Dihaloiodates(I): Synthesis with hydrogen peroxide and their halogenating activity

Article abstract of DOI:10.1016/j.tetlet.2012.08.036

Tetraalkylammonium and pyridinium dichloro- and dibromoiodates(I) were efficiently prepared from iodine and tetralkylammonium chloride or pyridine by oxidation with hydrogen peroxide in the presence of an equimolar amount of a hydrogen halide. Their halogenating activity was tested on 1,3-dimethoxybenzene and styrene as model substrates. The results show that ICl₂ ^- salts acted as iodinating reagents, while IBr₂ ^- salts brominated both substrates. 2012 Elsevier Ltd. All rights reserved.

Full text of DOI:10.1016/j.tetlet.2012.08.036

Tetrahedron Letters 53 (2012) 5555–5558
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Dihaloiodates(I): synthesis with hydrogen peroxide and their
halogenating activity
a,b,c,
⇑
ˇ a
Leon Bedrac , Jernej Iskra
a
ˇ
Laboratory of Organic and Bioorganic Chemistry, Department of Physical and Organic Chemistry, ‘Jozef Stefan’ Institute, Jamova 39, 1000 Ljubljana, Slovenia
b The Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins (CIPKeBiP), Jamova 39, 1000 Ljubljana, Slovenia
c Laboratory for Organic and Polymer Chemistry and Technology, Faculty of Chemistry and Chemical Technology, University of Maribor, Smetanova ulica 17, Maribor, Slovenia
a r t i c l e i n f o
a b s t r a c t
Article history:
Tetraalkylammonium and pyridinium dichloro- and dibromoiodates(I) were efficiently prepared from
iodine and tetralkylammonium chloride or pyridine by oxidation with hydrogen peroxide in the presence
of an equimolar amount of a hydrogen halide. Their halogenating activity was tested on 1,3-dimethoxy-
Received 23 June 2012
Revised 30 July 2012
Accepted 9 August 2012
Available online 16 August 2012
À
benzene aÀnd styrene as model substrates. The results show that ICl2 salts acted as iodinating reagents,
while IBr2 salts brominated both substrates.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Dihaloiodates
Iodination
Polyvalent iodine compounds
Oxidation
Hydrogen peroxide
In organic compounds, iodine can be found in different oxida-
tion states and forms. Being the heaviest, the most polarizable,
and the least electronegative amongst the halogens, iodine is capa-
ble of forming stable, hypervalent compounds, typically I(III) and
I(V) species.1 The chemistry of hypervalent iodine compounds
has undergone rapid development and they have become indis-
pensible in organic synthesis.2 The reasons for this are their useful
properties, combined with low toxicity, good availability, ease of
handling, and high reaction efficiency.3 Iodine(V) reagents, such
as Dess–Martin periodinane and 2-iodoxybenzoic acid (IBX) have
been used in oxidation reactions and in the total syntheses of nat-
ural products.4 Iodine(III) compounds, such as iodosylarenes,
(dihaloiodo)arenes, and [bis(acyloxy)iodo]arenes have been
employed for the oxidation of alcohols and alkenes, as well as in
while 18-crown-6 supported DCI was developed as a soluble coun-
À
terpart.10 It is reported that Me4N+ICl2 is a very reactive iodinat-
ing reagent which is able to iodinate 4-nitrotoluene in 35 min at
room temperature.11 This increase in reactivity however, can only
be achieved in the presence of superacids, as reported by the group
of Filimonov.12 Nothing, apart from their structure, is known abÀou13t
the reactivity of the other two dihaloiodides, IBr2À (DBI) and IF2
.
Intrigued by these contradictory reports and the dearth of data
on the properties of dihaloiodates(I) (IX2À), we have attempted to
gain an insight into the chemistry of these compounds. In addition
DCIs are prepared using strong and dangerous oxidants that is ICl,
Cl2, or hypochlorite. We are interested in the use of ‘green’ oxidants
for oxidative halogenations.14 Therefore, we present herein the
results of our studies on the synthesis of dihaloiodides with hydro-
gen peroxide as an oxidant, and an initial study on the halogenating
properties of dichloroiodates(I) and dibromoiodates(I).
First, we investigated the oxidation of iodine into iodine(I) using
50% aqueous hydrogen peroxide. HCl was used as a source of chlo-
rine atoms, which at the same time provides acidic conditions nec-
essary to prevent the decomposition of H2O2 catalyzed by halogen
and halides under basic conditions. Therefore, we mixed iodine,
hydrogen peroxide, and hydrochloric acid, but found that the
iodine did not react. Different solvents were also tested without
success. Only when we used 50% H2O2 under solvent-free condi-
tions, homogenized the mixture in a ceramic mortar and allowed
the reaction to proceed at room temperature, did we observe the
formation of a bright-yellow solution indicating the conversion of
the
a-functionalization of carbonyl compounds and halogen-
ations.5 Moreover, iodonium salts have been widely used in
metal-catalyzed cross-coupling reactions and in arylation reactions
of various organic substrates.6 They are also bioactive compounds.7
Iodine(I) compounds differ in their chemistry from both iodi-
ne(III) and (V) compounds by acting mainly as electrophilic iodin-
ating reagents (ICl, NIS, IPy2BF4).8 Dichloroiodates(I) (DCI) are
lesser known analogues used in the iodination of aromatics,
alkenes, enaminones, and flavones.9–12 Mainly, potassium
(K+ICl2À) and tetramethylammonium (Me4N+ICl2À) salts were used,
⇑
Corresponding author.
E-mail address: jernej.iskra@ijs.si (J. Iskra).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.08.036

