The electrochemical methods8,9 have received significant
an aromatic compound gave much a better yield of the
10
research interest from both academia and industry because
corresponding aromatic iodide than the electrolysis of a mixture
11
13
they serve as environmentally benign processes for organic
synthesis. It is particularly noteworthy that the electrochemical
reactions serve as excellent methods for the generation of
of I
2
and an aromatic compound (in situ method). This is
presumably because of undesirable side reactions such as the
side-chain oxidation caused by direct electron transfer from the
aromatic compound.
12
reactive species under mild conditions. In the 1970s Miller
and co-workers reported that the electrochemical oxidation of
The sequential method has another advantage over the in
situ method. The polyiodination problem for highly reactive
+
iodine gave “ I ”, which reacted with a wide range of aromatic
13
16
compounds to give the corresponding aromatic iodides (eq 2).
aromatic compounds based on disguised chemical selectivity
17
could also be avoided by extremely fast 1:1 micromixing of
a solution of preformed I and a solution of an aromatic
+
15
compound.
For these reasons, we decided to employ the one-pot
sequential method for developing a practical electrochemical
iodination of aromatic compounds.
Supporting Electrolyte/Solvent System. The choice of a
supporting electrolyte/solvent system is very important for the
success of the reaction because it determines the nature of a
reactive intermediate generated by the electrolysis. The choice
of a supporting/electrolyte system is also important from a
practical point of view, such as cost, ease of product separation,
and wastes.
Recently, we reported that selective monoiodination of highly
reactive aromatic compounds with the electrochemically gener-
+
14
ated “ I ” could be achieved using extremely fast 1:1 mixing
using a micromixer.1
5
With such information in hand, we initiated our study on a
practical method of electrochemical iodination of aromatic
compounds that is suitable for industrial production of aromatic
iodides. Herein we report the results of this study.
Miller and co-workers reported that the use of LiClO4/
CH
.0 F/mol based on I
of water in anhydrous LiClO
of Et NClO /CH CN gave better results and that Bu
CH Cl could be also used for the oxidation of I .
3
CN requires an excess amount of electricity (greater than
) presumably because of the contamination
. They also reported that the use
NBF
2
2
Results and Discussion
4
4
4
3
4
4
/
The in Situ Method or the Sequential Method. Miller and
co-workers reported that the sequential method involving anodic
2
2
2
4 4
Quaternary ammonium salts such as Bu NBF are commonly
+
oxidation of I
2
to form reactive I followed by the addition of
used for laboratory electroorganic synthesis because of good
solubility in organic solvents. However, the use of such
quaternary ammonium salts is problematic from a viewpoint
of industrial applications, because of high costs and difficulty
in separation from products after electrolysis. Recovery and
reuse of quaternary ammonium salts are also difficult.
(
8) (a) Lund, H.; Hammerich, O. Organic Electrochemistry, 4th ed.;
Marcel Dekker: New York, 2001. (b) Shono, T. Electroorganic
Chemistry as a New Tool in Organic Synthesis; Springer: Berlin, 1984.
(
2
c) Fry, A. J. Electroorganic Chemistry, 2nd ed.; Wiley: New York,
001. (d) Shono, T. Electroorganic Synthesis; Academic Press:
London, 1990. (e) Little, R. D., Weinberg, N. L., Eds. ; Electroorganic
Synthesis; Marcel Dekker: New York, 1991. (f) Shono, T. In The New
Chemistry; Hall, N., Ed; Cambridge University Press: Cambridge,
Inorganic salts are usually much cheaper than quaternary
ammonium salts. However, low solubility of inorganic salts in
common organic solvents causes severe limitation in electro-
2
000; p 55. (g) Grimshaw, J. Electrochemical Reactions and Mech-
2
organic synthesis. It is noteworthy that I dissolves in organic
anisms in Organic Chemistry; Elsevier: Amsterdam, 2000. (h) Sains-
bury, M., Ed.; Rodd’s Chemistry of Carbon Compounds; Elsevier:
Amsterdam, 2002. (i) Torii, S. Electroorganic Reduction Synthesis;
Kodansha: Tokyo, 2006; Vols. 1 and 2.
solvents and that solubility of I in water is very low.
2
Therefore, we initiated our study with searching for sup-
porting electrolyte that is suitable for industrial applications.
We focused on protic acids (HX) as supporting electrolyte,
because reduction of proton is expected to serve as a good
(
9) Selected reviews: (a) Sch a¨ fer, H. J. Angew. Chem., Int. Ed. Engl. 1981,
2
0, 911. (b) Shono, T. Tetrahedron 1984, 40, 811. (c) Utley, J. Chem.
