1720
M. Kodomari et al. / Tetrahedron Letters 43 (2002) 1717–1720
(Table 1), whereas in the reaction with the unsupported
reagents system the yield was a trace and in the reaction
with the reagents system in which one reagent is sup-
ported on inorganic solid and the other is unsupported,
the yield was lower than that with the supported
reagents system.
from readily available starting materials. This method
may find wide application for the laboratory-scale and
combinatorial synthesis of substituted 2-aminothia-
zoles. These experimental results demonstrate that two
reagents reacting with each other in homogenous solu-
tion are rendered mutually inactive by supporting them
onto separate inorganic supports, and two-step reac-
tions are possible in one-pot by using a couple of
supported reagents.
In a typical procedure, a mixture of 1 (1 mmol),
9
10
KSCN/SiO2 (5 mmol) and NH4OAc/Al2O3 (6 mmol)
was stirred in benzene at 80°C for 6 h, and then the
used solid reagents were removed by filtration. The
filtrate was evaporated to leave crude products, which
were purified by column chromatography over silica
gel. As shown in Table 2, a-halo ketones react with
KSCN/SiO2 and NH4OAc/Al2O3 in one-pot to produce
the corresponding 2-aminothiazoles in high yields. To
obtain the high yield, both supported reagents were
required in large excess. Ammonium acetate was the
most effective among the amine salts tested: ammonium
acetate, ammonium benzoate and ammonium chloride.
When a-chloro ketone was used instead of a-bromo
ketone, the yield was the same as that in the reaction
with a-bromo ketone. The halo ketones in which the
halogen is attached to the secondary carbon afforded
lower yields than that with the halo ketones in which
the halogen is attached to the primary carbon (Table 2,
entries 1–5). When the halo ketones in which halogen is
attached to the secondary carbon were used, uncharac-
terized byproducts were generated along with the thia-
zoles. However, with the halo ketone in which the
halogen is attached to the benzyl carbon, no side
reactions were observed (Table 2, entries 6–8). This
procedure can be efficiently applied to primary and
secondary amines. The reaction of 2-bromo-2-phenyl-
acetophenone with primary or secondary amines gave
N-substituted-4,5-diphenyl-2-aminothiazoles in high
yields (see Table 3). The yields of 2-aminothiazoles
from the reaction with primary and secondary aliphatic
amines (Table 3, entries 1 and 4) were lower than that
with alicyclic amines (Table 3, entries 5–7). The success-
ful use of 2-hydroxypropylamine and allylamine indi-
cates that this procedure is unaffected by the presence
of a functional group such as the CꢀC double bond and
the hydroxyl group in an amine part.
References
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1983, 141. Silica gel-supported potassium thiocyanate
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10. Alumina-supported ammonium acetate was prepared as
follows. Alumina (ICI Biomedical N-Super 1, 9.23 g) was
added to a solution of ammonium acetate (10 mmol, 0.77
g) in methanol, and the mixture was stirred at room
temperature for 0.5 h. The methanol was removed, and
the resulting reagents were dried in vacuo (15 mmHg) at
room temperature for 2 h.
In summary, we have developed a simple and efficient
procedure for synthesizing 2-aminothiazoles in one-pot