Conversion of aryl iodides into aryliodine(III) dichlorides by an oxidative halogenation strategy using 30% aqueous hydrogen peroxide in fluorinated alcohol

Article abstract of DOI:10.3390/molecules15042857

Oxidative chlorination with HCl/H₂O₂ in 1,1,1-trifluoroethanol was used to transform aryl iodides into aryliodine(III) dihalides. In this instance 1,1,1-trifluoroethanol is not only the reaction medium, but is also an activator of hy

Full text of DOI:10.3390/molecules15042857

Molecules 2010, 15, 2857-2871; doi:10.3390/molecules15042857
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Conversion of Aryl Iodides into Aryliodine(III) Dichlorides by
an Oxidative Halogenation Strategy Using 30% Aqueous
Hydrogen Peroxide in Fluorinated Alcohol
Ajda Podgoršek and Jernej Iskra *
Department of Physical and Organic Chemistry, “Jožef Stefan” Institute, Jamova cesta 39,
1000 Ljubljana, Slovenia; E-Mail: ajda.podgorsek@ijs.si (A.P.)
* Author to whom correspondence should be addressed; E-Mail: jernej.iskra@ijs.si.
Received: 7 January 2010; in revised form: 24 February 2010 / Accepted: 19 March 2010 /
Published: 20 April 2010
Abstract: Oxidative chlorination with HCl/H2O2 in 1,1,1-trifluoroethanol was used to
transform aryl iodides into aryliodine(III) dihalides. In this instance 1,1,1-trifluoroethanol is
not only the reaction medium, but is also an activator of hydrogen peroxide for the oxidation
of hydrochloric acid to molecular chlorine. Aryliodine(III) dichlorides were formed in 72–
91% isolated yields in the reaction of aryl iodides with 30% aqueous hydrogen peroxide and
hydrochloric acid at ambient temperature. A study of the effect that substituents on the
aromatic ring have on the formation and stability of aryliodine(III) dichlorides shows that
the transformation is easier to achieve in the presence of the electron-donating groups (i.e.
methoxy), but in this case the products rapidly decompose under the reported reaction
conditions to form chlorinated arenes. The results suggest that oxidation of hydrogen
chloride with hydrogen peroxide is the initial reaction step, while direct oxidation of aryl
iodide with hydrogen peroxide is less likely to occur.
Keywords: oxidative halogenation; hydrogen peroxide; fluorinated alcohol; hypervalent
iodine halides; chlorination

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1. Introduction
With the development of the chemistry of hypervalent iodine compounds, aryliodine(III) dihalides,
like (dichloroiodo)benzene, have received growing interest in organic synthesis as mild and selective
chlorinating and oxidizing agents. Due to the fact that they are readily available and can be handled
safely, such compounds offer a practical advantage over gaseous chlorine. Moreover, they serve as
starting substrates for the synthesis of other hypervalent iodine compounds, i.e., iodosylarenes,
(diacyloxyiodo) arenes, (difluoroiodo) arenes and iodylarenes, which are themselves important
synthetic reagents [1-4]. However, the broader application of (dichloroiodo) benzene, as well as other
hypervalent iodine compounds, has been limited due to the often tedious separation of the residual
iodobenzene from the desired products. To circumvent this problem, several recyclable aryliodine (III)
dichlorides have been developed for solid-liquid or liquid-liquid organic/aqueous phase separation
[5–8]. Recently, we have reported a synthesis and characterization of several fluorous aryl and alkyl
iodine (III) dichlorides and detailed their use as recyclable chlorinating reagents for representative
types of organic molecules [9].
The most frequently encountered representative amongst the (dichloroiodo) arenes is (dichloroiodo)
benzene, that was first prepared by Willgerodt [10] in 1886 by passing chlorine through a solution of
iodobenzene in an organic solvent, usually either dichloromethane or chloroform at a low temperature;
this remains the most general method [1,9,11–13]. However, the inconvenient use of hazardous, toxic
and corrosive gaseous chlorine can be avoided by using different chlorinating agents under various
reaction conditions [1,2,13,14]. For instance, oxidative halogenation has emerged as an
environmentally more benign process via the in situ formation of molecular halogen from the
oxidation of an halide with a suitable oxidant [15]. Therefore, mono and biphasic oxidative procedures
based on generating chlorine from concentrated hydrochloric acid used either as a separate phase or
co-solvent in the presence of an oxidant have been developed [1-4,14]. Skulski and others have used
strong oxidants, such as KMnO4, activated MnO2 [16], KClO3 [17], concentrated HNO3 [16],
Na2S2O8 [18], CrO3 [19], NaClO2 and NaClO [20], usually in excess, to synthesize various
(dichloroiodo) arenes. Oxidative methods for the synthesis of (dichloroiodo) arenes have also been
extended to derivatives of hydrogen peroxide as safer, easier to handle and environmentally less harmful
oxidants, like sodium perborate (NaBO3·H2O or NaBO3·4H2O, SPB) [16,21] sodium percarbonate
(Na2CO3·1.5H2O2, SPC) [16] and urea hydrogen peroxide (NH2CONH2·H2O2, UHP) [16,22]. With an
400% of excess of NaBO3·4H2O in CH3CN or CCl4 various (dichloroiodo)arenes were prepared in
60–98% yields at room temperature [21], meanwhile a 200% excess of NaBO3·H2O was sufficient to
obtain ArICl2 in similar yields (63–99%) in an AcOH-Ac2O medium [16]. Under solvent-free
conditions using UHP at 85 °C and an excess of concentrated HCl, the preparation of ArICl2 in good to
excellent yields was achieved [22]. All of the aforementioned methods use the iodoarenes as starting
substrates and the reactions are generally performed in either AcOH or CCl4 at 0–5 °C, except in the
case of Na2S2O8 where preheating to 45–50 °C is necessary. Alternatively, procedures for a one-pot
conversion of arenes to (dichloroiodo)arenes were also reported using, in the first step, either a
combination of I2/CrO3 [23], I2/NaIO4 or NaIO3 [24] in Ac2O/AcOH/conc. H2SO4 medium, followed
by treatment with concentrated HCl.

