Sulfonic acid based cation-exchange resin: A novel proton source for one-pot diazotization-iodination of aromatic amines in water

Article abstract of DOI:10.1055/s-2007-990950

A convenient and simple one-pot method for the preparation of iodoarenes at room temperature has been developed, by sequential diazotization-iodination of aromatic amines with NaNO₂/KI in the presence of a sulfonic acid based cation-exchange resin in water. This inexpensive, noncorrosive and eco-friendly synthetic route is general in nature and allows for the preparation of iodoarenes with an electron-donating or -withdrawing group in various positions from the corresponding amines in 50-98% yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-990950

SHORT PAPER
185
Sulfonic Acid Based Cation-Exchange Resin: A Novel Proton Source for
One-Pot Diazotization–Iodination of Aromatic Amines in Water
a
ater D. Filimonov,* Nadya I. Semenischeva, Elena A. Krasnokutskaya, Alexei N. Tretyakov, Ho Yun Hwang,
a
a
a
b
O
V
ne-Pot
D
iazotiz
a
i
tion–Io
c
dination of
t
A
rom
a
o
tic
A
mine
s
i
r
W
b
Ki-Whan Chi*
a
Department of Organic Chemistry, Tomsk Polytechnic University, 634050 Tomsk, Russia
Fax +7(3822)563637; E-mail: filimonov@tpu.ru
b
Department of Chemistry, University of Ulsan, 680-749 Ulsan, Republic of Korea
E-mail: kwchi@ulsan.ac.kr
Received 14 September 2007; revised 19 October 2007
aqueous medium if sulfonic acid based resins are used as
an acid source. The reaction proceeds in two stages in the
one-pot method: firstly, amines 1–11 are diazotized by
Abstract: A convenient and simple one-pot method for the prepa-
ration of iodoarenes at room temperature has been developed, by se-
quential diazotization–iodination of aromatic amines with NaNO2/
KI in the presence of a sulfonic acid based cation-exchange resin in
6
mixing with NaNO and cation-exchange resins for 25–
2
water. This inexpensive, noncorrosive and eco-friendly synthetic 420 min, then KI is sequentially added to the resulting
route is general in nature and allows for the preparation of iodo- mixture followed by continuous stirring for 50–600 min-
arenes with an electron-donating or -withdrawing group in various
positions from the corresponding amines in 50–98% yields.
utes (Scheme 1).
Key words: iodoarenes, aromatic amines, diazotization, potassium
iodide, sodium nitrite, cation-exchange resin
1
2) KI
) NaNO2/sulfonated-resin/H2O
Ar-NH2
–11
Ar-I
5
0–600 min, r.t., 50–98%
1
a–11a
1
Iodoaromatic compounds are useful synthetic building Scheme 1 Diazotization–iodination of aromatic amines
blocks in organic synthesis. They are valuable, versatile
synthetic intermediates and have wide applications in
The advantages of this new synthetic method also include
1
,2
medicine and biochemistry. One of the first and most
commonly used methods for the preparation of iodoarenes
is the substitution of a diazo group by iodine (often called
monitoring simplicity: at the first stage the diazotization
proceeds till the starting amines disappear as verified by
TLC, and the iodination stage is carried out until the reac-
tion mixture reveals a negative result with the b-naphthol
test. This reaction can be applied to a wide range of
amines with either electron-donating or -withdrawing
substituents in various positions in relation to the amino
group. There is no clear dependence between electronic
properties or position of substituents and reaction rate
3
the Sandmeyer reaction). The fundamental advantage of
this reaction, over other methods involving direct electro-
philic iodination of aromatic compounds, is the selective
introduction of iodine into a specific position of the aro-
matic ring, whereas direct electrophilic iodination fre-
quently gives a mixture of isomers.
The process of diazotization–iodination is usually carried along with yields of iodorenes. For example, para-iso-
out with sodium nitrite at low temperature in two steps: di- mers of nitroaniline 1 and aminobenzoic acid 7 provide
azotization of the amine in aqueous hydrochloric or sulfu- higher yields of iodorenes than ortho-isomers 2 and 8, al-
ric acid and a subsequent reaction with iodine and KI, though for the para-isomer 7, the iodination stage takes
3
sometimes in the presence of copper salts. As an alterna- more time than 8. On the other hand, 4-iodoaniline (4) re-
tive to these traditional methods, more expensive methods acts more slowly than the ortho-isomer 5 and provides
involving alkyl nitrites in the presence of diiodomethane much less iodoarene 4a. A slow reaction rate in the diaz-
4
or other sources of iodine have been reported. Recently, otization stage was clearly observed with 2,4,6-trichloro-
a one-pot method for introducing iodine into an aromatic aniline (9) which has two ortho-substituents. It is likely
substrate was suggested which involves a sequence in- that the results of the reactions studied are influenced by a
cluding diazotization-iodination of the corresponding number of factors – amine basicity, water solubility, re-
amines with HI/KNO in DMSO or KI/NaNO /PTSA in agent diffusion rate into the polymeric matrix, product
2
2
5
acetonitrile. These one-pot methods, however, require diffusion rate from the polymeric matrix, strength of inter-
organic solvents as a reaction medium.
action between starting arylammonium (and/or formed
aryldiazonium) cations, and the polymeric matrix.
