Easy, inexpensive and effective oxidative iodination of deactivated arenes in sulfuric acid

Article abstract of DOI:10.1016/j.tet.2004.07.095

Two 'model' deactivated arenes, benzoic acid and nitrobenzene, were effectively monoiodinated within 1 h at 25-30 °C, with strongly electrophilic I⁺ reagents, prior prepared from diiodine and various oxidants (CrO₃, KMnO₄, active MnO₂, HIO ₃, NaIO₃, or NaIO₄) in 90% (v/v) concd sulfuric acid (ca. 75 mol% H₂SO₄). Next, an I₂/ NaIO₃/90% (v/v) concd H₂SO₄ exemplary system was used to effectively mono- or diiodinate a number of deactivated arenes. All former papers dealing with the direct iodination of deactivated arenes are briefly reviewed.

Full text of DOI:10.1016/j.tet.2004.07.095

Tetrahedron 60 (2004) 9113–9119
Easy, inexpensive and effective oxidative iodination of deactivated
arenes in sulfuric acid
*
Lukasz Kraszkiewicz, Maciej Sosnowski and Lech Skulski
Chair and Laboratory of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street,
02-097 Warsaw, Poland
Received 2 April 2004; revised 5 July 2004; accepted 28 July 2004
Available online 28 August 2004
Abstract—Two ‘model’ deactivated arenes, benzoic acid and nitrobenzene, were effectively monoiodinated within 1 h at 25–30 8C, with
strongly electrophilic IC reagents, prior prepared from diiodine and various oxidants (CrO3, KMnO4, active MnO2, HIO3, NaIO3, or NaIO4)
in 90% (v/v) concd sulfuric acid (ca. 75 mol% H2SO4). Next, an I2/NaIO3/90% (v/v) concd H2SO4 exemplary system was used to effectively
mono- or diiodinate a number of deactivated arenes. All former papers dealing with the direct iodination of deactivated arenes are briefly
reviewed.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
which the iodinating agent is believed to be AgIC2 )
monoiodinated e.g. nitrobenzene in 55% yield at 100 8C
and within ca. 1 h. Arotsky and co-workers7 used diiodine in
20% oleum for the iodination of a range of aromatic nitro-
compounds. The iodination of nitrobenzene for 19.5 h at
room temperature gave 3-iodonitrobenzene in 52% crude
yield; at 100 8C with 3 equiv of iodinating agent, 1,3,5-
triiodobenzene was obtained in 26% crude yield, similar
reaction at 180 8C gave hexaiodobenzene in only 3% crude
yield—these were the first examples of iodo-denitration.
They also monoiodinated 1,3-dinitrobenzene in 89% crude
yield, and diiodinated 1,2-dinitrobenzene in 57% crude
yield, at 170–180 8C during 105 min, but they failed to
likewise iodinate 1,4-dinitrobenzene. Olah and co-workers8
iodinated several deactivated aromatics with N-iodosuccini-
mide (NIS) in trifluoromethanesulfonic acid (triflic acid); it
is believed that the active agent is ‘superelectrophilic’
protosolvated iodine(I) triflate, which is generated in situ.
For example, at room temperature and within 2 h,
3-iodonitrobenzene was formed from nitrobenzene in 86%
yield. Kobayashi and co-workers9 reacted various aromatics
with diiodine in the presence of silver triflate; it gave e.g.
3-iodonitrobenzene in 45% yield based on the silver salt,
when an excess of nitrobenzene was reacted at 150 8C for
1.5 h. Chambers and co-workers10 passed F2/N2 mixtures
through the systems containing diiodine and various
deactivated arenes suspended in concd H2SO4 mixed with
various inert co-solvents, at room temperature. In this way,
e.g. nitrobenzene afforded 3-iodonitrobenzene in 58–82%
crude yields, while 1,3- and 1,4-dinitrobenzenes were
unaffected; the details of the said process are still uncertain.
