Zinc Base Assisted Amination of 2-Chloropyrimidines by Aniline Derivatives at Room Temperature

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.

zinc base - amination - nucleophilic aromatic substitution - 2-anilinopyrimidine - heterocycles

References and Notes

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<A NAME="RB12811ST-12">12</A>

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.