A direct and convenient synthesis of periodoarenes using molecular iodine

Article abstract of DOI:10.1055/s-0029-1217072

Molecular iodine exhaustively iodinates aromatic hydrocarbons in the presence of potassium peroxodisulfate, concentrated sulfuric acid, and trifluoroacetic acid to give the periodinated aromatic compounds. Benzene and other moderately activated and deactivated arenes are readily converted into the corresponding periodinated derivatives in good to high yields.

Full text of DOI:10.1055/s-0029-1217072

SHORT PAPER
27
A Direct and Convenient Synthesis of Periodoarenes Using Molecular Iodine
S
ynthesis of Periodoar
d
ene
s
U
sing
M
.
olecula
r
Iod
A
ine taur Rahman, Fumiaki Shito, Tsugio Kitamura*
Department of Chemistry and Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi, Saga 840-8502,
Japan
Fax +81(952)288550; E-mail: kitamura@cc.saga-u.ac.jp
Received 5 August 2009; revised 3 September 2009
system is convenient and powerful even in the case of de-
Abstract: Molecular iodine exhaustively iodinates aromatic hydro-
activated arenes. Thus, we extended this method to perio-
carbons in the presence of potassium peroxodisulfate, concentrated
dination of aromatic compounds.
sulfuric acid, and trifluoroacetic acid to give the periodinated aro-
matic compounds. Benzene and other moderately activated and de-
Our present periodination method is quite different from
activated arenes are readily converted into the corresponding
the previously reported methods.8–10 The present periodi-
periodinated derivatives in good to high yields.
nation method is effective for the arenes bearing moder-
ately deactivating groups as well as moderately activating
groups. Moreover, the reaction conditions are milder than
Key words: arenes, molecular iodine, periodoarenes, iodination,
potassium persulfate
those of the reported periodination methods.
We have studied the direct periodination reaction to apply
Poly- and periodinated aromatic compounds are tradition-
it to a wide variety of aromatic compounds. Table 1 shows
ally prepared by time-consuming multi-step procedures
the results of direct periodination of different aromatic
from the corresponding amines involving acetylation, ni-
compounds with molecular iodine in the presence of
tration, diazotization, and reduction.1 Another method for
K2S2O8 and sulfuric acid in trifluoroacetic acid (TFA) and
the preparation of polyiodinated aromatic compounds di-
1,2-dichloroethane (DCE). The outline of the periodina-
rectly from commercially available iodo compounds us-
tion is illustrated in Scheme 1. Aromatic compounds bear-
ing sulfuric acid is based on the migration of iodine atoms
ing weakly deactivating groups such as chloro, bromo,
present in the nucleus of the aromatic iodo compounds
fluoro, and iodo groups gave periodination products in
(Jacobsen reaction).2 The scope of this method is very
good to high yields. Moderately activated aromatic com-
limited. The preparation of periodinated aromatic com-
pounds such as toluene, o-, m- and p-xylenes also gave pe-
pounds through mercuration followed by iododemercura-
riodination products in good to high yields. This method
tion with potassium triiodide has been reported.3–5
is not applicable for highly electron-rich aromatic com-
Molecular iodine is not commonly used for iodination of
pounds as well as for aromatic compounds bearing strong-
aromatic compounds due to its low electrophilic property.
ly electron-withdrawing groups.
To carry out the direct iodination reaction using molecular
iodine requires an appropriate oxidizing agent to convert
R
molecular iodine into a powerful electrophile.6,7 Prepara-
R
I
I
I
I
tion of periodinated aromatic compounds using molecular
iodine in the presence of fuming sulfuric acid as an oxidiz-
ing agent was reported.8,9 Recently, Mattern10 reported the
preparation of periodinated aromatic compounds using
molecular iodine in the presence of H5IO6 in sulfuric acid.
Although such reported methods for the preparation of pe-
riodinated aromatic compounds are excellent and power-
ful in most cases, these methods have drawbacks such as
the need for longer reaction time and strong acidic or se-
vere reaction conditions to carry out the reaction. There-
fore, it is desirable to seek a convenient and milder
method for the preparation of periodinated aromatic com-
pounds.