Chaikovski, Filimonov and co-workers11–13 reported on the
Aromatic iodides are widely used in organic synthesis;
hence many different synthetic methods (direct and
indirect), or their improvements, have been reported for
their effective preparation.1 Moreover, they are able to form
a large variety of stable aromatic iodine(III or V)
compounds, which have found increasing applications in
modern organic synthesis.2 Our two latest reviews3,4 relate
and explain a variety of aromatic iodination methods
suitable for both activated and deactivated aromatics,
devised in our laboratory since 1990, as well as our novel
methods for preparing several classes of aromatic hyper-
valent iodine compounds, easily attainable from aromatic
iodides.
There is a large number of synthetic methods for the direct
iodination of activated aromatics, but those suitable for the
deactivated ones are less numerous. Initially, diiodine in hot
50–65% oleum, in which the electrophile is probably IC2 ,
has been used to polyiodinate strongly deactivated mol-
ecules, but it is difficult to use such systems for partial
iodination under controlled conditions.1 Masson5 remarked
that IC3 in concentrated sulfuric acid would monoiodinate
nitrobenzene and triiodinate chlorobenzene, but his obser-
vations were not exploited. Barker and Waters6 showed that
diiodine and silver sulfate in ca. 90% concd sulfuric acid (in
Keywords: Iodoarenes; Deactivated arenes; Iodine; Direct oxidative
iodination; Oxidation.
* Corresponding author. Fax: C48-22-5720643;
e-mail: lskulski@farm.amwaw.edu.pl
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.07.095

9114
L. Kraszkiewicz et al. / Tetrahedron 60 (2004) 9113–9119
Scheme 1.
Scheme 2.
effective iodination of numerous deactivated arenes with
some very active IC species. The superelectrophilic
iodinating reagent (reagent ‘IC’) was primarily prepared11
in the reaction of iodine(I) chloride with silver sulfate in
90% (v/v) concd H2SO4; mononitroarenes were easily
iodinated at 0–20 8C within 15–150 min, while dinitro-
arenes required heating to 100–170 8C and longer reaction
times. Along with the iodination, a side chlorination process
also took place to a certain extent. Later, the same Russian
chemists12 effectively iodinated various deactivated arenes,
also in 90% (v/v) concd H2SO4, with a new powerful
reagent, 2,4,6,8-tetraiodo-2,4,6,8-tetraazabicyclo[3.3.0]-
octane-3,7-dione (2,4,6,8-tetraiodoglycoluril, TIG) at 0 8C
and within 30–90 min, to obtain 40–82% yields of the
purified mono- or diiodinated products. Finally,13 they
monoiodinated only nitrobenzene (in 79% yield) with NIS
in 90% (v/v) concd H2SO4, at room temperature for 20 min.
It is known,8,14 that N-iodoimides can be a useful source of a
positive iodine, IC, when their reactions proceed in
strongly polar and/or acidic media. Lulinski et al.15
monoiodinated several deactivated arenes, however not
nitrobenzene, with sodium periodate used alone as the
iodinating reagent. They failed to isolate the expected (and
still hypothetical) periodyl intermediates, ArIO3. After
completing the reactions, carried out in the NaIO4/AcOH/
Ac2O/concd H2SO4 system, they were quenched with aq
Na2SO3 solutions to give the expected iodoarenes in
45–78% yields.
generate in the iodinating mixtures some strongly electro-
philic I3C intermediates to afford the effective iodination
of some halobenzenes and deactivated arenes, the
appropriate combinations of the reactants were used (see
Scheme 1).† The reactions took place in warm iodinating
mixtures containing iodine(III) sulfate or more reactive
iodine(III) hydrogensulfate.3 The cooled reaction mixtures
were quenched with excess aq Na2SO3 solutions to destroy
unreacted diiodine and any oxidized species (Scheme 1).
After simple workups (see experimental sections in our
former papers),3,16 the purified iodoarenes were obtained in
18–95% yields. On the other hand, our oxidative iodinations
of benzene, some halobenzenes and activated arenes were
the most effective by generating in anhydrous solvent
mixtures, AcOH/Ac2O/concd H2SO4, some less electro-
philic IC intermediates. The appropriate combinations of
the reactants were used (see Scheme 2).18 The reactions
took place in warm iodinating mixtures containing iodine(I)
sulfate or more reactive iodine(I) hydrogensulfate3 (Scheme
2). The reactions were quenched with excess aq Na2SO3
solutions. After simple workups, the purified iodoarenes
were obtained in 22–92% yields.