Soc. ReV. 1997, 26, 157. (d) Moeller, K. D. Tetrahedron 2000, 56,
9
527. (e) Lund, H. J. Electrochem. Soc. 2002, 149, S21. (f) Sperry,
cathodic reaction as a counterpart of the anodic oxidation of I
as shown in Figure 2. I loses two electrons at the anode to
generate two I . X that is derived from HX serves as a
2
J. B.; Wright, D. L. Chem. Soc. ReV. 2006, 35, 605. (g) Yoshida, J.;
Kataoka, K.; Horcajada, R.; Nagaki, A. Chem. ReV. 2008, 108, 2265.
2
+
-
(
10) Industrial applications of electroorganic reactions. For examples:(a)
Hoormann, D.; Kubon, C.; J o¨ rissen, J.; Kr o¨ ner, L.; P u¨ tter, H. J.
Electroanal. Chem. 2001, 517, 215. (b) Pletcher, D.; Walsh, F. C.
Industrial Electrochemistry, 2nd ed.;Chapman and Hall: London, 1990.
+
+
counteranion of I . At the cathode two H that are derived from
HX receive two electrons to generate H . Therefore, HX is
2
expected to serve as both a proton source and supporting
electrolyte.
(
c) Beck, F. J. Appl. Electrochem. 1972, 2, 59. (d) Baizer, M. M.
J. Appl. Electrochem. 1980, 10, 285.
(
(
11) Matthews, M. A. Pure Appl. Chem. 2001, 73, 1305.
Thus, the electrochemical oxidation reactions of I
2
(0.5
12) Recently we have developed a one-pot sequential method involving
electrochemical generation of highly reactive organic cations followed
by the reaction with a nucleophile (the cation-pool method). (a)
Yoshida, J.; Suga, S.; Suzuki, S.; Kinomura, N.; Yamamoto, A.;
Fujiwara, K. J. Am. Chem. Soc. 1999, 121, 9546. (b) Suga, S.; Suzuki,
S.; Yamamoto, A.; Yoshida, J. J. Am. Chem. Soc. 2000, 122, 10244.
mmol) were carried out in CH CN using various protic acids
3
as supporting electrolyte. An H-type divided cell (4G glass filter)
equipped with a platinum plate anode (25 mm × 30 mm) and
(
c) Yoshida, J.; Suga, S. Chem. Eur. J. 2002, 8, 2650. (d) Suga, S.;
(14) CSI-MS studies suggested that I+ is mainly existing as (CH3CN)2I+
+
Watanabe, M.; Yoshida, J. J. Am. Chem. Soc. 2002, 124, 14824. (e)
Suga, S.; Nishida, T.; Yamada, D.; Nagaki, A.; Yoshida, J. J. Am.
Chem. Soc. 2004, 126, 14338. (f) Okajima, M.; Suga, S.; Itami, K.;
Yoshida, J. J. Am. Chem. Soc. 2005, 127, 6930. (g) Maruyama, T.;
Suga, S.; Yoshida, J. J. Am. Chem. Soc. 2005, 127, 7324. (h) Suga,
S.; Matsumoto, K.; Ueoka, K.; Yoshida, J. J. Am. Chem. Soc. 2006,
and that CH3CN is partially liberated to give CH3CNI . Hereafter,
reactive iodine species generated by electrochemical oxidation is
+
simply designated as I in this paper.
(15) Midorikawa, K.; Suga, S. Yoshida. J. Chem. Commun. 2006, 3794.
(16) (a) Rys, P. Acc. Chem. Res. 1976, 10, 345. (b) Rys, P. Angew. Chem.,
Int. Ed. Engl. 1977, 12, 807.
1
28, 7710.
(17) For example: (a) Nagaki, A.; Togai, M.; Suga, S.; Aoki, N.; Mae, K.;
Yoshida, J. J. Am. Chem. Soc. 2005, 127, 11666. (b) Suga, S.; Nagaki,
A.; Yoshida, J. Chem. Commun. 2003, 354. (c) Yoshida, J.; Nagaki,
A.; Iwasaki, T.; Suga, S. Chem. Eng. Technol. 2005, 28, 259.
(
13) (a) Miller, L. L.; Kujawa, E. P.; Compbell, C. B. J. Am. Chem. Soc.
1970, 92, 2821. (b) Miller, L. L.; Watkins, B. F. J. Am. Chem. Soc.
1976, 98, 1515.
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