NMR study on the structure and stability of 4-substituted aromatic iodosyl compounds

Article abstract of DOI:10.1002/mrc.1875

Two 4-substituted aromatic iodosyl compounds were investigated with regard to their solubility, stability and chromatographic behaviour. 1-Iodosyl-4-methoxy- and 1-iodosyl-4-nitro-benzene are soluble in methanol and provide acceptable ¹H and

Full text of DOI:10.1002/mrc.1875

MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2006; 44: 955–958
Published online 10 August 2006 in Wiley InterScience
(
www.interscience.wiley.com) DOI: 10.1002/mrc.1875
Note
NMR study on the structure and stability of
4
-substituted aromatic iodosyl compounds
Achim Hiller,1 J o¨ rg T. Patt and J o¨ rg Steinbach
∗
1
1,2
1
Institute of Interdisciplinary Isotope Research, Permoserstrasse 15, D-04318 Leipzig, Germany
Institute of Radiopharmacy, Research Centre Rossendorf, D-01314 Dresden, Germany
2
Received 26 April 2006; Accepted 31 May 2006
Two 4-substituted aromatic iodosyl compounds were investigated with regard to their solubility, stability
and chromatographic behaviour. 1-Iodosyl-4-methoxy- and 1-iodosyl-4-nitro-benzene are soluble in
1
13
methanol and provide acceptable H and C NMR spectra; however, gradual oxidation of the solvent
was observed. LC-MS analyses suggest that unlike the parent substance, iodosylbenzene, which has a
polymeric structure, both compounds rather exist in the monomeric form. Copyright  2006 John Wiley &
Sons, Ltd.
KEYWORDS: NMR; H NMR; 13C NMR; aromatic iodosyl compounds; oxidation; HPLC-MS
1
7
INTRODUCTION
4-chloro- and 4-methyl-iodosylbenzene exist as monomers.
1
3
8
Solid-state C NMR spectra indicated sharp signals and
some degree of crystallinity for substituted aryliodosyl com-
pounds, such as 1-iodosyl-4-methoxy-benzene, but broad-
ened signals for 1-iodosyl-4-nitro-benzene pointing more
likely to an amorphous polymeric structure. Owing to the
insolubility in non-reactive NMR solvents and possible oxi-
dation reactions in reactive ones, there are no solution NMR
data available for substituted aromatic iodosyl compounds.
In connection with radio-high performance liquid chro-
matography (radio-HPLC) investigations on astatine-211
labelled 4-substituted aromatic compounds and assumed
astatosyl species Ph–AtO (unpublished data), we were inter-
ested in the solubility and chromatographic behaviour of
selected aromatic iodosyl compounds for comparison.
Hence, 1-iodosyl-4-methoxy-benzene (1) and 1-iodosyl-4-
nitro-benzene (2) as two simple model substances containing
para-substituents, with electron-donating and withdrawing
substituents, respectively, were investigated. In this study,
Hypervalent organic iodine compounds with iodine (III) or
(
V) as substituent on the phenyl ring has attracted consider-
1
–3
able attention in organic chemistry.
The most important
feature of these substances is their electrophilic charac-
ter, which facilitate many chemical transformations with
nucleophilic substrates, in particular, oxidation reactions.
For example, the parent substance iodosylbenzene has been
proven to be suitable e.g., for, transition-metal-mediated
regioselective oxidations of a variety of compounds (sum-
marized in Refs. 1 and 3). The Dess–Martin reagent (1,1,1-
triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one) has been
frequently applied in organic synthesis for the selective oxi-
dation of primary and secondary alcohols to aldehydes
4
or ketones. Diaryliodonium salts also play an important
1
,2
role
in radiopharmacy particularly in introducing no-
1
8
carrier-added (n.c.a.) [ F]fluoride into the aromatic ring via
nucleophilic F-fluorination, to obtain [ F]fluoroarenes.
1
8
18
5
Iodosylarenes have some special features. EXAFS
extended X-ray absorption fine structure) analysis has
1
13
we present the H and C NMR spectra of these two
(
iodosylarenes and data concerning their stability in CD
solutions (Scheme 1).
3
OD
revealed that iodosylbenzene consists of a zigzag poly-
mer structure in which monomeric Ph–IO units are linked
ÐÐÐ
6
by intermolecular non-symmetric I–O I bridges. Owing
to the polymeric structure, iodosylbenzene is insoluble
in all non-reactive solvents. The introduction of electron-
withdrawing or donating substituents on the phenyl ring
of iodosylbenzene changes the properties of the compound,
RESULTS AND DISCUSSION
1-Iodosyl-4-methoxy-benzeneand1-iodosyl-4-nitro-benzene
were prepared according to the literature by oxidation of the
corresponding iodo aromatics with sodium periodate NaIO
and sodium perborate NaBO in glacial acetic acid, respec-
tively, followed by an alkaline treatment of the isolated
4
influencing both the degree of association (R–Ph–IO)
n
and its
3
reactivity as an oxidant. Hence, according to X-ray analysis,
9
–11
(
diacetoxyiodo)benzene derivatives
Substituted iodyl aromatics (R–Ph–IO
obtained from iodo compounds and sodium periodate but
(Scheme 2).
2
) can also be
Ł
Correspondence to: Achim Hiller, Institute of Interdisciplinary
Isotope Research, Permoserstrasse 15, D-04318 Leipzig, Germany.
E-mail: hiller@iif-leipzig.de
1
0
require more drastic reaction conditions. Compounds 1
Copyright  2006 John Wiley & Sons, Ltd.

