A facile synthesis of 2-aryloxypyrimidine derivatives via a tandem reductive amination/intermolecular SNAr sequence

• Published in: Journal of Zhejiang University. B. Science Vol. 11; no. 2; pp. 94 - 101
• Main Authors: Wu, Hai-feng, Zhang, Pei-zhi, Wu, Jun
• Format: Journal Article
• Language: English
• Published: Heidelberg SP Zhejiang University Press 01.02.2010; Zhejiang University Press
• Subjects: Aldehydes; Amines; Ar序列; Biological; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cutting; Derivatives; Sodium; Solvents; Synthesis; 亲核取代反应; 分子间; 对甲苯磺酸; 简便合成; 衍生物; 还原胺化; Ar; Amine; Reductive amination/intermolecular S; O62; C-O and C-N bonds; Herbicide; Pyrimidine
• ISSN: 1673-1581; 1862-1783
• DOI: 10.1631/jzus.B0900293

A novel tandem reductive amination/intermolecular nucleophilic aromatic substitution （SNAr） sequence has been established for the synthesis of amine containing pyrimidine in formation of one carbon-oxygen and one carbon-nitrogen bonds in a one-pot fashion. Treatment of aldehyde with arylamine, 2-methanesulfonyl-4,6-dimeth- oxypyrimidine and sodium borohydride provides good overall yield. The p-toluenesulfonic acid （PTSA） can be used as activator and is generally needed in the reaction. Dioxane is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran （THF）, MeCN, toluene and dichloromethane. The procedure is carried out effectively in the presence of K2CO3. The reaction proceeds smoothly with aromatic aldehydes and arylamines possessing electron-donating or -withdrawing groups. This method can be applied to the synthesis of the oilseed rape herbicide and is superior to the classical one in several aspects： cutting out several purification steps, minimizing solvent use and chemical waste, and saving time. Its advantages such as operational convenience, high-efficient synthesis, and starting material availability make it a desirable method for preparing amines with molecular diversity and biological activity.