Eco-friendly oxidative iodination of various arenes with sodium percarbonate as the oxidant http://www.mdpi.org

Article abstract of DOI:10.3390/10101307

Six easy laboratory procedures are presented for the oxidative iodination of various aromatics, mostly arenes, with either molecular iodine or potassium iodide (used as the sources of iodinating species, I⁺ or I ³⁺), in the presence of sodium percarbonate (SPC), a stable, cheap, easy to handle, and eco-friendly commercial oxidant.

Full text of DOI:10.3390/10101307

Molecules 2005, 10, 1307–1317
molecules
ISSN 1420-3049
http://www.mdpi.org
Eco-friendly Oxidative Iodination of Various Arenes with
†
Sodium Percarbonate as the Oxidant
Agnieszka Zielinska and Lech Skulski*
Chair and Laboratory of Organic Chemistry, Faculty of Pharmacy, Medical University, 1 Banacha
Street, 02 – 097 Warsaw, Poland.
†
Preliminary results were presented at the Eighth Electronic Conference on Synthetic Organic
Chemistry (ECSOC-8, http://www.mdpi.net/ecsoc-8), November 1-30, 2004 (paper A022)
*
To whom the correspondence should be addressed; E-mail: lechskulski@yahoo.com; Tel./Fax: +(48)
2 5720643
2
Received: 17 May 2005; in revised form: 12 July 2005 / Accepted: 13 July 2005 / Published: 31
October 2005
Abstract: Six easy laboratory procedures are presented for the oxidative iodination of
various aromatics, mostly arenes, with either molecular iodine or potassium iodide (used
+
3+
as the sources of iodinating species, I or I ), in the presence of sodium percarbonate
SPC), a stable, cheap, easy to handle, and eco-friendly commercial oxidant.
(
Keywords: Iodoarenes, arenes, iodine, sodium iodide, sodium percarbonate as oxidant
Introduction
Aromatic iodides are generally more reactive, albeit are more costly, than the respective bromides
and chlorides. There are many different methods, direct and indirect, for their synthesis [1], and they
are widely used in organic synthesis in chemical laboratories and, to a lesser extent, in industry.
Moreover, they are able to form a variety of aromatic hypervalent iodine derivatives, which have
found increasing applications in modern organic synthesis [2]. Our two latest reviews [3, 4] relate and
explain a variety of direct oxidative iodination methods, suitable for both activated and deactivated
aromatics, mostly arenes, devised in our laboratory since 1990, as well as our novel methods for
preparing several classes of aromatic hypervalent iodine compounds, easily attainable from aromatic
iodides. See also our former paper [5].

Molecules 2005, 10
1308
2 2
Three solid commercial products, viz. a urea–hydrogen peroxide adduct (UHP), H NCONH ·
H
2
O
2
, sodium perborate (SPB), NaBO
3 2 3 2
·H O or NaBO ·4H O, and sodium percarbonate (SPC), 2
Na
2
CO ·3H , may be considered as ‘dry carriers’ of the hazardous and unstable hydrogen peroxide,
3
2 2
O
are easy to handle, safe and stable at room temperature. Their ability to release oxidative species in
water and organic media has made them useful oxidants in organic synthesis [6, 7]. The oxidative
iodination reactions with using UHP [5] or SPB [7] were already reported. However, so far nobody has
used SPC as a cheap [8] and eco-friendly oxidant in the oxidative iodination reactions of various
aromatics, both activated and deactivated ones, which has been the aim of our present work (vide
infra).
Results and discussion
First we have attempted to oxidatively monoiodinate four exemplary aromatic amines (Table 1)
according to the stoichiometry shown in Scheme 1 (Procedure 1).
I
2
+ H
ArH + 2 AcOI
ArH + I + H
2
O
2
+ 2 AcOH
2 AcOI + 2 H
2 ArI + 2 AcOH
2 ArI + 2 H
2
O
2
2
2
2
O
2
2
O (a preliminary stoichiometry)
AcOEt/AcOH
6
ArH + 3 I
2
+ 2 Na
2
CO
3
· 3 H O
2 2
+ 4 AcOH
2 2
6 ArI + 4 AcONa + 2 CO + 8 H O
r.t., 0.5 h,
then 45-50 °C, 3.5 h
Scheme 1.
+
Supposedly, only some transient iodine(I) species, I i.e. AcOI, are preponderantly acting here as
weak electrophiles. Powdered diiodine was suspended in a mixture made up of ethyl acetate and
glacial acetic acid (the latter was used in a large excess to decompose in full all Na
2 3
CO , releasing
2 2
H O
). SPC (in a 14% excess) was slowly added portionwise with stirring. Next, an aromatic amine
was added, and the reaction mixture thus obtained was stirred first at room temperature for 30 min, and
next at 45−50 ºC for ca. 3.5 hours. The reactions were complete when the iodine coloration faded.
