Selective monoiodination of aromatic compounds with electrochemically generated I+ using micromixing

Article abstract of DOI:10.1039/b607284d

Selective monoiodination of aromatic compounds such as dimethoxybenzene has been successfully achieved with I⁺, which is generated by anodic oxidation of I₂ in acetonitrile, using micromixing. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b607284d

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Selective monoiodination of aromatic compounds with electrochemically
+
generated I using micromixing{
a
Koji Midorikawa, Seiji Suga and Jun-ichi Yoshida*
b
b
Received (in Cambridge, UK) 23rd May 2006, Accepted 17th July 2006
First published as an Advance Article on the web 3rd August 2006
DOI: 10.1039/b607284d
Selective monoiodination of aromatic compounds such as
+
dimethoxybenzene has been successfully achieved with I ,
place selectively using a microsystem consisting of a micromixer
and a microtube reactor.
which is generated by anodic oxidation of I
using micromixing.
2
in acetonitrile,
Miller and co-workers reported that the electrochemical
+
oxidation of iodine (I ) in acetonitrile gave CH CNI (equivalent
2
3
+
of I ) (eqn (1)) and that this reagent reacted with aromatic
Aromatic iodides are important intermediates in the synthesis of
1
functional materials and biologically active compounds. Although
compounds to give the corresponding iodinated aromatic com-
+
pounds (eqn (2)), although CH CNI was not well-characterized
3
8
various methods for the synthesis of aromatic iodides have been
2
developed so far, iodination of aromatic compounds serves as one
spectroscopically.
3
(1)
of the most straightforward routes to aromatic iodides.
Iodination of aromatic compounds, however, is sometimes
problematic because diiodination takes places together with
monoiodination, especially in the case of highly reactive aromatic
compounds. Selectivity for such competitive consecutive reactions
is intrinsically determined by kinetics. However, if the reaction is
faster than mixing, simple kinetics based on the homogeneity of
the solution does not work. Rys proposed the concept of
+
+
ArH + ‘‘CH
CN–I ’’AAr–I + CH
CN + H
(2)
3
3
+
CNI was obtained as
Romakhin et al. also reported that CH
3
9
cream-coloured powder by the anodic oxidation of I in CH CN.
2 3
Although they said that the powder did not exhibit IR absorption
due to the vibration of the CN triple bond, no other information
was available.
‘
‘disguised chemical selectivity’’ and pointed out the importance
4
of the way of mixing to control chemical reactions. Thus, we
It is important to know the nature of the reactive species in
order to carry out 1 : 1 mixing strictly using a micromixer. We
began our study with characterizing the electrochemically
envisioned that the problem of monoiodination/diiodination
selectivity can be solved by controlling the way of mixing.
Recently, we have reported that the product selectivity of
extremely fast competitive consecutive reactions such as Friedel–
Crafts alkylation of highly reactive aromatic compounds with an
electrochemically generated highly reactive N-acyliminium ion
generated reactive iodine species. Following Miller’s protocol,
+
‘I ’’ was generated by the anodic oxidation of I (0.0625 M) in
‘
2
0
4 4 3
.1 M Bu NBF –CH CN at 0 uC. The electrolysis was carried out
using a platinum plate anode and a platinum plate cathode under
constant current conditions in an H type divided cell. The mixture
thus obtained was directly measured by CSI-MS (cold spray
ionization mass spectrometry, a variant of electrospray (ESI) MS
operating at low temperature, which is quite useful to identify
5
6
pool was improved significantly by using micromixing. The
monoalkylation product was obtained selectively when two
reaction components were mixed in 1 : 1 ratio using an
multilamination type micromixer (IMM micromixer), whereas a
significant amount of dialkylation product was formed in a macro-
scale batch process (reaction using a flask with magnetic stirring).
The observations indicate that micromixing is quite effective for
the improvement of product selectivity of extremely fast reactions
10
labile reactive species). The signal which could be assigned to
+
CH
Fig. 1). It is interesting to note that (CH
observed (m/z = 208.9569, Calcd: 208.9570). The intensity of the
3
CNI (m/z = 167.9300, Calcd: 167.9305) was observed at 0 uC
+
2
I
(
3
CN)
was also
+
+
7
3 2 3
peak of (CH CN) I was larger than that of CH CNI , and
using highly reactive reagents.
the relative intensity depended on the ionization temperature on
As to the iodination reagent, we chose to study electrochemi-
+
cally generated ‘‘I ’’ because this method serves as an environ-
mentally benign industrial process for the synthesis of various
aromatic iodides. In this paper, we report that monoiodination of
