手性化合物的重要制备方法消旋联萘酚的合成与拆分.pptVIP

手性化合物的重要制备方法—拆分 消旋联萘酚的拆分 Introduction: Resolution Classical kinetic resolution The most often used resolving agents Some methods of resolution of racemic binaphthol A novel resolution procedure Selection of a resolving agent Finding a suitable method for diastereomer separation Purification of the separated diastereomer or the enantiomer prepared therefrom To realize a resolution, several problems have to be solved What kind of resolving agent has to be applied? What should the molar ratio of racemate and resolving agent be? Which is the best solvent or is any solvent necessary at all? What are the best conditions for diastereomer separation (concentration, temperature, time, etc.)? Resolution of racemic 1,10-bi-2-naphthol using N-benzylcinchoninium chloride N-benzylcinchoninium chloride (20.21 g, 48 mmol) was added to the solution of racemic 1,10-bi-2-naphthol (22.88 g, 80 mmol) in acetonitrile (300 mL). The mixture was heated to reflux for 4 h and then allowed to cool to room temperature. The resulting white solids were collected by filtration and washed with acetonitrile (3×20 mL). The solids were characterized to be two-component molecular crystals of (R)-(+)-binol and N-benzylcinchoninium chloride in a 1:1 molar ratio. The enriched (S)-(2)-1 was left in the mother liquor. SeedingAn initiation step of Crystallization Adding a small amount of the pure compound (a seed crystal) to the saturated solution Scratching the glass surface to create a seeding surface for crystal growth. Even dust particles can act as simple seeds. Fractional crystallization If a mixture of two or more substances in solution is allowed to crystallize, for example by allowing the temperature of the solution to decrease, the precipitate will contain more of the least soluble substance. The proportion of components in the precipitate will depend on their solubility products If the solubility products are very similar, a cascade process will be needed to effectuate a complete separ