K2S2O8, H2SO4
TFA, DCE
+
I2
I
Scheme 1
During the periodination of different aromatic compounds
an excess of iodine was used to obtain the completely io-
dinated products. Benzene, iodobenzene, and 1,4-diiodo-
benzene were easily converted into hexaiodobenzene (1)
in high yields (Table 1, entries 1–3). The moderately acti-
vated arenes such as toluene, o- and p-iodotoluenes, p-xy-
lene, ethylbenzene, and butylbenzene were smoothly
periodinated to give the products 2, 5, 6, and 7 in high
yields (entries 4–6, 9, 11), except for ethylbenzene (entry
10). Ethylbenzene gave 36% of periodinated product 6.
o-Xylene and m-xylene readily underwent periodination
at low temperature, but the yields were relatively lower
than those of the periodination products of toluene, p-xy-
lene and butylbenzene (entries 7 and 8). The moderately
deactivated aromatic compounds such as chlorobenzene,
In the iodination reaction of arenes with molecular iodine,
we have found that the reaction of arenes with molecular
iodine occurs very easily in the presence of K2S2O8 as an
oxidant and give iodoarenes in good yields.11 This reagent
SYNTHESIS 2010, No. 1, pp 0027–0029
x
x
.
x
x
.2
0
0
9
Advanced online publication: 22.10.2009
DOI: 10.1055/s-0029-1217072; Art ID: F15409SS
© Georg Thieme Verlag Stuttgart · New York

28
M. A. Rahman et al.
SHORT PAPER
Table 1 Direct Periodination of Arenesa
Entry
1
Arene
Temp (°C)
60
Time (h)
48
Product
Yield (%)b
89
benzene
hexaiodobenzene (1)
2
iodobenzene
60
48
1
87
3
p-diiodobenzene
toluene
60
48
1
90
4
30
36
pentaiodotoluene (2)
79
5
o-iodotoluene
p-iodotoluene
o-xylene
r.t.
r.t.
0–5
0–5
r.t.
30
36
2
82
6
36
2
80
7
48
1,2,3,4-tetraiodo-5,6-dimethylbenzene (3)
1,2,3,5-tetraiodo-4,6-dimethylbenzene (4)
1,2,4,5-tetraiodo-3,6-dimethylbenzene (5)
ethylpentaiodobenzene (6)
butylpentaiodobenzene (7)
chloropentaiodobenzene (8)
8
53
8
m-xylene
48
31
9
p-xylene
14
70
10
11
12
13
14
15
16
17
18
19
20
21
22
ethylbenzene
78
36
butylbenzene
r.t.
60
48
65
chlorobenzene
1-chloro-4-iodobenzene
o-dichlorobenzene
m-dichlorobenzene
p-dichlorobenzene
bromobenzene
1-bromo-4-iodobenzene
o-dibromobenzene
p-dibromobenzene
fluorobenzene
1-fluoro-4-iodobenzene
48
86
60
24
88
60
48
1,2-dichloro-3,4,5,6-tetraiodobenzene (9)
1,3-dichloro-2,4,5,6-tetraiodobenzene (10)
1,4-dichloro-2,3,5,6-tetraiodobenzene (11)
bromopentaiodobenzene (12)
12
60
60
48
87
60
36
54
60
18
97
60
36
87
60
18
1,2-dibromo-3,4,5,6-tetraiodobenzene (13)
1,4-dibromo-2,3,5,6-tetraiodobenzene (14)
fluoropentaiodobenzene (15)
15
84
60
08
86
45
60
71
60
18
51
a Reaction conditions: arene (1.0 mmol), I2 (5.0 mmol), K2S2O8 (5.0 mmol), H2SO4 (1.0 mmol), TFA (4.0 mL), and DCE (10 mL).
b Isolated yields.
1-chloro-4-iodobenzene, o-dichlorobenzene, m-dichloro- All solvents and starting materials were used during the research
works as received without further purification, unless otherwise in-
benzene, p-dichlorobenzene, bromobenzene, 1-bromo-4-
iodobenzene, o-dibromobenzene, p-dibromobenzene,
fluorobenzene, and 4-fluroiodobenzene were easily con-
verted into the corresponding periodination products 8–15
dicated. 1H NMR and 13C NMR were recorded on a Jeol JNM-AL-
300FT-NMR spectrometer in DMSO-d6 solution (TMS as an inter-
nal standard). Melting points of the pure compounds were recorded
on a Yanaco melting point apparatus and are uncorrected. Elemen-
tal analysis was performed by the Service Center of the Elemental
Analysis of Organic Compounds, Faculty of Science, Kyushu Uni-
versity, Japan.
