Aryl diazonium nanomagnetic sulfate and potassium iodide: An iodination process

Article abstract of DOI:10.1016/j.tetlet.2014.02.073

A simple and efficient procedure for the synthesis of iodoarenes is developed which involves the sequential diazotization-iodination of aromatic amines with sodium nitrite, nanomagnetic supported sulfonic acid, and potassium iodide under solvent-free conditions at room temperature.

Full text of DOI:10.1016/j.tetlet.2014.02.073

Accepted Manuscript
Aryl diazonium nanomagnetic sulfate and potassium iodide: an iodination proc-
ess
Eskandar Kolvari, Ali Amoozadeh, Nadiya Koukabi, Somayeh Otokesh,
Mohsen Isari
PII:
S0040-4039(14)00315-3
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.02.073
TETL 44260
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
19 June 2013
25 October 2013
20 February 2014
Please cite this article as: Kolvari, E., Amoozadeh, A., Koukabi, N., Otokesh, S., Isari, M., Aryl diazonium
nanomagnetic sulfate and potassium iodide: an iodination process, Tetrahedron Letters (2014), doi: http://
dx.doi.org/10.1016/j.tetlet.2014.02.073
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Graphical Abstract
Aryl diazonium nanomagnetic sulfate and
potassium iodide: an iodination process
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Eskandar Kolvari, Ali Amoozadeh, Nadiya Koukabi, Somayeh Otokesh, Mohsen Isari

1
Tetrahedron Letters
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Aryl diazonium nanomagnetic sulfate and potassium iodide: an iodination process
*
Eskandar Kolvari , Ali Amoozadeh , Nadiya Koukabi , Somayeh Otokesh, Mohsen Isari
*
*
Department of Chemistry, Semnan University, Semnan 3535119111, Iran
ARTICLE INFO
ABSTRACT
Article history:
Received
A simple and efficient procedure for the synthesis of iodoarenes is developed which involves the
sequential diazotization–iodination of aromatic amines with sodium nitrite, nanomagnetic
supported sulfonic acid and potassium iodide under solvent-free conditions at room temperature.
Received in revised form
Accepted
2
009 Elsevier Ltd. All rights reserved.
Available online
Keywords:
Aryl diazonium nanomagnetic sulfate
Solvent-free condition
Aryl iodide
Iodination
1
9
2 4
acidic medium (H SO , HCl). The “green” approach to
chemical processes has stimulated the use of recyclable strong
solid acids as replacements for such unrecyclable “liquid acid”
reagents. We have previously reported the synthesis of
nanomagnetic-supported sulfonic acid and its applications in
organic synthesis. Magnetic nanoparticles have emerged as
viable alternatives to porous materials for use as robust, readily
available, high surface area heterogeneous supports in organic
transformations. They possess the added advantage of being
magnetically recoverable, which facilitates reaction work-up and
rapid sample processing, and most importantly, reduces solvent
As the iodine atom is an excellent leaving group, iodo-
substituted aromatic compounds have, for a long time, been
recognized as valuable synthons or precursors in reactions such
as the Heck arylation, and Stille, Negishi, Suzuki, Buchwald, and
Sonogashira couplings. In addition, the iodoarene moiety is an
important structural motif in biologically active molecules (e.g.,
20
13
thyroxine) and a synthetic intermediate for a variety of fine
1
sweeteners ),
chemistry
radiopharmaceuticals, and numerous bioactive compounds such
products
2
(e.g.,
iso-vanillyl
3
4
as camptothecin, cephalosporin derivatives, dehydrotubifoline,
5
consumption. For these reasons, it is of interest to use
20
nanomagnetic-supported sulfonic acid ( γ-Fe O -SO H) for the
2 3 3
6
7
8
morphine, sangliferine A, and ecteinascidine. Galanthamine is
one example of a prescription drug synthesized from an
conversion of aryl amines into aryl iodides. Herein, we report an
efficient, rapid, and convenient procedure for the synthesis of
aryl iodides employing aryl diazonium nanomagnetic sulfates in
the presence of potassium iodide at room temperature (Scheme
iodoarene intermediate, which
is used, for symptomatic
9
treatment of dementia in Alzheimer patients. Despite their
utility, aryl iodides are more expensive, and fewer aryl iodides
are commercially available than aryl bromides and aryl chlorides.
Direct iodination of aromatic compounds with iodine is difficult
due to the weak electrophilicity of molecular iodine. Also, the
regioselectivity of direct iodination is poor and gives a mixture of
1
).
isomers. Hence, the Sandmeyer reaction
0
(reaction of
arenediazonium salts with iodide) is an effective alternative
1
1
1-14
method for the preparation of aromatic iodides.
significant developments have been achieved in the synthesis of
Although
Scheme 1. One-pot iodination of aryl amines via an aryl diazonium
nanomagnetic sulfate.
iodoarenes, their preparation via direct iodination has some
limitations.
15-18
+
The remarkable leaving group ability of -N
2
enables high-
energy reactive aryl cation intermediates to be generated via
The search for mild conditions for the synthesis of aryl
iodides is important in organic chemistry. As aromatic amines are
generally available, most methods for the preparation of
substituted aromatic iodides have focused on improving the
diazotization–iodination reaction. Diazotization reactions are
usually carried out via protonation of nitrous acid in a strongly
diazoniation (Scheme 2).

