D. A. Gorlushko et al. / Tetrahedron Letters 49 (2008) 1080–1082
1081
The essence of this method involves carrying out the
diazotization and subsequent iodination in a water-paste
form. Reaction details are as follows: An aromatic amine
(2 mmol) was ground with 0.2 mL of water and solid
p-TsOH hydrate (6 mmol) in an agate mortar for a few
minutes. The diazotizating reagent, NaNO2 (5 mmol),
was added. The diazotization reaction lasted approxi-
mately 10 min with periodic grinding using a pestle. The
formation of diazonium salt was verified using the color-
test with b-naphthol.1a Then, commercially available KI
(5 mmol) was added to the diazonium salt paste, and grind-
ing continued for 10–20 min. The iodination reaction
began immediately after KI addition, and the paste volume
increased due to the evolution of nitrogen gas. The whole
process of diazotization and iodination took 20–30 min.
The crude product paste was treated with water and aque-
ous Na2SO3 (10%, 15 mL). Precipitated aromatic iodide
products were filtered and dried. Only when the product
was liquid was the reaction mixture extracted with diethyl
ether (3 ꢀ 15 mL). The product aryl iodides were purified
by recrystallization or flash chromatography.
This new, simple method can be successfully applied for
the synthesis of a wide range of aryl iodides starting from
the corresponding aryl amines. Various aromatic amines,
1–14, with electron-withdrawing groups as well as elec-
tron-donating groups, were transformed into aromatic
iodides, 1a–14a, in good yields (Table 1). Iodination of
two substrates: weakly-basic 2,4-dinitroaniline and 5-
aminouracil provided only moderate yields of the corre-
sponding iodo derivatives 15a and 16a.
It should be emphasized that the reaction requires a
small amount of water for the formation of the water-paste
and must be carried out in a stepwise fashion for a success-
ful outcome. When KI was added together with NaNO2, a
complex product mixture was produced with much lower
yields of aryl iodides. This indicates that the iodination
reaction in a water-paste form occurs differently than the
diazotization–iodination in an aprotic solvent, where
sodium nitrite and KI are treated together with aromatic
amines.6b
It is known that the co-grinding of dry diazonium
nitrate salts with KI results in the formation of aryl iodides
in quantitative yield.7 However, Kaupp’s method7 requires
cumbersome gas phase reagents for the preparation of di-
azonium salts and a lengthy reaction time for iodination.
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 was safer in this sense, as the reactions
were carried out in a water-paste. Besides, it is known that
diazonium salts, such as ArN2þAr0SO3ꢁ, are relatively
stable and non-explosive.8a Previously, these kinds of salts
were prepared only for analytical purposes by ion exchange
between aryl diazonium chlorides and aryl sulfonates.8b,c
The aryldiazonium tosylates, ArN2þp-TsOꢁ, that we
prepared were sufficiently stable to be kept at room temper-
ature either in a paste form or dried state. For example, p-
nitrophenyldiazonium p-tosylate (NPAT)9 was prepared in
crude form as described here and kept at room temperature
in a desiccator. After one month, the addition of water and
KI to the stored tosylate salt provided almost the same
yield of p-iodonitrobenzene (1a) as that from freshly-pre-
pared salt (Table 1). Besides, NPAT did not reveal any
explosive character. The thermal stability of NPAT in pure
or crude form was verified by DSC under a nitrogen atmo-
sphere and did not show any exothermic reactions up to
150 °C.
We have also successfully applied this new method on a
larger scale. For example, up to 15 mmol of anthranilic
acid (9) could be converted into 2-iodobenzoic acid (9a)
without any loss of efficiency.
Table 1
Syntheses of aryl iodides by means of the diazotization–iodination of
aromatic amines in a water-paste form at room temperature (substrate:
NaNO2/KI/p-TsOH = 1:2.5:2.5:3 molar ratio)
Acknowledgments
Entry Substrate
Product
Isolated yield
(%)
This work was supported by the 2007 Research Fund of
the University of Ulsan, and Victor Filimonov is grateful
for the Brain Korea 21 program in Korea.
1
2
3
4
5
6
7
8
4-NO2C6H4NH2
4-NO2C6H4I
2-NO2C6H4I
4-CH3COC6H4I
2-CH3COC6H4I
1,4-I2C6H4
72
72
75
87
87
79
63
67
80
77
2-NO2C6H4NH2
4-CH3COC6H4NH2
2-CH3COC6H4NH2
4-IC6H4NH2
Supplementary data
2-IC6H4NH2
1,2-I2C6H4
Supplementary data associated with this article can be
2,4,6-Cl3C6H2NH2
2-NH2C6H4CO2H
4-NH2C6H4CO2H
4-NH2,2-OH–
2,4,6-Cl3C6H2I
2-IC6H4CO2H
4-IC6H4CO2H
4-I,2-OH-
9
10a
C6H3CO2Na
C6H3CO2H
11
12
13
14
15
16
a
3-NCC6H4NH2
4-NCC6H4NH2
4-MeOC6H4NH2
4-PhC6H4NH2
2,4-(NO2)2C6H3NH2
5-Aminouracil
3-NCC6H4I
4-NCC6H4I
4-MeOC6H4I
4-PhC6H4I
2,4-(NO2)2C6H3I
5-Iodouracil
85
79
70
81
38
41
References and notes
1. (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, 52, 440–445; (c) Galli, C.
Chem. Rev. 1988, 88, 765–792; (d) Roglans, A.; Pla-Quintana, A.;
Moreno-Manas, M. Chem. Rev. 2006, 106, 4622–4643.
Molar ratio of reagents Ar–NH2/NaNO2/KI/p-TsOH = 1:2:2.5:4.
Gorlushko, Dmitry A.
