Catalytic Synthesis And Comparative Study On HPLC Analysis Of P-Hydroxybenzoate

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.