Note: Descriptions are shown in the official language in which they were submitted.
Z002599
PROCESS FOR THE ELECTROCHEMICAL
IODINATION OF AROMATIC COMPOUNDS
Field of Invention
The present invention relates to the
electrochemical iodination of aromatic compounds to
selectlvely and efflciently form a para-substituted
iodobenzene derivative.
Back~round of the Invention
Iodoaromatics are desirable materials because of
the wide variety of transformations they can
undergo. For example, they can be catalytically
; carbonylated to form aromatic carboxylic acids and
esters. Iodoaromatics are therefore possible
starting materials for polycarbonates,~polyamides,
polysulfides, and polyesters. The halogenation with
i molecular''halogen is one of the classic reactions of
: ! aromatic substitution and has been thoroughly
investigated owing to its'theoretical as well as
synthetic value (H. P. Braendlin and E. T. McBee in
; ' Friedel-Crafts and Related'Reactions ed. G. A. Olan,
Wiley, New York, 1964, Volume 3, Ch. 46.) The
electrophilicity of molecular chlorine and bromine
allo~s~thé~direct reactlon ~of these halogens with
arenes. ~The diréct iodination of aromatic substrates
with molecular iodine has~`proven difficult and needs
the presènce of an activator to be successfully
carried out except for a~"few~special cases. The most
widely employed strategy consists of the use of a
powerful oxidant in order to produce a strongly
electrophilic species (A.-Shlmizu,~K. Yamataka, and
T. Isoya,-Bull. Chem. Soc.~-JaP., 58, 1611 (1985) and
references ci~ed therein.").; Other approaches have
I included polarizing I2 with a Lewis acid,
t ' ~ ~
2002599
(S. Uemura, A. Onoe, and M. Okano Bull. Chem. Soc.
JaP., 47(1), 147 (1974); T. Sugita, M. Idei,
Y. Ishibashi, and Y. Takegami, Chem. Lett., 1481
(1982)), thallation followed by reaction with iodide
ion, (A. McKillop, et al., J. Am. Chem. Soc., 93,
4841 (1971)), chloro mercuration followed by reaction
with iodine, (L. F. Fieser and M. Fieser Rea~ents for
Or~anic Smthesis, Wiley, New York, 1967, p 497), and
diazonium salt reaction with iodide ion.
(N. I. Foster, N. D. Heindell, H. D. Burns, and
W. Muhr, Smthesis, 572 (1980)). All of these
procedures have deficiencies.
The electrochemical iodination of aromatics has
been reported. (L. L. Miller, E. P. Kujawa, and
C. B. Campbell, J. Am. Chem. Soc., 92, 2821 (1970);
R. Lines and U. D. Parker Acta Chem. Scand., Ser B,
34, 48 (1980)). Parker and co-workers found that the
anodic oxidation of iodine in trifluoroacetic acid
containing solvents produces a highly reactive iodine
species. However, the selectivity of the system
toward the desirable para disubstituted isomers was
poor. (R. Lines and U. D. Parker Acta Chem. Scand.,
Ser B, 34, 48 (1980)). It would be desirable to have
an electrolytic process that will afford high
reactivity as well as high selectivity to the highly
desirable para-disubstituted arenes.
SummarY of the Invention
The present process is an electrolytic process
that provides selective and efficient formation of a
para-substituted iodobenzene derivative. This
process makes use of a graphitic carbon anode. More
specifically, the present invention is directed to an
electrolytic process for the formation of a
20025i99
para-substituted iodobenzene derivative comprising
contacting:
an anolyte solution of a divided electrolytic
cell, wherein said divided electrolytic cell
comprises:
an anode compartment comprising a graphitic
carbon anode and said anolyte solution
which comprises solvent and an electrolyte;
and a cathode compartment comprising a
cathode and a catholyte solution which
comprises solvent and an electrolyte;
wherein said anode compartment and cathode
compartment are separated by a separator,
with
an iodine source, and a mono-substituted
compound of the formula:
.~ \.
