Hydroxyl radical promotes the direct iodination of aromatic compounds with iodine in water: A combined experimental and theoretical study

Article abstract of DOI:10.1002/adsc.201100765

It is still a challenge to develop green, simple and effective approaches to prepare aromatic iodides. Herein, a novel and green strategy for the direct mono-iodination of aromatic compounds starting with molecular iodine has been developed. The strategy uses ceria nanocrystals to decompose hydrogen peroxide, giving hydroxyl radicals which are demonstrated experimentally and computationally to be crucial to promote the iodinations. Copyright

Full text of DOI:10.1002/adsc.201100765

FULL PAPERS
DOI: 10.1002/adsc.201100765
Hydroxyl Radical Promotes the Direct Iodination of Aromatic
Compounds with Iodine in Water: A Combined Experimental and
Theoretical Study
Peng Zhang,a Dongqing Sun,a Mingwei Wen,a Jingkui Yang,a Kebin Zhou,a,*
and Zhixiang Wanga,*
a
College of Chemistry and Chemical Engineering Graduate University of Chinese Academy of Sciences, Beijing 100049,
Peopleꢀs Republic of China
Fax : (+86)-10-8825-6092; e-mail: kbzhou@gucas.ac.cn or zxwang@gucas.ac.cn
Received: October 2, 2011; Revised: November 16, 2011; Published online: February 23, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100765.
Abstract: It is still a challenge to develop green, gen peroxide, giving hydroxyl radicals which are
simple and effective approaches to prepare aromatic demonstrated experimentally and computationally to
iodides. Herein, a novel and green strategy for the be crucial to promote the iodinations.
direct mono-iodination of aromatic compounds start-
ing with molecular iodine has been developed. The Keywords: aromatic compounds; ceria nanocrystals;
strategy uses ceria nanocrystals to decompose hydro- hydrogen peroxide; hydroxyl radicals; iodination
Introduction
because water is the only side product. Direct iodina-
tion using H2O2 as oxidant has been extensively inves-
Aromatic iodides, generally more reactive than bro- tigated.[7] For example, Narender et al.[8] studied the
mides and chlorides, are important reagents to make reaction of aromatic compounds with NH4I and 30%
carbon-carbon or carbon-heteroatom bonds,[1] and H2O2 in acetic acid at room temperature without any
find wide applications in organic synthesis.[2] Howev- catalyst. They found that more activated compounds,
er, because of the weaker electrophilicity of iodine as that is, anilines, substituted anilines, phenols, substi-
compared to chlorine and bromine, the iodination of tuted phenols and methoxynaphthalenes could be
aromatic compounds starting with molecular iodine is converted directly into the corresponding iodinated
much more difficult.[3] To carry out a direct iodina- products, while deactivated and weakly activated
tion, iodine is required to be oxidized to the more re- compounds failed to undergo iodination. Methoxy-
active intermediate such as an I+-type species.[4] Vari- benzene derivatives, despite their marked activity in
ous oxidizing agents have been applied for this pur- electrophilic reactions, were not iodinated. The sub-
pose, including nitric acid, sulfuric acid, iodic acid, strate structure-dependent reactivity has also been re-
sulfur trioxide and heteropolyacid.[5] However, several ported by Skulski et al.[9] To accelerate the reaction
disadvantages prevent wide applications of these for deactivated and weakly activated arenes, strong
methods: the oxidizing agents are often hazardous acids and homogeneous transition metal salt catalysts
and expensive; the reactions were carried out in or- were often employed. For example, Firouzabadi et
ganic solvents and produced toxic wastes; and homo- al.[10] developed a novel catalytic method using
geneous transition metal catalysts were often re- CeCl3·7H2O as an efficient catalyst for the iodination
quired, which cause inconvenience for product isola- of arenes by NaI to their monosubstituted halides
tion and catalyst recycle. These limitations have en- using 35% H2O2 in neat water as the terminal oxi-
couraged chemists to develop green, simple and effec- dant. With this protocol, the iodinations of reactive
tive approaches to prepare aromatic iodides, yet this arenes such as anilines, and less reactive arenes, such
is still a challenge.[6]
as benzene, bromobenzene and chlorobenzene were
From a perspective of “green” chemistry, hydrogen found proceeded well with high regioselectivity at the
peroxide (H2O2) could be an ideal oxidant candidate para position.