Taking into account all the aforesaid literature reports, we
have tried to achieve the effective oxidative iodination of
deactivated arenes, including nitrobenzene, with some
strongly electrophilic IC intermediates, simply generated
from diiodine and various oxidants according to Scheme 2,
but in 90% (v/v) concd H2SO4. In our opinion, water present
there in a deficit, ca. 25 mol% H2O, acts as a stronger base,
considerably increasing the general polarity of so prepared
Previously, we reported (see Ref. 3, pp 1332–1345) on
the oxidative iodination of a number of deactivated
arenes, including nitrobenzene, always in anhydrous
solvent mixtures, AcOH/Ac2O/concd H2SO4 (a catalyst
and reagent; other inorganic acids were less effective), by
using the following oxidants for this purpose: CrO3,
KMnO4, active MnO2, NaIO3, NaIO4, and quite recently a
urea-hydrogen peroxide adduct (UHP).16 In order to
† See the following review in which such stable, though strongly
hygroscopic, compounds as I2(SO4)3, I(OSO3H)3, ArISO4, and
ArI(OSO3H)2 are discussed and referred to the literature: Kasumov, T.
M.; Koz’min, A. S.; Zefirov, N. S. Usp. Khim. 1997, 66, 936–952; Russ.
Chem. Rev. 1997, 66, 843–857.

L. Kraszkiewicz et al. / Tetrahedron 60 (2004) 9113–9119
9115
iodinating systems: H2O (a base)CH2SO4 (in excess)/
(H3O)C(HSO4)K. This favors the full ionization of the
iodinating intermediates, IOSO3H, to form more reactive
solvated species, IC and HSOK4 . We have expected that
such iodinating solutions would react as the super-
electrophilic iodinating reagents, IC, capable to iodinate
various deactivated arenes. Our expectations have indeed
been fulfilled to a great extent (vide infra).
oxidants, as well as for the volumes of 90% (v/v) concd
H2SO4, used by us in each of the preliminary iodination
reactions. Next, using a ‘direct’ method of aromatic
iodination, either benzoic acid or nitrobenzene (10 mmol;
0% excess) was added to the appropriate iodinating
solution, and the stirring was continued for 1 h at 25–
30 8C. The final reaction mixtures were poured into ice-
water, the crude products were collected by filtration,
washed with cold water, air-dried in the dark, and
recrystallized from appropriate organic solvents (Table 1).
These experiments confirmed our former expectations (vide
supra). We extended the said ‘direct’ iodination method
onto a number of deactivated arenes; for more details see the
experimental section, and the yields given in Table 2 (in
brackets).
2. Results and discussion
At first, we carried out the preliminary oxidative iodination
reactions as follows: finely powdered diiodine was
suspended in 90% (v/v) concd H2SO4, followed by an
oxidant added portionwise with stirring and keeping the
temperature below 30 8C; altogether, seven various inor-
ganic oxidants (Table 1) were checked out by us
experimentally. The stirring was continued for 30 min at
25–30 8C to afford dark brown solutions having very strong
iodinating properties—which remained virtually
unchanged, even after their storing for several days in the
dark at room temperature. We have found that for the most
effective monoiodination of benzoic acid (a ‘model’
moderately deactivated arene), the IC intermediates gener-
ated in the previously prepared iodinating solution should be
used in ca. 10% excess, whereas for the most effective
monoiodination of nitrobenzene (a ‘model’ strongly deac-
tivated arene) they should be used in ca. 100% excess; see
Table 1 for the definite amounts of diiodine and particular
Furthermore we selected, just for example, only one of the
above iodinating systems, viz. I2/NaIO3/90% (v/v) concd
H2SO4 (Table 1), to effectively mono- or diiodinate a
number of more or less deactivated arenes (Table 2).
However, we have established experimentally that more
uniform crude products were obtained from mildly
deactivated arenes, forming readily the hardly separable
mixtures of mono- and diiodinated products, when an
‘inverse’ method of aromatic iodination was applied; see
Section 4.2.6. in the experimental section. Next, this method
was consequently used for all substrates shown in Table 2.
