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