摘要：4-氯乙酰乙酸乙酯是一种很好的医药合成中间体,主要用于医药领域，是氮氯地平、阿托伐他汀钙，头孢他定等治疗心脑血管疾病的高效疗药的重要中间体，具有广阔的市场前景。本课题以二氯甲烷与双烯酮为起始原料合成4-氯乙酰乙酸乙酯，采用重力自然降膜反应器，这一降膜反应器体积小，反应时有效冷却面积大，可以更高效控制反应温度，缩短了反应时间，降低了能耗，控制了多氯代物，提高了反应选择性，使精馏相对容易，提高了产品收率和纯度，粗品精馏得含量大于99%的4-氯乙酰乙酸酯类产品。57362

毕业论文关键词： 4-氯乙酰乙酸乙酯；双烯酮；二氯甲烷；合成；中间体

The Research of ethyl 4-chloroacetoacetate Synthetic Technology

Abstract:4-chloro-ethyl acetoacetate is a good pharmaceutical intermediates, mainly used in the field of medicine, is nitrogen amlodipine, atorvastatin calcium, cefotaxime in the treatment of cardiovascular and cerebrovascular diseases and efficient remedy important intermediates and has broad market prospect. This subject to two chlorine methane and double en ketone for starting raw materials synthesis 4-chlorine acetyl acetic acid b ester, used gravity natural drop film reactor, this a drop film reactor volume small, reaction Shi effective cooling area big, can more efficient control reaction temperature, shortened has reaction time, reduced has energy, control has more chlorine generation real, improve has reaction selective, makes fine distillation relative easy, improve has products received rate and purity, rough products fine distillation have content is greater than 99% of 4-chlorine acetyl acetic acid ester class products.

Key Words: ethyl 4-chloroacetoacetate   Diketene   Methylene chloride   Synthesis Intermediate

目录

1  绪论 1

1.1 课题研究的背景 1

1.2 课题意义及研究内容 3

2 文献综述 5

2.1 产品及主要原料的理化性质及标准 5

2.1.1 4-氯乙酰乙酸乙酯的理化性质及标准 5

2.1.2 二氯甲烷的理化性质及标准 5

2.1.3 双烯酮的理化性质及标准 5

2.2 目前国内外生产4-氯乙酰乙酸乙酯的工艺方法 6

2.2.1 一种比较简单合理的合成方法 6

2.2.2 氯乙酸乙酯法 6

2.2.3 双烯酮法 6

2.3  4-氯乙酰乙酸乙酯制备路线的选择 7

3 实验部分 8

3.1 试验主要设备 8

3.2 反应方程式 8

3.3 反应过程 8

4 结果与讨论 11

4.1 反应条件优化 11

4.1.1 温度对反应的影响 11

4.1.2 氯气流量考察 11

4.1.3 氯气分配情况考察 12

4.1.4 氯气管开孔孔径的大小考察 12

4.1.5 氯气分布器的抗腐蚀性实验 13

4.1.6 浓度优化实验 13

4.1.7 溶剂优化实验