In this case, the appropriate iodinating solutions were very
slowly added dropwise to the stirred suspensions of
iodinated arenes in given volumes of 90% (v/v) concd
H2SO4. After completing the reactions within 1 h, mostly at
25–30 8C, the reaction mixtures were poured into ice-water,
and the precipitated monoiodinated products were worked
up as above. When some arenes were purposely diiodinated
(Table 2), we used only half of their amounts, i.e. 5 mmol,
with respect to those used for their monoiodination, i.e.
10 mmol, and the diiodination reaction times were pro-
longed to 2 h. Generally, all the iodinated arenes, taken in
strictly stoichiometric amounts (0% excess), were always
reacted with the iodinating solutions used in the excesses:
10, 50, or 100%. For more details see the Section 4.
Table 1. Monoiodination of benzoic acid or nitrobenzene: reaction
conditions and final yields of pure products, using the ‘direct’ method of
aromatic iodination
90% concd
H2SO4 (mL)
Diiodine
(g; mmol)
Oxidant (g; mmol)
Yielda (%)
(a) Oxidative iodination of PhCOOH (1.22 g; 10 mmol; 0% excess) to give
pure 3-iodobenzoic acid, mp 187–188 8C (from CCl4)b; lit.12 mp 185–
186 8C (from 50% aq i-PrOH)
37.5
37.5
37.5
1.40; 5.5
1.40; 5.5
1.40; 5.5
CrO3: 0.37; 3.7
KMnO4: 0.35; 2.2
MnO2 (85%): 0.56;
5.5
78
80
68
It is possible to put forward some plausible reaction paths
for the oxidative iodination of deactivated arenes with the
applied I2/NaIO3/90% (v/v) concd H2SO4 liquid system, as
well as to derive the resulting stoichiometries (Scheme 3).
For the other iodinating systems shown in Table 1, a similar
reasoning is applicable; see Ref. 3, pp 1332–1345.
37.5
1.40; 5.5
MnO2 (90%): 0.53;
5.5
85
30.0
30.0
32.0
1.12; 4.4
1.12; 4.4
1.20; 4.7
HIO3: 0.39; 2.2
NaIO3: 0.44; 2.2
NaIO4: 0.34; 1.6
80
80
80
(b) Oxidative iodination of PhNO2 (1.23 g; 10 mmol; 0% excess) to give
pure 3-iodonitrobenzene, mp 37–38 8C (from petroleum ether); lit.13 mp
35–36 8C (from EtOH)
In Scheme 3 we suggest that the apparently less reactive
I2SO4 intermediates (in our opinion, 2IC and SO42- are there
more tightly bound together that IC and HSO4K in iodine(I)
hydrogensulfate)3 would react with excess H2SO4 to give
the more reactive IOSO3H intermediates, which are fully
ionized in very strongly polar iodinating solutions. This is
why all the iodinating solutions applied in this work do
represent, in fact, the superelectrophilic iodinating reagents,
IC, capable to iodinate various deactivated arenes, inclu-
ding nitrobenzene, under relatively mild conditions, in good
yields, and within short times; see our results shown in
Tables 1 and 2, as well as the reaction conditions reported in
the experimental section.
68.0
68.0
68.0
2.54; 10.0
2.54; 10.0
2.54; 10.0
CrO3: 0.67; 6.7
KMnO4: 0.63; 4.0
MnO2 (85%): 1.0;
10.0
MnO2 (90%): 0.96;
10.0
HIO3: 0.70; 4.0
NaIO3: 0.79; 4.0
NaIO4: 0.61; 2.8
77
61
69
68.0
2.54; 10.0
76
55.0
55.0
58.0
2.03; 8.0
2.03; 8.0
2.18; 8.6
75
85
70
a
The given yields were optimized.
b
From our repeated crystallization experiments with crude 3-IC6H4-
COOH we have established that CCl4 was a most effective and selective
solvent as compared with 50% aq i-PrOH12 or CHCl3; the respective
crystallization losses were as follows: 17, 25, and 22%, and the product
recrystallized once from CCl4 showed a higher purity (mp, TLC).

