Research On The Synthesis And Fluorination Of β-dicarbonyl Compounds

Organic fluorine compounds have stronger stability, physiological activity, fat soluble and hydrophobic, which can adjust parameters such as electronic, lipotropy sex. So many fluorinated drugs have the advantages of less dosage, low toxicity, high efficacy and strong metabolic capacity, resulting in a significant impact on the pharmacodynamic and pharmacokinetic properties of the drug. So research on the simple and highly effective method of fluorination methods has the vital significance.In this paper, the research content is fluorination reaction of β-dicarbonyl compounds, possible to achieve the fluorination and difluorination of P-dicarbonyl compounds selectively under mild conditions. Greatly simplifies the original experimental conditions and the process of separating. The reaction is carried out at room temperature without the catalyst, post-treatment operation is simple and the yields are high.Research on the synthesis of a series of β-dicarbonyl compounds by the Claisen Reaction of acetophenone and ethyl benzoate. The reaction added excess NaH as base to catalyst. The optimum reaction conditions as follow:acetophenone:ethyl benzoate=1:1.2, feed temperature is 0℃, the reaction time is 24h, the yield is more than 90%. In the fluorination reaction, β-dicarbonyl compounds react with different equivalents of Selectfluor (a fluorinating agent), which can be obtained fluoro- or difluoro-substituted products selectively. The optimum reaction conditions as follow:room temperature, the reaction time is 24h-48h, the solvent is a mixture of acetonitrile and water, and the yield is 95%. The intermediates and the target product were characterized by 1H NMR,19F NMR.