Abstract
The amination of 2-chloropyrimidines was performed with several
aniline derivatives in the presence of tolylzinc bromide as a base.
The organozinc compound has a profound effect on the reactivity
of the amines, so that the reaction takes place at room temperature.
Further studies gave insight into the reaction mechanism and favor
a nucleophilic substitution over a catalytic process.
Key words
zinc base - amination - nucleophilic aromatic
substitution - 2-anilinopyrimidine - heterocycles
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General Procedure
for the Amination of 2-Chloro-pyrimidines: An oven-dried Schlenk
flask was equipped with a stirring bar, a septum and was flushed
with nitrogen. The flask was charged with a solution of 9 (0.8 M, 3 mL) in MeCN. The amine (2.5
mmol) and 2-chloropyrimidine (3 mmol) were added and the resulting
mixture was stirred for 2 h. Another aliquot of the solution of 9 (0.8 M, 3 mL) was added and the reaction
mixture was stirred for further 3 h. The reaction was quenched with
a sat. NH4Cl solution (100 mL) and the aqueous phase
was extracted with CH2Cl2 (3 × 30
mL). The combined organic layers were washed with brine solution
(20 mL) and dried over MgSO4. The drying reagent was
filtered off and the filtrate was concentrated under reduced pressure.
The crude product was purified by flash chromatography on silica
or aluminum oxide.