2
Tetrahedron Letters
NH2
1
9
9
40
78
203-4
H2N
1
1
0
1
35
45
82
74
67-71
oil
Scheme 2. Diazotization process for the generation of aryl
diazonium nanomagnetic sulfate.
1
1
2
3
40
40
30
84
72
80
oil
oil
However, the intrinsic instability and explosive nature of
diazonium compounds limits the applications of these
derivatives. Usually, these compounds are synthesized around
°
1
0
0 C, and to avoid their decomposition, they are handled below
°
C. In this new method, iodination of various aromatic amines,
with electron-withdrawing groups as well as electron-donating
groups, can be successfully carried out in good yields under
solvent-free conditions at room temperature (Table 1). The
14
151-4
2
1
process was carried out in two steps: the amine, nanomagnetic-
supported sulfonic acid, sodium nitrite and 0.2 mL of water were
homogenized by grinding in a mortar with a pestle for a few
minutes. The diazotization proceeded in 5–30 min. During this
time, the starting amine was consumed. Next, potassium iodide
was added to the diazonium salt and grinding continued until the
intermediate aryl diazonium nanomagnetic sulfate was
exhausted; this was determined simply by the negative probe
with β-naphthol. As is indicated in Table 1, the diazotization-
iodination process took 20–60 minutes. The crude product was
extracted with ethyl acetate, and after evaporation of the solvent,
the crude product was purified by recrystallization or short
column chromatography. This new, simple method was applied
successfully with aryldiazonium nanomagnetic sulfates
possessing electron-deficient or electron-rich groups.
1
97-
200
1
5
50
81
16
50
55
67
70
39-41
37-39
1
7
In comparison with electron-withdrawing groups, aryldiazonium
nanomagnetic sulfates with electron-donating groups reacted
more slowly (Table 1, entry 4). The steric effects of ortho
substituents had relatively little influence on the yields and
reaction times (Table 1, entries 8, 16 and 17). It should be
emphasized that the reaction required a small amount of water
for the formation of a paste and had to be carried out in a
stepwise fashion for a successful outcome. When KI was added
Table 1 Synthesis of aryl iodides by means of the diazotization–iodination of
aromatic amines under solvent-free conditions at room temperature
(
substrate: Ar-NH
2
/NaNO
2
/KI = 1:2:2.5 molar ratio, 0.65 g of γ-Fe
2
O
3
3
-SO H)
and 0.2 ml of water.
Time
min)
Yield
(%)
Mp
°
( C)
Entry
1
Substrate
Product
(
together with NaNO , a complex product mixture was produced
2
with much lower yields of the aryl iodides. This indicates that
1
9
20
83
80
80
172-3
the iodination reaction in the water-paste occurs differently than
the diazotization–iodination in an aprotic solvent, where sodium
22
nitrite and KI are treated together with aromatic amines.
1
9
Furthermore, neat reactions with dry diazonium salts may be
more dangerous and explosive than wet reactions, or those that
take place in solution. Our diazotization–iodination method is
safer in this sense, as the reactions were carried out in a water-
paste. It should be noted that the aryldiazonium salts supported
on nanomagnetic-supported sulfonic acid were relatively stable
and could be kept at room temperature in a desiccator without
any loss of activity. After the times specified in Table 2, the
addition of KI to the stored sulfate salt provided almost the same
yield of product as that from freshly-prepared salt. As shown in
Table 2, aryl diazonium nanomagnetic sulfates with electron-
withdrawing groups on the aromatic rings were more stable than
those with electron-donating groups because of the instability of
2
3
45
30
84-5
51-2
1
9
I
19
4
5
6
7
60
40
30
25
78
88
79
70
35-7
55-6
40-2
1
9
19
2
0
23
oil
the resulting aryl cation.
Table 2 The stability of some examples of aryl diazonium nanomagnetic
a,b
sulfates at room temperature
1
9
8
50
55
162
Diazonium salt
After 6 h
After 24 h
After 48 h