956
A. Hiller, J. T. Patt and J. Steinbach
3
2
3
3
2
oxidizes the solvent to form formaldehyde and/or formic
acid, following approximately a pseudo first-order kinetics
5
4
1
4
1
(
Fig. 2). It is somewhat surprising that the relative oxidation-
IO
IO
H CO
O N
2
3
resistant nitrile group of acetonitrile was more easily
oxidized by 2 than methanol. As expected, warming of
the mixture accelerated the reaction. According to the
literature the oxidation of primary alcohols to aldehydes or
carboxylic acids is typical for iodosylbenzene derivatives.1
The oxidation of primary alcohols, for example, in the
presence of a ruthenium catalyst has been reported.1 The
disproportionation of 2 into 4-nitro-iodylbenzeneand 1-iodo-
3
2
2
1
2
,18
Scheme 1. Iodosyl compounds studied with numbering of C/H
atoms (see Table 1).
9
1
5
and 2 are white and yellow-orange solids, respectively. The
analytical data available for the two substances are limited,
and mainly consist of infrared spectroscopy. The infrared
spectra are characterized by I O vibrations in the range from
20 to 790 cm ; and all other vibrations are very similar to
those of the substituted iodo aromatics.
Iodosylbenzene is insoluble in weakly polar solvents.
Its solubility in anhydrous methanol is the result of the
reaction producing (dimethoxy)iodobenzene PhIꢀOCH
The solubility of iodosylbenzene in acetic acid is based on its
4-nitro-benzene could not be observed; the corresponding
1
aromatic proton signals in the H NMR were absent.
1
2
1-Iodosyl-4-methoxy-benzene was less reactive towards
1
methanol; after 24 h at r.t., the H NMR spectrum remained
ꢀ
1
7
unchanged and only 18% of 1 was converted to 1-iodo-
4-methoxy-benzene after warming for 1.5 h at 60 C. The
stability of the neat solid compounds is similar; while 1
1
3
°
can be stored under nitrogen atmosphere at approx. 0
°
C
1
4
over months, compound 2 was largely converted to the iodo
compound within several weeks (under loss of oxygen?).
Unlike iodosylbenzene, the two compounds did not react
with methanol to give the iodosyl-dimethoxide derivative
(see above). Attempts with stirring in methanol at r.t. or at
elevated temperature for 1 h under nitrogen afforded always
mixtures of iodosyl and iodo compounds in highly varying
compositions.
3
ꢁ
2
.
1
5
conversion to iodosylbenzene diacetate PhI(OAc)2.
Therefore, we tested the solubility of freshly prepared 1
and 2 in more polar solvents such as deuterated dimethylsulf-
oxide (DMSO), acetonitrile and methanol, monitoring the
solutions by H NMR. DMSO proved to be inapplicable;
since it reacted with 2 causing a complete reduction of the
iodosyl group. Only the H NMR signal characteristics of
-iodo-4-nitro-benzene were detected. The solubility of 1 in
acetonitrile was too low, whereas 2 could be largely dissolved
only by heating (5 min at 70 °C), thereby changing the orange
red suspension to a pale yellow solution. According to the H
1
1
The 13C NMR spectra (Table 1) confirm the substantial
decrease of the strong shielding of the ipso-carbon atom by
iodine, typical for aryl iodides and described as a general
feature for a wide range of substituted polyvalent iodine
1
7
1
compounds.
NMR spectrum, only the signals of 1-iodo-4-nitro-benzene
were observed suggesting that acetonitrile was also oxidized.
To our knowledge, the direct oxidation of nitriles by polyva-
lent iodine compounds has not been reported except for the
Table 1. 1H and 13C NMR data of iodosyl derivatives 1 and 2;
the assignment of the latter is based on APT experiment
H/C
1H
13C
reaction of aldoximes with (dichloroiodo)benzene (PhICl
2
),
which afforded reactive, mostly unstable, nitrile oxides and
corresponding dimerization products via 1,3 cycloaddition.
CD3OD
1
6
1
1
2
3
4
5
1
1
2
3
4
-Iodosyl-4-methoxy-benzene (1)
The two substances are moderately soluble in methanol
–
113.2
135.6
117.4
163.3
56.2
1
and provided reasonable H NMR spectra (Table 1) with
7.93–7.97, AA‘XX’
7.07–7.11, AA‘XX’
a significant downfield shift of aromatic proton signals
versus the iodo compounds. This is consistent with the
distinct electron-withdrawing effect of the iodosyl group
–
3.88
1
7
as expected from calculated group electronegativities.
-Iodosyl-4-nitro-benzene (2)
Methanolic solution of 1-iodosyl-4-nitro-benzene has no
long-term stability. After it was allowed to stand for
–
127.6
133.9
126.5
150.8
8.37–8.41, AA‘XX’
8.25–8.29, AA‘XX’
–
1
several hours at room temperature, the H NMR signals
of 1-iodo-4-nitro-benzene appeared and increased steadily
(Figs 1, 2). This can be explained by the fact that 2 gradually
H COCO
OCOCH3
3
I
I
IO
R = CH O:
3
NaIO4/glacial acetic acid
NaOH/THF
R = NO2:
NaBO × 4H O/glacial acetic acid
3
2
R
R
R
Scheme 2. Preparation of 1-iodosyl-4-methoxy-benzene (1) and 1-iodosyl-4-nitro-benzene (2).
Copyright  2006 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2006; 44: 955–958
DOI: 10.1002/mrc