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L. Kraszkiewicz et al. / Tetrahedron 60 (2004) 9113–9119
Table 2. Final yields and melting points (uncorrected) of pure monoiodinated or diiodinated products, with using the I2/NaIO3/90% (v/v) concd H2SO4
iodinating systems. These results were obtained by the ‘inverse’ method of aromatic iodination. For comparison, also the yields obtained by the ‘direct’
iodination method are given below (in brackets), while the corresponding melting points were practically the same
Substrate
Product
Yielda (%)
Mp (8C)/Sb
Lit. mp (8C)
(a) Oxidative monoiodination of some deactivated arenas
c
C6H5NO2
3-IC6H4NO2
83 (85)
74
76
37–38/P
55–56/E
97–99/E
93–96/E
108–110/E
187–188/C
215–216/B
265–266/E
208–210/E
242–243/E
50–51/P
35–3613
54–5611a
9720
4-CH3C6H4NO2
2-CH3OC6H4NO2
4-CH3OC6H4NO2
4-IC6H4NO2
C6H5COOH
3-I-4-CH3C6H3NO2
5-I-2-CH3OC6H3NO2
3-I-4-CH3OC6H3NO2
3,4-I2C6H3NO2
84
9720
56 (58)
78 (80)
82 (83)
46 (46)
77e
109–11111b
185–18612
216–21720
258–25920
210–21220
233–23420
50–5217
95–9720
186.520
d
3-IC6H4COOH
4-ClC6H4COOH
4-IC6H4COOH
4-CH3C6H4COOH
4-CH3OC6H4COOH
C6H5COOCH3
4-Cl-3-IC6H3COOH
3,4-I2C6H3COOH
3-I-4-CH3C6H3COOH
3-I-4-CH3OC6H3COOH
3-IC6H4COOCH3
3-I-4-CH3OC6H3COOCH3
3-IC6H4CONH2
3-IC6H4SO2NH2
3-IC6H4CHO
4-Cl-3-IC6H3CHO
1,4-I2C6H4
80e
76 (78)
67
74 (74)
77 (79)
57 (56)
73 (73)
50e
4-CH3OC6H4COOCH3
d
C6H5CONH2
97–98/E
185–187/E
151–152/W
53–54/E
114–116/E
125–126/E
d
C6H5SO2NH2
152–15321
54–5612
11720
C6H5CHOd
4-ClC6H4CHO
C6H5I
128–12912
(b) Oxidative diiodination of some deactivated arenes
115–11611b
133–13520
303–30422
289–29020
334–33523
255–25620
152–15320
122–12324
127–12811a
d
4-CH3C6H4NO2
4-CH3OC6H4NO2
4-ClC6H4COOHd
4-IC6H4COOHd
3,5-I2K4-CH3C6H2NO2
3,5-I2-4-CH3OC6H2NO2
4-Cl-3,5-I2C6H2COOH
3,4,5-I3C6H2COOH
3,5-I2K4-CH3C6H2COOH
3,5-I2-4-CH3OC6H2COOH
3-IC6H4COC6H4I-30
3-IC6H4SO2C6H4I-30
77 (77)
78 (78)
73 (74)
54f (57)
68 (71)
66 (66)
33e
111–113/E
130–132/E
288–290/E
300–302/E
330–332/D
253–255/E
151–153/A
122–123/E
124–126/E
d
4-CH3C6H4COOHd
4-CH3OC6H4COOHd
C6H5COC6H5
d
C6H5SO2C6H5
C6H5COCOC6H5
61 (61)
54
3-IC6H4COCOC6H4I-30
a
The given yields were optimized. Satisfactory microanalyses obtained for the purified products: IG0.3%; their purities and homogeneities were checked by
TLC and 1H NMR spectra (not shown here).19
b
Solvent (S) used for crystallization: A—Me2CO; B—aq AcOH; C—CCl4; D—extracted with boiling EtOH and hot-filtered; E—EtOH; P—petroleum
ether, bp 35–60 8C; W—water.
c
Nitrobenzene was monoiodinated with the previously prepared iodinating solution containing the IC intermediates in ca. 100% excess.