We discovered that diazotization–iodination reactions
easily and successfully proceed at room temperature in Reactions with all the studied amines proceeded smoothly
at room temperature except for 4-methoxyaniline (6). Di-
azotization–iodination of 6 was successful only at 7–10
SYNTHESIS 2008, No. 2, pp 0185–0187
x
x
.
x
x
.2
0
0
7
°C. Higher temperatures decreased the yield of 4-iodoani-
sole (6a) due to resinification and a high degree of volatil-
ity of 6a.
Advanced online publication: 07.12.2007
DOI: 10.1055/s-2007-990950; Art ID: Z21607SS
Georg Thieme Verlag Stuttgart · New York
©

1
86
V. D. Filimonov et al.
SHORT PAPER
Although water is safer, more convenient, and meets the in reactivity by washing with acetone, water, and then
Green Chemistry’ requirements as a reaction medium, treating with aqueous hydrochloric acid.
‘
we also studied the possibility of using organic solvents
such as DMSO and acetonitrile in this diazotization–iodi-
nation method. We found out that in these organic sol-
vents, in contrast to aqueous medium, the diazotization
stage for amines 1–11 proceeds with low conversion of
the starting amines. This may be attributed to the hydro-
philic nature of the cation-exchange resins used and their
nonswelling ability in aprotic media.
+
It should be noted that the aryldiazonium cations, ArN ,
2
prepared at the first stage have strong interactions with the
polymeric resin matrix and the salts can be isolated by fil-
tration. For example, after the diazotization stage the
polymer-supported diazonium salt of amine 1 was fil-
tered, washed with water, and then allowed to stand open
at room temperature for nine days. After this period of
time, the salt reacts with KI in an aqueous solution to give
Another attempt at carrying out the diazotization–iodina- 4-iodonitrobenzene (1a) in a 71% yield, which is only a
tion in water with cation-exchange resins in one stage, that little less than that obtained under normal one-pot condi-
is, with simultaneous treatment of NaNO and KI, was in tions (Table 1).
2
vain. During this procedure, we observed the release of el-
emental iodine and the formation of product mixtures with
were obtained via the ion exchange of preliminarily syn-
an incomplete conversion of the starting amines.
Previously, diazonium salts supported on sulfonic resins
+
2
–
thesized aryldiazonium chlorides, ArN Cl , with the so-
The yields of iodoarenes 1a–11a obtained by the devel- dium form of sulfonic resin (Amberlyst A-15), and also
oped method can be compared with the results of tradi- revealed high storage stability and reactivity in obtaining
7
tional diazotization-iodination methods, although the an azo dye library.
9
reactions proceed at a slower rate due to the polymeric na-
In summary, we have demonstrated for the first time that,
in the presence of sulfonic acid based cation-exchange
resins, diazotization of aromatic amines successfully pro-
ceeds at room temperature in water. The resulting diazo-
ture of the acidic agent (Table 1). After iodination was
completed, providing products 1a–11a, the sulfonic acid-
based resin could be recycled without any significant loss
Table 1 The Diazotization–Iodination of Aromatic Amines 1–11 with NaNO and Cation-Exchange Resins in Water at Room Temperature
2
b
Molar ratio of reagents
a
Substrate:NaNO :KI (mmol)
Substrate
Reaction time (min)
Diazotization/Iodination
Product
Yield (%)
Mp (°C)
2
1
1
1
1
1
1
1
1
1
1
1
:2:2.5
:2:2.5
:2:2.5
:2:2.5
:2:2.5
:2:2.5
:2:2.5
4-NO C H NH
2
25/65
30/60
4-NO C H I
2
81
71
75
50
90
61
98
65
53
56
50
172–173
(171–173)
6
4
2
2
6
4
c
1
1a
2-NO C H NH
2
2-NO C H I
2
52-53
(49–51)
6
4
6
4
c
2
2a
4-MeCOC H NH
6
40/50
4-MeCOC H I
6
84–85
(82–84)
4
2
4
c
3
3a
4-IC H NH
6
55/300
45/95
1,4-I C H
4
128–129
(131–133)
4
2
2
2
6
c
4
4a
1,2-I C H
4
2-IC H NH
6
oil
(oil)
4
2
6
c
5
5a
d
4-MeOC H NH
6
40/60
4-MeOC H I
6
51–52
(50–53)
4
2
4
c
6
6a
4-NH C H CO H
2
140/600
180/190
420/100
100/80
100/85
4-IC H CO H
4
269–270
(270–273)
2
6
4
6
2
c
c
7
7a
: 2: 2.5
:2:2.5
:4:2.5
:2:2.5
2-NH C H CO H
2
2-IC H CO H
6
161–162
(160–162)
2
6
4
4
2
8
8a
2,4,6-Cl C H NH
6
2,4,6-Cl C H I
2
50–51
(53–54)
3
2
2
3
6
5
b
9
9a
4-CNC H NH
4
4-CNC H I
6
125–127
(124–128)
6
2
4
c
c
1
0
10a
4-PhC H NH
4
4-PhC H I
4
112–113
(110–114)
6
2
6
1
1
11a
a
b
c
d
An amount of 5 g of cation-exchange resin was used with 2 mmol of the substrate.