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Hydroxyl Radical Promotes the Direct Iodination of Aromatic Compounds with Iodine in Water
On the other hand, the hydroxyl radical (COH), a
non-specific and extraordinarily strong oxidant, can
react with molecules at near diffusion-controlled
rates. Hydroxyl radicals can be generated in situ via
catalytic decomposition of H2O2, enhancing the oxi-
dizing ability of the original H2O2 system. Although
the hydroxyl radical may be an ideal green oxidant to
activate iodine, a protocol for the iodination of aro-
matic compounds that uses hydroxyl radicals as oxi-
dant has not been established.
Scheme 1. Hydroxyl radicals facilitate the direct iodination
of aromatic compounds with iodine in water.
It has been reported that cerium oxide (CeO2) tals/H2O2 system to activate molecular iodine
nanoparticles, like the Fenton reagent (a mixture of (Scheme 1). To our delight, we observed that aromatic
ferrous iron salts and H2O2 that can produce hydroxyl compounds can be iodinated selectively and effective-
radicals), could facilitate the decomposition of H2O2 ly.
to produce hydroxyl radicals via the following pro-
cess:[11]
Results and Discussion
Characterization of CeO2 Nanocrystals
The TEM image in Figure 1, a) shows that the CeO2
nanocrystals exhibit rod-like morphology, 100–300 nm
where Ce3+ stems from the oxygen vacancies in CeO2 in length and about 10–20 nm in diameter. Powder
nanoparticles. The ability of the CeO2 to generate the XRD analysis [Figure 1, b)] shows that CeO2 nano-
hydroxyl radical depends on the ease of the Ce3+/Ce4+ rods can be indexed to the pure fluorite cubic struc-
redox cycle.[11] In our previous study, we found that tures. These results are consistent with our data re-
the Ce3+/Ce4+ redox property could be greatly en- ported previously.[12b]
hanced by forming larger sized oxygen vacancy clus-
ters or by preferentially exposing some reactive crys-
tal facets, as realized in our rod-like CeO2 nanocrys- Generation of Hydroxyl Radicals via H2O2
tals.[12] We envisioned that our rod-like ceria nano- Decomposition Catalyzed by CeO2 Nanocrystals
crystals [Figure 1, a) and b)] may also promote fast
COH production from H2O2, which encouraged us to EPR analysis was carried out to verify the hydroxyl
explore the direct iodination of using CeO2 nanocrys- radical production in the H2O2/CeO2 system,[13] and
Figure 1. a) TEM image of the fresh CeO2 nanocrystals; b) XRD patterns of the fresh CeO2 nanocrystals.
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Peng Zhang et al.
Table 1. Iodination of benzene at various conditions.[a]
FULL PAPERS
Entry
System
Product and yield[b] [%]
1
2
3
3
4
H2O2
CeO2
H2O2, CeO2
H2O2, CeO2, DMSO
H2O2, CeO2 and 1,3-
dimethylthiourea
none
none
72 (iodobenzene)
none
none
[a]
The reaction was carried out with 1 mmol of benzene,
0.5 mmol of I2, reaction time: 10 h; when necessary,
CeO2 nanocrystals (0.05 g), H2O2 (2 mL of 35 wt% H2O2
aqueous solution); the products were analyzed by
1H NMR and 13C NMR.