The respective deactivated arenes were iodinated with the previously prepared iodinating solutions containing the IC intermediates in ca. 50% excess.
Except of nitrobenzene, the remaining ones were iodinated with the previously prepared iodinating solutions containing the IC intermediates in ca. 10%
excess.
d
e
f
The respective iodination reactions were carried out at 0–5 8C, whereas the remaining ones were carried out at 25–30 8C.
When we increased the preparative scale 10-fold, the same purified product was obtained in 55% yield, mp 302–303 8C. It can be used as the substrate for
preparing X-ray contrasts.
Scheme 3.
3. Conclusions
excluded the hazardous uses of F2/N2 gaseous mixtures,
fuming sulfuric acid (oleum), or toxic iodine(I) chloride.
Organic solvents are used only for purification of the crude
iodinated products. The strongly acidic wastes left after
some of the iodination reactions, i.e. after those with using
HIO3, NaIO3 or NaIO4 as the oxidants, can be neutralized,
diluted with water, and disposed of without problem—
hence, such iodination reactions are environmentally
benign,17 and in our opinion can be safely scaled up.
The good yields, mild and easy experimental conditions,
and low prices of the commercial inorganic reagents used
for preparing the fairly stable iodinating solutions are
attractive features of this novel oxidative iodination method.
In our work, we excluded the use of costly N-iodoimides,
silver salts, and triflic acid, formerly applied (vide supra) for
the effective iodination of deactivated arenes. We also

L. Kraszkiewicz et al. / Tetrahedron 60 (2004) 9113–9119
9117
4. Experimental
from ethanol (15 mL) to give pure 3-iodobenzamide in 74%
yield; 1.83 g.
4.1. General
Quite similarly, also benzenesulfonamide, benzaldehyde,
and 4-iodonitrobenzene (10 mmol, 0% excess) were mono-
iodinated. After recrystallizations from appropriate
solvents, the respective yields are given in Table 2 (in
brackets).
The structures of the purified mono- or diiodinated products
(their purities and homogeneities were prior checked with
TLC), all reported in the literature, were supported by their
melting points (uncorrected) compared with the literature
data (Tables 1 and 2). The structures were also supported by
correct elemental analyses (%I) and 1H NMR solution
spectra (not shown here) compared with the respective
spectra of authentic samples.19 Elemental analyses were
carried out at the Institute of Organic Chemistry, The Polish
4.2.4. ‘Direct’ monoiodination of nitrobenzene; cf.
Table 1. Nitrobenzene (1.23 g, 10 mmol; 0% excess) was
added to the iodinating solution containing the IC
intermediates in ca. 100% excess, and the stirring was
continued for 1 h at 25–30 8C. The final reaction mixture
was poured, with stirring, into ice-water (300 g). The
following workup was the same as above; see Section 4.2.2.
The crude solid product was recrystallized from petroleum
ether, bp 35–60 8C (30 mL) to give pure 3-iodonitrobenzene
in 85% yield; 2.12 g.
1
Academy of Sciences, Warsaw. H NMR spectra were run
at the Department of Physical Chemistry, Medical
University of Warsaw. The commercial reagents and
solvents (Aldrich) were used without further purification.
Molecular iodine should be finely powdered in order to
facilitate its dissolution in the reaction mixtures.
4.2. General procedures, with using the I2/NaIO3/90%
(v/v) concd H2SO4 system
4.2.5. ‘Direct’ diiodination of anisic acid. Anisic acid
(0.76 g, 5 mmol, 0% excess) was added to the iodinating
solution containing the IC intermediates in ca. 50% excess,
and the stirring was continued for 2 h at 25–30 8C. The final
reaction mixture was poured, with stirring, into ice-water
(300 g). The following workup was the same as above; see
Section 4.2.2. The crude solid product was recrystallized
from ethanol (16 mL) to give pure 3,5-diiodoanisic acid in
66% yield; 1.34 g.