(entries 12–22) in good to high yields.
In summary, we have demonstrated a direct and conve-
nient preparation of periodoarenes using molecular io-
dine. This method covers many aromatic substrates
including from moderately activated alkylbenzenes to de-
activated halobenzenes. Moreover, the periodination reac-
Direct Periodination of Aromatic Compounds; General Proce-
dure
Required molar amount of arene (1.0 mmol), molecular I2 (1.27 g,
tion proceeds under the mildest conditions among the 5.0 mmol), and K2S2O8 (1.35 g, 5.0 mmol) were dissolved in DCE
(10 mL). The reaction mixture was stirred in an ice bath for about 5
procedures reported so far. Therefore, the present period-
min, and then TFA (4 mL) and aq concd H2SO4 (0.18 mL, 1 mmol)
ination method is a suitable process for the synthesis of
were gradually added with constant stirring. The mixture was
polyfunctionalized materials.
stirred for about 10 min in the ice bath and stirred further for 15 min
at r.t. The temperature of the mixture was then gradually increased
to the required temperature and stirred until the completion of the
Synthesis 2010, No. 1, 27–29 © Thieme Stuttgart · New York

SHORT PAPER
Synthesis of Periodoarenes Using Molecular Iodine
29
reaction. The mixture was cooled and poured into ice-cold H2O
(40–50 mL). The precipitated solid was collected by suction,
washed with H2O (30–40 mL), and CH2Cl2 (20–25 mL) or CH2Cl2–
hexane (1:1, 20–30 mL) to remove the unreacted I2 (Table 1).
1,2-Dichloro-3,4,5,6-tetraiodobenzene (9)
Yellow crystalline solid; mp 275–308 °C.
13C NMR (75 MHz, DMSO-d6): d = 133.74, 123.53, 115.04.
Anal. Calcd for C6Cl2I4: C, 11.08. Found: C, 11.49.
Hexaiodobenzene (1)
Yellow crystalline solid; mp 355–375 °C (dec.) [Lit.10 mp 380–
419 °C (dec.)].
1,3-Dichloro-2,4,5,6-tetraiodobenzene (10)
Yellow crystalline solid; mp 258–262 °C.
13C NMR (75 MHz, DMSO-d6): d = 142.74, 126.96, 111.18,
101.71.
13C NMR (75 MHz, DMSO-d6): d = 121.65.
Pentaiodotoluene (2)
Anal. Calcd for C6Cl2I4: C, 11.08. Found: C, 11.34.
Yellow crystalline solid; mp 289–304 °C (dec.) [Lit.10 mp 310–
313 °C (dec.)].
1,4-Dichloro-2,3,5,6-tetraiodobenzene (11)12
Pale yellow crystalline solid; mp 248–275 °C.
13C NMR (75 MHz, DMSO-d6): d = 139.27, 114.91.
1H NMR (300 MHz, DMSO-d6): d = 3.29 (s, 3 H, CH3).
13C NMR (75 MHz, DMSO-d6): d = 147.06, 125.39, 119.52,
112.53, 47.05.
Bromopentaiodobenzene (12)
Yellow crystalline solid; mp 316–325 °C (dec.) [Lit.4 mp 340 °C
(dec.)].
1,2,3,4-Tetraiodo-5,6-dimethylbenzene (3)
Pale yellow crystalline solid; mp 254–262 °C (Lit.5 mp 263–
264 °C).
1H NMR (300 MHz, DMSO-d6): d = 2.70 (s, 6 H, CH3).
13C NMR (75 MHz, DMSO-d6): d = 134.29, 124.26, 121.34,
114.99.
13C NMR (75 MHz, DMSO-d6): d = 141.24, 121.69, 116.94, 33.78.
1,2-Dibromo-3,4,5,6-tetraiodobenzene (13)
Yellow crystalline solid; mp 260–272 °C.
13C NMR (75 MHz, DMSO-d6): d = 129.28, 123.67, 117.58.
1,2,3,5-Tetraiodo-4,6-dimethylbenzene (4)
Pale yellow crystalline solid; mp 253–255 °C (dec.) (Lit.5 mp 252–
254 °C).