After cooling, the reaction mixtures were quenched by pouring into excess aqueous Na
2 3
SO solutions
(a reductant, used to destroy unreacted diiodine and any oxidized species). The oily or solid crude
products were typically isolated and purified (see the Experimental section for details) to give the
purified iodinated products in 67−86% yields (Table 1). When aniline was diiodinated in 85% yield,
we added only half of the amount, i.e. 3 H-Ar-H equivalents (Scheme 1), to the starting iodinating
mixture. However, N,N-dimethylaniline and 2-chloroaniline gave only some tarry products under the
above reaction conditions. Such easily oxidizable aromatic amines were however readily
monoiodinated according to the stoichiometry shown in Scheme 2 (Procedure 2).
AcOEt
6
ArH + 3 I
2
+ 2 Na
2
CO
3
· 3 H O
2 2
+ 2 AcOH
3 2
6 ArI + 2 AcONa + 2 NaHCO + 6 H O

Molecules 2005, 10
1309
r.t., 0.5 h,
then 45-50 °C, 4 h
Scheme 2.
By comparing Schemes 1 and 2 one may deduce that the reaction media in Procedure 2 were
notably less acidic, which was favorable for the successful oxidative iodination of the two aromatic
amines. With the exception of this single important difference, the remaining reaction conditions and
the reaction mechanism in Procedure 2 were nearly the same as those in Procedure 1, giving 4-iodo-
N,N-dimethylaniline and 2-chloro-4-iodoaniline in 60 and 73% (purified) yields, respectively.
However, the comparative monoiodinations of 2-bromoaniline and 2-toluidine were less effective than
those in Procedure 1 (Table 1).
Uracil, benzene, two halobenzenes, and five weakly deactivated arenes (Table 1) were effectively
oxidatively monoiodinated according to the stoichiometry shown in Scheme 3 (Procedure 3).
2 2 4
AcOH/Ac O/H SO
6
ArH + 3 I
2
+ 2 Na
2 3 2 2 2 4 2
CO · 3 H O + 4 H SO + 8 Ac O
45-50 °C, 2 h
6
4 2
ArI + 4 NaHSO + 2 CO + 16 AcOH
Scheme 3.
+
Supposedly, only some transient iodine(I) species, I , i.e. IOSO
as moderate electrophiles. As above, powdered diiodine and SPC (in a 54% excess), and next a chosen
arene were suspended in anhydrous AcOH/Ac O mixtures, then the mixtures were strongly acidified
with varied amounts [9] of conc. (98%) H SO slowly added dropwise with stirring and keeping the
temperature below 10 ºC. The reaction mixtures were next heated and stirred for 2 hours at 45−50 ºC,
where the following iodinating reactions underwent: ArH + IOSO H → ArI + H SO . The reactions
were quenched as above by pouring the final reaction mixtures into excess aqueous Na SO solutions.
3
H, are preponderantly acting there
2
2
4
3
2
4
2
3
The crude products were collected by filtration and worked up typically to give the purified iodinated
products in 40−92% yields. When benzene was diiodinated in 83% yield, only half of the amount, i.e.
3
H-Ar-H equivalents (Scheme 3), was added to the starting iodinating mixture.
Five more strongly deactivated arenes were oxidatively monoiodinated according to the
stoichiometry shown in Scheme 4 (Procedure 4).

Molecules 2005, 10
1310
I
2
+ 3 H
2
O
2
+ 6 H
2
SO
4
3 3 2 2
2 I(OSO H) + 6 H O (removed by excess Ac O added)
2
2
ArH + 2 I(OSO
3
H)
3
2 ArI(OSO
3
H)
2
+ 2 H
2
SO
4
ArH + I
2
+ 3 H
2
O
2
+ 4 H
2
SO
4
2 ArI(OSO
3
H)
2
2
+ 6 H O (a preliminary stoichiometry)
2 2 4
AcOH/Ac O/H SO
2
ArH + I
2
2 3 2 2 2 4 2
+ 2 Na CO · 3 H O + 8 H SO + 8 Ac O
3
5-40 °C, 2 h
+ 2 CO + 16 AcOH
2
3
ArI(OSO H)
2
+ 4 NaHSO
4
2
(not isolated)
Scheme 4.
