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Scheme 2 Competitive
formation of 1-unsubstituted
and 1-substituted
2-amino-1H-imidazoles upon
microwave irradiation
Table 1 Investigation of the
condensation under
conventional heating and
microwave irradiation
All reactions were carried out on
a 1 mmol scale of
2-methylaminopyrimidine
(1, R1 = Me) with 1.35 equiv. of
α-phenacylbromide (2, R2 =Ph)
in MeCN (5 mL)
a Isolated yield after
recrystallization from MeCN
N
N
NHMe
N
Br
N
4
5
+
+ Br
NHR 1
O
R 2
MW
O
Ph
4 (R 1 = Me) 5 (R 2 = Ph)
between 2-aminopyrimidines 4 and α-bromoketones 5 performed
at 80–100 ◦ C gave 2-hydroxy-2,3-dihydroimidazo
[1,2-a]pyrimidinium salts 3, while irradiation of the
reaction mixture at temperatures above 100 ◦ C provided
aromatic 1-substituted imidazo[1,2-a ]pyrimidinium salts
6 (Scheme 2). The hydrazinolysis of the salts 3 and 6 leads to
the corresponding 1-unsubstituted and 1-substituted
2-amino-1H-imidazoles 1 and 7. Thus, by performing the
reaction at 130−150 ◦ C, we were able to prepare a library of
1,4,5-trisubstituted 2-aminoimidazoles 7 via a one-pot twostep
protocol [18].
In continuation of our ongoing studies, herein we report
a simple one-pot procedure for the synthesis of 1-unsubstituted
2-amino-1H-imidazoles 1 from 2-aminopyrimidines 4
and α-bromoketones 5 under microwave irradiation.
123
100 °C
N
Br
Conditions
N
N
3
6
N
N
OH
R 2
Br
N
Br
R 2
N
R 1
R 1
3
N
N 2H 4
MW
N 2H 4
MW
N Me
OH
Ph
+
R 1HN
H 2N
N
Mol Divers
N
N
H
N
N
R 1
1
7
Ph
R 2
R 2
N
Br
N Me
Entry Conditions Time (min) T ( ◦ C) 3 (Yield %) a 6 (Yield %) a
1 30 80 64 0
2 60 80 77 0
3 30 100 81 Traces
4 60 100 85 Traces
5 30 120 68 17
6 60 120 53 28
7 MW 30 80 88 0
8 60 80 85 0
9 30 100 48 33
10 60 100 45 35
11 30 120 12 79
12 60 120 Traces 84
Results and discussion
We carefully investigated the formation and dehydratation of
salt 3 resulting in the formation of salt 6 under conventional
heating conditions as well as upon microwave irradiation.
As a proof of concept, the condensation of 2-methylaminopyrimidine
(4,R1 = Me) and α-phenacylbromide (5,R2 = Ph)
was studied (Table 1). A sealed vial containing a solution of
the starting compounds in acetonitrile was conventionally
heated with an oil bath (Table 1, entries 1–6) or irradiated
with microwaves (Table 1, entries 7–12) at different temperatures
for 30–60 min. The formation of the 2-hydroxy
salt 3 was faster under microwave irradiation, and this compound
was obtained in 88% yield within 30 min. Further
increase of the temperature up to 120 ◦ C using conventional
6