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L. Bedrac, J. Iskra / Tetrahedron Letters 53 (2012) 5555–5558
5556
iodine into an iodine(I) species. Complete reaction occurred only in
the mortar and it seemed that mechanical forces, developed during
grinding, were necessary to initiate the reaction, while further
grinding was not necessary, except to homogenize the mixture
again. An analogous reaction, performed in a round-bottomed flask
and stirred with a magnetic stirrer did not occur on this time scale.
Different forms of hydrogen peroxide were tested under neat reac-
tion conditions. An equivalent of a 50% aqueous solution of H2O2
was able to oxidize iodine quantitatively within 1 h. Similary, the
use of a complex of urea-hydrogen peroxide (UHP) resulted in
quantitative conversion of iodine into an iodonium(I) species.
However, the reaction was slower and was complete in 4 h. A
30% aqueous H2O2 solution, in an equimolar amount to I2, was inef-
ficient and did not convert iodine completely after 24 h. By using a
100% excess of 30% H2O2, quantitative conversion was achieved
within 3 h. Hence, we chose to use a 50% aqueous solution of
hydrogen peroxide for the preparation of various DCI salts since
the reaction was fast, occurred with only 1 equiv of oxidant, and
water was the only by-product. Treatment of the yellow reaction
product of the oxidation of iodine with tetraalkylammonium chlo-
Figure 1. Changes in the UV spectra of an ethanolic solution of Me4N+ICl2À (2a). The
inset shows the time-dependent absorbance at 343 nm.
Table 2
Synthesis of tetraalkylammonium dibromoiodates
rides (Q+ClÀ) (1) in MeCN enabled the preparation of tetraalkylam-
1) 50% H2O2 (1 eq.)/4 HBr
monium DCIs (Q+ICl2
) (2a–2d), while addition of pyridine
À
-
2 Q+IBr2
I2
+
- 1
2) 2 Q Cl ( )/ MeCN
resulted in the formation of pyridinium DCI (2e) (Table 1). We tried
to prepare trialkylammonium DCIs, however when we added
triethylamine to the reaction mixture, we observed only decompo-
sition of the product giving a dark-brown solution of iodine.
The Q+ICl2À products are yellow crystalline salts, soluble in eth-
anol, and acetonitrile, partially soluble in dichloromethane and
water, and insoluble in nonpolar solvents, such as hexane. They
can be stored in solid form at room temperature for extended peri-
ods without any significant decomposition. The stability of an eth-
anolic solution of 2a was followed using UV spectroscopy over
2 weeks and only minimal decomposition was noticed (Fig. 1). Sim-
ilarly, the stabilities of ethanolic solutions of 2b, 2c, 2d, and 2e
were assayed using UV spectroscopy and iodometric titrations. A
trend was observed in which the stability of the DCI increased with
the length of the alkyl chain on the cationic part of the salt. After
2 weeks, the compositions of the ethanolic solutions were as fol-
lows: 96% (2a), 97% (2b) 99% (2c), 99% (2d), and 98% (2e). On the
other hand, the DCIs in their solid form, remained 100% active over
the same period of time.
Q=R4N, RNMe3, PyH
Entry
Salt
Yielda (%)
À
1
2
3
4
5
Me4N+IBrÀ2 (3a)
86
89
92
94
91
Et4N+IBr2 (3Àb)
BnN+Me3IBr2 À(3c)
OctN+MeÀ3IBr2 (3d)
PyH+IBr2 (3e)
a
Yield of isolated pure product.
salts 3 were more stable as determined by following the absorption
of light of a solution of 3a in ethanol at 373 nm using UV spectrom-
etry (Fig. 2). In addition, the stabilities of 3b, 3c, 3d, and 3e were
monitored over 2 weeks and the results showed that the DBI salts
did not decompose and remained 100% active in ethanolic solution
as well as in the solid form.
Difluoroiodates have been poorly investigated and only one re-
port exists regarding their preparation.13d Furthermore, IF2 salts
À
are unstable and very easily hydrolyzed. The formation of IX2À salts
presumably occurs through the oxidation of HX by H2O2 followed
We next applied a similar strategy to the preparation of dibro-
moiodate salts (Table 2), and as expected, because HBr is more
readily oxidized compared to HCl, the reaction was faster. The ini-
tial step of the reaction was complete within 5 min as indicated by
the disappearance of iodine and the formation of a reddish-brown
solution. Following the addition of 1, tetralkylammonium DBIs
(Q+IBr2À) were formed and isolated in high yields. We also
prepared pyridinium DBI (3e) by adding pyridine to the reaction
mixture (Table 2).
À
by reaction with I2. IF2 salts present a good test for this reaction
since H2O2 is unable to oxidize HF (the oxidation potentials are
À3.06 V and 1.8 V for HF and H2O2, respectively). Different sources
of HF were used in the reaction (Et3N.3HF, Py.HF, PhN(Me3)+OHÀ/
HF), however, we did not observe the formation of any iodine(I)
compounds indicating that the first step in the reaction is the
The Q+IBr2 products were red-brown crystalline salts with
À
similar properties to their chloride analogues. Interestingly, DBI
Table 1
Synthesis of tetraalkylammonium dichloroiodates
1) 50% H2O2 (1 eq.)/4 HCl
-
2 Q+ICl2
I2
2) 2 Q+Cl-(1)/ MeCN
Q=R4N, RNMe3, PyH
Entry
Salt
Yielda (%)
Me4N+ICl2 (2a)
97
94
96
99
91
À
1
2
3
4
5
À
Et4N+ICl2 (2Àb)
BnN+Me3ICl2 À(2c)
OctN+Me3ICl2 (2d)
PyH+ICl2 (2e)
À
Figure 2. Changes in the UV spectra of an ethanolic solution of Me4N+IBr2 (3a).
The inset shows the time-dependent absorbance at 373 nm.
À
a
Yield of isolated pure product.