The oxidative iodination reactions were carried out in anhydrous AcOH/Ac
2
O mixtures, containing
diiodine, the said arenes and SPC, and next they were strongly acidified with varied amounts [9] of
conc. (98%) H SO (a catalyst and reactant, which also decomposed in full all Na CO , with releasing
), while keeping the temperature below 10 ºC. SPC was applied here in a 53% excess in respect to
the amount demanded by the stoichiometry shown in Scheme 4. But in the said reaction mixtures some
2
4
2
3
2 2
H O
3
+
strongly electrophilic iodinating intermediates, I i.e. I(OSO
reacted with the arenes to form the assumed, soluble organic iodine(III) intermediates, ArI(OSO
10]. After completing the reactions carried out for 2 hours at 35−40 ºC, the cooled final reaction
3
H)
3
[10], were generated, which readily
3
H)
3
[
2 3
mixtures were poured into excess aqueous Na SO solutions to destroy any oxidizing and oxidized
species and unreacted diiodine; see Scheme 5.
ArI(OSO
3
H)
2
+ Na
2
SO
3
2
+ H O
4 2 4
ArI + 2 NaHSO + H SO
(not isolated)
Scheme 5.
The crude monoiodinated products were isolated and purified similarly to those obtained in
Procedures 1−3 (see the experimental section for details) to give pure monoiodinated arenes in
60−94% yields. When benzene and benzophenone were oxidatively diiodinated, we added only half of
the amount, i.e. 1 H-Ar-H equivalent (Scheme 4), to the starting reaction mixtures; the purified 1,4-
diiodobenzene was obtained in 83% yield, while pure 3,3’-diiodobenzophenone was afforded in 51%
yield (Table 1). However, nitrobenzene was likewise monoiodinated in only ca. 5% yield; cf. Ref. 5.
Anisole, two methoxynaphthalenes, and (for comparison) aniline were oxidatively monoiodinated
using potassium iodide as the source of iodine(I) transient species, IOSO
3
H. According to Merkushev
[1c], a possibility of replacement of elemental iodine, usually requiring its careful grinding before use,
by readily accessible and cheap alkali iodides, is often convenient − albeit larger quantities of the
oxidants are spent in such oxidative iodination reactions. The said four monoiodination reactions
obeyed the stoichiometry shown in Scheme 6 (Procedure 5).

Molecules 2005, 10
1311
KI + H
ArH + IOSO
ArH + KI + H
2
O
2
+ 2 H
2
SO
4
3 4 2
IOSO H + KHSO + 2 H O
3
H
ArI + H
SO
2
SO
4
O
2 2
+ H
2
4
ArI + KHSO
4
2
+ 2 H O
(a preliminary stoichiometry)
EtOH/H SO
2 4
3
ArH + 3 KI + 2 Na
2
CO
3
· 3 H
O
2 2
2
+ 7 H SO
4
40-60 ºC, 2-3 h
3
ArI + 3 KHSO
4
+ 4 NaHSO
4
+ 2 CO
2
2
+ 8 H O
Scheme 6.
Potassium iodide dissolved in a little water was added to stirred ethanol (which can be replaced by
methanol). A chosen arene and next SPC (used in ca. 54% excess) were added portionwise with
2 4
stirring. Next, a definite volume of conc. H SO was slowly added dropwise with stirring, while
keeping the temperature below 10 ºC. The reaction mixtures thus obtained were stirred and heated
under a reflux condenser for 2−3 hours at 40−60 ºC; for more details see the experimental section.
After cooling, the final reaction mixtures were poured into vigorously stirred CH
2 2 2 3
Cl /2% aq. Na SO
biphasic mixtures. The separated organic layers dried over Na SO were filtered, next the solvent was
2
4
distilled off. The solid residues were recrystallized to give pure monoiodinated products in 53−68%
yields. Recently, Iskra and co-workers [9] oxidatively iodinated several highly activated arenes with
one equivalent of KI and two equivalents of 30% aqueous hydrogen peroxide solution, in methanol in
the presence of conc. H
aqueous H
- and 4-nitrophenol, 4-cresol, and 8-hydroxyquinoline were oxidatively diiodinated in 50% (v/v)
2 4
SO − it is close to our Procedure 5, however with avoiding the use of 30%
O .
2 2
2
aqueous acetic acid, using KI as the source of iodine(I) transient species, IOAc. The stoichiometry
shown in Scheme 7 was obeyed (Procedure 6).
5
0% AcOH
3
2 3 2 2
H-Ar-H + 6 KI + 2 (2 Na CO · 3 H O ) + 14 AcOH
40-50 ºC, 1-2 h
3
I-Ar-I + 6 AcOK + 8 AcONa + 4 CO + 16 H O
2
2
Scheme 7.