3
(
%)
(%)
76
(%)
70
15.
Hajipour, A. R.; Arbabian, M.; Ruoho, A. E. J. Org.
Chem. 2002, 67, 8622-8624.
8
7
7
5
3
7
1
1
6.
7.
Olah, G. A.; Wang, Q.; Sandford, G.; Surya Prakash, G. K.
J. Org. Chem. 1993, 58, 3194-3195.
Agarwal, S.; Aware, U.; Patil, A.; Rohera, V.; Ghate, M.;
Jain, M.; Patel, P. Bull. Korean Chem. Soc. 2012, 33, 377-
61
65
50
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3
78.
Johnsson, R.; Meijer, A.; Ellervik, U. Tetrahedron 2005,
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1
1
8.
9.
6
Zolinger, H. Azo and Diazo Chemistry, Aliphatic and
Aromatic Compounds; London: Interscience Publishers
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a
The yields refer to isolated pure products after adding KI to the diazonium
salts within the specified times.
b
Each product yield was compared with that obtained using fresh diazonium
salt.
20.
21.
Koukabi, N.; Kolvari, E.; Zolfigol, M. A.; Khazaei, A.;
Shaghasemi, B. S.; Fasahati, B. Adv. Synth. Catal. 2012,
To summarize, we have described a new, rapid, efficient and
experimentally simple method for the diazotization–iodination of
aromatic amines on nanomagnetic-supported sulfonic acid at
room temperature. The resulting diazonium salts are stable and
react rapidly with potassium iodide to produce iodoarenes in
good yields. Our new method offers several advantages including
short reaction times, the use of mild reaction conditions, avoids
the use of harmful acids and involves a simple work-up
procedure. Further investigations on the new applications of this
method are ongoing in our laboratory.
3
54, 2001-2008.
Diazotization–Iodination of Aromatic Amines; General
Procedure: An aromatic amine (1 mmol), nanomagnetic-
supported sulfonic acid (γ-Fe O -SO H) (0.65 g), NaNO
2
3
3
2
(
2
2 mmol, 0.138 g) and 0.2 mL of H O were homogenized
by grinding in a mortar with a pestle for a few minutes.
Formation of a reddish-brown gas was observed as soon as
2
H O was added. The diazotization reaction lasted
approximately 5-30 min. Next, KI (2.5 mmol, 0.415 g) was
added to the diazonium salt and grinding was continued for
Acknowledgment
1
0–20 min. After completion of the reaction, the mixture
was triturated with EtOAc (5 mL). The γ-Fe -SO K was
separated from the solution using a magnetic bar. The
organic layer was treated with aq. 10% Na SO (15mL),
then dried over anhydrous Na SO . After evaporation of
2
O
3
3
The authors gratefully acknowledge Semnan University
Research Council for financial support of this work.
2
3
References and notes
2
4
the solvent, the crude product was afforded. Purified
products were obtained by recrystallization from ethanol or
by flash chromatography (n-hexane-EtOAc, 95:5).
CAUTION! Although we did not experience any
problems, diazonium salts are known to be explosive. Care
must be exercised in handling them, especially when they
are subjected to grinding.
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