!\R
wherein R is alkyl, halo, unsubstituted aryl, or
aryl substituted with up to 5 electron-donating
groups such as hydroxyl, thiol, -SR', -OR',
wherein R' is a Cl-C6 alkyl, or phenyl, and
applying to the anode and the cathode an electric
potential; the proportions of materials, electrical
potential, and other conditions being effective to
form a para-substituted iodobenzene derivative in
said anode compartment.
This process for the formation of a
para-substituted iodobenzene derivative shall be
referred to herein as "Process I."
In a preferred process of the invention benzene
is used as a starting material to form iodobenzene
followed by the further iodination of the
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_ 4 _
iodobenzene. Therefore, the present invention also
encompasses an electrolytic process for preparing
iodobenzene comprising contacting:
an anolyte solution of a divided electrolytic
cell, wherein said divided electrolytic cell
comprises:
an anode compartment comprising a graphitic
carbon anode and said anolyte solution
which comprises a solvent and an
electrolyte; and a cathode compartment
comprising a cathode and a catholyte
solution which comprises a solvent and an
electrolyte; wherein said anode compartment
and cathode compartment are separated by a
separator,
with
an iodine source, and benzene, and
applying to the anode and the cathode an electric
potential; the proportion of materials, electric
potential, and other conditions being effective to
form iodobenzene.
This process for preparing iodobenzene shall be
referred to herein as "Process II."
In carrying out the present invention, it was
found that a diiodobenzene could conveniently be
deiodinated cathodically, in the presence of a
palladium on carbon catalyst, to iodobenzene, which
facilitates a continuously run operation. Therefore,
the present invention is also directed to an
30 electrolytic process for preparing iodobenzene
comprising contacting a catholyte solution of a
divided electrolytic cell wherein said divided
electrolytic cell comprises
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- 5 -
an anode compartment comprising an anode and an
anolyte solution which comprises a solvent and
an electrolyte; and a cathode compartment
comprising a cathode and a catholyte solution
S which comprises a solvent and an electrolyte;
wherein said anode compartment and cathode
compartment are separated by a separator,
with
a diiodobenzene compound of the formula
I~.,i!
in the presence of a catalytic amount of palladium on
carbon, and applying to the anode and cathode an
electric potential; the proportion of materials,
electric potential, and other conditions being
sufficie~nt to form iodobenzene.
This cathodic deiodination process shall be
referred to herein as "Process III."
As used herein, the term "halo" refers to
chloro, bromo, fluoro or iodo; the term "alkyl"
refers to Cl to C16 straight, branched or cyclic
alkyls; and the term "aryl" refers to aryls
containing six to 14 carbon atoms.
Detailed DescriPtion of the Invention
~ Any of Process I, Process II, or Process III can
be carried out batchwise; however, for most
industrial applications, it is preferred to perform
these processes continuously. Therefore, it is
preferred to couple Process I with Process II and/or
Process III. A preferred process of the present
invention is a continuous process in which Process I
is performed simultaneously with Process III. This
preferred process can be described as a continuous
Z00259!3
- 6 -
electrolytic process for the formation of
para-diiodobenzene comprising:
(A) contacting
an anolyte solution of a divided electrolytic
cell, wherein said divided electrolytic cell
comprises:
an anode compartment comprising a graphitic
carbon anode and said anolyte solution
which comprises a solvent and an
electrolyte, and a cathode compartment
comprising a cathode and a catholyte
solution which comprises a solvent and an
electrolytet wherein said anode compartment
and cathode compartment are separated by a
separator, and wherein said catholyte
solution and said anolyte solution are the
same and comprise a tetrafluoroborate
electrolyte and an acetonitrile solvent;
with
an iodine source, and iodobenzene, and
applying to the anode and the cathode an
electric potential; the proportions of
materials, electric potential, and other
conditions being effective to form
para-diiodobenzene,
(B) filtering the anolyte solution containing
para-diiodobenzene formed in Step (A) to obtain
a solid which comprises para-diiodobenzene and a
filtrate which comprises an electrolyte, a
solvent and at least one diiodobenzene compound
of the formula:
.~ \./
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(C~ adding the filtrate from Step (B) to said
cathode compartment,
(D) deiodinating the diiodobenzene compound in the
cathode compartment from Step (C) to form
iodobenzene by applying to the anode and cathode
an electric potential, wherein the catholyte
solution and diiodobenzene compound are in the
presence of a catalytic amount of palladium on
carbon; the proportions of materials, electric
potential, and other conditions being suficient
~o form iodobenzene; and
(E) recycling the iodobenzene formed by Step (D) as
a starting material for Step (A).