A definite amount of KI, a chosen phenol, and next SPC (used in ca. 84% excess) were
subsequently slowly added to stirred 50% (v/v) aqueous acetic acid. The stirring was continued for
1−2 hours at 40−50 ºC. The cooled final reaction mixtures were poured into vigorously stirred
CH Cl /2% aq. Na SO biphasic mixtures. The separated organic layers dried over Na SO were
2
2
2
3
2
4
filtered, the solvent was distilled off, and the residues were recrystallized to give pure diiodinated
products in 59−85% yields (Table 1). For comparison, we likewise monoiodinated aniline and 4-
iodoaniline to obtain pure 4-iodo- and 2,4-diiodoaniline in 77 and 59% yields, respectively, with using
the stoichiometry shown in Scheme 7, but corrected as follows: let one inserts there 6 ArH in place of
3
H-Ar-H to obtain the respective 6 ArI equivalents of the monoiodinated products.

Molecules 2005, 10
1312
Conclusions
Summing up, our easy and widely varied iodinating Procedures 1−6 reported in this paper gave
mono- or diiodinated products from a large variety of different aromatics: highly activated arylamines
and phenols, benzene, uracil, halobenzenes, and some activated or deactivated arenes in moderate to
good yields (Table 1). The novel application of an eco-friendly, cheap [8], stable and easy to handle
oxidant, viz. sodium percarbonate (SPC), makes our iodination methods to be attractive for organic
chemists. In our opinion, the presented herein iodination reactions can be safely scaled up.
Experimental
General
The melting points of the freshly purified iodinated products are uncorrected and are compared
with the literature data (Table 1). Their homogeneities were checked by TLC, next they were
1
13
microanalyzed (% I ± 0.4), and finally their H and C NMR spectra (not shown here) were recorded
at r.t. with a Brucker Avance DMX 400 MHz spectrometer in appropriate solvents, next compared
with the same spectra of authentic samples and/or computed theoretical spectra. All the reagents and
solvents were commercial (Aldrich, Lancaster) and were used without further purification. Elemental
iodine (diiodine) should be finely powdered to facilitate its dissolution in the reaction mixtures. SPC
2 2 2 3
(Aldrich) used in our iodinating experiments contained ca. 25% H O [8] (theoretically, for 2 Na CO ·
3H
2
O
2
calc. 32.5% H ).
2 2
O
Optimized iodinating procedures, with using sodium percarbonate (SPC) as the oxidant
Procedure 1, applicable for some arylamines
Powdered diiodine (0.51 g, 2.0 mmol; 0% excess) was suspended in a mixture made of AcOEt (8
mL) and glacial AcOH (10 mL), then SPC (0.31 g, 2.3 mmol H ; 14% excess) was slowly added
2
O
2
portionwise, with stirring, within 20−30 min, next followed by an aromatic amine (4.2 mmol; 5%
excess to prevent the possible diiodination) [when aniline was diiodinated, only 2.0 mmol (0% excess)
of the aniline was added]. The stirring was continued for 30 min at r.t., next the temperature was raised
to 45−50 ºC, and the stirring was continued for a further 3.5 h under a reflux condenser. After cooling,
2 3 2 3
the reaction mixtures were slowly added to stirred aq. Na SO solutions (1 g Na SO dissolved in 70
mL water). The precipitated crude products were collected by filtration, washed well with cold water
until the filtrates were neutral, dried preliminarily by the suction, and next air-dried in the dark; they
were recrystallized from appropriate organic solvents. If the semisolid crude products could not be
efficiently isolated, they were extracted with CHCl
3
(3 x 10 mL), the combined extracts were washed
SO , filtered, the solvent was distilled off, and
with 2% aq. Na SO and water, dried over anhydr. Na
2
3
2
4
the solidified residues were recrystallized from appropriate organic solvents to give the purified
iodinated products in the yields shown in Table 1.

Molecules 2005, 10
1313
Procedure 2, applicable for easily oxidizable arylamines
Powdered diiodine (0.51 g, 2.0 mmol; 0% excess) was suspended in a mixture made of AcOEt (20
mL) and glacial AcOH (0.11 mL, 2.0 mmol), and SPC (0.31 g, 2.3 mmol H ; 14% excess) was
2
O
2
slowly added portionwise, with stirring, within 20−30 min, next followed by an aromatic amine (4.2
mmol; 5% excess to prevent the possible diiodination). The reaction mixture was stirred at r.t. for 30
min and next at 45−50 ºC for 4 h under a reflux condenser [only for the iodination of 2-toluidine: at
5
0−55 ºC for 6 h]. After cooling, it was slowly poured, with stirring, into an aq. Na
2 3
SO solution (1 g
Na SO dissolved in 70 mL water) and the crude solid product was collected by filtration. The
2
3
following workups were the same as those in Procedure 1 to give pure iodinated products in the yields
shown in Table 1.
