实验十 苯妥英钠的制备
Experiment 10. Preparation of Phenytoin Sodium
10.1 目的要求 Purpo
星期一英语
（1）掌握抗癫痫药苯妥英钠的合成方法。
（2）通过了解苯妥英钠合成路线中各步化学反应的原理，深入理解反应的操作过程。
（3清清语言培训机构创始人）熟练进行回流、水浴加热、抽滤、重结晶、测熔点等实验操作。
（4）掌握测定化合物水溶液pHtex值的方法。
（5）本实验分4次，共22学时。
10.2 背景介绍 Background Information
癫痫是一种由大脑神经元异常放电引起的短暂神经功能失常为特征的慢性脑部疾病，具有突然发生、反复发作的特点。苯妥英钠（phenytoin sodium）作为抗癫痫药，主要适用于治疗
复杂部分性发作、单纯部分性发作、全身强直阵挛性发作和癫痫持续状态。苯妥英钠还可用于抗心律失常等。
Phenytoin Sodium
苯妥英钠的化学名为：5,5-二苯基-2,4-咪唑啉二酮钠盐（5,5-diphenyl-2,4-imidazolidinedione sodium salt）。苯妥英钠别名大伦丁钠，二苯乙内酰脲钠。为白色粉末，无臭，味苦，微有引湿性。在水中易溶，在乙醇中溶解，在三氯甲烷或乙醚中几乎不溶。苯妥英钠在空气中渐渐吸收二氧化碳，分解成苯妥英；水溶液显碱性反应，常因部分水解而发生混浊[1]。
10.3 实验原理 Important Reactions
本实验以苯甲醛为原料，经过四步化学反应制备苯妥英钠。第一步反应是安息香( benzo
in, 2-羟基-1,2-二苯乙二酮)缩合反应：在维生素B1催化下2分子苯甲醛缩合生成安息香。第二步反应是安息香通过六水合三氯化铁氧化生成1,2-二苯乙二酮 (benzil)。第三步反应中，1,2-二研究生考试总分苯乙二酮在碱性条件下和尿素缩合并发生重排，酸化后生成苯妥英。第四步反应是苯妥英和氢氧化钠成盐，得到苯妥英钠。具体合成路线如下：
Benzaldehyde Benzoin Benzil
Phenytoin Phenytoin sodium
在本实验的第一步，即安息香缩合反应中，除了以维生素B1催化的方法之外，还可以用氰化钾[2]做催化剂。因为氰化钾是剧毒品，现已采用维生素B在线翻译器百度在线翻译1代替氰化钾制备安息香。
在第二步氧化反应中，通常采用浓硝酸氧化。为了更适于学生实验的需要，用六水合三氯化铁作为氧化剂，操作更为简单，且减少了实验室的污染。
10.4 实验操作 Experimental Procedures
10.4.1 2-羟基-1,2-二苯乙二酮(安息香)的合成Synthesis of 2-Hydroxy-1,2-diphenylethanone ( Benzoin)（4 hours）
风格styleThiamine hydrochloride (1.75 g) is put into a 50-mL Erlenmeyer flask and distilled water (4 mL) is added to dissolve the solid. Then 95% alcohol (15 mL) is added into the solution. 2 mol/L aqueous solution of sodium hydroxide (5 mL) is added dropwi. The mixture is stirred at room temperature for 5 min. Finally benzaldehyde (10 mL) is added and the mixture is stood at room temperature for a week. The solid is collected on a Buchner filter by suction filtration. The solid is washed with a small amount of cold water.
Then the solid is dried and the crude product of benzoin is obtained. The yield is calculated. The melting point is measured.
Notes:
(1) What is the crystal product when 1 mL of benzaldehyde and 5 mL of saturated solution of sodium bisulfite are mixed for a few minutes and then the mixture is cooled in an ice bath?
(2) Benzaldehyde ud in this reaction should be newly distilled.
(3) The 2 mol/L NaOH aqueous solution should be prepared accurately.
Questions:
(1) What is the mechanism of this reaction?
(2) Why the benzaldehyde should be newly distilled?
(3) What is the catalytic mechanism of potassium cyanide?
21天掌握当众讲话诀窍10.4.2 1,2-二苯乙二酮的合成 Synthesis of 1,2-diphenylethanone (Benzil)（4 hours）
Benzoin (2.12 g), ferric chloride hexahydrate (9.0 g), and water (5 mL) are added into a 100-mL round-bottomed flask. Then two pieces of zeolite are added into the mixture. Then glacial acetic acid (10 mL) is added after the flask is fitted with a refluxing condenr. The reaction mixture is heated to keep boiling for about 60 minutes. Then 50 mL of water is added into the flask. And the mixture is heated until the solution is boiling again. The residue in the flask is cooled. Some solid is precipitated. The solid is collected on a Buchner filter by suction filtration. Then the crude product of benzil is obtained.
The crude product, a piece of zeolite, and 12 mL of ethanol are put into a pear-shaped flask. The flask is fitted with a refluxing condenr and is heated until the crude product is dissolved. Then the solution is cooled and some active charcoal is added into the solution. The mixture is heated to keep boiling for 10 minutes. Then the hot mixture is filtr
ated quickly on a Buchner filter by suction filtration. The filtrate is poured into a beaker quickly, cooled first at room temperature and then in an ice bath. When crystals of benzil are fully precipitated, collect the solid on a Buchner filter by suction filtration. The solid is washed with a small amount of cold mixture of ethanol and ether, dried and weighed. The yield of benzil is calculated and the melting point is measured[3].
Notes:
(1) In this reaction, glacial acetic acid should be added into the round flask after the refluxing condenr has been attached.
(2) Keep the contents of the flask boiling gently to avoid excessive evaporation of the solvent.
(3) During the recrystallization process, we should filter the hot solution of benzil containing夏令营注意事项 activated charcoal rapidly under vacuum. And the funnel and the leaching bottle should be preheated first.
(4) The benzil should not be dried rapidly by washing it with ether.
Questions:
(1) Can concentrated nitric acid be ud to oxidize benzoin in this experiment?
(2) Why do we u ferric chloride hexahydrate as an oxidant instead of concentrated nitric acid in our experiment?
10.4.3 5,5-百度英汉翻译器二苯基-2,4-咪唑烷二酮 （苯妥英）的合成 Synthesis of 5,5-Diphenyl-2,4-imidazolidinedione ( Phenytoin) 无所谓英语（5 hours）
