Superactive iodination reagent on a base of iodine chloride and silver sulfate

Article abstract of DOI:10.1055/s-1999-3475

After reaction of ICl and Ag₂SO₄ in sulfuric acid and separation of resulting AgCl a stable solution is formed, containing very active forms of electrophilic iodine. This solution has a powerful iodination ability with respect to aromatic compounds. Deactivated arenes are iodinated easily and in mild conditions by action of this new reagent in generally good yields of the iodoarenes.

Full text of DOI:10.1055/s-1999-3475

7
48
SHORT PAPER
Superactive Iodination Reagent on a Base of Iodine Chloride and Silver Sulfate
Vitold K. Chaikovski, Tatjana S. Kharlova, Victor D. Filimonov,* Tamara A. Saryucheva
Department of Organic Chemistry, Tomsk Polytechnic University, Tomsk 634004, Russia
Fax +7(3822)415235; E-mail: filim@org.chtd.tpu.edu.ru
Received 23 October 1998
reported that with heating a mixture of I and Ag SO in
sulfuric acid under 100 °C a precipitation of AgI is not
2
2
4
Abstract: After reaction of ICl and Ag SO in sulfuric acid and sep-
aration of resulting AgCl a stable solution is formed, containing
very active forms of electrophilic iodine. This solution has a power-
2
4
formed within 12 hours. Silver iodide is formed only after
7
ful iodination ability with respect to aromatic compounds. Deacti- the addition of an aromatic substrate. In other words only
vated arenes are iodinated easily and in mild conditions by action of in the presence of the substrate does generation of electro-
this new reagent in generally good yields of the iodoarenes.
philic iodine from I and Ag SO occur (an alternative ex-
2
2
4
Key words: iodination, iodine chloride, aromatic compounds
planation of this phenomenon consists of the assumption
+
8
that iodination agent in this case is AgI , but there are
2
not clear experimental confirmations of this assumption).
Contrary to this fact we have found that addition of two
equivalents of ICl into the suspension of one equivalent of
Ag SO in sulfuric acid (90 wt% in water) at room tem-
Iodoarenes are valuable, versatile synthetic intermediates
and have found wide applications in medicine and bio-
chemistry. But the electrophilic nature of iodine is weaker
than bromine and chlorine. For this and other reasons
there are few methods for direct iodination of deactivated
2
4
perature leads to the immediate precipitation of AgCl. The
weight of the precipitation is an average of 90% from the
calculated. After the separation of AgCl by means of fil-
tration a stable dark-brown solution is formed. The com-
position of this solution to the best of our knowledge is
unknown and further studies are in progress in our labora-
tory. Probably the solution contains sulfate and (or) bisul-
1
aromatics known. Some arenes having electron-with-
drawing substituents can be iodinated by the I /Ag SO
2
2
4
system in sulfuric acid. Under these conditions nitroben-
zene (1a) is transformed into 3-iodonitrobenzene (2a) at
2
1
00 °C within 2–3 hours. The use of iodine in 20% fum-
+
fate of iodine or solvated I ions. Whatever the real
ing sulfuric acid (oleum) for iodination of a range of aro-
matic nitro compounds was described.3 In these
composition and structure of this solution is, it has an ex-
tremely strong ability for iodination of various deactivat-
ed aromatics 1a–g (Table). Conditionally we will
conditions nitrobenzene (1a) can be iodinated to 3-iodoni-
trobenzene (2a) at room temperature and within 20 hours
with 52% yield. Specific iodination of some deactivated
+
designate this iodination reagent here as “I ”.
+
arenes was achieved by using iodine with fluorine as the Two variants of the iodination using reagent “I ” were