Procedure 3, applicable for benzene and some weakly deactivated arenes
Powdered diiodine (0.51 g, 2.0 mmol; 0% excess) was suspended in a mixture made of glacial
AcOH (6 mL) and Ac
added portionwise, with stirring, within 20−30 min. The stirred mixture was slowly warmed up to
0−35 ºC, and a chosen arene (4.2 mmol; 5% excess to diminish the possible diiodination) or benzene
2.0 mmol; 0% excess – for its diiodination) were added. After cooling the reaction mixtures to 5−10
2 2 2
O (3 mL), and next SPC (0.42 g, 3.1 mmol H O ; 54% excess) was slowly
3
(
2 4
ºC, the given below varied amounts [9] of conc. (98%) H SO were slowly added dropwise with
stirring and keeping the temperature below 10 ºC:
(
(
(
a) 4.26 mL H
b) 4.80 mL H
c) 5.33 mL
2
2
SO
SO
4
4
(7.84 g; 80 mmol) for the iodination of C
6
H
H
5
6
NHAc or uracil;
6 5
, C Br or C H Cl;
(8.83 g; 90 mmol) for the iodination of C
6
6
H
5
H
2
SO
COOMe, 4-O
d) 7.50 mL H SO (13.8 g; 140 mmol) for the diiodination of PhH.
4
(9.80 g; 100 mmol) for the iodination of 4-MeC
6 4
H COOH,
4
-MeC
6
H
4
2
NC Me or 4-O NC OMe;
6
H
4
2
6 4
H
(
2
4
The reaction mixtures were stirred at 45−50 ºC for 2 h under a reflux condenser. After cooling, they
were slowly poured, with stirring, into aq. Na SO solutions (1 g Na SO dissolved in 50 mL water).
2
3
2
3
The precipitates were collected by filtration. The following workups were the same as those in
Procedure 1 to give the purified iodinated products in the yields shown in Table 1.
Procedure 4, applicable for benzene and some more strongly deactivated arenes
Powdered diiodine (0.56 g, 2.2 mmol; 10% excess) was suspended in a mixture made of glacial
2 2 2
AcOH (8 mL) and Ac O (5 mL), and next SPC (1.25 g, 9.2 mmol H O ; 53% excess) was slowly
added portionwise, with stirring, within 20−30 min. The reaction mixture was slowly warmed up to
3
0−35 ºC, and a deactivated arene (4.0 mmol; 0% excess) or benzene, or benzophenone (2.0 mmol;
% excess – for the diiodination reactions) were added. After cooling the reaction mixtures to 5−10 ºC,
0
2 4
the given below varied amounts [9] of conc. (98%) H SO were slowly added dropwise with stirring
and keeping the temperature below 10 ºC:
(
2 4
a) 3.60 mL H SO (6.60 g; 67.5 mmol) for the iodination of PhCOOH;

Molecules 2005, 10
1314
(
b) 4.80 mL
-MeC
c) 6.80 mL H
H
2
SO
COOH, 4-O
SO (12.5 g; 127 mmol) for the diiodination of PhCOPh.
4
(8.83 g; 90.0 mmol) for the iodination of PhI, PhCOOMe,
4
6
H
4
2 6 4
NC H Me, and for the diiodination of PhH;
(
2
4
Next, the reaction mixtures were stirred at 35−40 ºC for a further 2 h under a reflux condenser. After
cooling, they were slowly added to stirred aq. Na SO solutions (2 g Na SO dissolved in 50 mL
water). The precipitates were collected by filtration and further were worked up as those in Procedure
to give the purified iodinated products in the yields shown in Table 1.
2
3
2
3
1
Procedure 5, applicable for some aromatic ethers and aniline
KI (0.66 g, 4.0 mmol; 0% excess) prior dissolved in a little water (ca. 1 mL) was added with
stirring to ethanol (20 mL). An aromatic ether or aniline (4.2 mmol; 5% excess to prevent the
diiodination) and next SPC (0.84 g, 6.2 mmol H
stirring, within 20−30 min. After cooling the mixtures to 5−10 °C, conc. (98%) H
1.2 mmol) was slowly added dropwise with stirring and keeping the temperature below 10 ºC. Next,
the reaction mixtures were stirred and heated under a reflux condenser as follows:
2
O
2
; 54% excess) were slowly added portionwise with
2
SO (0.6 mL, 1.1 g;
4
1
(
(
(
a) for 2 h at 40 °C for the iodination of PhOMe;
b) for 2 h at 50−60 °C for the iodination of 1- or 2-MeOC10
c) for 3 h at 40 °C for the iodination of PhNH .