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However, several of these methods are effective only for selected iodoarenes and especially aryl
iodine (III) dichlorides with electron-withdrawing substituents on the aromatic nucleus are usually
obtained in lower yields. The main disadvantage of the current methods lies in the use of a very strong
and environmentally harmful oxidant, usually in excess amounts, which additionally complicates the
purification of the product. Furthermore, many oxidants have to be previously activated and added
portion-wise to a vigorously stirred reaction mixture of iodoarene in an organic solvent (AcOH or
chlorinated solvent) to control the exothermic reactions and to enable the slow reaction of the Cl2
generated in situ with the substrate.
In continuation of our research on sustainable and ecologically more acceptable halogenation
protocols [25–29], we investigated the use of 30% aqueous hydrogen peroxide and hydrochloric acid
for the synthesis of various aryliodine (III) dichlorides from the corresponding aryl iodides. The use of
dilute aqueous H2O2 offers advantages over solid UHP since it is cheaper and since the only reaction
byproduct is water, the atom economy of the process is higher. In 2003, Neumann et al . reported
oxidative chlorination in a HCl-H2O2 system in 1,1,1-trifluoroethanol (CF3CH2OH, TFE), whose
activating effect enabled the use of 1.5 equivalents of HCl for the quantitative chlorination of non-
activated aromatics at room temperature [30]. With DFT calculations it was shown that TFE stabilizes
the polar transition state by acting as a charge template with charges complementary to those in the
transition state and therefore lowers its energetic barrier relative to EtOH by ~6 kcal/mol. Encouraged
by these results, we decided to apply TFE as a template catalyst for the activation of H2O2 for the
oxidative chlorination of iodoarenes at room temperature and for substitute activation by either heating
or using an acetic acid medium.
2. Results and Discussion
2.1. Synthesis of Aryl Iodine (III) Dichlorides
Iodobenzene (1a) was chosen as the initial substrate to be transformed to the corresponding
iodobenzene dichloride (1b) by a novel oxidative chlorination procedure (Table 1). Iodobenzene was
suspended in 1,1,1-trifluoroethanol into which was then added 1.0 mol equiv. of 30% aqueous H2O2
and 2.0 mol equiv. of 37% aqueous hydrochloric acid (Entry 1, Method A). The heterogeneous
mixture was then stirred at room temperature for 4 h. The solvent was removed under reduced pressure
to give 1b as a yellowish precipitate which was filtered off, washed with distilled water and air-dried
to give pure 1b in 80% yield. In the next step, the quantities of H2O2 and HCl were increased to 2.0
and 4.0 mol equiv., respectively (Method B) which enhanced the isolated yield of 1b to 89%. The
yields obtained in this oxidative procedure were then compared to the classical method, where a
solution of 1a in hexane was saturated with molecular Cl2 and stirred for 3 h at ambient temperature
(Method D). In this case, (dichloroiodo) benzene (1b) was obtained in 96% yield.
Next, the same procedure was applied to the synthesis of other aryl iodine (III) dichlorides 2b–8b
and the effect that the substituents on the aromatic ring have on the yield was studied. Application of
Method A for chlorination of aryliodides 2a and 3a with either a methyl or t-butyl group at the para
position gave lower yields of 2b and 3b, probably because of the lower solubility of 2a and 3a in TFE
(Entries 2 and 3). To obtain yields of 3b comparable to those obtained using molecular chlorine, an
excess of H2O2 and HCl had to be used (Method C). A similar effect of lowering the yield of formation

