Application of [Hcpy]HSO4 Broensted acidic ionic liquid for the synthesis of aryl iodides from aromatic amines

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Application of [Hcpy]HSO Brönsted
4
Acidic Ionic Liquid for the Synthesis of
Aryl Iodides from Aromatic Amines
a b
a
Abdol Reza Hajipour
& Mohadeseh Seddighi
a
Department of Chemistry, Pharmaceutical Research Laboratory,
Isfahan University of Technology, Isfahan, 84156, Iran
b
Department of Pharmacology, University of Wisconsin Medical
School, Madison, WI, 53706-1532, USA
Available online: 09 Jun 2011
To cite this article: Abdol Reza Hajipour & Mohadeseh Seddighi (2011): Application of [Hcpy]HSO4
Brönsted Acidic Ionic Liquid for the Synthesis of Aryl Iodides from Aromatic Amines, Organic
Preparations and Procedures International: The New Journal for Organic Synthesis, 43:3, 292-296
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Organic Preparations and Procedures International, 43:292–296, 2011
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2011.582384
OPPI BRIEFS
Application of [Hcpy]HSO Br o¨ nsted Acidic Ionic
4
Liquid for the Synthesis of Aryl Iodides from
Aromatic Amines
1
,2
1
Abdol Reza Hajipour and Mohadeseh Seddighi
1Department of Chemistry, Pharmaceutical Research Laboratory,
Isfahan University of Technology, Isfahan 84156, Iran
2
Department of Pharmacology, University of Wisconsin Medical School,
Madison, WI 53706-1532, USA
Aryl iodide are versatile and useful compounds in organic synthesis, mainly for C–C and
1
,2
C–N bonds formation in metal-catalyzed cross-coupling reactions such as the Suzuki,
Heck, Stille and Negishi reactions.3 Some aryl iodides can be employed for the syn-
–5
thesis of pharmaceutical and bioactive compounds, X-ray contrast agents or radioactive
6
labeled markers in radioimmunoassay. The general procedure for their preparation in-
volves preparation of aryldiazonium salts by the reaction of aryl amines with sodium nitrite
at low temperature in aqueous hydrochloric or sulfuric acid, following treatment with io-
7
8–12
dine or iodide ion; several other procedures have been used recently.
Aryl iodides have
been prepared in one-pot reaction of diazotization-iodination of amines with HI/KNO2
13
14
15
in DMSO, NaNO2/PTSA/KI in acetonitrile, NaNO2/sulfonated-resin/KI in water,
p-TsOH/NaNO2/KI in water-paste form16 and NaNO2/wet silica sulfuric acid/KI.17 How-
ever, some of these methods suffer from disadvantages such as the use of expensive reagents,
long reaction times, necessity for temperature control, instability of diazonium salts and
the use of organic solvents as a reaction medium.
Over the last years, ionic liquids have been used as solvent or catalyst in organic
synthesis due to their remarkable properties such as non-flammability, negligible vapor
pressure, high thermal, chemical and electrochemical stability, easy recyclability and high
solvating ability. The use of Br o¨ nsted acidic ionic liquids has also brought major improve-
ments both as catalyst or in the dual role of catalyst and solvent in many reactions such
1
8
19
as the Pechmann reaction, the chemoselective synthesis of 1,1-diacetates, the Prins
20
21
22
reaction, the Fischer indole synthesis, the thioacetalization of aldehydes, the synthesis
of 1-amidoalkyl-2-naphthols,23 the biodiesel synthesis and the azidation of alcohols. In
24
25
Submitted May 21, 2010.
Address correspondence to Abdol Reza Hajipour, Department of Chemistry, Pharmaceutical Re-
search Laboratory, Isfahan University of Technology, Isfahan 84156, IRAN. E-mail: haji@cc.iut.ac.ir
292

Synthesis of Aryl Iodides from Aromatic Amines
293
continuation of our effort to develop efficient and green method in organic synthesis,26–29
herein we report the application of 3-carboxypyridinium hydrogen sulfate [Hcpy]HSO4 as
a novel, inexpensive, green and efficient acidic ionic liquid for the synthesis of aryl iodides
from aromatic amines via diazonium salt carried out at room temperature and under mild
condition with good to high yields with grinding under safe conditions.