ˇ
L. Bedrac, J. Iskra / Tetrahedron Letters 53 (2012) 5555–5558
5557
no reaction
OCH3
OCH3
0.5 I2 + 0.5 H2O2 + 2 AF
AF = Et3N.3HF, Py.HF,
Me4N+ICl2- (2a)
PhN+(Me3)OH- / HF
OCH3
OCH3
I
5
1) 0 °C, MeCN, 24 h
2) Et4N+F-
4
-
I
2 + XeF2 or 2AgF
Et4N+ IO3
MeCN, 24 h
29%
97%
MeCN, H2SO4 (0.1 equiv.), 6 h
Scheme 1. Oxidation of iodine in the presence of fluorides.
MeCN, Na2CO3 (0.1 equiv.), 24 h 31%
Scheme 2. Reactions of 1,3-dimethoxybenzene (4) with Me4N+ICl2 (2a).
À
oxidation of HX. In order to oxidize I2, we had to use xenon difluo-
ride (XeF2) as the oxidant and source of FÀ, however, after the reac-
tion in MeCN, only the IO3À salt was isolated as determined by MS
spectroscopy. Similar results were obtained by applying silver(I)
fluoride, in an attempt to generate iodine monofluoride (IF) that
would lead to the product (Scheme 1). Again, only the iodate signal
was observed by ES/MS analysis and it appeared that difluoroio-
date(I) salts were not stable enough to be isolated, despite the
reaction being performed under an inert atmosphere.
OCH3
OCH3
OCH3
-
Q+IBr2 ( )
3
+
OCH3
OCH3
OCH3
Base (Q+)
I
5
Br
7
4
To test the reactivity of DCIs and DBIs as halogenating agents
two substrates were chosen: 1,3-dimethoxybenzene (4) for substi-
tution, and styrene (8) for the addition reaction. We tested the
reactivity of various salts since we observed that cations with long-
er alkyl chains produced more stable salts and this could also be
reflected in their reactivity. First, we studied the iodination of 4
with DCI under solvent-free (SF) conditions, which are reported
to be highly efficient.11 The reactions were performed by grinding
DCI with the substrate and allowing the mixture to rest at room
temperature. Under such conditions only the pyridinium salt 2e
gave selectively 4-iodo-1,3-dimethoxybenzene (5) in good yield,
while the reactivity of the tetraalkylammonium salts decreased
with increasing stability and length of the alkyl chain, and 5 was
isolated in modest yields (Table 3). Next, we tested the reactivity
of DCIs in acetonitrile, where a similar trend was observed.
Amongst the tetralkylammonium DCI compounds, tetramethyl 2a
and benzyl 2c derivatives showed similar reactivity, while longer
alkyl chain derivatives were only slightly active. Again, 2e was
the most reactive. Addition of 0.1 equiv of sulfuric acid activated
the reaction with 2a and 97% of 5 was formed, confirming the find-
ings of Filimonov et al. (Scheme 2).12 Alternatively, the presence of
carbonates (Na2CO3, K2CO3) did not activate the iodination of 4 un-
like in the reaction reported for crown ethers.10
Me4N+ (3a) MeCN, rt, 24 h
18%
7%
49%
42%a
30%
46%
TFE, rt, 1 h
PyH+ (3e)
MeCN, rt, 24 h 60%
TFE, rt, 1 h
32%
atrace of dibrominated product was apparant
Scheme 3. Reactions of 1,3-dimethoxybenzene (4) with DBIs.
an increase in the halogenating activity, which is surprising since
they are more stable than ICl2À. DBI salts acted predominately as
brominating reagents. Salts with smaller cations (i.e. 3a) were
again more reactive and gave a higher proportion of brominated
7 over the iodinated product 5. The pyridinium salt 3e reacted dif-
ferently with 90% conversion and iodination as the main reaction
channel (Scheme 3). TFE had a strong effect on the reactivity and