[b]
The yield here is determined by GC.
show that the hydroxyl radicals were indeed generat-
ed during the process. To further verify the role of hy-
droxyl radicals in iodination, we performed other con-
Figure 2. EPR spectra of the DMPO-system aqueous: a) trol experiments. Some well-known hydroxyl radical
H2O2; b) CeO2; and c) H2O2 and CeO2; EPR spectra of the
DMPO-benzene iodination reaction system with hydroxyl
radical scavengers: d) DMSO; and e) 1,3-dimethylthiourea.
scavengers, such as DMSO or 1,3-dimethylthiourea,
were added in the benzene/H2O2/CeO2 iodination
system. This time, no EPR signal of hydroxyl radicals
[Figure 2, d) and e)] could be observed and consis-
tently, no iodination product was produced. Appa-
the results are shown in Figure 2. It was found that no rently, this is because the hydroxyl radicals were scav-
detectable hydroxyl radicals could be observed either enged by DMSO or 1,3-dimethylthiourea.[13] The
in the pure H2O2 aqueous solutions [Figure 2, a)] or above experiments demonstrate that the hydroxyl
in the CeO2 nanocrystals-water suspensions [Figure 2, radicals play a vital role in benzene iodination.
b)]. However, four characteristic signals with a peak
ratio of 1:2:2:1 could be detected once the H2O2
aqueous solutions and CeO2 nanocrystals were mixed The Effects of pH Values for Benzene Iodination
together [Figure 1, c)]. The g-value (1.992) and hyper-
fine coupling constant could be assigned to a DMPO- If free hydroxyl radicals were involved in the system,
OH spin adduct,[14] further proving the generation of one may reason that phenol could be produced
hydroxyl radicals in the ceria-hydrogen peroxide through an intermediate aromatic radical mecha-
system.[15]
nism.[16] However, the present results show no detect-
able hydroxylated aromatic by-products. Walling
et al.[17] studied the hydroxylation of benzene by Fen-
tonꢀs reagent (a mixture of ferrous iron salts and
H2O2 that can produce hydroxyl radicals) and found
that the phenol yield was considerably pH dependent;
Iodination of Benzene under Several Control
Conditions
Several control reactions (Table 1) were carried out under strongly acidic condition, only very low phenol
for benzene iodination. It should be noted that the yields were obtained. They proposed that under such
pH value strongly affects the reactivity as will be conditions, most intermediate aromatic radicals could
demonstrated in the next section. In all runs the pH be collapsed and reduced back to benzene, preventing
value of the water layer is kept at 3.0 for comparison. further hydroxylation.[18]
It was found that adding either H2O2 or CeO2 nano-
To investigate the effects of the acidity on the iodi-
crystals alone to the system generally did not yield nation of benzene, reactions were carried out at vari-
any iodination product even upon increasing reaction ous pH values. As mentioned in the Experimental
temperature and prolonging reaction time to 24 h. In Section, the automatically generated pH value of the
contrast, in the presence of both H2O2 and CeO2, that water layer by the H2O2 aqueous solution is 3.0. For
is, when hydroxyl radicals were present, the reaction more strong acidity or basicity, it could be maintained
was improved remarkably and afforded the mono-io- by adding strong acids (HCl) or bases (NaOH). The
dination product in 72% yield (and 4% of the product EPR results at different pH values are shown in
is the 1,4-diiodobenzene). The EPR experiments Figure 3. It can be found that COH could be generated
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Hydroxyl Radical Promotes the Direct Iodination of Aromatic Compounds with Iodine in Water
nation of other arenes under similar reaction condi-
tions. The electron density of the aromatic ring of the
arenes affects the effectiveness of the iodination.
When there are electron-donating substituents, such
as methyl group or methoxy group, the conversions
(entries 1–3) are excellent with the yield ranging from
89% to 97%. The reactions even tolerate weakly elec-
tron-withdrawing substituents such as chlorobenzene
(entry 6); the yield is nearly 70% within 10 h. Howev-
er, for aromatic compounds with strongly electron-
withdrawing groups (e.g. benzonitrile, entry 7) the io-
dination reaction is difficult; even at elevated temper-
ature (808C) after long reaction time (24 h) no prod-
ucts could be detected. The electron density-depend-
ence is in agreement with the well-documented elec-
trophilic aromatic substitutions.[5,16]
Another important feature of the iodination proto-
col is that the substitution reactions exhibit high site
selectivity. As shown in Table 3, 1,3-dimethoxyben-
zene (1a), 1,3-dimethylbenzene (2a), anisole (3a),
Figure 3. EPR spectra of the reaction system at different pH methylbenzene (4a), and chlorobenzene (6a) led to
values: a) pH 3.0; b) pH 4.5; c) pH 6.0.
