【作者】 曾立华；

【导师】 尹笃林；

【作者基本信息】 湖南师范大学 ， 有机化学， 2008， 硕士

【摘要】 论文的第一部分概述了对羟基苯甲酸酯的用途、历史及发展趋势,综述了对羟基苯甲酸酯的合成方法。以对羟基苯甲酸和醇为原料,分别用磺酸树脂、氨基磺酸作催化剂,合成了系列对羟基苯甲酸酯,考察了反应温度、反应时间、物料比、催化用量及循环使用等因素对产品产率的影响,得到了较佳的合成条件;比较了几种磺酸类催化剂的催化活性。用红外光谱图表征了产品的结构,并测定了其熔点。通过反应规律的考察,发现以氨基磺酸为催化剂的较优反应条件为:0.3mol丁醇,0.05 mol对羟基苯甲酸,2g氨基磺酸,回流反应4小时,产率为89.7%,采用脱水装置产率可达94.5%,但是该催化剂的重复使用性能差。用磺酸树脂作催化剂,用0.25mol丁醇,0.05 mol对羟基苯甲酸,1.5g磺酸树脂,回流反应5小时,丁酯产率可达82.5%,该催化剂具有可重复使用、与产物易分离、副反应少等优点;磺酸树脂适合催化合成三碳以上醇的酯。论文的第二部分研究分别用甲醇-水和乙醇-水作流动相时对羟基苯甲酸酯混合物的液相色谱分析方法,探讨了高效液相色谱中流动相的组成和柱温变化对对羟基苯甲酸酯流出行为的影响规律,建立了同时测定复方硝酸益康唑乳膏中对羟基苯甲酸甲酯和丙酯的高效液相色谱方法。通过比较研究C₁₈柱上分别以甲醇或乙醇与水的二元混合物作流动相时的液相色谱流出特性,发现四种对羟基苯甲酸酯的保留时间随着烷基链从甲基到丁基的增长而延长,随着流动相中甲醇或乙醇的增加而缩短,当流动相为甲醇∶水=60∶40（体积比）或流动相为乙醇∶水=45∶55（体积比）时柱效最好。分别以甲醇-水和乙醇-水为流动相时,对羟基苯甲酸酯同系物在液相色谱中的保留时间随着柱温的下降而延长,其焓变随烷基中C原子数的增加而线性增加。以乙醇-水作流动相建立了对羟基苯甲酸酯的HPLC绿色化学分析方法,并将其应用于药品中对羟基苯甲酸酯的分析,测得复方硝酸益康唑乳膏中对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的质量分数分别为1.97‰(g.g^-1)、0.95‰(g.g^-1),含量测定重复性RSD分别为0.62%、1.5%,回收率为94.58%—103.83%。该方法操作方便、灵敏度高。更多还原

【Abstract】 In the first part of this paper,the uses,history,development trends and synthetic methods of p-hydroxybenzoate were summarized.Butyl p-hydroxybenzoate were synthesized from p-hydroxybenzoic acid and butanol using sulfoacid resin and aminosulfonic acid as catalyst, respectively.The influences of reaction time,temperature,raw materials ratio,the quantity of catalyst and recycling use performance of the catalyst on the yield of product were investigated.The optimal technological condition was also obtained.The relatively catalytic activity of several sulfoacid catalysts was compared.And the product was characterized by FT-IR and measurement of its melting point.By investigating reaction rules,the optimal conditions using aminosulfonic acid as catalyst were found as follows:the ratio of butanol to p-hydroxybenzoic acid is 0.30 mol:0.05 mol,aminosulfonic acid 2 g refluxing time 4 h,and the yield was 89.7%.The yield can increase to 94.5%when using dehydration equipment refluxing.However the repeated use performance of aminosulfonic acid was become poor.When using sulfoacid resin as catalyst the optimal conditions were as follows:the ratio of butanol to p-hydroxybenzoic acid is 0.25mol:0.05mol,sulfonic acid resin 1.5g,refluxing for 5 h using water separator.The yield reached 82.5%.The catalyst shows the advantages of repeatable use,less side reactions,and being separated easily from products.Sulfoacid resins can thus be proved to be good catalyst for esterification of p-hydroxybenzoic acid with alcohols containing more than three carbon atoms in alkyls.In the second part of this paper,a liquid chromatographic analysis method of p-hydroxybenzoate was studied by using methanol-water and ethanol-water as mobile phase,respectively.The influence of mobile phase composition and column temperature for then outflow behavior of p-hydroxybenzoate was investigated.The high performance liquid chromatography method of determining the nipagin and nipasol simultaneously in the compound econazole nitrate cream was established.By comparing the outflow performance of p-hydroxybenzoate liquid chromatography on C₁₈ column using the binary mixture of methanol-water or ethanol-water as mobile phase,it was found that the retention time of p-hydroxybenzoate was prolonged with increasing number of carbon atoms in alkyls,and the retention time of p-hydroxybenzoate was shortened with the increase of methanol or ethanol in the mobile phase.Under the selected liquid chromatographic conditions of this experiment,the column efficiency is the best when the ratio of methanol to water is 60:40（v/v） or the ratio of ethanol to water is 45:55（v/v）.While using methanol-water or ethanol-water as the mobile phase,the retention time of nipagin homologues in liquid chromatography was prolonged with the decrease of column temperature. The enthalpy change of nipagin homologues has a linear relationship with increasing number of carbon atoms in alkyls.The HPLC analysis method of green chemistry of nipagin esters was established using ethanol-water as mobile phase.It has been used to determine p-hydroxybenzoate in medicine.The nipagin and the nipasol of the compound econazole nitrate cream were measured to be 1.97‰(g.g^-1) and 0.95‰(g.g^-1),respectively.The RSD of reproducibility was 0.62% and 1.5%,respectively.The average recovery of the two components was 94.58%～103.83%.The method is reliable,and has high sensitivity and good reproducibility.更多还原