To optimize the reaction conditions for preparation of aryl iodides from corresponding
amines, 4-aminobenzoic acid was used as a model reaction and we observed that the
iodination of 4-aminobenzoic acid with sodium iodide and [Hcpy]HSO4 in H2O as solvent
in an ice bath gave only 25% yields after 2 h while using the grinding conditions led to
higher yields and very shorter reaction times. The best results were obtained using 3 mmol
of ionic liquid, 1 mmol of amine, 2 mmol NaNO2, 1.5 mmol NaI and 1 ml water at
room temperature; increasing the amount of [Hcpy]HSO4 did not improve the yield of
the yield. In addition, without the use of water the majority of starting material was not
converted to the corresponding diazonium salt even after longer reaction time (Table 1).
Table 1
a
Synthesis of Iodoarenes in the Presence of [Hcpy]HSO4
Cmpd
Time (min)
Yield (%)
mp. (lit. mp.)
1
5
5
4
4
2
3
4
4
4
4
4
2
2
3
4
3
4
4
4
-HO2CC6H4I
-CNC6H4I
20
25
20
20
20
20
20
25
25
30
45
45
25
30
20
20
20
20
85
83
88
80
91
75
71
68
51
47
38
40
89
88
80
84
86
85
272–273 (270–273)
123–125 (124–128)
49–51 (49–51)
Oil
1
15
-O2NC6H4I
-O2NC6H4I
-O2NC6H4I
-PhCOC6H4I
-MeCOC6H4I
-IC6H4I
14
171–173 (172–173)
1
7
98–100 (101–102)
17
83v84 (84–85)
129–131 (130–131)
1
4
7
17
-BrC6H4I
39–41 (40–42)
1
-HO2CC6H4I
,4-(NO2)2C6H3I
.5-(NO2)2C6H3I
-PhCOC6H4I
-PhCOC6H4I
-PhC6H4I
161–162 (160v161)
1
7
99–101 (99–101)
1
7
99–101 (97–99)
102–103 (97–99)
1
7
17
40v42(40–41)
17
111–114 (110–112)
1
7
-MeOC6H4I
-MeC6H4I
51v52 (49–50)
35–38 (35–37)
Oil (oil)
17
17
C6H5I
a
1
All products were characterized by IR, H NMR and melting points

294
Hajipour and Seddighi
Table 2
Comparison of Results using [Hcpy]HSO4 with by Methods for 2-Nitroiodobenzene
Entry
Reagent
Conditions
Time (min) Yield (%)
Ref.
◦
1
2
3
4
5
6
NO2, NaI
NaNO2, KI, p-TsOH
Sulfonated-resin, KI, NaNO2 H2O/ r.t
p-TsOH, NaNO2, KI
Wet-SSA, NaNO2
CH3CN/85 C
15
50
90
20–30
30
20
92
81
71
72
83
88
[12]
[15]
[16]
[17]
[18]
◦
CH3CN/H2O/10 C
H2O, grinding/r.t
H2O, grinding/r.t
H2O, grinding/r.t
[Hcpy]HSO4, NaNO2, KI
This work
Various aromatic amines bearing either electron-withdrawing or electron-donating groups
were converted rapidly to the corresponding aryl iodides. However, weakly basic aromatic
amines such as 2,4-dinitroaniline and 3,5-dinitroaniline were converted to the corresponding
aryl iodides only in moderate yields (Table 1). Steric hindrance did not has any significant
effect on the yields, For example, more hindered ortho-substituted aromatic amines such
as 2-nitroaniline gave 88% yield in comparison to 91% yield of 4-nitroaniline.
The stability of the generated diazonium salts was studied. When the diazonium salt of
4-nitroaniline was kept at room temperature in air and 0.5 ml of water and sodium iodide
were added to the reaction mixture after different periods of time, the results showed that the
yield did not change significantly even after keeping the diazonium salt for 10 days under
ambient conditions in comparison to the yields of using freshly prepared diazonium salt.