almost exclusive iodination products at the para posi-
tion (analyzed by GC and H NMR). It is well known
1
under all the conditions. And the lower the pH value, that the electron density of the aromatic ring and
the stronger was the ERP signal of COH that could be steric hindrance have important effects on the site se-
observed. When the pH value was 1.5, H2O2 decom- lectivity of substitution reactions,[20] and an electron-
posed rapidly and violently, the EPR spectrum could donor substituent is ortho/para-directing, where the
not be obtained.
electron density is relatively high.[21] The high site se-
The products were then analyzed and summarized lectivity here may be mainly due to the combination
in Table 2. When the pH value was 3.0 or less, iodo- of high electron density at the para-position and the
benzene was the only product; whereas at a pH value influence of steric hindrance.[22]
higher than 6.0, phenol was the only product. At a pH The influence of the solvent should also be men-
value of around 4.5, both iodobenzene and phenol tioned. It has been reported that the concentration of
were produced.
water had a significant effect on the rate of the iodi-
Thus the low pH value could be responsible for the nation and the products.[23] In the present experi-
high yield of iodobenzene and the absence of phenol ments, we found that some unexpected by-products
in the present study.[19]
could be detected although the reaction rate could be
improved by adding other organic solvents (e.g., alco-
hol and cyclohexane) into the system. While this pro-
cess is still unclear, we observed the the adoption of
water does make the products get a good selectivity
Iodination of Other Arenes in the CeO2/H2O2 System
The scope of the hydroxyl radical-promoted iodina- in our case.[24]
tion was examined. Table 3 shows the results of iodi-
Table 2. Iodination of benzene at different pH values.[a]
The Effect of H2O2 and I2 Dosages on Iodination
Entry
pH
Product and yield[b] [%]
The effect of H2O2 dosage on iodination was investi-
gated and the results are shown in Table 4. It can be
seen that the conversion of both benzene and 1,3-di-
methoxybenzene increase remarkably with the in-
crease of the dosage of H2O2, although an excess
amount of the H2O2 was employed. It is well-known
that hydroxyl radicals are highly reactive and conse-
quently short-lived. To achieve high conversion of the
substrates, an excess of H2O2 dosage was adopted in
our above experiments.
1
2
3
4
1.5
3.0
4.5
6.0
74 (iodobenzene); 0 (phenol)
72 (iodobenzene); 0 (phenol)
12 (iodobenzene); 7 (phenol)
0 (iodobenzene); 12 (phenol)
[a]
The reaction was carried out with 1 mmol of benzene,
0.5 mmol of I2, CeO2 nanocrystals (0.05 g), H2O2 (2 mL
of 35 wt% H2O2 aqueous solution) and distilled water
(1 mL); the products of all these reactions were analyzed
by 1H NMR and 13C NMR.
[b]
the yield here is determined by GC.
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Table 3. Iodination of aromatic compounds using I2/H2O2/CeO2 nanocrystals.[a]
Entry
Substrate
Product
Time [h]
Conversion [%][b]
Yield [%][c]
97
1
0.5
~100
2
3
4
5
6
1.5
2
~100
92
92
89
75
72[d]
68
0
4
80
10
14
24
78
73
7
0
[a]
The reaction was carried out with 1 mmol of arenes, 0.5 mmol of I2, CeO2 nanocrystals (0.05 g), H2O2 (2 mL of 35 wt%
1
H2O2 aqueous solution) and distilled water (1 mL); the products of all these reactions were analyzed by H NMR and
13C NMR.
[b]
[c]
[d]
The conversion was determined by GC.
The yield here was determined by GC.
4% of the product is 1,4-diiodobenzene.
Using the iodination of 1,3-dimethoxybenzene as
an example, the effect of the amounts of I2 on the
product was tested. When one equivalent of I2 was
Table 4. The effect of H2O2 dosage on our iodination.[a]
employed, only mono-iodination of aromatic com-
pounds (2,4-dimethoxyiodobenzene) could be ob-
tained. If excess amounts of I2 (with an I2/arene ratio
of 1.2:1) were employed, at the initial stage of the re-
action, only the mono-iodination product could be
formed. However, once the mono-iodination was
completed, the diiodination product started to form,
and was the only product after a longer reaction time.