NMR study of aromatic iodosyl compounds 957
1
Figure 1. H NMR spectrum of freshly dissolved 1-iodosyl-4-nitro-benzene in CD3OD. Inset A: after 3 h, inset B: after 96 h.
100
9
8
7
6
5
4
0
0
0
0
0
0
0
10
20
30
40
50
60
70
80
90
100
Time (h)
room temp.
15 min at 60°C
Figure 2. Temporal decrease of the concentration of 2 in CD3OD at ambient and elevated temperature.
Thin layer chromatography (TLC) of 1 and 2 points to a
much higher polarity of these substances in comparison to the
iodo compounds. To confirm this and to identify the degree
of aggregation for compounds 1 and 2, we performed HPLC-
MS analyses. Both compounds demonstrated very different
retention times from the iodo- and all other halogen reference
substances. In the ESI-MS spectra we found molecular peaks
by methanol without further reaction. Regarding the two
C
ꢀ
resonating structures I O !ꢀ I –O , the iodine–oxygen
2
0
bond has probably at least a semipolar character.
The υ values of the aromatic protons for 2 are clearly
shifted downfield compared to 1, i.e. the electron density at
the C–H bonds is reduced because of the –I, –M effect of the
nitro group. The electron density at the iodine–oxygen bond
in 1-iodosyl-4-nitro-benzene should also be decreased, thus
leading to a facilitated release of oxygen and to an increased
oxidizing effect. Conversely, electron-donating substituents
are expected to enhance the nucleophilicity of R–Ph–IO and
possibly promote the association tendency of monomeric
C
of medium intensity, strong peaks for the [R ꢀPh ꢀI]
fragment, and weak signals probably consistent with dimeric
molecules but no evidence for higher units. Interestingly,
distinct fragment peaks were observed for compound 1
C
that match with corresponding iodoniumions [ꢀR-Phꢁ
2
ꢀI] .
2
1
These results are less compatible with a polymeric structure,
confirming that the structure of iodosylbenzene is different
from these substituted derivatives. This suggests that 1 and
units. However, both electron-donating (–OCH
3
) and
electron-withdrawing (–NO ) substituents seem to affect
2
2
1
similarly the iodosyl group. Gao et al. observed such
2
exist rather as monomeric units or are depolymerized
an effect of enhanced reactivity towards metal carbonyls.
Copyright  2006 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2006; 44: 955–958
DOI: 10.1002/mrc

958
A. Hiller, J. T. Patt and J. Steinbach
On the other hand, the function of iodosylbenzene as an
oxygen donor for the epoxydation of stilbene was completely
stopped by insertion of a para-nitro group.
Acknowledgement
The authors thank Dr T. Kniess (Institut f u¨ r Radiopharmazie,
Forschungszentrum Rossendorf) for providing independent ESI-MS
analyses.
1
1
EXPERIMENTAL
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-Iodosyl-4-methoxy-benzene (1)
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ꢀ
1
(
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-Iodosyl-4-nitro-benzene (2)
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Copyright  2006 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2006; 44: 955–958
DOI: 10.1002/mrc