Synthesis Process For The Preparation Of 4-aminoantipyrine

In recent years,the existing production processes of fine chemicals such as 4-aminoantipyrine（AA）are facing great pressure under the situation that the government encourages industrial upgrading&transformation and attaches great importance to environmental protection issues.Currently,the AA synthesis process is a semi-intermittent process,which has some problems such as large environmental pressure,unstable product purity&yield,and impurities such as nitrogen oxides as well as colloids during the production process.At present,domestic and foreign research mainly focuses on post-product treatment,which does not reduce or even avoid the generation of nitrogen oxides,colloids and other substances from the source,and without changing the status quo of the existing semi-intermittent process.The objective of this project is the continuous improvement of the AA synthesis process.Due to insufficient knowledge of the AA production process and lack of basic data at the initial stage of the investigation,the key reactions in the AA semi-intermittent process were first selected as the research object,and process parameter optimization as well as reaction mechanism were conducted,aiming to address the generation of impurities such as nitrogen oxides.Secondly,based on the investigation of semi-batch process,the continuous improvement of AA synthesis process was carried out.In the study of semi-batch process parameter optimization,the main task was to optimize the process parameters for nitrosation,reduction,and hydrolysis reactions.The effects of parameters such as material ratio,reaction time and reaction temperature on the purity and yield of AA were investigated by single-factor experimental method and response surface analysis（RSM）,which the effects of interactions between different factors on the response values were analyzed.The optimal conditions for the nitrosation reaction were:n（AT-SO₄）:n（Na NO₂）=1:1.19,n（AT）:n（H₂SO₄）=1:0.58,nitrosation reaction temperature of 17°C and reaction time of 2 min.The optimal conditions for the reduction reaction were that m（AT-SO₄）:m（reducing agent）=1:0.82,the cold reduction reaction temperature of 40°C,reaction time of 30 min,the hot reduction reaction temperature of 70°C and reaction time of 90 min.The optimal conditions for the hydrolysis reaction were that n（AT-SO₄）:n（H₂SO₄）=1:1.33,hydrolysis reaction temperature of 98°C,and reaction time of 95 min.Repeatability experiments were carried out with all the above optimized parameters.The purity of AA was above 81%,the yield was above 92%.Compared with the original process without optimization,the purity of AA was increased by about 8%,the yield was improved by about 3%,and impurities such as waste gas and colloid were significantly reduced.After purification,the purity of AA was above 98.7%.The nitrosation and hydrolysis reactions were studied by material characterization and theoretical analysis.The mechanism of nitrosation reaction showed that nitrous acid was protonated and lost a water molecule,which in turn produced nitrosyl ion（NO⁺）.NO⁺had strong electrophilicity and could replace the hydrogen on the heterocyclic ring to obtain the target product.Excess NO⁺could replace the hydrogen on the benzene ring to generate secondary nitrosation products.In the process of hydrolysis reaction,4-aminoantipyrine sulfonate could undergo electrophilic substitution reaction with water under acidic condition to form 4-aminoantipyrine sulfate,in which H⁺was the electrophilic reagent.The reduction reaction process was investigated by measuring the degree of reduction,which the results showed that the reduction degree first decreased and then stabilized as the reaction time increases.The higher the temperature,the shorter the time for the reduction degree to stabilize.In addition,under the reaction process parameters of hydrolysis reaction,the kinetics was investigated by differential method,and the kinetic equation was finally derived.Based on the above semi-intermittent process research,a small-scale continuous test was conducted to improve the AA synthesis process.The continuous small-scale process route was designed and verified to be reasonable through experiments.When the continuous reaction device was operated continuously for 72 hours,the purity of AA was 74.81%and the yield was 85.06%.The research of AA semi-intermittent process,including the optimization of process parameters,reaction mechanism analysis,reduction process analysis and hydrolysis kinetics analysis,is of great guidance to the solution of industrial production problems.Currently,AA semi-intermittent process has inherent defects such as low automation level,low production efficiency,and high raw materials&energy consumption.However,the research of AA small-scale continuous process provides a new idea to solve the inherent defects of the current AA semi-batch process,which can provide process route support for optimization of subsequent continuous process parameters or amplification verification of the process route.