These results indicate that the process of mono- and
diiodination of arenes could be well separated by ad-
justing the amounts of I2.
Entry Substrate
Dosage of Reaction
Yield
[%][b]
H2O2
Time [h]
1
2
1 mmol
1
17
92
5 mmol
1
3
4
5
20 mmol
5 mmol
1
97
33
57
72
10
10
10
Recovery and Reuse of CeO2 Nanocrystals
10 mmol
20 mmol
Besides the environmentally benign feature, another
clear advantage of this iodination protocol is the easy
recycle of the catalyst. Due to the insolubility of
CeO2 nanocrystals in water, the CeO2 nanocrystals
can be easily recovered by centrifugation (10 min,
4000 rpm). In a typical procedure, the recovered
CeO2 nanocrystals were washed by deionized water
and alcohol, and then dried in air. The recovery rates
6
[a]
The reaction was carried out with 1 mmol of arene,
0.5 mmol of I2, CeO2 nanocrystals (0.05 g), distilled water
(1 mL) and different dosages of H2O2 (35 wt%).
The yield here was determined by GC.
[b]
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Hydroxyl Radical Promotes the Direct Iodination of Aromatic Compounds with Iodine in Water
Table 5. CeO2 nanocrystals recycling experiments with ben-
phology and there is no change in length and diame-
ter.
zene.[a]
Run
1
2
3
4
5
Conversion [%][b]
78
76
76
77
78
Computational Results
[a]
Reaction conditions: benzene (1 mmol), I2 (0.1270 g,
0.5 mmol), H2O2 (2 mL of 35 wt% H2O2 aqueous solu-
tion), CeO2 nanocrystals (recycled 0.05 g), deionized
The above experimental study indicates that both
COH radical and acidic conditions are crucial for the
benzene iodination. To gain insights into the mecha-
nism, M05-2X[25] DFT calculations were performed
using benzene iodination as an example. The reliabili-
ty of the M05-2X DFT functional has been demon-
waterACHTUNGTRENNUNG
[b]
of CeO2 nanocrystals were 97.8%–98.4%. Table 5 strated by calibrations and successful applications.[26]
shows the five sequential runs of benzene iodination The free energies were discussed, otherwise specified,
by using sequentially recycled CeO2 nanocrystals. It and the enthalpy results are included in the Scheme 3
can be seen that there was no change in morphology and Scheme 4 for reference.
of the CeO2 nanocrystals and they could be well
reused without loss of activity.
It has been recognized that I+-type intermediates
are important in various iodination reactions.[20a,27] We
The TEM image [Figure 4, a)] and the powder reasoned that similar species also play a role in our
XRD analysis [Figure 4, b)] show that after the reac- reaction, according to which the first question is how
tion the CeO2 nanocrystals still have the rod-like mor- hydroxyl radical activates I2 to give the desired I+-
Figure 4. a) TEM image of the recycled CeO2 nanocrystals. b) XRD patterns of the recycled CeO2 nanocrystals.
Scheme 2. Free energy (in kcalmolꢀ1) profile for I2 activation, along with the key bond lengths in ꢂ. The values in the
square brackets are enthalpies in kcalmolꢀ1.
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Peng Zhang et al.
FULL PAPERS
type species. Our calculations unveil that I2 can be cleavage is 28.9 kcalmolꢀ1 measured from I2(OH)2,
oxidized into two IOH species via the mechanism but it is only 3.1 kcalmolꢀ1 higher than I2 +2OH. The
shown in Scheme 2.
I2 activation is strongly exergonic by 52.0 kcalmolꢀ1.