2
7
H ;
After cooling, the final reaction mixtures were slowly poured into vigorously stirred biphasic mixtures
made of CH Cl (50 mL) and 2% aq. Na SO (40 mL). The organic phases were separated, washed
with water, dried over anhydr. Na SO , filtered, and the solvent was distilled off. The crude solid
2
2
2
3
2
4
products were recrystallized from appropriate organic solvents to give the purified iodinated products
in the yields shown in Table 1.
Procedure 6, applicable for some phenols and aromatic amines
(
a) For the diiodination of four phenols, KI (1.4 g, 8.5 mmol; 6.1% excess) prior dissolved in a
little water (ca. 2 mL) was added with stirring to 50% (v/v) aq. AcOH (30 mL) containing a given
phenol (4.0 mmol; 0% excess), next followed by slow addition of SPC (2.0 g, 14.7 mmol H ; 84%
2
O
2
excess) within 20−30 min. The stirring was continued for 2 h at 40−50 °C under a reflux condenser.
After cooling, the final reaction mixtures were slowly poured into vigorously stirred biphasic mixtures
made of CH
in Procedure 5 to obtain pure diiodinated phenols in the yields given in Table 1.
b) For the monoiodination of PhNH or 4-IC NH , KI (1.3 g, 8.0 mmol; 0% excess) prior
2 2 2 3
Cl (50 mL) and 2% aq. Na SO (40 mL). The following workups were the same as those
(
2
6
H
4
2
dissolved in a little water (ca. 2 mL) was added with stirring to a solution of an aromatic amine (8.4
mmol; 5% excess to prevent the diiodination) in 50% (v/v) aq. AcOH (30 mL). SPC (2.0 g, 14.7 mmol
H
2
O
2
; 84% excess) was slowly added portionwise with stirring within 20−30 min. The stirring was
continued for 1 h at 40−50 °C under a reflux condenser. After cooling, the final reaction mixtures were
slowly poured into vigorously stirred biphasic mixtures made of CH Cl (50 mL) and 2% aq. Na SO
40 mL). The following workups were the same as those in Procedure 5 to obtain pure monoiodinated
arylamines in the yields given in Table 1.
2
2
2
3
(

Molecules 2005, 10
1315
Note. The final yields given in Table 1 for the purified iodinated products were calculated from the
amounts of those reagents (arenes, diiodine or KI) which were used in the oxidative iodination
reactions in strictly stoichiometric quantities (0% excess).
Table 1. Iodinated Pure Products Prepared.
b
Mp (°C) (S), or bp
Yield (°C/mmHg);
Substrate
Procedure
Product
a
(
%)
Lit. [12] mp (°C), or bp
°C/mmHg)
(
PhNH
PhNH
2
2
1
1
1
1
1
2
2
2
2
4-IC
6
H
4
NH
2
68
85
78
67
86
60
73
62
48
63−65 (H); 63−65
93−94 (H); 95−96
96−97 (H); 95−96
71−74 (Hp); 71−72
86−87 (H); 88
2,4-I
2,4-I
2
2
C
C
6
H
H
3
NH
NH
2
2
4
2
2
-IC
-BrC
-MeC
6
H
4
NH
2
6
3
6
H
4
NH
2
2-Br-4-IC
4-I-2-MeC
4-IC NMe
2-Cl-4-IC
2-Br-4-IC
6
H
3
NH
NH
2
6
H
4
NH
2
2
6
H
3
2
2
PhNMe
2
6
H
4
2
81−83 (E); 82
2
2
2
-ClC
-BrC
-MeC
6
H
4
NH
2
6
H
3
NH
2
60−61 (H); 62−63
70−73 (Hp); 71−72
87−88 (H); 86−88
bp 76−78/20;