4
oxidant. Probably nowadays the most active iodination worked out. In Method A one equivalent of the substrate
5
agent is N-iodosuccinimide in CF SO H. Deactivated immediately adds to the solution of two equivalents of re-
3
3
+
arenes were found to react easily with this reagent giving agent “I ” (calculated on the basis of the starting ICl).
iodoarenes with good yields. So, for example, nitroben- Method B consists of dropwise addition of 1.5 equivalents
+
zene (1a) gives iodonitrobenzene 2a (86%) within two of reagent “I ” to the stirred suspension of the substrate in
5
hours at room temperature.
sulfuric acid. Method A is more appropriate for the most
strong deactivated arenes 1a–c. On the other hand Method
B provides better results in the case of the iodination of
substrates 1d–g (Table).
Recently we have shown that ICl in H SO is a convenient
2
4
reagent for iodination of activated as well as mildly deac-
6
tivated arenes. However nitrobenzene was not iodinated
+
under these conditions.
After addition of nitrobenzene 1a to reagent “I ” at 20 °C
sizeable amounts of iodonitrobenzene 2a arise in 1–2 min,
and in 7–10 min starting substrate 1a remains only in trace
amounts in the reaction mixture (TLC). Iodination of ni-
trobenzene 1a can be realized even at 0°C but the reaction
time is longer for the completion of the reaction (Table).
In this context it is significant to mention that bromination
of nitrobenzene 1a by action of Br /Ag SO /H SO sys-
H2SO4
+
ICl
+
+
Ag2SO4
"I "
+
AgCl
H2SO4
-20 oC, 15-150 min
0
+
ArH
"I "
ArI
5
3-77%
2
2
4
2
4
ArH = C6H5NO2 , 4-MeC6H4NO2 , 4-ClC6H4NO2 ,
-BrC6H4NO2 , C6H5CHO , C6H5COOH , PhCOCOPh
9
tem is accomplished at room temperature in 16 hours.
4
+
Thus the electrophilic activity of reagent “I ” is at least
not smaller than of the bromination.
+
The activity of reagent “I ” is so high that it can be used
As an extension of our attempts in search of the most ac-
tive and available iodination reagents we concentrated at-
tention on ICl and a silver salts system. It was long ago
for a successful iodination of nitrotoluene 1d only at 0 °C
Method B). Much higher temperature iodination of the
(
Synthesis 1999, No. 5, 748– 750 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Superactive Iodination Reagent on a Base of Iodine Chloride and Silver sulfate
749
substrate 1d leads to a complicated mixture of isomers of Tl(OCOCF ) /CF COOH) lead to destruction of CO–CO
3
3
3
1
0
iodo- and diiodonitrotoluenes.
bond of benzil 1g. Earlier benzil 1g was iodinated by I /
2
Ag SO /H SO system at 90 °C within 2 hours with gen-
2
4
2
4
Synthesis of iodobenzils by a direct iodination of benzil
eral yield of a mixture of 2,2’- diiodobenzil, 4,4’-diiodo-
1
g is not a simple task. Many common reagents are used
10
benzil and 3,3’-diiodobenzil 2g 84%. In the case of the
iodination of benzil 1g by using one equivalent reagent
usually in an oxidative iodination of arenes (I /HNO /
2
3
H SO , I /HIO , I /H IO , I2/oleum, I /O , KI/
2
4
2
3
2
5
6
2
2
Table Iodination of arenes 1a-g with reagent “I+”
Substrate 1 Product 2
Time
Temp.
(°C)
Yield (%)a
74b
mp (°C)
(solvent)
Lit. mp
(°C)
(min)
15
20
34–36
36–375
NO2
NO2
(EtOH)
a
a
I
a
a
150
50
0
64b
67b
34–36
EtOH)
(
74–755
98–995
53–542
572
NO2
NO2
NO2
NO2
20
73–74
EtOH)
(
Cl
Cl
I
I
b
b
120
40
20
53b
65c
61c
94–96
EtOH)
(
Br
Br
c
c
NO2
NO2
0
54–56
EtOH)
(
H3C
H3C
I
d
d
CHO
CHO
40
20
54–56 (etha-
nol)
I
e
e
e
e
60
60
0
0
67c
57c
55–57
186–1877
COOH
COOH
184–186
(50% iso-
propanol)
I
f
f
PhCOCOPh
g
60
0
77c
127–128
(EtOH)
128–
129
I
1
0
COCO
I
g
a
Yield of pure, isolated product
Method A
Method B
b
c
Synthesis 1999, No. 5, 748– 750 ISSN 0039-7881 © Thieme Stuttgart · New York