When Process I is coupled with Process II, it is
preferred that such process be performed
consecutively in the same electrolytic cell. As a
result, the iodobenzene formed from Process II is
used as a starting material for Process I.
In any of the processes of the present invention
it is preferred that the electric potential applied
to the anode and cathode is about 1.5 to about 2.5
volts, more preferred is about 2 volts.
It is preferred that the processes of the
present invention are performed at a temperature of
about 25 to about 100C, more preferred is about 25
to about 50C; and at a pressure of about 1
atmosphere (atm) to about 10 atm, more preferred is
about 1-2 atms.
If one or more processes of the pre~ent
invention is run as a batch process, typically the
electric potential is applied for a period of time of
about 1 to about 25 hours, preferred is about 2 to
about 8 hours.
If desired, additives such as CF3CO2H,
(Et)4NBF4, or trisbromophenyl amine can be added
to the reaction medium in the processes of the
2002599
- 8 -
present invention; however, the presence of such
additives are not necessary. If one or more
additives are used, they are typically present in a
concentration of up to about 10 percent, based on
solvent weight.
In the processes of the present invention, the
cathode compartment and anode compartment are
separated by a separator such as a membrane, fritted
glass, and the like. Preferably this separator is a
membrane. A preferred membrane is a Nafion
membrane.
For Process I, the nature of the anode is
important. It has been found that the anode must be
comprised of graphitic carbon in order for the
iodination process to be sufficiently effective. The
graphitic anode can be comprised of spectral grade
graphite or can be any other suitable graphite
electrode.
The nature of the, cathode for any of the
processes of the invention, is not particularly
critical. The cathode can be comprised of platinum,
carbon, copper, lead, tin, palladium, stainless
cteel, or combinations thereof. However, since
Process III must proceed in the presence of palladium
or carbon, it is convenient for the cathode in
Process III to be comprised of palladium on carbon.
The solvents and electrolyte in the cathode and
anode compartments for any of the processes of the
present invention can be the same or different;
however, it is usually more convenient for the
electrolyte and solvents to be the same in each
compartment.
Preferred solvents are polar organic aprotic or
protic solvents. Examples include methanol, ethanol,
acetonitrile, tetrahydrofuran, dimethylformamide,
dimethylsulfoxide, dimethyl ether, diethyl ether,
20025;99
_ g _
acetic acid (HOAc), or a mixture thereof. The most
preferred solvent is acetonitrile.
The electrolyte is present in a concentration
sufficient to give the total reaction medium
sufficient conductivity at reaction conditions in
order for the desired process to proceed
satisfactorily. A preferred electrolyte is a
tetrafluoroborate. Examples include substituted
tetrafluoroborates such as, HBF4, NaBF4,
(Me)4NBF4, (Et)4NBF4, (Pr)4NBF4, or
(Bu)4NBF4 wherein Me is methyl, Et is ethyl, Pr
is propyl and Bu is butyl. The most preferred
electrolyte is HBF4, (Me)4NBF4 or
( )4 BF4.
In Process I, in addition to the formation of
said para-substituted iodobenzene derivative,
typically minor amounts of the other isomers are also
formed, espécially an ortho-substituted iodobenzene
derivative. It is an advantage of the present
invention that the yield of the para-substituted
compound is greater than the yield of the
ortho-substituted compound. Preferably the mole
ratio of para-substituted iodobenzene derivative to
ortho-substituted iodobenzene derivative after
reaction is greater than about 1:1 to about 100:1.