An COH radical first binds to I2 to form the complex The IM1 complex is less stable than the two IOH spe-
(I2OH), which is exergonic by 11.7 kcalmolꢀ1. Subse- cies in terms of free energy, so it can be dissociated
quently, another COH attacks the I2OH complex to into two IOH species readily.
give another complex [I2(OH)2]. Interestingly, the
The iodine species (IOH) has character of Id+-type
second COH prefers attacking the same I atom as that species, but it is not electrophilic enough to promote
in the first attack, rather than the innocent I atom. iodination. No s-complex could be located between
This is reasonable because the first COH binding benzene and IOH and the barrier for the reaction
makes the attacked I atom electrophilic. Consequent- (IOH+C6H6!C6H5I+H2O) is very high (64.8 kcal
ly, the I I bond in I2(OH)2, 3.072 ꢂ, is even shorter molꢀ1, see Scheme 3).
ꢀ
than the 3.428 ꢂ in I2OH. After passing the three-
However, under the strongly acidic condition, the
ꢀ
membered transition state (TS1), the I I bond splits, IOH species can be protonated to more electrophilic
giving the complex IM1. The barrier for the I I bond IOH2 . Our predicted mechanism for the IOH2 -initi-
ated iodination, together with the energetic and geo-
+
+
ꢀ
metric results, are illustrated in Scheme 4. As expect-
+
ed, the IOH2 can form a stable cationic s-complex
(IM2+) with benzene that is 14.1 kcalmolꢀ1 more
+
stable than benzene+IOH2 . In the structure of
+
ꢀ
IM2 , the I O bond is elongated to 2.575 ꢂ from
+
ꢀ
2.072 ꢂ in the free I OH2 3 species and the length of
ꢀ
the newly formed I C (sp carbon) bond is 2.343 ꢂ.
With the s-complex (IM2+) formed, another IOH
then abstracts the hydrogen on the sp3 carbon of the
s-complex by crossing a barrier (TS2+) of 12.8 kcal
molꢀ1. Note that a weak complex (IM3+) prior to
TS2+ can be located, but it is less stable than IM2+ +
IOH after thermal and entropic corrections. The hy-
drogen abstraction leads to the complex (IM4+). The
Scheme 3. Geometric and energetic results of benzene iodi-
nation of via IOH.
Scheme 4. Energy (in kcalmolꢀ1) profile for benzene iodination, along with optimized structures. The key bond lengths are
given in ꢂ. The values in the square brackets are enthalpies in kcalmolꢀ1
.
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Hydroxyl Radical Promotes the Direct Iodination of Aromatic Compounds with Iodine in Water
+
+
ꢀ
gradually elongated I O (water O) distances [2.575 ic IOH2 under the strongly acidic conditions. IOH2
(IM2+), 2.588 (IM3+), 2.832 (TS2+), and 2.997 ꢂ can readily attack arenes to form s-complexes. An-
(IM4 )] and the shortened I C (sp carbon) bond other IOH species then abstracts the hydrogen from
lengths [2.343 (IM2+), 2.336 (IM3+), 2.190 (TS2+), the s-complex, resulting in the aromatic iodide. The
and 2.127 ꢂ (IM4+)], depict the leaving process of the predicted mechanism successfully elucidates why the
+
3
ꢀ
ꢀ
water molecule and the forming process of the I C reactions occur, but further study will be needed to
bond. The process from IM2+ +IOH to IM4+ is en- fully understand other features such as the regioselec-
thalpically favorable due to gaining aromaticity of the tivity.
benzene ring, but nearly thermoneutral in free energy
due to the cancelation of entropic penalty. Relative to
the final products (C6H5I+IOH2+ +H2O), the IM4+ Experimental Section
complex is enthalpically more stable, but it is
15.5 kcalmolꢀ1 less stable in terms of free energy. The Synthesis and Characterization of CeO2 Nanocrystals
entropic driving force separates the complex (IM4+),
giving the final products. The IOH2 species released
from the process can be “recycled” for the next ben-
CeO2 nanocrystals were prepared according to our previous-
ly reported method. CeCl3 7H2O (1.5 g) was dissolved in dis-
tilled water, and proper amounts of 10 wt% NaOH solution
+
.
zene iodization, in agreement with the experimental
fact that one equivalent iodine can iodize two equiva-
lents of aromatic compound. The mechanism requir-
ing protonation is consistent with the experimental
fact that no iodobenzene could be detected under the
weakly acidic conditions.