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of aryl iodine(III) dichlorides in the presence of alkyl substituents on the aromatic ring was also
observed using other oxidants, like CrO3 [19] or Na2S2O3 [18] where 2b was obtained with up to 14%
lower yield as 1b. On the contrary, reactions with SPB [21] or UHP [31] as oxidants gave 2b in
slightly higher yields (up to 5%) as 1b. 4,4’-Bis(dichloroiodo)biphenyl (4b) was isolated in 89% yield
in the reaction of 4a with 4.0 mol equiv. of H2O2 and 4.0 equiv. of H2O2 (Entry 4).
Scheme 1. Synthesis of aryliodine(III) dichlorides 1b–8b through oxidative chlorination or
directly with Cl2.
Table 1. Synthesis of Aryliodine(III) Dichlorides 1b–8b.
Entry Substrate
Method a
Time (h)
4
4
3
Yield b (%)
1b, 80
89
96
2b, 66
90
92
3b, 55
80
85
4b, 85
89
96
5b, 40
78
82
6b, 20
72
76
7b, 59
85
90
8b, 50
85
1
2
3
4
5
6
7
8
1a, R=H
A
B
D
A
B
D
A
C
D
B
C
D
A
B
D
B
C
D
B
C
D
B
C
D
2a, R=4-CH3
16
16
3
19
19
19
5
19
10
5
20
10
14
20
19
19
20
19
14
19
19
3a, R=4-C(CH3)3
4a, R=4-(4-I-C6H4)
5a, R=3-COOH
6a, R=3-NO2
7a, R=3-Cl
8a, R=4-Cl
92
Reaction conditions: Iodoarene 1a–8a (1.0 mmol), ambient temperature. aMethod A: conc.
HCl (2.0 mmol), 30% aq. H2O2 (1.0 mmol), TFE (1.0 mL); Method B: conc. HCl
(4.0 mmol), 30% aq. H2O2 (2.0 mmol), TFE (1.0 mL); Method C: conc. HCl (4.0 mmol),
30% aq. H2O2 (4.0 mmol), TFE (1.0 mL). Method D: Cl2 (excess), hexane (10 mL).
bIsolated yield.

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The presence of electron-withdrawing substituents on the aromatic nucleus led to a slower reaction
and reduced yields of (dichloroiodo)arenes. In the case of 3-iodobenzoic acid (5a) 4.0 mol equiv. of
HCl had to be used and a longer reaction time was necessary to obtain 5b in 78% yield (Entry 5).
Similarly, the reaction involving molecular chlorine was also less effective and only 82% of 5b was
isolated. With more powerful deactivating groups, like Cl and NO2, a further excess of reagents was
required (Method C) to produce 6b and 7b in 72% and 85% yield, respectively (Entry 6 and 7). No
significant difference in reactivity was observed with a chloro substituent at either the meta or para
position (Entry 8). Iodoarenes 1a–8a were also chlorinated with molecular chlorine in hexane (Method
D), which gave slightly higher yields of (dichloroiodo)arenes 1b–8b. However, the yields obtained in
HCl/H2O2/TFE are comparable with those obtained by other oxidative methods involving
stronger oxidants.
2.2. Chlorination of Activated Aryliodides with HCl/H2O2/TFE and with Molecular Chlorine
The chlorination of iodoarenes with electron-donating substituents was also studied since these
substrates have an activated aromatic ring suitable for chlorination as well as an iodine atom for
oxidation. For substrates having two or three methyl groups on the aromatic nucleus chlorination was
performed using either the oxidative procedure or with molecular chlorine (Scheme 2).
Scheme 2. Chlorination of 2,4-dimethyliodobenzene (9a).
CH3
CH3
CH3
CH3
Cl
Cl
decomposition
HClconc. / 30% aq. H2O2
TFE or
+
CH3
CH3
CH3
CH3
Cl2 / hexane
I
11
I
10
ICl2
9b
I
9a
2,4-Dimethyl-iodobenzene (9a) was treated with 2.0 mol equiv. of HCl and 1.0 mol equiv. of H2O2
in TFE and the reaction was followed by NMR. After 0.5 h only the signals corresponding to 9b were
observed, which was formed in 17% yield and it increased to 46% after 2 h as shown by its
1
characteristic signal in the H-NMR spectra at 8.07 ppm (d, J = 8 Hz) (Table 2, Entry 1 and 2). The
same sample was left for 24 hours at ambient temperature. The analysis revealed that 9b had started to
decompose into a mixture of ring chlorinated products (Entry 3). The reaction mixture was isolated,
whereupon 1H-NMR spectroscopy revealed the presence of 30% of 1-chloro-5-iodo-2,4-
dimethylbenzene (10) and 37% of 2-chloro-4-iodo-1,3-dimethylbenzene (11). Chlorinated products
were isolated by preparative TLC in a 35% yield as a mixture of 10 and 11, the structures of which
1
were determined by comparison of the H-NMR shifts with the literature data of related compounds
and confirmed by the mass peak and its isotope composition in GCMS. When an excess of reagents
were used the starting compound was completely consumed and both chlorinated products were
formed in a ratio 10:11 of 47:53 (Entry 4). As TFE is a polar solvent the decomposition of
(dichloroiodo)arene 9b to the ring-chlorinated products 10 or 11 during further stirring of the reaction
mixture was not surprising. However, an electrophilic attack by the positive chlorine species on the

