实验十五萘普生的制备.docVIP

实验十五 萘普生的制备 Experiment 15. Preparation of Naproxen 15.1 目的要求 Purpose （1）掌握Friedel-Crafts丙酰化反应原理和操作。 （2）掌握“一锅重排法”合成萘普生的具体操作。 （3）掌握萘普生光学异构体拆分的原理和方法。 （4）掌握旋光仪的使用方法,并能够熟练用于测量萘普生的比旋度。 （5）本实验分5次,共33学时。 15.2 背景介绍 Background Information Naproxen 萘普生（naproxen）是一个非常重要的非甾体消炎镇痛药，具有抗炎、解热、镇痛作用化学名为α-甲基- 6-甲氧基-2-萘乙酸((?S)-6-methoxy-?-methyl-2-naphthaleneacetic acid)。萘普生为白色或白色结晶性粉末；无臭或几乎无臭。α-溴代得到2-(2’-溴丙酰基)-6-甲氧基萘，再经缩酮化、重排、水解一锅合成外消旋萘普生，此方法为1,2-芳基迁移重排合成法。然后用拆分试剂葡辛胺进行拆分得到右旋光学活性体。其合成路线如下： 2-Methoxynaphthalene 2-propionyl-6-methoxynaphthalene 2-(2’-bromopropionyl)-6-methoxynaphthalene (RS)-Naproxen (S)-Naproxen 15.4 实验操作 Experimental Procedures 15.4.1 2-丙酰基-6-甲氧基萘的制备 Synthesis of 2-propionyl-6-methoxynaphthalene (12 hours) Add grinded 3.35 g of anhydrous aluminum chloride, 150 mL of dichloromethane into a 50mL round-bottom flask with a dropping funnel and a magnetic stirrer. Stir and dissolve. After cooling to about O℃, stirring is maintained constantly, add dropwise 2.1 mL of propionyl chloride (within 30 min). Keep the reaction at this temperature for 6 h and at room temperature for 18 h. Pour the mixture into 50 mL of 0.l mol/L cool hydrochloric acid, transfer to a separating funnel. After separation of organic phase, extract aqueous phase with dichloromethane (50 mL?), combine the aorganic phase. The dichloromethane extract is dried with anhydrous sodium sulfate. Filter, remove solvent and recrystallize with 95% ethanol to obtain the product. The solid is collected, dried and weighed. The yield is calculated and the melting point is measured[2]. Notes: (1) This is an exothermic Friedel-Crafts reaction. Drop gradually propionyl chloride into the mixture of chloroform, 2-methoxy naphthalene and anhydrous aluminum chloride so that the reaction carries out smoothly. (2) Before beginning, dry all glassware and materials thoroughly. Question: What should be paid attention to in Friedel-Crafts acylation operations? 15.4.2 2-(2’-溴丙酰基)-6-甲氧基萘的制备Synthesis of