4.2.1. Preparations of three various iodinating solutions.
Definite amounts of finely powdered diiodine and next
NaIO3 were suspended in given volumes of 90% (v/v) concd
H2SO4 (Table 1). The mixtures were stirred for 30 min at
25–30 8C to give the dark brown iodinating solutions,
containing either ca. 11 mmol (10% excess) of the IC
intermediates [used for the iodination of benzoic acid and
several substrates shown in Table 2] or ca. 20 mmol (100%
excess) of the IC intermediates [used only for the
monoiodination of nitrobenzene, Tables 1 and 2]. For the
mono- or diiodination of the remaining substrates (Table 2),
the iodinating solution containing ca. 15 mmol (50%
excess) of the IC intermediates was prepared, as above,
from diiodine (1.52 g, 6.0 mmol) and NaIO3 (0.60 g,
3.0 mmol) suspended in 90% (v/v) concd H2SO4 (41 mL).
Quite similarly, also 4-nitrotoluene, 4-nitroanisole,
4-chlorobenzoic acid, 4-iodobenzoic acid, 4-toluic acid, and
diphenyl sulfone (5 mmol, 0% excess) were diiodinated.
After recrystallizations from appropriate solvents, the
respective yields are given in Table 2 (in brackets).
4.2.6. ‘Inverse’ monoiodination of benzoic acid. Benzoic
acid (1.22 g, 10 mmol, 0% excess) was suspended in 90%
(v/v) concd H2SO4 (20 mL) at 25–30 8C. While keeping the
same temperature, we slowly added dropwise, with stirring
and within 45 min, the iodinating solution containing the IC
intermediates in ca. 10% excess, and the stirring was
continued at 25–30 8C for a further 15 min. The final
reaction mixture was poured, with stirring, into ice-water
(300 g). The following workup was the same as above; see
Section 4.2.2. The crude solid product was recrystallized
from CCl4 (60 mL) to give pure 3-iodobenzoic acid in 78%
yield; 1.94 g.
4.2.2. ‘Direct’ monoiodination of benzoic acid; cf.
Table 1. Benzoic acid (1.22 g, 10 mmol, 0% excess) was
added to the iodinating solution containing the IC
intermediates in ca. 10% excess, and the stirring was
continued for 1 h at 25–30 8C. The final reaction mixture
was poured, with stirring, into ice-water (300 g). The crude
solid product was collected by filtration, washed with cold
water until the filtrates were neutral, air-dried in the dark,
and recrystallized from CCl4 (60 mL) to give pure
3-iodobenzoic acid in 80% yield; 1.98 g.
Quite similarly, also 4-nitrotoluene, 2- and 4-nitroanisole,
4-chlorobenzoic acid, 4-iodobenzoic acid, methyl benzoate,
methyl anisate, and 4-chlorobenzaldehyde (10 mmol, 0%
excess) were monoiodinated. After recrystallizations from
appropriate solvents, the respective yields are given in
Table 2 (without brackets).
Quite similarly, also 4-chlorobenzoic acid, 4-iodobenzoic
acid, methyl benzoate, and 4-chlorobenzaldehyde
(10 mmol, 0% excess) were monoiodinated. After
recrystallizations from appropriate solvents, the respective
yields are given in Table 2 (in brackets).
4.2.3. ‘Direct’ monoiodination of benzamide. Benzamide
(1.21 g, 10 mmol; 0% excess) was added to the iodinating
solution containing the IC intermediates in ca. 50% excess,
and the stirring was continued for 1 h at 25–30 8C. The final
reaction mixture was poured, with stirring, into ice-water
(300 g). The following workup was the same as above; see
Section 4.2.2. The crude solid product was recrystallized
Note. 4-Toluic acid, anisic acid, and iodobenzene (10 mmol,
0% excess) were similarly monoiodinated, but their
iodination reactions were carried out at 0–5 8C to give
more uniform crude products as compared with those
obtained at 25–30 8C (TLC).