For Process I, the following are preferred
embodiments: the weight ratio of the iodine source
to the mono-substituted compound to the anolyte
solution is about 2.5:3.0:100 to about 1.0:15.0:100,
and the weight ratio of electrolyte to solent of the
anolyte solution is about 1:1 to about 1:100; said
election-donating group is alkyl, hydroxyl, thiol,
-OR', or -SR'; the iodine source is iodine (I2) or
an iodine salt such as HI, NaI, KI, or an alkyl
ammonium iodide.
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In Process I, most preferably R is I and the
iodine source is most preferably I2.
It is also an advantage of Process I that the
purity of the para-substituted iodobenzene derivative
is typically greater than about 98 weight percent,
preferably greater than about 99 weight percent,
after isolation by standard techniques. When forming
para-diiodobenzene, this compound can be isolated
simply by cooling the electrolysis mixture until the
desired compound becomes a solid, typically less than
about 15C, followed by filtering. By this simple
isolation procedure, typically greater than about 80
weight percent of the available para-isomer can be
obtained. It is also preferred that the yield of
para plus ortho derivatives is greater than about 60
percent preferably greater than about 90 percent,
based on the weight of consumed iodine source.
Typical by-products formed include iodonium salts.
For Process I, the selectivity for
para substitution appears to be independent of the
working potential. It is not desired to be bound by
any particular theory or mechanism; however, it is
believed that the independence of para selectivity
from working potential, together with the advantages
of using a graphitic carbon anode, suggests that the
mechanism of iodination may be more complex than a
simple electrophillic attack on an "I+" species.
For Process II, it is preferred that the weight
ratio of the iodine source to benzene to the anolyte
solution is about 1.25:2.0:100 to about 2.5:1.0:100,
the weight ratio of electrolyte to solvent in the
anolyte and catholyte solutions is about 1:10 to
about 1:100, and that the iodine source is iodine.
For Process III, it is preferred that the weight
ratio of the diiodobenzene compound:catholyte
solution is about l:10 to about 1:100; the weight
2002ti99
ratio of electrolyte:solvent in the anolyte and
catholyte solutions is about 1:10 to about 1:100; and
that the diiodobenzene starting material is
ortho-diiodobenzene.
Process III must be performed in a catalytic
amount of palladium on carbon catalyst. Such a
catalytic amount is typically at least about 0.001~,
based on the weight of diiodobenzene starting
material, preferably about 0.01%.
For the examples that follow, the following
experimental conditions were used: Electrolysis was
performed in an H-type cell where the anode and
cathode were separated by a Nafion membrane. In each
case, the cathode was a spectroscopic (UltraCarbon,
U50) carbon rod. All reactions were run at the
indicated constant potential by way of an ESC Model
410 potentiostatic controller. The electrochemical
apparatus was fitted with an ESC Model 630 digital
coulometer and, in each case, the theoretical number
of coulombs was collected. The cell temperature was
not controlled and usually rose to about 28~C in the
course of an experiment.
The following examples illustrate ~he invention
but should not be interpreted as a limitation
thereon.
EXAMPLES
ExamPle 1 - Iodination of Toluene
To the anode side of a laboratory H cell fitted
as previously described is added 100 milliliters (mL)
of a solution made up by adding sufficient 50%
aqueous HBF4 to acetic anhydride/acetic acid so the
final concentration of HBF4 is 10% by weight and
the water concentration is from 1% to 3~ by weight.
To this solution is added 2.54 grams (g) (0.01 mole)
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-- 12
iodine and 3.0 g (0.031 mole) toluene. The cell is
fitted with the various anodes as shown in Tables 1
and 2. To the cathode compartment is added the same
acetic acid/tetrafluoroboric acid solution as in the
anode. The cathode is a carbon rod in each case.
The potential is set at 2.00 volts versus SCE
(saturated calomel electrode), and current is passed
through the electrolysis solution. The electrolysis
is stopped after 1930 coulombs are passed. The
product is isolated by pouring the anode solution
into 500 mL of water and extracting three times with
50 mL of methylene chloride each time. The extracts
are combined and washed with 100 mL of water. The
organic layer is dried over magnesium sulfate and the
solvent is removed in vacuo to afford 4.3 8 of a
light color oil. The product is analyzed by
capillary gas chromatograph versus authentic samples
to establish the yield and ortho-para ratio.