+
aromatic compounds with electrochemically generated ‘‘I ’’ took
a
Technology Laboratory, Nippoh Chemicals Co., Ltd., Chiba, 298-0104,
Japan
b
Department of Synthetic Chemistry and Biological Chemistry,
Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto,
6
15-8510, Japan. E-mail: yoshida@sbchem.kyoto-u.ac.jp;
Fax: +81-75-383-2727; Tel: +81-75-383-2726
Electronic supplementary information (ESI) available: Experimental
details. See DOI: 10.1039/b607284d
+
Fig. 1 CSI-MS of electrogenerated I in 0.1 M Bu
{
4
NBF –CH
4
3
CN
21
2
(2.0 F mol based on I ).
3
794 | Chem. Commun., 2006, 3794–3796
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View Article Online
+
CNI increased at the expense of
CSI-MS. The amount of CH
3
+
CN) I at higher ionization temperature. These observations
(
CH
3 2
+
suggested that I is mainly existing as (CH
+
I and CH
3
CN)
2
3
CN is
+
11
partially liberated to give CH
knowledge, this is the first indication that (CH
major reactive species in solution generated by electrochemical
oxidation of I in CH CN.
3
CNI . To the best of our
+
3 2
CN) I is the
2
3
With the reactive iodine species characterized by CSI-MS in
hand, we next examined the reaction of 1,3-dimethoxybenzene
using a macro-scale batch reactor at 0 uC. The reaction with the
+
‘I ’’ generated from 0.625 equiv. of I
‘
2
(0.0625 M) in 0.3 M
21
Bu
4
NBF –CH CN with 2.1 F mol of electricity based on I gave
4 3 2
rise to the formation of the monoiodo compound as a major
product (45% yield) (eqn (3)). A significant amount of the diiodo
compound, however, was also formed (18% yield). Although roles
+
+
+
3 3 2
of the two reactive species (CH CNI and (CH CN) I ) in the
Fig. 2 Effect of flow rate of ‘‘I ’’ solution on the selectivity of iodination
of 1,3-dimethoxybenene (the flow rate of 1,3-dimethoxybenzene solution
was adjusted to the same flow rate).
iodination are not clear at present, the present observation
indicated the effectiveness of these species for the iodination of
aromatic compounds.
decreased dramatically with the decrease in flow rate. This
observation indicates that the observed improvement in selectivity
is ascribed to the extremely fast mixing.
ð3Þ
A similar effect of micromixing was observed for the reactions
of 1,2- and 1,4-dimethoxybenzene, and 1,3,5-trimethoxybenzene,
indicating the generality of the effect of micromixing on the
selectivity (eqn (4–6)).
Since a monoiodo compound should be less reactive than the
parent compound because the iodo group is an electron-with-
drawing group, the formation of the diiodo compound can be
ascribed to disguised chemical selectivity. Thus, we examined the
ð4Þ
ð5Þ
12
13,14
use of micromixing to solve the diiodination problem.
The
21
micromixing (flow rate 3.0 mL min
for each) of 1,3-
+
dimethoxybezene with electrochemically generated ‘‘I ’’ (generated
from 0.625 equiv. of I ) using a microsystem consisting of an IMM
2
single mixer (channel width 50 mm) and a microtube reactor (w =
5
00 mm 6 2 m) at 0 uC resulted in significant increase of the
selectivity (Scheme 1). The monoiodo compound was obtained in
8% yield, whereas the diiodo compound was obtained in only 4%
7
yield. The smaller effect of micromixing in the present reaction in
comparison with that observed for the Friedel–Crafts alkylation
seems to be attributed to the smaller rate of iodination because
CFD (computational fluid dynamics) simulation indicated that the
effect of the micromixing on the selectivity increases with the
ð6Þ
6b
increase in reaction rate.
The effect of the flow rate on the selectivity was examined,
because it is known that the mixing rate strongly depends on the
flow rate. The IMM single mixer gave a better mixing performance
+
In summary, (CH CN) I was found to be the major species
3
2
21 15
at larger volume flow rate (greater than a few mL min ). As
shown in Fig. 2, the selectivity of the monoiodo compound
2 3
generated by anodic oxidation of I in CH CN by using CSI-MS.
It was also revealed that the reaction with aromatic compounds
using micromixing led to selective monoiodination. The effect is
ascribed to extremely fast micromixing, which solves the problem
of disguised chemical selectivity. The present results speak well for
the potential of the combination of electrochemical generation of a
highly reactive species and the use of microsystems for selective
16–18
organic synthesis.
Further work aimed at revealing the precise
mechanism and the synthesis of various aromatic iodides in larger
1
9
scale is now in progress.
The authors are grateful to a Grant-in-aid for Scientific
Research for partial financial support.
Scheme 1 Selective monoiodination of 1,3-dimethoxybenene using
micromixing.
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3
796 | Chem. Commun., 2006, 3794–3796
This journal is ß The Royal Society of Chemistry 2006