6
H
4
NH
2
6
H
3
NH
2
6
H
4
NH
4-I-2-MeC
6
H
3
NH
PhH
3
PhI
40
bp 78-80/25 [5]
PhH
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
5
5
5
5
6
1,4-I
2
C
6
H
4
83
75
128−130 (L); 129
51−52 (N); 53−54
95−96 (L); 97
4
4
4
-O
-O
2
NC
6
6
H
4
Me
2-I-4-O
2
2
NC
NC
6
H
H
3
3
Me
2
NC
H
4
OMe
2-I-4-O
6
OMe
92
-MeOC
6
H
4
CO
2
Me
3-I-4-MeOC
4-IC NHCOMe
4-ClC
4-BrC
5-iodouracil
3-I-4-RC
6
H
4
CO
2
Me 85
62
93−95 (N); 95−97
183−185 (E); 184
55−56 (E); 57
PhNHCOMe
PhCl
6 4
H
6
H
4
I
80
PhBr
6
H
4
I
68
91−92 (L); 91−92
276−276.5 (E); 276−278
238−239 (W); 230
128−130 (L); 129
128−129 (L); 129
185−187 (C); 187−188
208−209 (C); 210−212
52−53 (L); 54−55
51−53 (N); 53−54
140−142 (A); 141−143 [5]
50−51 (H); 51−52
50−51 (E); 52−53 [11]
82−84 (E); 82−84 [11]
60−62 (H); 63−65
93−94 (E); 94 [13]
uracil
84
c
c
4-RC
6
H
4
CO
2
H
6
H
3
CO
2
H
92
PhH
PhI
1,4-I
1,4-I
2
2
C
C
6
H
H
4
4
83
6
94
PhCO
2
H
3-IC
3-I-4-MeC
3-IC CO
2-I-4-O NC
6
H
4
CO
2
H
93
4-MeC
6
H
4
CO
2
H
6
H
3
CO
2
H
79
PhCO
2
Me
6
H
4
2
Me
Me
I-3’
60
4
-O
PhCOPh
OMe
2
NC
6
H
4
Me
2
6
H
3
87
3-IC
6
6
H
H
4
4
COC
6
H
4
51
C
6
H
5
4-IC
OMe
64
1
-MeOC10
-MeOC10
H
7
7
4-I-1-MeOC10
1-I-2-MeOC10
H
6
68
2
H
H
6
62
PhNH
2
4-IC
6
H
4
NH
2
53
2
-O NC
2
6
H
4
OH
2,4-I
2
-6-O
2
NC
6
H
2
OH
80

Molecules 2005, 10
1316
Table 1. Cont.
-4-O NC OH
-4-CH OH
1
49−150 (E); 150−151
11]
58−59 (E); 55−58 [14]
4
4
8
-O
-CH
-hydroxyquinoline
2
NC
6
H
4
OH
6
6
6
2,6-I
2,6-I
2
2
2
6
H
2
72
83
85
[
3
C
6
H
4
OH
3 6 2
C H
5
,7-diiodo-8-
hydroxyquinoline
4-IC NH
2,4-I NH
216−217 dec. (E); ca. 214
dec.
PhNH
2
6
6
6
H
4
2
77
59
60−62 (H); 63−65
95−96 (H); 95−96
4
a
-IC
6
H
4
NH
2
2
C
6
H
3
2
Optimized yield of pure isolated product. Satisfactory microanalyses obtained for the purified
1
13
products: I% ± 0.4; their purities and homogeneities were checked by TLC and H and C
NMR solution spectra (not shown here).
b
c
S = Solvent used for recrystallization. A: acetone; C: CCl
L: EtOH−H O (4:1); N: EtOH−H O (3:2); W: H O−EtOH (5:1).
R = 4-MeCONH.
4
; E: EtOH; H: hexane; Hp: heptane;
2
2
2
References and Notes
1
. Reviews on aromatic iodination: (a) Roedig, A. In Houben-Weyl, Methoden der organischen
Chemie, 4th ed., Vol. 5/4; Mueller, E., Ed.; Thieme: Stuttgart, 1960, 517-678. (b) Merkushev, E.
B. Usp. Khim. 1984, 53, 583-594; Russ. Chem. Rev. 1984, 53, 343-353. (c) Merkushev, E. B.
Synthesis 1988, 923-937. (d) Sasson, Y. In The Chemistry of Halides, Pseudohalides and Azides,
Suppl. D1; Patai, S.; Rappoport, Z., Eds.; Wiley−Interscience: Chichester, 1995, 535-620. (e)
nd
Steel, P. G. In Rodd’s Chemistry of Carbon Compounds, 2 ed., Part 1, Vol. 3; Sainsbury, M.,
Ed.; Elsevier: Amsterdam, 1996, 178-224.
2
. The latest reviews on organic hypervalent iodine compounds: (a) Varvoglis, A. The Organic
Chemistry of Polycoordinated Iodine; VCH: Weinheim, 1992. (b) Stang, P. J.; Zhdankin, V. V.