the reactions were complete in 1 h with a higher degree of
bromination.
The reaction of styrene 8 was tested with the Me4N+ salt in
dichloromethane. DCI 2a converted styrene 8 completely and
selectively into 9 (Scheme 4). DBI 3a reacted similarly to the aro-
matic reactions and the dibromo adduct 10 was the only product
formed; the yield was only 34%.
In summary, we have prepared various tetraalkylammonium
dichloroiodates(I) and dibromoiodates(I) via the direct oxidation
of iodine with an equimolar amount of 50% aqueous H2O2 in the
presence of a hydrogen halide. Different sources and concentra-
tions of H2O2 can be used, while less reactive forms required an
excess amount. The cationic part of the DCI and DBI salts affected
both the stability and reactivity with salts having shorter alkyl
chains being less stable and more reactive. Their efficiency as hal-
ogenating reagents was tested on 1,3-dimethoxybenzene and sty-
rene. Our results revealed dichloroiodates to be efficient iodinating
reagents, especially when trifluoroethanol was used as the solvent,
while the DBIs mainly acted as brominating reagents although they
were more stable than DCIs. Further research into the preparation
of various mixed dihalo halogen(I) compounds and their reactivity
in the halogenation of organic compounds is underway and the
results and their structural features will be published in a full
paper.
As a solvent, 2,2,2-trifluoroethanol (TFE) is a good activator of
electrophilic processes. This was evident during the iodination
with DCIs 2, where the yields were significantly increased, albeit
the selectivity was completely lost with 4,6-diiodo-1,3-dimethoxy-
benzene (6) being the major product. Surprisingly, 2e reacted dif-
ferently resulting in mono-iodinated product
obtained selectively and quantitatively.
5 which was
For comparison, the reactivities of analogous DBI salts 3 were
tested using the same substrate (Scheme 3) and the results showed
Table 3
Reactions of 1,3-dimethoxybenzene (4) with DCIs
Base [Q+]
Yield of iodinated product 5a
SFb
MeCN (%)
TFE
2a: Me4N+
2b: Et4N+
23%
11%
/
29
4
22
4
12%, (35% 6)
12%, (25% 6)
27%, (21% 6)
11%, (41% 6)
99%, (<1% 6)
2c: BnN+Me3
2d: OctN+Me3
2e: PyH+
/
91%
67
Me4N+ICl2- (2a)
3a
Cl
-
Me4N+IBr2
(
)
Br
a
Yield of 5 was determined from the 1H NMR spectrum of the isolated reaction
Ph
CH2Cl2, rt, 16 h
CH2Cl2, rt, 16 h
Ph
9: 100%
I
Ph
10
Br
: 34%
mixture based on starting compound. The yield of diiodinated product 6 (4,6-
8
diiodo-1,3-dimethoxybenzene) in the reactions in TFE was determined from the 1
NMR spectrum of the isolated reaction mixture.
H
b
SF = solvent-free.
Scheme 4. Halogenation of styrene (8) with 2a and 3a in CH2Cl2.

ˇ
5558
L. Bedrac, J. Iskra / Tetrahedron Letters 53 (2012) 5555–5558
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The financial support of the Slovenian Research Agency is
greatly appreciated. The authors gratefully acknowledge the Slove-
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Supplementary data
Supplementary data (experimental procedures and full spectro-
scopic data for all new compounds) associated with this article can
be found, in the online version, at http://dx.doi.org/10.1016/
j.tetlet.2012.08.036.
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