PAPER
Scheme 4
Oxidative Iodination of Arenes
443
The crude monoiodinated products were isolated and pu-
rified similarly to those obtained in Procedures 1 or 2 (see
the experimental section) to give pure monoiodoarenes in
18–88% yields. We failed, however to iodinate nitroben-
zene, in spite of many attempts. Using Procedure 3, mod-
ified as above, we diiodinated benzophenone (46%) and,
for comparison, also benzene (44%).
in a mixture of AcOH (6 mL) with Ac2O (3 mL). Next, an appropri-
ate arene (4.2 mmol; 5% excess) [only 2.1 mmol (5% excess), when
benzene was diiodinated] was added. The stirred mixture was
cooled to 10 °C, and varied quantities17 (see below) of concd (98%)
H2SO4 were slowly added dropwise, with vigorous stirring, while
keeping the temperature at 10–15 °C (exothermic reaction), viz.:
(a) for acetanilide and uracil, 4.00 mL (7.36 g, 75 mmol) of concd
H2SO4 was added;
Summing up, our novel easy, relatively inexpensive, and
eco-friendly iodinating Procedures 1–3 presented in this
paper gave mono- or diiodinated products from some
highly activated arylamines, benzene, halobenzenes, and
several activated and deactivated arenes in moderate or
good yields (Table 1). In our opinion, particularly inter-
esting are our iodination experiments with arylamines and
moderately deactivated arenes, except nitrobenzene. It is
also of importance that no strongly toxic wastes are left af-
ter completing the oxidative iodination reactions reported
in this paper (cf. our two former eco-friendly oxidative io-
dination methods9,10).
(b) for benzene, bromobenzene, 4-nitroanisole, anisic acid, and its
methyl ester, 4.27 mL (7.85 g, 80 mmol) of concd H2SO4 was add-
ed;
(c) for chlorobenzene and 4-nitrotoluene, 4.53 mL (8.34 g, 85
mmol) of concd H2SO4 was added;
(d) for 4-acetylaminobenzoic acid, 5.33 mL (9.81 g, 100 mmol) of
concd H2SO4 was added; and
(e) for the diiodination of benzene, 6.93 mL (12.75 g, 130 mmol) of
concd H2SO4 was added.
The reaction mixture thus obtained was stirred for 2 h at 40 °C,
cooled to r.t., and poured with stirring into ice-water (50 g) contain-
ing prior dissolved Na2SO3 (0.5 g, 3.95 mmol). The crude iodinated
products were isolated, worked up and purified as above in Proce-
dure 1 (Table 1).
The structures of the purified iodinated products (their purity and
homogeneity were also checked by TLC), all known in the litera-
ture, were supported by their melting or boiling points (uncorrected)
that were compared with the literature data (Table 1). The structures
General Procedure 3
Applicable for the Oxidative Iodination of Halobenzenes and Deac-
tivated Arenes: Finely powdered I2 (0.56 g, 2.2 mmol; 10% excess)
and 98% UHP (0.87 g, 9 mmol; 50% excess) were suspended in a
mixture of AcOH (8 mL) with Ac2O (4 mL). Next, an appropriate
arene (4 mmol; 0% excess) [only 2.0 mmol (0% excess), when ben-
zene or benzophenone were diiodinated] was added. The stirred
mixture was cooled to 10 °C, and varied quantities17 (see below) of
conc. (98%) H2SO4 were slowly added dropwise, with vigorous stir-
ring, while keeping the temperature at 10–15 °C (exothermic reac-
tion), viz.:
1
were supported by elemental analyses (%I), and H NMR solution
spectra (not shown here),20 which were compared with the spectra
of authentic samples. Elemental analyses were carried out at the In-
stitute of Organic Chemistry, The Polish Academy of Sciences,
Warsaw. 1H NMR spectra were run at the Department of Chemistry,
University of Warsaw. The commercial reagents and solvents used
(Aldrich) were purified or dried, if necessary, prior to use. Molecu-
lar iodine should be finely powdered in order to facilitate its disso-
lution in the reaction mixtures.
(a) for benzoic acid, 3.20 mL (5.88 g; 60 mmol) of concd H2SO4
was added;
Possibly Optimized Iodinating Procedures
General Procedure 1
(b) for bromobenzene, iodobenzene, methyl benzoate, and 4-toluic
acid, 4.27 mL (7.85 g; 80 mmol) of concd H2SO4 was added;
Applicable for the Oxidative Iodination of Some Aromatic Amines:
Finely powdered I2 (0.51 g, 2 mmol; 0% excess) [for the diiodina-
tion of aniline, excess I2 (0.56 g, 2.2 mmol; 10% excess) was added]
and 98% UHP (0.25 g, 2.5 mmol; 25% excess) were suspended in
neat EtOAc (6 mL). Next, an appropriate arylamine (4.4 mmol;
10% excess) [only 2 mmol (0% excess), when aniline was diiodinat-
ed] was added and the obtained mixture was stirred for 0.5 h at r.t.,
and then at 45–55 °C for 1–3 h, until the iodine coloration faded.
After cooling to r.t., the reaction mixture was poured into a stirred
solution of Na2SO3 (0.5 g, 3.95 mmol) in H2O (70 mL). The precip-
itate was collected by filtration, washed well with cold H2O, air-
dried in the dark, and recrystallized from hexane or EtOH (Table 1).
The oily or semi-solid crude products, sometimes obtained, were
extracted with CHCl3 (3 × 10 mL), the collected extracts were dried
(MgSO4) and filtered, the solvent was distilled off, and the solidi-
fied residues were recrystallized from hexane or EtOH (Table 1).
(c) for 4-nitrotoluene and for the diiodination of benzene, 4.53 mL
(8.34 g; 85 mmol) of concd H2SO4 was added;
(d) for the monoiodination of , , -trifluorotoluene and for the di-
iodination of benzophenone, 6.40 mL (11.77 g; 120 mmol) of concd
H2SO4 was added; and
(e) for nitrobenzene, 12.79 mL (23.54 g; 240 mmol) of concd H2SO4
was added, but the following reaction did not proceed.
The reaction mixture thus obtained was stirred for 2 h at 40 °C,
cooled to r.t., and poured with stirring into ice-water (50 g) contain-
ing prior dissolved Na2SO3 (2.0 g, 15.8 mmol). The crude iodinated
products were isolated, worked up and purified as above in Proce-
dure 1 (Table 1).
Note: The yields of the purified iodinated products given in Table 1
were calculated from the total amounts of those reagents (I2 or are-
nes), which were used in the reactions in strictly stoichiometric
quantities (0% excess).
General Procedure 2
Applicable for the Oxidative Iodination of Benzene, Halobenzenes
and Activated Arenes: Finely powdered I2 (0.51 g, 2 mmol; 0% ex-
cess) and 98% UHP (0.29 g, 3 mmol; 50% excess) were suspended
Synthesis 2004, No. 3, 441–445 © Thieme Stuttgart · New York