Chem. Rev. 1996, 96, 1123-1178. (c) Varvoglis, A. Hypervalent Iodine in Organic Synthesis;
Academic Press: San Diego, 1997. (d) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523-
2
584. (e) Hypervalent Iodine Chemistry; Wirth, T., Ed.; Topics in Current Chemistry, Vol. 224;
Springer: Berlin, 2003. (f) Stang, P. J. J. Org. Chem. 2003, 68, 2997-3008. (g) Moriarty, R. M. J.
Org. Chem. 2005, 70, 2893-2903.
3
4
5
. Skulski, L. Organic Iodine(I, III, and V) Chemistry: 10 Years of Development at the Medical
University of Warsaw, Poland (1990-2000). Molecules 2000, 5, 1331-1371;
http://www.mdpi.org/molecules/papers/51201331.pdf
. Skulski, L. Novel Easy Preparations of Some Aromatic Iodine(I, III, and V) Reagents, Widely
Applied
in
Modern
Organic
Synthesis.
Molecules
2003,
8,
45-52;
http://www.mdpi.org/molecules/papers/80100045.pdf
. Lulinski, P.; Kryska, A.; Sosnowski, M.; Skulski, L. Eco-friendly Oxidative Iodination of Various
Arenes with a Urea – Hydrogen Peroxide Adduct (UHP) as the Oxidant. Synthesis 2004, 441-445.
We presented there three eco-friendly procedures for the oxidative iodination of both activated and
deactivated arenes, using UHP as the oxidant.

Molecules 2005, 10
1317
6. Reviews on the uses of a urea-hydrogen peroxide adduct (UHP) in organic synthesis: (a) Heaney,
H. Aldrichim. Acta 1993, 26, 35-45. (b) Heaney, H. In Organic Peroxygen Chemistry; Herrmann,
W. A. Ed.; Topics in Current Chemistry, Vol. 164; Springer: Berlin, 1993, 1−19.
7
. Reviews on the uses of sodium perborate (SPB) and sodium percarbonate (SPC) in organic
synthesis: (a) Muzart, J. Synthesis 1995, 1325-1347. (b) McKillop, A.; Sanderson, W. R.
Tetrahedron 1995, 51, 6145-6166. (c) McKillop, A.; Sanderson, W. R. J. Chem. Soc., Perkin
Trans. 1 2000, 471-476. SPB in the presence of a sodium tungstate catalyst was shown to be a
cheap oxidant for the iodination of aromatic amides using KI as the source of iodine(I) species;
see: Beinker, P.; Hanson, J. R.; Meindl, N.; Rodriguez Medina, I. C. J. Chem. Res. (S) 1998, 204-
2
05.
. Aldrich Advancing Science; Aldrich: Milwaukee, 2005−2006. The following prices are given
therein: (a) Sodium percarbonate (25% H ), 13.10 €/500 g. (b) Urea-hydrogen peroxide addition
8
2
O
2
compound (98%), 161.60 €/500 g. (c) Sodium perborate monohydrate, 83.60 €/500 g. (d) Sodium
perborate tetrahydrate, 26.80 €/500 g.
2 4
9. The varied amounts of conc. H SO added to the reaction mixtures (established experimentally and
given in the experimental section for each of the substrates iodinated) clearly depended on the
relative reactivities of the arenes investigated. The more deactivated the arene, the more conc.
2 4
H SO had to be added to catalyze better the oxidative iodination reaction. For more details see
Ref. 3, pp. 1334−1337.
2 4 3 3 3 4 3 2
10. Such strongly hygroscopic compounds as I (SO ) , I(OSO H) , ArISO , ArI(OSO H) are stable
under strongly acidic and anhydrous conditions. For more details see the following review:
Kasumov, T. M.; Koz’min, A. S.; Zefirov, N. S. The Chemistry of Inorganic Sulfates and
Sulfonates of Polyvalent Iodine. Usp. Khim. 1997, 66, 936-952; Russ. Chem. Rev. 1997, 66, 843-
8
57.
11. Iskra, J.; Stavber, S.; Zupan, M. Nonmetal-catalyzed Iodination of Arenes with Iodide and
Hydrogen Peroxide. Synthesis 2004, 1869-1873.
th
1
1
1
2. Dictionary of Organic Compounds, 6 ed.; Chapman & Hall: London, 1996.
3. Hodgson, H. H.; Smith, E. W. J. Chem. Soc. 1932, 503-505.
4. Bell, N. V.; Bowman, W. R.; Coe, P. F.; Turner, A. T.; Whybrow, D. Can. J. Chem. 1997, 75,
8
73-889.
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