Some mildly deactivated arenes, viz. 4-nitrotoluene, 2- and

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L. Kraszkiewicz et al. / Tetrahedron 60 (2004) 9113–9119
4-nitroanisole, 4-toluic acid, anisic acid, and its methyl
ester, and iodobenzene were effectively monoiodinated only
by the ‘inverse’ method (Table 2). When the same substrates
were monoiodinated by the ‘direct’ method, then the
corresponding crude products were heavily contaminated
by undesirable diiodinated side products (TLC); though
their repeated recrystallizations gave the same pure
monoiodinated products (mp, %I), but the inavoidable
crystallization losses lowered the yields by ca. 20–50%.
out at 0–5 8C to give a fairly uniform crude product, which
was recrystallized from acetone to give pure 3,30-diiodo-
benzophenone in only 33% yield; 0.72 g. At 25–30 8C, the
final crude product was notably contaminated with hardly
separable isomeric admixtures, and with a trace of a
triiodinated benzophenone (TLC, %I).
4.2.10. ‘Inverse’ diiodination of 4-nitrotoluene. 4-nitro-
toluene (0.68 g, 5 mmol, 0% excess) was suspended in 90%
(v/v) concd H2SO4 (10 mL) at 25–30 8C. While keeping the
same temperature, the iodinating solution containing the IC
intermediates in ca. 50% excess was slowly added dropwise,
with stirring and within 45 min. The stirring was continued
at 25–30 8C for a further 75 min. The final reaction mixture
was poured, with stirring, into ice-water (300 g). The
following workup was the same as above; see Section 4.2.2.
The crude solid product was recrystallized from ethanol
(27 mL) to give pure 2,6-diiodo-4-nitrotoluene in 77%
yield; 1.50 g.
4.2.7. ‘Inverse’ monoiodination of benzamide. Benza-
mide (1.21 g, 10 mmol, 0% excess) was suspended in 90%
(v/v) concd H2SO4 (20 mL) at 25–30 8C. While keeping the
same temperature, we slowly added dropwise, with stirring
and within 45 min, the iodinating solution containing the IC
intermediates in ca. 50% excess, and the stirring was
continued at 25–30 8C for a further 15 min. The final
reaction mixture was poured, with stirring, into ice-water
(300 g). The following workup was the same as above; see
Section 4.2.2. The crude solid product was recrystallized
from ethanol (15 mL) to give pure 3-iodobenzamide in 74%
yield; 1.83 g.
Quite similarly, also 4-nitroanisole, 4-chlorobenzoic acid,
4-iodobenzoic acid, 4-toluic acid, anisic acid, and diphenyl
sulfone (5 mmol, 0% excess) were diiodinated. After
recrystallizations from appropriate solvents, the respective
yields are given in Table 2 (without brackets).
Quite similarly, also 4-iodonitrobenzene, benzenesulfona-
mide, and benzaldehyde (10 mmol, 0% excess) were
monoiodinated. After recrystallizations from appropriate
solvents, the respective yields are given in Table 2 (without
brackets).
These results were partly presented at the XLVIth Annual
Meeting of the Polish Chemical Society, Lublin, 15–18
September, 2003.
4.2.8. ‘Inverse’ monoiodination of nitrobenzene. The best
result was attained as follows: nitrobenzene (1.23 g,
10 mmol, 0% excess) was suspended in 90% (v/v) concd
H2SO4 (20 mL) at 25–30 8C. While keeping the same
temperature, the iodinating solution containing the IC
intermediates in ca. 100% excess was added at once, in
one portion, and the stirring was continued at 25–30 8C for
1 h. The final reaction mixture was poured, with stirring,
into ice-water (300 g). The following workup was the same
as above; see Section 4.2.2. The crude solid product was
recrystallized from petroleum ether, bp 35–50 8C (30 mL) to
give pure 3-iodonitrobenzene in 83% yield; 2.07 g.
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ethanedione (1.05 g, 5 mmol, 0% excess) was suspended in
90% (v/v) concd H2SO4 (10 mL) at 25–30 8C. While
keeping the same temperature, the iodinating solution
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slowly added dropwise, with stirring and within 45 min.
The stirring was continued at 25–30 8C for a further 75 min.
The final reaction mixture was poured, with stirring,
into ice-water (300 g). The following workup was the
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14.7% 2,20-, and only 0.2% 4,40-diiodobenzil. It shows that on increasing
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