Anal. Calcd for C6Br2I4: C, 9.75. Found: C, 10.15.
1H NMR (300 MHz, DMSO-d6): d = 3.08 (s, 6 H, CH3).
13C NMR (75 MHz, DMSO-d6): d = 145.77, 126.93, 110.38,
104.42, 42.61.
1,4-Dibromo-2,3,5,6-tetraiodobenzene (14)12
Pale yellow crystalline solid; mp 271–285 °C (dec.).
13C NMR (75 MHz, DMSO-d6): d = 133.86, 117.55.
1,2,4,5-Tetraiodo-3,6-dimethylbenzene (5)
Light purple crystalline solid; mp 237–243 °C (Lit.5 mp 245–
248 °C).
1H NMR (300 MHz, DMSO-d6): d = 3.23 (s, 6 H, CH3).
13C NMR (75 MHz, DMSO-d6): d = 145.29, 116.81, 46.02.
Fluoropentaiodobenzene (15)
Yellow crystalline solid; mp 261–263 °C (Lit.4 mp 262–264 °C).
13C NMR (75 MHz, DMSO-d6): d = 158.78 (J = 239.9 Hz), 123.89,
117.58 (J = 3.8 Hz), 96.41 (J = 30.9 Hz).
Ethylpentaiodobenzene (6)
Yellow crystalline solid; mp 262–266 °C.
References
(1) Houben–Weyl Methoden der Organischen Chemie, Vol. V/
4; Muller, E., Ed.; Thieme Verlag: Stuttgart, 1960, 639–647.
(2) Suzuki, H.; Goto, R. Bull. Chem. Soc. Jpn. 1963, 36, 389.
(3) Conley, N. R.; Lagowski, J. J. Synth. React. Inorg., Met-Org.
Chem. 2003, 33, 1741.
1H NMR (300 MHz, DMSO-d6): d = 3.67 (q, J = 7.5 Hz, 2 H, CH2),
1.02 (t, J = 7.5 Hz, 3 H, CH3).
13C NMR (75 MHz, DMSO-d6): d = 151.58, 126.38, 120.20,
111.80, 50.86, 11.89.
(4) Deacon, G. B.; Farquharson, G. J. Aust. J. Chem. 1977, 30,
1701.
Anal. Calcd for C8H5I5: C, 13.06; H, 0.69. Found: C, 13.50; H, 0.78.
(5) Yagupol’skii, L. M.; Popov, V. I.; Kondratenko, N. V. Zh.
Org. Khim. 1976, 12, 916; Chem. Abstr. 1976, 85, 446115.
(6) Butler, A. R. J. Chem. Ed. 1971, 48, 508.
(7) Durand, J. F.; Mancet, M. Bull. Soc. Chim. Fr. 1935, 2, 665.
(8) Arotsky, J.; Butler, R.; Darby, A. C. J. Chem. Soc. C 1970,
1480.
(9) Suzuki, H. Bull. Chem. Soc. Jpn. 1971, 44, 2871.
(10) Mattern, D. L. J. Org. Chem. 1984, 49, 3051.
(11) Hossain, Md. D.; Oyamada, J.; Kitamura, T. Synthesis 2008,
690.
Butylpentaiodobenzene (7)
Pale yellow crystalline solid; mp 157–159 °C.
1H NMR (300 MHz, DMSO-d6): d = 3.75 (t, J = 7.5 Hz, 2 H, CH2),
1.60–1.39 (m, 4 H, CH2CH2), 0.98 (t, J = 7.2 Hz, 3 H, CH3).
13C NMR (75 MHz, DMSO-d6): d = 152.02, 125.12, 117.65,
110.34, 58.89, 29.36, 22.56, 13.71.
Anal. Calcd for C10H9I5: C, 15.73; H, 1.19. Found: C, 15.89; H,
1.13.
(12) Reddy, C. M.; Kirchner, M. T.; Gundakaram, R. C.;
Padmanabhan, K. A.; Desiraju, G. R. Chem. Eur. J. 2006,
12, 2222.
Chloropentaiodobenzene (8)
Yellow crystalline solid; mp 323–331 °C (dec.) (Lit.10 mp 356–
358 °C).
13C NMR (75 MHz, DMSO-d6): d = 140.02, 124.83, 120.90,
111.70.
Synthesis 2010, No. 1, 27–29 © Thieme Stuttgart · New York