Yield of isolated product.
Reference 8.
The reaction proceeded at 7–10 °C.
Synthesis 2008, No. 2, 185–187 © Thieme Stuttgart · New York

SHORT PAPER
One-Pot Diazotization–Iodination of Aromatic Amines in Water
187
nium salts are generally stable and readily react with KI to Acknowledgment
form iodoarenes in moderate to high yields. This new
This work was supported by the 2007 Research Fund of University
of Ulsan, and the Brain Korea 21 program in Korea.
method has a number of advantages over traditional diaz-
otization–iodination methods with sodium nitrite. These
advantages include the use of water as solvent, strong
acid-free conditions, mild reactions at room temperature,
ease of separation of the intermediates and products from
the reaction mixture, and the possibility of recycling the
resins.
References
(
1) (a) Liu, Y.; Gribble, G. W. Tetrahedron Lett. 2001, 42,
2949. (b) Soderberg, B. C. Coord. Chem. Rev. 2004, 248,
1085. (c) Kotha, S.; Lahiri, K.; Kashinath, D. Tetrahedron
2002, 58, 9633. (d) Bellina, F.; Carpita, A.; Rossi, R.
Synthesis 2004, 2419. (e) Guiry, P.; Kiely, D. Curr. Org.
Chem. 2004, 8, 781. (f) Prajapati, D.; Gohain, M.
Tetrahedron 2004, 60, 815. (g) de Vries, J. G. Can. J. Chem.
Commercially available reagents and solvents were used as re-
ceived without further purification. Column chromatography was
performed using silica gel 60 (40–60 mm mesh). Merck silica gel 60
2
001, 79, 1086. (h) Cacchi, S.; Fabrizi, G.; Goggiomani, A.
Heterocycles 2002, 56, 613.
(2) (a) Volkert, W. A.; Hoffman, T. J. Chem. Rev. 1999, 99,
1
13
F254 aluminum sheets were used for analytical TLC. H and
NMR spectra were recorded in CDCl on a Bruker AC 300 MHz
C
3
spectrometer. Melting points were determined on a Büchi B-540 ap-
paratus and are uncorrected. Commercially available sulfonic acid-
based cation-exchange resins KU-2-8 (Russia) and Trilite SPC-
2
269. (b) Yu, S.-B.; Watson, A. D. Chem. Rev. 1999, 99,
2353.
(
3) (a) The Chemistry of Diazonium and Diazo Groups; Patai,
S., Ed.; Wiley: New York, 1978. (b) Godovikova, T. I.;
Rakitin, O. A.; Khmelnitskii, L. I. Russ. Chem. Rev. 1983,
160H (South Korea) with exchange capacity of 4.9–5.1 mg equiv/g
were treated in the following way for subsequent reactions.
52, 440. (c) Galli, C. Chem. Rev. 1988, 88, 765.
Cation Exchange Resins
(
(
4) (a) Friedman, L.; Chlebowsky, J. F. J. Org. Chem. 1968, 33,
1636. (b) Smith, W. B.; Ho, O. C. J. Org. Chem. 1990, 55,
KU-2-8 Resin: At first the resin (200 g) was allowed to swell in sat.
aq NaCl (250 mL). Then, the crude cation exchange resin KU-2-8
in the Na-form (200 g) was treated with aq 5% NaOH (250 mL) for
2543.
5) (a) Baik, W.; Luan, W.; Lee, H. J.; Yoon, C. H.; Koo, S.;
Kim, B. H. Can. J. Chem. 2005, 83, 213.