Molecules 2010, 15
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aromatic nucleus cannot be excluded. In the absence of TFE, H2O2 was not able to oxidize HCl and
after 20 h the starting compound 9a was recovered. Similar results were obtained in reaction with
molecular chlorine in hexane, where reaction took place at the iodine atom to yield 9b, which was
isolated by filtration in 45% yield, but is not stable in solution and it decomposes to form a mixture of
chlorinated products.
Table 2. Chlorination of 2,4-dimethyliodobenzene (9a).
Distributionb (%)
9a : 9bc : 10 : 11
Entry Methoda
Time (h)
1
2
3
4
5
A
A
A
B
D
0.5
2
20
20
6
83 : 17 :
54 : 46 : trace : trace
/
:
/
33 :
/
/
:
:
30
47
28
:
:
:
37
53
31
/
:
19 : 22 :
a
Reaction conditions: 9a (1.0 mmol), ambient temperature. Method A: conc. HCl
(2.0 mmol), 30% aq. H2O2 (1.0 mmol), TFE (1.0 mL); Method B: conc. HCl (4.0 mmol),
30% aq. H2O2 (2.0 mmol), TFE (1.0 mL); Method C: conc. HCl (4.0 mmol), 30% aq. H2O2
b
(4.0 mmol), TFE (1.0 mL). Method D: Cl2, hexane (10 mL). Distribution of products
determined by 1H-NMR spectroscopy. c 9b was determined by its characteristic signals for
ArICl2 compounds in 1H-NMR spectra of the reaction mixture – 8.07 ppm (d, J = 8 Hz, 1H).
Furthermore, more activated 2,4,6-trimethyliodobenzene (12a) was studied (Scheme 3). Contrary to
9a, when 12a reacts with 2.0 mol equiv. of HCl and 1.0 mol equiv. of H2O2 in TFE, 12b is not
1
detected in the H-NMR spectra of the reaction mixture and a new signal was observed at 6.99 ppm
which was attributed to 1-chloro-5-iodo-2,4,6-trimethylbenzene (13) (16% and 29% yield after 0.5 h
and 2 h, respectively). When oxidative chlorination was performed for 19 h 81% of 13 was formed and
isolated in 72% yield (Scheme 3). The structure of 13 was determined by comparison with the
literature data of structurally related data and GCMS analysis (mass signal and its isotope distribution).
Very similar result was observed on chlorination of 12a with Cl2 in hexane and 12b could be isolated
only after the reaction was performed in CHCl3, as already reported [36]. On standing at room
temperature, 12b was completely converted in the product 13. We can conclude from this that 12b is
insufficiently stable to be detected by NMR and it most likely decomposes with concomitant ring
chlorination into 13.
Scheme 3. Chlorination of 2,4,6-trimethyliodobenzene (12a).

Molecules 2010, 15
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According to these results, the formation of an electrophilic substitution product in oxidative
chlorination of iodoarenes containing a strong electron-donating group, like a methoxy moiety, in
1,1,1-trifluoroethanol, is not surprising. 4-Methoxyiodobenzene (14a) is converted with 2.0 mol equiv.
of H2O2 and 1.0 equiv. of HCl in 14 h to chlorinated product 15, isolated in 83% yield, most likely via
the formation of (dichloroiodo)arene 14b as an intermediate product. Interestingly, the product 14b
was detected by 1H-NMR of the reaction mixture, where it was identified by a characteristic signal for
ArICl2 compounds, namely 8.06 ppm (d, J = 9 Hz) and 6.95 ppm (d, J = 9 Hz). However the direct
chlorination of 14a in polar TFE to give the chlorinated product 15 cannot be excluded. In contrast, in
chlorination with chlorine only iodine dichloride 14b in a 96% yield was isolated (Scheme 4).
1
Nevertheless, 14b is unstable and H-NMR analysis reveals clearly its rapid decomposition with
concomitant ring chlorination. Interestingly, when using other oxidants like SPB [21], UHP [22],
KClO3 [17] or Na2S2O3 [18] in combination with HCl, (dichloroiodo)-4-metoxybenzene (14b) is
obtained in good yields, and there is no observable chlorination at the aromatic nucleus. In some cases
CCl4 was used rather than polar solvents [18,21]. However, it must be emphasized that it is preferable
to obtain (dichlororiodo) arenes from iodoanisole and other highly activated iodoarenes by either
using biphasic conditions or the classic Willgerodt method, where ArI and molecular chlorine are both
dissolved and react in an inert solvent [18]. Alternatively, appropriate liquid phase oxidative
chlorination protocols seem to be more suitable for deactivated aryliodides, since such substrates need
to be activated by the solvent effect of TFE in order to react.
Scheme 4. Chlorination of 4-iodoanisole (14a).
2.3. Investigation of the Nature of Reactive Chlorinating Species
An investigation was then made into the transformation of aryl iodides into aryliodine(III)
dichlorides by an oxidative chlorination pathway. As already mentioned, when aryliodine dichlorides
were synthesized using a combination of an urea hydrogen peroxide complex and hydrochloric acid in
glacial acetic acid, the authors anticipated that chlorine is formed in situ [16]. In a similar reaction
under solvent-free conditions at 85 °C the same authors suggested that the composite mixtures of urea
with iodosylarenes, ArIO, and probably also admixed with iodylarenes, ArIO2 is formed [22]. After
cooling, the resultant melts were added portion-wise to excess concentrated hydrochloric acid, which
resulted in the formation of the desired (dichloroiodo)arenes. In our case, after the addition of
concentrated HCl to a suspension of aryl iodide and H2O2 in TFE a yellow color appeared indicating
the oxidation of HCl took place. The occurrence of this initial stage of reaction was confirmed by

