Studies On The Synthesis Of 6-fluoro 2-substituted-chroman-4-ones

Chroman-4-ones have a broad array of biological activity, such as antiplatelet aggregation, antiinflammatory, antifungal, enzyme inhibition, antiarrhythmic, antiestrogen, antioxidant and anticancer, and chromans, as the reduction products of chroman-4-ones, are important pharmaceutical intermediates. Moreover, fluorine substitution is commonly used in contemporary medicinal chemistry with high fat-soluble and hydrophobic, can significantly improve the biological activity of the compounds. Synthesis of fluoro-containing chroman-4-ones is an important direction of pharmaceutical development. Chiral chroman-4-ones often have remarkable biological activity, therefore, the asymmetric synthesis of chroman-4-ones become a hot research topic in recent years.In this paper, 6-fluoro-2-alkylchroman-4-ones and 6-fluoro-2-arylchroman-4-ones were synthesized in high yields from 5-fluoro-2-hydroxyacetophenone by using two different catalysts. In addition, based on 6-fluoro-2-phenylchroman-4-one, the asymmetric synthesis method of (2R)-6-fluoro-2-phenylchroman-4-one was explored. The products were characterized by IR, 1H NMR, 13C NMR and HRMS spectral data.This work is composed of the follows:1. A series of 6-fluoro-2-alkylchroman-4-ones were obtained from 5-fluoro-2-hydroxy- acetophenone by using pyrrolidine as catalyst in anhydrous EtOH in the condition of refluxing.2. 2′-Hydroxychalcones were synthesized from 5-fluoro-2-hydroxyacetophenone by using pyrrolidine as catalyst in anhydrous EtOH at room temperature. Then, a series of 6-fluoro-2-arylchroman-4-ones were synthesized from 2′-hydroxychalcones by intramolecular oxa-Michael addition catalyzed by BF3·OEt2.3. 6-Fluoro-2-phenylchroman-4-one was prepared from 5-fluoro-2-hydroxyacetophenone and benzaldehyde by using four different kinds of organic catalysts in anhydrous EtOH at room temperature, and their asymmetric synthesis conditions were studied. 4. The fluorescence activity of 6-fluoro-2-alkyl/arylchroman-4-ones was detected and the affect of different substituted groups was investigated.