2O
OMe
O
I
4
69
32
a Isolated yield, based on enolether.

8750
R. S. Ribeiro et al. / Tetrahedron Letters 48 (2007) 8747–8751
12. Barluenga, J.; Marco-Arias, M.; Gonzales-Bobes, F.;
´
on the crude reaction products by the analytical proce-
dures employed (HRGC–MS, 1H NMR and 13C
NMR spectroscopy). As previously observed,23 excep-
tions were observed in the reactions with 1-octene that
produced a mixture of regioisomers in which the pri-
mary iodide predominated (Table 1, entries 13 and
14). High trans-stereoselectivity was also observed for
additions to cyclohexene and 1-methycyclohexene
(Table 1, entries 7–12).
´
Ballesteros, A.; Gonzales, J. M. Chem. Eur. J. 2004, 10,
1677.
13. Kolvani, E.; Ghorbani-Choghamarani, A.; Salehi, P.;
Shirini, F.; Zolfigol, M. A. J. Iran. Chem. Soc. 2007, 4,
126.
14. de Souza, S. P. L.; da Silva, J. F. M.; de Mattos, M. C. S.
Quim. Nova 2006, 29, 1061.
15. (a) Vankar, Y. D.; Kumaravel, G. Tetrahedron Lett. 1984,
25, 233; (b) Sniady, A. Synlett 2006, 960; (c) de Mattos, M.
C. S.; Bernini, R. B. Heterocycl. Commun. 2006, 12,
411.
16. Dolenc, D. Synlett 2000, 544; Urankar, D.; Rutar, I.;
Modec, B.; Dolenc, D. Eur. J. Org. Chem. 2005, 2349.
Enolethers (2 mmol) reacted quickly and smoothly with
TICA (0.67 mmol) at room temperature in MeOH to
produce the corresponding iodo-dialkylacetals (Table
2, entries 1–3).30 However, if the reaction was performed
with 1-methoxycyclohexene in water, the hemiacetal was
very unstable and 2-iodocyclohexanone was obtained in
69% yield (entry 4).
17. Mendonc¸a, G. F.; Magalhaes, R. M.; de Mattos, M. C. S.;
˜
Esteves, P. M. J. Braz. Chem. Soc. 2005, 16, 695;
Mendonc¸a, G. F.; Sanseverino, A. M.; de Mattos, M. C.
S. Synthesis 2003, 45; Wengert, M.; Sanseverino, A. M.; de
Mattos, M. C. S. J. Braz. Chem. Soc. 2002, 13, 700.
18. De Almeida, L. S.; Esteves, P. M.; de Mattos, M. C. S.
Synlett 2006, 1515; de Almeida, L. S.; Esteves, P. M.; de
Mattos, M. C. S. Synthesis 2006, 221; Tozetti, S. D. F.; de
Almeida, L. S.; Esteves, P. M.; de Mattos, M. C. S. J.
Braz. Chem. Soc. 2007, 18, 675; de Almeida, L. S.; Esteves,
P. M.; de Mattos, M. C. S. Synlett 2007, 1687.
In conclusion, we have presented an efficient and eco-
friendly alternative reagent for the regioselective coio-
dination of alkenes, affording good to excellent yields
of iodohydrins, b-iodoethers and b-iodoacetates under
mild conditions.
19. Sanseverino, A. M. Quim. Nova 2000, 23, 102.
20. Gottardi, W. Monatsh. Chem. 1970, 101, 655.
21. Procedure for the preparation of TICA. Iodine
(184.6 mmol, 46.85 g) and trichloroisocyanuric acid
(55.93 mmol, 13.00 g) were added to a 100 mL sealed tube
and heated in a sand bath at 180 ꢁC. After 24 h, the ICl
produced was distilled off under reduced pressure and the
sealed tube was heated again at 230 ꢁC during 48 h.
Evaporation of ICl under reduced pressure and heating
gave triiodoisocyanuric acid as a brown solid in 90% yield.
At room temperature TICA decomposes slowly with the
formation of I2. On the other hand, in the presence of light
the decomposition is very fast. However, if stored in dark
in a freezer, TICA proved to be stable for at least one year.