Molecules 2010, 15
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addition of cyclooctene (16) to HCl/H2O2/TFE system where it was transformed into the corresponding
chlorohydrin 17 (Scheme 5, Table 3, entry 1). When the same chlorination was performed without
TFE, reaction mixture had to be heated to initiate the transformation (Table 3, entry 2). Therefore, we
can conclude that H2O2 is activated to the same extent either with TFE or by heating. For comparison,
reactions using UHP as an oxidant were performed. At room temperature only 5% of 17 was formed
(Entry 3), while heating to 85 °C increased conversion only to 17% (Entry 4). This result was curious
because similar reaction conditions were used in solvent-free synthesis of PhICl2 [22]. One possibility
is that UHP is activated by heating at 85 °C for 30 min prior to the reaction. When thus activated UHP
was used for oxidative chlorination of 16 reaction proceeded (Entry 5). This might indicate that small
changes in the structure of the UHP complex effects its activity. Again, by using TFE no additional
activation is necessary and oxidative chlorination of 16 with UHP and HCl occurs at room temperature
(Entry 6).
Scheme 5. Oxidative chlorination of cyclooctene (16).
Table 3. Oxidative chlorination of cyclooctene (16).
Entry Oxidant
React. cond.a
TFEc, 2 h at r.t.
2 h at 85°C
2 h at r.t.
Conv.b (%)
60
62
5
17
38
84
1
2
3
4
5
H2O2
H2O2
UHP
UHP
UHPd
UHP
2 h at 85°C
2 h at r.t.
6
TFEc, 2 h at r.t.
a
Reaction conditions: 2.0 mmol (0.164 mL) of conc. HCl was added to 1.0 mmol
(0.102 mL) of 30% aq. H2O2 or 1.0 mmol (94 mg) UHP, after quoted time 1.0 mmol (110
mg) of cyclooctene (16) was added and stirred for 2 h at room temperature. b Conversion of
1
c
d
16 by H-NMR spectroscopy. 1 mL of TFE. 1.0 mmol (94 mg) of powdered UHP was
heated for 30 min at 85 °C, after cooling 2.0 mmol (0.164 mL) of conc. HCl and 1.0 mmol
(110 mg) of 16 were added.
The above results point to the conclusion that TFE activates hydrogen peroxide for oxidation of
HCl at ambient temperature, regardless of the form of peroxide. Next, we approached the study from a
different point and investigated the possibility of oxidation of iodobenzene (1a) with hydrogen
peroxide and UHP complex as a first step of the reaction. In the solvent-free reaction synthesis of
(dichloroiodo)arenes with UHP/HCl it was proposed that the first step of transformation is oxidation of
iodoarene [22]. However, it is known that the oxidation of the iodine atom of aryliodide is difficult to

