【作者】 李园园；

【导师】 康从民；

【作者基本信息】 青岛科技大学 ， 制药工程（专业学位）， 2013， 硕士

【摘要】 5-苯戊酸类化合物是一类重要的医药化工中间体,应用较为广泛。由于目前工业合成方法的收率较低,然而市场需求量较大。所以找出一种简单、合理、产率较高的合成方法是有必要的。本文通过逆合成分析,并结合相应的文献,找出了一种新的思路来合成5-苯戊酸的衍生物,此思路主要采用了迈克尔加成反应的方法。迈克尔加成反应在有机合成中越来越多的应用,为苯乙酮和丙烯酸甲酯的缩合奠定了可行的基础。苯乙酮和丙烯酸甲酯通过迈克尔加成反应合成4-苯甲酰基-1,7-庚二酸甲酯。此方法,合成路线简便,反应条件温和,环境污染小。但是对于此反应的具体影响因素,仍需实验的进一步探索。因此,这是5.苯戊酸衍生物合成研究的一个重要方向。以下是本文研究的主要内容：1以苯乙酮和丙烯酸甲酯为原料,采用迈克尔加成方法,对4-苯甲酰基-1,7-庚二酸甲酯的合成进行了探索。在无水环境下,以甲醇钠为催化剂,甲醇为溶剂,考察了温度、反应时间和原料配比等因素对合成4-苯甲酰基-1,7-庚二酸甲酯的影响。具体合成的反应方程式可表示为：2以3-硝基苯乙酮和丙烯酸甲酯为原料,通过迈克尔加成反应的方法来合成4-(3-硝基)苯甲酰基-1,7-庚二酸甲酯。因为中间体——间硝基苯乙酮分子中有硝基的吸电子的作用,会使反应更容易进行。通过对反应条件的优化,确定反应的最佳的合成方案。具体合成的反应方程式可表示为：3以苯和戊二酸酐为原料,经过付克酰基化反应、硝化反应、还原反应,最终得到5-(间氨基)苯戊酸。在研究过程中,对每一个过程的反应条件都进行了探索和优化,使反应过程更加合理,并提高了各步的反应收率。所有合成的化合物都经过1HNMR确认。具体合成的反应方程式可表示为：更多还原

【Abstract】 5-Phenylvaleric acid derivatives are very important chemical and medical intermediates in industry, and applied very widely. Now its industrial synthesis gave relatively low yield, the market demands are great, so it is necessary to find a simple, reasonable, and high yield synthesis route for5-phenylvaleric acid derivatives.In this paper, through retrosynthesis analysis, combined with the corresponding literature, a new way of synthesizing5-phenylvaleric acid derivatives is found. This way mainly adopted Michael addition reaction.The4-Benzoyl-heptanedioic acid dimethyl ester is synthesized through Michael addition reaction of acetophenone and methyl acrylate. This synthetic method was a satisfactory way with simple synthetic route, ambient conditions and low environment pollution. But the specific influencing factors of reactions need to be further explored. Therefore, it is an important direction for synthesis of5-Phenylvaleric acid derivative. The following is the main content of this paper:1Acetophenone and methyl acrylate are used as raw materials, and the synthesis of4-Benzoyl-heptanedioic acid dimethyl ester by Michael addition reaction have been explored. This method is in the environment of absolute anhydrous. The catalyst is sodium methanolate. The effect of temperature, reaction time and ratio of raw material on the synthesis of4-Benzoyl-heptanedioic acid dimethyl ester was studied. The reaction equation is expressed as follows:23-Nitro-acetophenone and methyl acrylate are used as raw materials, synthesizing4-(3-nitro)Benzoyl-heptanedioic acid dimethyl ester by Michael addition reaction method.The effect of electron-withdrawing by nitro group makes the reaction more easily. At last, the reaction condition was optimized by the experimental studies. The reaction equation is expressed as follows:3Benzene and glutaric anhydride are used as raw materials, to synthesize5-(3-amino) phenyl valerate by Friedel-Crafts acylation reaction, nitration reaction, and reduction reaction. In the course of this study, each step of the reaction conditions are explored and optimized, so that the reaction process is more reasonable, and the reaction yield is higher. All synthesized compounds are confirmed by1HNMR. The reaction equation is expressed as follows:更多还原