To support our proposed mechanism, we have run
the iodination of methoxybenzene in the I2/H2SO4/
H2O2 system. It was observed that iodination of the
arene occurred, with a methoxyiodobenzene yield of
83% after a reaction time of 2 h, providing further ex-
perimental evidence for the hydroxyl radical mecha-
nism.
were rapidly added with stirring vigorously. A purpure pre-
cipitate of amorphous Ce(OH)3 appeared. After about
15 min of stirring, all of the slurry (the volume was about
35 mL) was transferred into a 50 mL autoclave, which was
filled with deionized water up to 80% of the total volume
(the final NaOH concentration in the autoclave is about
2M), and heated at 1208C under autogenous pressure for
12 h. Then the system was allowed to cool to room tempera-
ture. The final product was collected by filtration, washed
with deionized water and alcohol to remove any possible
ionic remnants, and then dried at room temperature.
Powder X-ray diffraction (XRD) data were collected on
MSAL-XD2 using Cu-Ka radiation (l=1.5418 ꢂ). The size
and morphology of CeO2 nanocrystals were measured with
a Philips CM120 transmission electron microscopy.
Combining the experimental and computational
study, we propose the mechanism for the direct iodi-
nation, which includes five steps: the COH generation
from H2O2 catalyzed by CeO2 nanocrystals; the I2 ac-
tivation promoted by COH giving two IOH species;
the protonation of IOH leading to more electrophilic
EPR Measurements
Electron paramagnetic resonance (EPR) spin trapping tech-
niques were used to study the production of hydroxyl radi-
cals. Since the life time of a hydroxyl radical is only 10ꢀ9 s, it
cannot be detected directly by EPR. Thus, spin trap, 5,5-di-
methyl-1-pyrroline 1-oxide (DMPO), was used to capture
COH to generate a long-lived free radical (spin adduct,
DMPO-OH) which can then be detected by EPR spectros-
copy. The EPR experiments were carried out with a JES-
FA200 instrument operating in the X-band. For the DMPO
(5,5-dimethyl-1-pyrroline N-oxide) spin trapping EPR ex-
periments, the samples were suspended in water (at a con-
centration of 0.5 mmolLꢀ1) and sonicated for 5 min. An
aqueous (0.01M) of DMPO spin trap (supplied by Sigma)
was prepared shortly before the experiment and kept on ice
during the whole set of experiments and bidistilled water
was employed for these preparations. H2O2 used in the ex-
periments was diluted with water (1:5). 100 mL of the solid
suspension, 100 mL diluted H2O2 and 20 mL of the DMPO
solution were mixed into an EPR flat quartz capillary under
atmospheric air at room temperature. And the capillary was
immediately transferred to the spectrometer cavity for EPR
analysis. The spectra were recorded at room tempertaure by
accumulating two scans.
+
I+-type species (i.e., IOH2 complex); the attack of
+
IOH2 to arenes to form the s-complex; and the hy-
drogen abstraction by another IOH, finally resulting
in the aromatic iodide.
Conclusions
In summary, we have developed a green strategy for
direct mono-iodination of arenes in aqueous medium
starting with molecular iodine. The strategy uses rod-
like CeO2 nanocrystals to promote the decomposition
of hydrogen peroxide, giving hydroxyl radicals which
then activate I2 to complete the iodination. The new
strategy has the advantages of easy product isolation,
high regioselectivity, good yields, no hazardous waste,
and convenient recycle of the catalyst. The computa-
tional study reveals the following mechanism for the
hydroxyl radical-promoted iodination. Two hydroxyl
radicals first activate I2 giving two IOH species. The
IOH species is not electrophilic enough to promote
iodination but can be protonated to more electrophil-
Adv. Synth. Catal. 2012, 354, 720 – 729
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
727

Peng Zhang et al.
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Acknowledgements
This work was supported by the National Natural Science
Foundation of China (20703065, 20877097, 20973197) and
the Ministry of Science and Technology of China
(2008AA06Z324).
728
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