Molecules 2010, 15
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achieve and harsh reaction conditions are usually required [1]. In the reaction between 1a and 2 equiv.
of UHP at 85 °C for 30 min only the starting compound was recovered after isolation (Scheme 6, Path
A). Also, no reaction occurred when 1a was stirred with 2 equiv. of H2O2 in TFE. Nevertheless, when
concentrated HCl was added to the preheated mixture from the example A on Scheme 6, 90% of
PhICl2 was isolated (Path B). However, when HCl was replaced by acetic anhydride in combination
with acetic acid (Path C) no reaction occurred. This is further proof that PhIO is not formed, since it is
known that PhIO after treatment with AcOH produces (diacetoxyiodo)benzene [32].
Scheme 6. Oxidative transformations of iodobenzene (1a).
3. Experimental Section
All chemicals were obtained from commercial sources and used without further purification.
1
13
Column chromatography was carried out using Silica gel 60 (0.063–0.200 mm). H- and C-NMR
spectra were recorded in CDCl3 using a Varian Inova 300 MHz spectrometer operating at 300 and 76
MHz, respectively.. The chemical shifts (δ) are reported in ppm units relative to TMS as an internal
standard for 1H-NMR and CDCl3 for 13C-NMR spectra. Melting points were determined using a Büchi
535 melting point apparatus. GCMS were performed with GC - HP 6890: capilary column DB-5 MS
length 30 m, ID 0,25 mm, 0,25 μm (5% fenil-methylpolysyloxane) stacionary phase, detection: EI
(70eV).
3.1. General Reaction Procedure for the Synthesis of Aryliodine(III) Dichlorides 1b-8b with HCl H2O2
(Methods A, B and C, Table 1)
In a typical experiment aryliodide 1a–8a (1.0 mmol) was suspended in 1,1,1-trifluoroethanol
(1 mL) to which 30% aqueous H2O2 (0.102 mL, 1.0 mol equiv., Method A or 0.204 mL, 2.0 mol
equiv., Method B, or 0.408 mL, 4.0 mol equiv., Method C) and 37% aqueous hydrochloric acid (0.164
mL, 2.0 mol equiv., Method A, or 0.328 mL, 4.0 mol equiv., Methods B and C) were added. The
mixture was stirred at room temperature for 4-24 h. The progress of the reaction was followed by TLC.
At the end of the reaction 1,1,1-trifluoroethanol was removed under reduced pressure to give a

Molecules 2010, 15
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yellowish precipitate, which was filtered off and washed with 5 mL of distilled water. The product was
then air-dried, analyzed by 1H- and 13C-NMR spectroscopy and its melting point measured. The purity
of the aryliodine(III) dichlorides was determined by iodometric titration, which afforded the starting
aryl iodides as determined by 1H-NMR spectroscopy.
3.2. General Reaction Procedure for the Synthesis of Aryliodine(III) Dichlorides 1b–8b with Cl 2 in
Hexane (Method D, Table 1)
In a typical experiment aryl iodide 1a–8a (1.0 mmol) was dissolved in hexane (10 mL). The
solution was saturated with molecular chlorine and then stirred at room temperature for 3–9 h under an
atmosphere of excess chlorine. The precipitate was filtered off, air-dried and analyzed by 1H-NMR.
(Dichloroiodo)benzene (1b): Yellow solid; yields: Method A: 220 mg (80%), Method B: 245 mg
1
(89%), Method C: 264 mg (96%); mp (capillary) 118–120 °C (110–112 °C [23]); H-NMR (CDCl3)
7.44–7.51 (m, 2H, Ar-H), 7.57–7.63 (m, 1H, Ar-H), 8.17–8.21 (m, 2H, Ar-H); 13C-NMR
(CDCl3) 122.8, 131.6, 132.1, 133.8. Purity 99%.
4-Methyl(dichloroiodo)benzene (2b): Yellow solid; yields: Method A: 191 mg (66%), Method B:
1
260 mg (90%), Method D: 266 mg (92%); mp (capillary): 110–112 °C (108–118 °C [22]); H-NMR
(CDCl3) 2.46 (s, 3H, CH3), 7.26 (d, J = 8.6 Hz, 2H, Ar-H), 8.04 (d, J = 8.6 Hz, 2H, Ar-H); 13C-NMR
(CDCl3) 21.4, 121.9, 132.3, 133.8, 137.2. Purity 97%.
4-tert-Butyl(dichloroiodo)benzene (3b): Yellow solid; yields: Method A: 182 mg (55%), Method C:
1
265 mg (80%), Method D: 281 mg (85%); mp (capillary): 88–90 °C (84 °C [33]); H-NMR (CDCl3)
13
1.34 (s, 9H, C(CH3)3), 7.47 (d, J = 8.8 Hz, 2H, Ar-H), 8.08 (d, J = 8.8 Hz, 2H, Ar-H); C-NMR
(CDCl3) 31.1, 35.2, 121.8, 127.5, 128.9, 133.6. Purity 95%.
4,4’-bis(Dichloroiodo)biphenyl (4b): Yellow solid; yields: Method B: 464 mg (85%), Method C:
486 mg (89%), Method D: 524 mg (96%); mp (capillary): 153 °C (153 °C [7]). Purity 98%.
3-(Dichloroiodo)benzoic acid (5b): Yellow solid; yields: Method A: 128 mg (40%), Method B: 249
1
mg (78%), Method D: 262 mg (82%); mp (capillary): 187–190 °C (187–190 °C [7]); H-NMR
13
(CDCl3) 7.33–7.38 (m, 1H), 8.00–8.08 (m, 2H), 8.30–8.34 (m, 1H); C-NMR (CDCl3) 129.8, 131.5,
133.8, 134.4, 139.23, 142.7, 166.1. Purity 98%.
3-Nitro(dichloroiodo)benzene (6a): Yellow solid; yields: Method A: 64 mg (20%), Method B: 230 mg
(72%), Method D: 242 mg (76%); mp (capillary): 91–94 °C (90 °C [21]); 1H-NMR (CDCl3) 7.72 (dd,
J = 8.3, 8.3 Hz, 1H, Ar-H), 8.46 (ddd, J = 8.3, 2.0, 0.9 Hz, 1H, Ar-H), 8.55 (ddd, J = 8.3, 2.0, 0.9 Hz,
1H, Ar-H), 9.09 (dd, J = 2.0, 2.0 Hz, 1H, Ar-H); 13C-NMR (CDCl3) 123.2, 126.8, 129.0, 132.0, 139.0.
Purity 100%.