3
–4 h with frequent shaking. Treatment with a 5% solution of
NaOH was repeated until the color of the solution faded. After the
alkaline treatment, the cation exchange resin was washed with 10
volumes of distilled H O and then aq HCl: first, 5 volumes of a 5%
solution, then 5 volumes of a 10% solution, and finally, by a 15%
solution until the complete absence of ferrous ions in the solution
(
b) Krasnokutskaya, E. A.; Semenischeva, N. I.; Filimonov,
V. D.; Knochel, P. Synthesis 2007, 81.
2
(6) KU-2-8 (Russia) and Trilite SPC-160H (South Korea) were
used as cation-exchange resins. No significant difference
was found in the result of reactions with these two resins.
(test by ammonium thiocyanate). After the acid treatment, the cat-
ion exchange resin was thoroughly washed with distilled H O until
the pH reached 6–7 in order to remove traces of acid. Finally, the
processed cation exchange resin was collected by filtration and
dried in the open air.
(
7) Previous reaction conditions and yields: 1a: tert-BuSNO /
2
10
11
2
KI/C H , 80%; NaNO /HBF /KI/DMSO, 90%; NaNO /
6 6 2 4 2
12
HBF /Me SiI/MeI, 91%; i-C H NO /CH I , 90%;
13
4
3
5
11
2
2 2
14
NO (liq)/NaI/MeCN/–20 °C, 98%; i-C H NO /o-benzene-
2
5
11
2
15
disulfonimide/Bu NI/MeCN, 92%; NaNO /KI/MeCN,
4
2
5
b
5a
8
2%. 2a: KNO /HI/DMSO, 89%; NaNO /KI/MeCN,
2 2
Trilite SPC-160H Resin: The cation exchange resin Trilite SPC-
160H (South Korea) in H-form was washed with distilled H O until
2
the pH reached 6–7.
5
1%. 7a: NO (liq)/anhyd KI, 100% (potentially
b
8
explosive!). 8a: NaNO /HCl/KI, 67%; NaNO /KI/
2
1
6
17
2
2
5
b
MeCN, 50%. 9a: NaNO /KI/MeCN, 80%.
5b
2
(
(
8) Aldrich Handbook of Fine Chemicals and Laboratory
Equipment; Aldrich: Milwaukee, 2006-2007.
9) Merrington, J.; James, M.; Bradley, M. Chem. Commun.
Iodoarenes 1a–11a; General Procedure
The respective aromatic amine 1–11 (2.0 mmol) was added to the
cation-exchange resin (5.0 g) in H O (50 mL). After stirring for 10
2
2002, 140.
min, NaNO (4.0 mmol, 0.276 g) was added to the mixture. Then,
2
(
(
(
10) Oae, S.; Shinhama, K.; Kim, Y. H. Chem. Lett. 1979, 939.
11) Citterio, A.; Arnoldi, A. Synth. Commun. 1981, 11, 639.
12) Keumi, T.; Umeda, T.; Inoue, Y.; Kitajima, H. Bull. Chem.
Soc. Jpn. 1989, 62, 89.
13) Smith, W. B.; Ho, O. C. J. Org. Chem. 1990, 50, 2543.
14) Suzuki, H.; Nonoyama, N. Tetrahedron Lett. 1998, 39, 4533.
15) Barbero, M.; Degani, I.; Dughera, S.; Fochi, R. J. Org.
Chem. 1999, 64, 3448.
the mixture was stirred for the time specified in Table 1, and the
process was accompanied by the substrate dissolution. The reaction
was followed by monitoring the complete disappearance of starting
aromatic amine by TLC. Then, KI (5.0 mmol, 0.830 g) was added
to the mixture and stirred for the time specified in Table 1. The re-
action was monitored by the b-naphthol color test. The formation of
iodoarene precipitates was observed in most reactions. After the io-
dination was complete, the reaction mixture was treated with aq
(
(
(
(
16) Kaupp, G.; Herrmann, A.; Schmeyers, J. Chem. Eur. J. 2002,
1
ins were filtered and washed with H O, and then treated with ace-
0% Na SO (15 mL). The solid products and cation-exchange res-
2 3
8, 1395.
2
(
17) Tietze, L. F.; Eicher, T. Reaktionen und Synthesen im
organisch-chemischen Praktikum und Forschungs-
laboratorium; Thieme-Verlag: Stuttgart, 1991.
tone (10 mL). To this acetone solution was added H O to precipitate
2
the iodoarene products, which were then collected by filtration and
dried. In the case of liquid products, the mixture extracted with Et O
2
(
3 × 15 mL) and worked up in the usual way. All the products were
characterized by comparison of melting points with the literature
values (Table 1).
Synthesis 2008, No. 2, 185–187 © Thieme Stuttgart · New York