Study On The Synthetic Process Of Aromatic Acids And Their Derivatives Prepared By Carboxylation Of Carbon Dioxide

As an important chemical and pharmaceutical intermediates,aromatic acids are widely used in medicines,materials,pesticides,dyes and other fields.In recent years,with the development of the pharmaceutical and chemical industry,the demand for various aromatic acids have gradually increased.At present,aromatic acids are mainly synthesized by oxidation,leading to a series of problems such as poor economic benefit,low atomic utilization,and pollution of“three wastes”.Therefore,it is necessary to optimize the synthesis process by developing more economical and environmentally friendly routes.Utilization of carbon dioxide has attracted more and more attention,since it is cheap and easy to obtain which has a wide range of applications in industry.In the context of the Chinese government’s strategic call of"carbon peaking"and"carbon neutrality",using carbon dioxide as the C 1 synthon to introduce a carboxyl group into a compound is an ideal method for carboxylation,since CO₂is efficiently utilized,which is more economical and environmentally friendly.In this thesis,4-hydroxysalicylic acid and 4-aminosalicylic acid have been synthesized by carboxylation of carbon dioxide using resorcinol and m-aminophenol as starting materials,respectively.The process optimization was carried out with an aim to maximize product yield and purity.Furthermore,the large-scale industrial production of 4-hydroxysalicylic acid has been realized.This thesis is divided into the following three parts:The first part is the synthesis of 4-aminosalicylic acid by carbon dioxide carboxylation of m-aminophenol.Two synthetic routes are investigated:（1）without adding boric acid,（2）adding boric acid.The best reaction conditions of route 1 are as follows:m-aminophenol and sodium hydroxide in a molar ratio of 1:2 are dissolved in water（m-aminophenol:water（v/v）=1:8）.The reaction mixture is kept at 110℃under a pressure of carbon dioxide of 2.0 MPa for 8 h.As a result,the yield of reaction is 31.32%,and the purity of product is 96.00%.When it comes to the route 2,the best reaction conditions of route 2 are as follows:m-aminophenol,sodium hydroxide and boric acid in a molar ratio of 1:2:2 are dissolved in water（m-aminophenol:water（v/v）=1:8）.The reaction mixture is kept at 110℃and a pressure of carbon dioxide 2.0 MPa for 12 h.The yield of reaction is 52.70%,the purity of product is 99.74%.The second part is the process optimization of resorcinol to synthesize4-hydroxysalicylic acid by carbon dioxide carboxylation.The optimal reaction conditions are as follows:resorcinol and potassium carbonate in a molar ratio of 1:1,then adding them into 4.5 times as much water as resorcinol.The reaction mixture is kept at 90℃under a carbon dioxide pressure of 0.4 MPa for 3 h.The first precipitation yield of the reaction is 44.00%,and the purity is 100.00%.After acid precipitation,the filtrate is passed through the resin column,and eluted with potassium carbonate solution,then the obtained filtrate is recycled.Thus,zero-emission of phenolic wastewater is realized.The comprehensive yield after recovery is 76.50%.The third part is the optimization of synthesis process of methyl4-hydroxysalicylate and methyl 4-acetamidosalicylate,including feeding ratio of materials,reaction temperature,reaction time and so on.（1）The best reaction conditions for the synthesis of methyl 4-acetylaminosalicylate are as follows:20 g of p-aminosalicylic acid is dissolved in 7.5 times as much methanol as 4-aminosalicylic acid.Then 40 m L of concentrated sulfuric acid is slowly added into this solution at0-5℃.After that,the reaction mixture is kept at 80℃for 3 hours.The reaction yield is 91.63%.Then 5 g of the obtained product is added into 12 times volume of ethyl acetate,1.37 eq of saturated sodium bicarbonate solution and 1.37 eq of acetyl chloride.This reaction mixture is kept at 15℃then 3 eq of sodium bicarbonate and1.37 eq of acetyl chloride are added,leading to a yield of 81.26%with 99.56%purity.（2）The best reaction conditions for the synthesis of methyl 4-hydroxysalicylate are:12 g of 4-hydroxysalicylic acid is added into 84 m L of methanol,and then 5 m L of concentrated sulfuric acid is added dropwise.The reaction mixture is kept at 85℃for30 hours.The yield is 83.41%,and the purity is 99.39%.