IR (cmÀ1): m 3211, 3053, 2884, 2830, 2780, 1700, 1665,
1459, 1372, 1145, 1061, 1051, 732, 663, 533.20
Acknowledgements
The authors thank CNPq, CAPES and FAPERJ for the
financial support. We also thank Professor Vitor Fran-
cisco Ferreira and Mrs. Sabrina Baptista Ferreira (Insti-
tuto de Quımica/UFF) for the kind donation of butyl
vinyl ether. One of the referees is also acknowledged
for useful suggestions.
´
References and notes
22. General procedure for coiodination of alkenes. To a stirred
solution of the alkene (2 mmol) in an appropriated solvent
(8 mL of acetone and 4 mL of H2O for iodohydrins, or
10 mL of alcohols or acetic acid for b-iodoethers and b-
iodoacetates), TICA (0.67 mmol) was added at room
temperature. The reaction was monitored by HRGC–MS.
After the specified time shown in Table 1 (for alkenes),
CH2Cl2 (10 mL) was added, cyanuric acid was filtered off
and the resulting solution was treated with 10% aq
NaHSO3 (50 mL). The aqueous phase was washed with
CH2Cl2 (2 · 10 mL), the organic extract was dried (anhy-
drous Na2SO4) and filtered. The solvent was evaporated
on a rotatory evaporator to give the pure product.
23. Sanseverino, A. M.; de Mattos, M. C. S. Synth. Commun.
1998, 28, 559.
1. Rodrigues, J.; Dulcere, J.-P. Synthesis 1993, 1177; Sans-
everino, A. M.; da Silva, F. M.; Jones, J., Jr.; de Mattos,
M. C. S. Quim. Nova 2001, 24, 637; da Silva, F. M.; Jones,
J., Jr.; de Mattos, M. C. S. Curr. Org. Synth. 2005, 2, 393.
2. Gribble, G. W. Acc. Chem. Res. 1998, 31, 141; Gribble, G.
W. Chemosphere 2003, 52, 289.
3. De Mattos, M. C. S.; Sanseverino, A. M. J. Chem. Res.
(S) 1994, 440.
4. Sanseverino, A. M.; de Mattos, M. C. S. J. Chem. Res.
2004, 638, and references cited therein.
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Antonioletti, R.; D’Auria, M.; De Mico, A.; Piancatelli,
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Zupan, M.; Stavber, S. Green Chem. 2005, 7, 100.
6. Sanseverino, A. M.; de Mattos, M. C. S. Synthesis 1998,
1584.
7. Villegas, R. A. S.; Santo, J. L. E., Jr.; de Mattos, M. C. S.;
de Aguiar, M. R. M. P.; Guarino, A. W. S. J. Braz. Chem.
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8. Kirschning, A.; Kunst, E.; Ries, M.; Rose, L.; Scho¨nber-
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R. S. Ribeiro et al. / Tetrahedron Letters 48 (2007) 8747–8751
8751
29. Davidson, R. I.; Kropp, P. J. J. Org. Chem. 1982, 47,
1904.
Selected spectroscopic data for 1-(2-iodo-1-methoxy-
ethoxy)butane: 1H NMR (200 MHz, CDCl3): d 0.93 (t,
3H), 1.35–1.59 (m, 4H), 3.20–3.22 (d, 2H), 3.37 (s, 3H),
3.47–3.63 (m, 2H), 4.54 (br s, 1H). 13C NMR (50 MHz,
CDCl3): d 4.9, 13.9, 19.4, 31.8, 53.5, 66.8, 102.7. MS
(70 eV): m/z 227 (M+ÀOMe), 201, 185, 171, 170, 141, 117,
61 (100%), 41.
30. General procedure for coiodination of enolethers. To a
stirred solution of the enolether (2 mmol) in MeOH
(10 mL), TICA (0.67 mmol) was added at room temper-
ature. After 2 min, CH2Cl2 (10 mL) was added, cyanuric
acid was filtered off and the solution was extracted with
CH2Cl2 (2 · 10 mL). The organic extract was dried
(anhydrous Na2SO4), filtered and the solvent was evapo-
rated on a rotatory evaporator to give the pure product.
31. D’Auria, M.; D’Onofrio, F.; Piancatelli, G.; Scettri, A.
Synth. Commun. 1982, 12, 1127.
32. Dolenc, D. Synth. Commun. 2003, 33, 2917.