Example 2 - Iodination of Iodobenzene
The electrolysis apparatus employed is as
previously described. The catholyte and anolyte
solutions are prepared as described for the
electrolysis of toluene. To the anode compartment is
added 1.26 8 of iodine (5 mmols) and 2.04 g of
iodobenzene (10 mmols). The system is electrolyzed
at a constant potential of 1.7 volts versus SCE.
After pa~sing 965 coulombs, the electrolysis is
stopped. The anode mixture is cooled to 15C and the
resulting solid isolated by filtration. After water
wash and air drying, the solid weighs 2.1 g (64%
isolated yield) and is shown by capillary gas
chromatography to be 100~ ~-diiodobenzene.
200ZS99
- 13 --
ExamPle 3 - Iodination of Benzene
The electrolysis apparatus is as previously
described. The catholyte and anolyte solutions are
prepared as described for the electrolysis of
toluene. To the anode compartment is added 2.54 g
(0.01 mole) iodine and 2.42 g (0.031 mole) benzene.
The system is electrolyzed at a constant potential of
2.0 volts vs SCE. The electrolysis is stopped after
1950 coulombs are passed. The product is isolated by
pouring the anode solution into 500 mL water and
extracting three times with 50 mL of methylene
chloride. The extracts are combined and washed with
100 mL water. The organic layer is dried over
magnesium sulfate and the solvent removed in vacuo to
afford 4.1 g of a light yellow oil. The product is
analyzed by capillary gas chromatography to afford
iodobenzene chemical yield of 95~ based on iodine.
ExamPle 4 - Iodination of Toluene
The procedure of Example 1 is substantially
repeated except that the working potential is
varied. The para selectivity versus working
potential is shown in Table 3.
Z002S99
- 14 --
TABLE l
Electrochemical Iodination of
Toluene in HoAc/10~ HBF4
Products - ~ Yield op + pp
5Iodine p-Iodo- o-Iodo- Iodonium
Anode Source Additives toluene tolueneSalt
Graphitic I2 None53.8 32.1 8.4
Carbon
Graphitic HI None62.0 32.6 1.2
Carbon
Graphitic I2 Et4NBF440.8 38.5
8.0
Carbon
Graphitic I2 CF3C02H9.2 5.5
29.7
Carbon
Pt I2 CF3CO2H1.0 0.4
2.8
RVC3 I2 None 3.9 2.5
20 Pt/Ir/Ti I2 None 2.9 1.8
Graphitic I2 Trisbromo- 54.0 32.9 7.2
Carbon phenyl
Amine
Ebonex I2 None 10.6 6.0
25 Footnotes:
All reactions were run in a divided cell with a
Nafion membrane at 2.00 volts versus SCE.
Isolated yield based on iodine.
RVC = reticulated vitreous carbon.
op + pp = ortho para and para para.
Ebonex is a trade name for conductive TiO2.
20025i99
- 15 -
~ o cl
a~ ~ I _, ~ ,,
o I o o . ~ ~
o ~ 0
l I Q~
o~ O C
~o :~ o o , ~ o
O I O O ~ 0
o ~ Z _~
V ~ O O ~ ~
o Q~ ~I c o o
V , :~ .
C U oC Q~ ~ C a~
Q~ ~ C ~: C
~t V V V ~ V _~ o
. ' ' ~'` ~ , ~
2002599
- 16 ~-
TABLE 3
Para Selectivity of Toluene
Iodination Versus
Working Potential
5 Workin~__otential % Para Iodotoluene
1.7 v 62%
1.8 v 61%
1.9 v 66%
2.0 v 65%
2.1 v 62%
At carbon anode in a divided cell.
2Potential versus SCE.
The invention has been described in detail with
particular reference to preferred embodiments
thereof, but it will be understood that variations
and modifications can be effected within the spirit
and scope of the invention.
