| Coumestan, known as 6H-benzofuran [3, 2-c] benzopyran-6-one, is a class of important natural products with significant pharmaceutical activities, such as antibacterial, hemostatic, phytoestrogenic effects and so on. Therfore, many organic chemists focus on their synthesis. This paper is mainly about its facile synthesis by FeCl3-mediated oxidative cyclization of 4-hydroxy-3-aryl coumarin.According to the reference, 4-hydroxy-3-aryl coumarins were synthesized by the following methods: 1. First condensation of methyl salicylate with substituted phenyl acetic acids to form the intermediate ester, then the intramolecular condensation of the ester to form the targets. 2. Condensation of resorcin with substituted phenyl acetic acids, methylation, and then condensation with dimethyl carbonate （DMC） to form the coumarin. 3. Condensation of phloroglucinol with substituted phenylacetonitrile, methylation, and then condensation with DMC to form the coumarin. A series of coumarins with different substituents were formed by the above methods.A series of coumestan were obtained by FeCl3-mediated oxidative cyclization of 4-hydroxy-3-aryl coumarin under the optimized conditions. The workup was more convenient and the yield was improved by using FeCl3/SiO2 instead of FeCl3. We found that the substrates with different substituents such as methoxy, methyl, halogen, or no substituent could provide the corresponding products. However, when the substrates with strong electron-withdrawing group CF3, methoxy on the meta position, or methyl on the ortho site, no products were obtained.As many natural coumestan possess hydroxyl group, and hydroxyl group has something important with the activities of coumestan. When the synthesized 9-Methoxy-4-methyl-6H-benzofuro [3, 2-c] chromen-6-one was subjected to BBr3, the corresbonding hydroxylated coumestan was obtained.9-Methoxy coumestrol is a natural coumestan. We also applied our method to its synthesis by using a protection– deprotection protocol. |
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