Molecules 2010, 15
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3-Chloro(dichloroiodo)benzene (7a): Yellow solid; yields: Method A: 183 mg (59%), Method C: 263
1
mg (85%), Method D: 279 mg (90%); mp (capillary): 95–96 °C (92–94 °C [34]); H-NMR (CDCl3)
7.42 (dd, J = 8.2, 8.2 Hz, 1H, Ar-H), 7.57 (ddd, J = 8.2, 1.9, 0.8 Hz, 1H, Ar-H), 8.10 (ddd, J = 8.2, 1.9,
0.8 Hz, 1H, Ar-H), 8.19 (dd, J = 1.9, 1.9 Hz, 1H, Ar-H); 13C-NMR (CDCl3) 124.0, 131.7, 132.1, 132.6,
133.5, 136.4. Purity 100%.
4-Chloro(dichloroiodo)benzene (8a): Yellow solid; yield; Method A: 155 mg (50%), Method C: 263
1
mg (85%), Method D: 285 mg (92%); mp (capillary): 108–110 °C (110–112 °C [23]); H-NMR (300
13
MHz; CDCl3) 7.44 (d, J = 8.9 Hz, 2H, Ar-H), 8.11 (d, J = 8.9 Hz, 2H, Ar-H); C NMR (76 MHz;
CDCl3) 121.8, 131.7, 135.1, 138.9. Purity 96%.
2,4-Dimethyl(dichloroiodo)benzene (9b): Yellow unstable solid; yields: Method D: 136 mg (45%); mp
(capillary): 94–96 °C (95–98.5 °C [23]). NMR could only be obtained for the reaction mixture and
1
signals for 9b were assigned by comparison with known analogous compounds: H-NMR (CDCl3)
2.43 (s, 3H), 2.80 (s, 3H), 7.06 (m, 1H), 7.29 (m, 1H), 8.07 (d, J = 8.2 Hz, 1H). Compound 9b
decomposes in the solution and only a mixture of two chlorinated products, 10 and 11, can be isolated
by preparative TLC (SiO2, hexane) from the reaction mixture obtained after 20 h reaction under
method A in a yield of 35% (93 mg). Products were determined by comparison of the 1H-NMR shifts
with the literature data of related compounds and confirmed by GCMS (intensity of peaks
M:M+2 = 3:1) [35].
1
1-Chloro-5-iodo-2,4-dimethylbenzene (10) H-NMR (CDCl3) 2.23 (s, 3H), 2.37 (s, 3H), 7.06 (s, 1H)
1
and 7.79 (s, 1H), and 2-Chloro-4-iodo-1,3-dimethylbenzene (11) H-NMR (CDCl3) 2.33 (s, 3H), 2.60
(s, 3H), 6.78 (d, J = 8.2 Hz, 1H), 7.60 (d, J = 8.2 Hz, 1H); GCMS (EI) 266 (M, 100), 268 (M+2, 35),
231 (10), 141 (19), 139 (58), 103 (52), 77 (42).
2,4,6-Trimethyl(dichloroiodo)benzene (12b) [36]: Yellow unstable solid; yield: Method D (in CHCl3):
63 mg (20%); mp (capillary): 67–68 °C. After standing for 24 h 12b decomposed and only one product
was formed. It was identical to the product obtained by Method A and characterized by comparison of
the NMR shifts with the literature data of related compounds and by GCMS (intensity of peaks
M:M+2 = 3:1) as 1-chloro-5-iodo-2,4,6-trimethylbenzene (13) [37]: Yield: Method A, 274 mg (72%);
1H-NMR (CDCl3) 2.28 (s, 3H), 2.39 (s, 3H), 2.62 (s, 3H), 6.99 (s, 1H). 13C-NMR (CDCl3) 20.7, 27.7,
29.7, 105.3, 127.9, 129.0, 135.8, 138.9, 140.0; GCMS (EI) 280 (M, 100), 282 (M+2, 42), 245 (13), 155
(14), 153 (44), 115 (46), 91 (25).
4-Methoxy(dichloroiodo)benzene (14b): Yellow unstable solid; yield: Method D: 293 mg (96%); mp
(capillary): 58–61 °C (75–78 °C [23]). NMR could only be obtained for the reaction mixture and
1
signals for 14b were elucidated by a comparison with known analogous compounds: H-NMR
(CDCl3) 3.87 (s, 3H), 6.94 (d, J = 9 Hz, 2H), 8.05 (d, J = 9.0 Hz, 2H). 14b decomposes in the solution
into a chlorinated product 15.