7
50
V. K. Chaikovski et al.
SHORT PAPER
I+” per one equivalent of the substrate (Method B) mix- 3-Iodonitrobenzene (2a) (Method A)
“
Nitrobenzene (1a; 1.23 g, 10 mmol) was added in one portion to a
ture consisting of starting compounds 1g, 3-iodobenzil
and compound 2g is formed. At the same time with using
double the amount of reagent "I " at 0 °C mild diiodina-
+
well-stirred solution of reagent “I ” (50 mL) at r.t. The mixture was
then stirred for 15 min at r.t. In this period 0.15 g AgCl was precip-
itated additionally. The mixture was poured into H O (150 mL).
Product 2a was extracted with CHCl (2 x 20 mL). The solvent was
+
2
tion of benzil 1g occurred with good yield of diiodobenzil
3
2
g (Table).
removed in vacuo to efford a yellow oil, which was cooled to
+
–10 °C, washed with EtOH (5 mL) at the same temperature, and
As a rule we used reagent “I ” within two–three days of
the preparation. But one can keep it for a longer period of
recrystallized from EtOH to give 3-iodonitrobenzene (2a); yield:
5
1
.84 g (74%); mp 34–36 °C (Lit. , mp 36–37 °C).
time. So the iodination of nitrobenzene 1a with reagent
I ” which was kept for one month at room temperature
provided iodonitrotoluene 2a with 53% yield. It should be
+
”
2
-Iodo-4-nitrotoluene (2d) (Method B)
To a mixture of 4-nitrotoluene (1d; 1.37 g, 10 mmol) in 90% concd
+
+
also noticed that not only reagent “I ” but a simple mix- H SO (10 ml) was added reagent “I ” (37.5 ml) dropwise with stir-
2
4
ture of ICl–Ag SO –H SO is able to iodinate arenes 1a– ring at 0 °C over 40 min. The mixture was poured into H O (100
2
4
2
4
2
ml), product 2d was removed by filtration, dried, and recrystallized
from EtOH to give 2-iodo-4-nitrotoluene 2d; yield: 1.71 g (65%);
g. However in this case the reaction is longer and the prod-
uct contains, besides iodo compounds 2a–g, sizeable
amounts of the corresponding chloroarenes.
+
2
mp 54–56 °C (Lit. , mp 53–54 °C).
Thus the proposed reagent “I ” is probably the most reac- 3-Iodobenzoic Acid (2f) (Method B)
tive known reagent in iodination of aromatic compounds. To a mixture of benzoic acid (1f; 1.22 g, 10 mmol) in 90% conc.
+
H SO (10 mL) was added reagent ”I ” (37.5 ml) dropwise with stir-
The proposed method is also not too expensive because it
allows the recovery of 90–95% of the exploitable silver.
Another advantage of the proposed method is the absence
of strong oxidizers which are employed in most cases in
2
4
ring at 0 °C over 40 min. The resulting mixture was stirred for 20
min at the same temperature and poured into H O (100 mL). The
solid product was filtered and solvated in hot 50% isopropanol. Af-
ter filtration the hot solution from a residue AgCl and cooling crys-
tals of compound 2f were filtered; yield: 1.27 g (57%); mp
2
1
iodination processes. As a result of this, compounds 1d,e
7
are exposed only to iodination without casual oxidation of 185–186 °C (Lit., mp 187–188 °C).
CH and even CHO groups. However we must say that
3
along with the iodination a chlorination process takes
place to a small extent. So the crude product of the iodina-
Acknowledgement
tion of nitrobenzene 1a before the purification contains We thank Russian Foundation for Fundamental Researchers (grant
N 96-03-033054a) for the financial support of this work.
9
4.2% of iodnitrobenzene 2a, 2.1% of 3-chloronitroben-
zene and 3.7% of isomers of chloroiodonitrobenzenes
GS-MS data). We believe that the minor chlorination is a
result of a presence impurity of chlorine in ICl.
(
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(
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1
13
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(
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+
Preparation of the Iodination Reagent “I ”
1
A suspension of Ag SO (3.12 g, 10 mmol) in concd H SO (45 ml)
2
4
2
4
(
and H O (5 ml) was stirred at r.t. for 15 min. Then ICl was added
2
(
10) Novikov, A. N.; Grigoriev, M. G. Izv. Vysshikh Ucheb. Zave-
and the mixture was stirred at r.t. for 1 h. The precipitated AgCl
denii. Khim. i Khim. Technol. 1977, 20, 1716; Chem. Abstr.
(
2.58 g) was removed by filtration. The resultant dark-brown solute
1978, 88, 89293.
was kept in darkness and used for iodination.
Article Identifier:
437-210X,E;1999,0,05,0748,0750,ftx,en;P05398SS.pdf
1
Synthesis 1999, No. 5, 748– 750 ISSN 0039-7881 © Thieme Stuttgart · New York