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Synlett 2011(16): 2325-2328  
DOI: 10.1055/s-0030-1261220
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Lukas B. Delvos, Jeanne-Marie Begouin, Corinne Gosmini*
Laboratoire ‘Hétéroéléments et Coordination’, École Polytechnique, CNRS, 91128 Palaiseau Cedex, France
Fax: +33(1)69334440; e-Mail: Corinne.gosmini@polytechnique.edu;
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Publication History

Received 7 July 2011
Publication Date:
08 September 2011 (online)

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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

    References and Notes

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12

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.