We observed that all the aryldiazonium obtained employing this procedure were safe
and non-explosive, this may be because the reactivity of these aryldiazonium salts decreases
when they are generate in ionic liquids. Therefore, our diazotization–iodination method
is safe and grinding of these aryldiazonium salts in a mortar is not hazardous under
our laboratory conditions. In contrast to traditional methods, the diazotization–iodination
reaction rate increases using this procedure because these aryldiazonium salts are more
stable, however, we recommend carring the reaction under hood. To evaluate the method
and its safety, we scale up the iodination of aniline to 100 mmol without any explosion and
decrease the yield.
The efficiency of [Hcpy]HSO4 were compared with those of reported procedures. As
illustrated in Table 2, the present method in most cases is superior to the other methods.
The present study describes a novel procedure for the synthesis of aryl iodides from
corresponding aryl amines by the use of [Hcpy]HSO4 under mild and green conditions.
In this method, the as intermediate diazonium salts are stable for long time at room
temperature without decomposition. The use of Br o¨ nsted ionic liquid as a green acid
is another advantages of this method. As the diazonium salts in this acidic ionic liquid are
stable, the reaction is safe and the procedure may be scaled up.
Experimental Section
All yields refer to isolated products after purification. All of the products were characterized
1
by comparison of their spectral (IR, H-NMR, TLC and GC) and physical data (combustion

Synthesis of Aryl Iodides from Aromatic Amines
295
analysis, melting and boiling points) All H-NMR and 13C-NMR spectra were obtained at
1
300 and 75 MHz in CDCl3 relative to TMS as an internal standard.
Synthesis of 3-Carboxypyridinium Hydrogen Sulfate ([Hcpy]HSO4)
In a round-bottomed flask, 5.3 ml conc. sulfuric acid (98%, d 1.84) was added dropwise
to a mixture of nicotinic acid (12.3 g, 100 mmol) in dichloromethane (40 ml) in an ice
bath. The reaction mixture was stirred at room temperature for 30 min and then the solvent
was evaporated under reduced pressure to obtain 3-carboxypyridinium hydrogen sulfate as
1
colorless liquid in quantitative yield. H NMR (300MHz, D2O): δ 7.89 (m, 1H), 8.68 (m,
1
3
1
1
6
H), 8.72 (m, 1H), 8.99 (m, 1H) ppm. C NMR (75MHz, D2O): δ 127.67, 130.41, 127.24,
44.35, 147.17, 164.59 ppm. IR (KBr): 2465–3270, 1733, 1603, 1397, 1271, 1033, 735,
−1
65 cm .
Anal. Calcd for C6H7NO6S: C, 32.58; H, 3.19; N, 6.33; S 14.50. Found: C, 32.70; H, 3.30;
N, 6.80; S 14.30
General Procedure for the Synthesis of Iodoaromatic compounds
An aromatic amine (1 mmol), sodium nitrite (0.14 g, 2 mmol) and [Hcpy]HSO4 (3 mmol,
0.66 g) were ground in a mortar with a pestle for 2–3 min to afford a homogeneous mixture.
Then, 1 ml water was added and the reaction mixture was ground with pestle for 15–20 min
until gas evolution ceased to give the corresponding aryldiazonium salt. Finally, sodium
iodide (0.23 g, 1.5 mmol) was added to the paste-like diazonium salt. The iodination started
immediately after the NaI was added, the volume of the paste increased due to the evolution
of nitrogen gas. Then 20 ml of Na2S2O3 (5%) was added to the reaction mixture and the
precipitated were collected. The pure products were isolated by column chromatography
with ethyl acetate: n-hexane (1:5) as eluent.
Acknowledgements
We gratefully acknowledge the funding support of this project by the Isfahan University of
Technology (IUT), IR Iran (A.R.H.). Further financial support from Center of Sensor and
Green Chemistry Research (IUT) is gratefully acknowledged.
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