Molecules 2010, 15
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1
2-Chloro-4-iodoanisole (15) [38]: Yield; Method A: 223 mg (83%). H-NMR (CDCl3) 3.88 (s, 3H,
OCH3), 6.68 (d, J = 8.6 Hz, 1H, Ar-H), 7.51 (dd, J = 8.6, 2.2 Hz, 1H, Ar-H), 7.66 (d, J = 2.2 Hz, 1H,
Ar-H).
3.3. Oxidative chlorination of cyclooctene (16, Scheme 6)
Aqueous HCl (37 %, 0.164 mL, 2.0 mmol) and either 30% aq. H2O2 (0.204 mL, 2.0 mol) or urea
hydrogen peroxide (188 mg, 2.0 mmol) were mixed together according to the conditions listed
underneath the Table 2. Then cyclooctene (16, 110 mg, 1.0 mmol) was added and the reaction mixture
was further stirred for 6 h at ambient temperature. The reaction mixture was isolated by extraction with
CH2Cl2 and analyzed by 1H-NMR spectroscopy.
2-Chlorocyclooctanol (17) [39]: From 16 (1.0 mmol), H2O2 (2. 0 mmol), HCl (2.0 mmol) and 1,1,1-
trifluoroethanol (1 mL). The product was isolated by column chromatography (SiO2, CH2Cl2). Yield:
1
90 mg (56%). H-NMR (MHz; CDCl3) 1.30–2.30 (m, 12H), 3.87 (m, 1H), 4.10 (ddd, J = 9.3, 7.2,
2.7 Hz, 1H).
3.4. Oxidative transformations of iodobenzene (1a, Scheme 6)
Iodobenzene (1a, 204 mg, 1.0 mmol) was added to the finely powdered urea hydrogen peroxide
(188 mg, 2.0 mmol) and the mixture was stirred for 30 min at 85 °C. After cooling to room
temperature the procedure quoted in Scheme 6 followed; Path A: Isolation of the reaction mixture by
extraction with CH2Cl2, Path B: Addition of 37% aq. HCl (1.64 mL, 20.0 mmol) and stirring at room
temperature for 4 h. The yellow precipitate was then washed with water. Path C: Addition of Ac2O
(1.89 mL, 20.0 mmol) and AcOH (0.114 mL, 2.0 mmol), stirring at room temperature for 4 h. In all
cases the isolated reaction mixture was analyzed by 1H-NMR spectroscopy and the product determined
by comparison of chemical shifts with literature.
4. Conclusions
Reported herein is a simple method for the synthesis of aryliodine(III) dichlorides from various aryl
iodides under mild reaction conditions, in which a combination of aqueous hydrochloric acid and
aqueous hydrogen peroxide in 1,1,1-trifluoroethanol was used. The use of H2O2 as a ‘‘green’’ oxidant
produces water as the only by-product, which not only increases the overall atom economy but also
facilitates subsequent isolation of the product. Furthermore, 1,1,1-trifluoroethanol as a reaction
medium and a template catalyst activates H2O2 for the oxidation of HCl and enables reactions to occur
at room temperature. It has also been established that, in this system, chlorine is formed initially that
then reacts with aryl iodide to give aryliodine(III) dichloride in yields comparable with those obtained
by other oxidative methods using either stronger oxidants or molecular chlorine. This, together with
the already mentioned advantages makes it a good alternative to existing methods. From a study into
what effect the substituents on the aromatic ring have on yield we can conclude that the presence of
electron-withdrawing groups result in a slower reaction and lower yields of (dichloroiodo)arenes. On

Molecules 2010, 15
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the contrary, in the case of chlorination of iodoarenes with electron-donating substituents (i.e.,
methoxy), ring chlorinated products were formed together with (dichloroiodo)arenes, most likely from
their decomposition in polar 1,1,1-trifluoroethanol.
Acknowledgements
The Ministry of Higher Education, Science and Technology of the Republic Slovenia, the Young
Researcher Program (A.P.) of the Republic Slovenia have supported this research. The authors are
grateful to staff of the National NMR Centre at the National Institute of Chemistry in Ljubljana and
Ester Heath and Silva Perko at the Department of Environmental Sciences of “Jožef Stefan” Institute
for GCMS measurements.
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Sample Availability: Samples of the compounds 1b-8b are available from the authors.
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