Synthesis Of Indapamide And The Adsorption Of Tetrahydrofuran+Water Solution Mixture On Molecular Sieve

The synthesis process of indapamide and the adsorption equilibrium and kinetics of tetrahydrofuran + water solution mixture on molecular sieve 3A and 4A in a batch system and a fixed bed system has been studied in this paper.Indapamide is a specific drug for the treatment of hypertension. Based on the review of the literatures, a synthesis process of indapamide from cheap an easily available p- chlo robenzoic acid has been studied and developed. The synthetic route comprises four steps: chlorosulfonation, aminate, acyl chlorination, condensation and so on. The overall yield of indapamide was 66.01% (purity 95.85%) and 10.29% higher than the yield in the literature.Chlorosulfonation of p-chlorobenzoic acid was carried out by using self-investigated sulfonating agent and catalyst agent, p-chlorobenzoic acid / chlorosulfonicacid (mol/mol)^ 1:6.0, at 140℃ for 6 hours, the yield was 92.63% (purity 97.78%) and 12.63% higher than the yield in the literature and the waster reduce 50%;In the aminate step, 97.72% yield was obtained when 4-chloro-3- chlorosulfonyl benzoic acid:ammonia(mol/mol) = 1:4.0, and react at 30°C for 4 hours;4-chloro-3-chlorosulfonyl benzoyl chloride was obtained in 97.81 % yield with the mol ratios of 4-chloro-3-sulfamoyl benzoic acid /sulfurous oxnychloride (mol/mol) =1:20,and react at 78℃ for 4 hours;With tetrahydrofuran used for solvent and nitrogen purged, indapamide was obtained in 83.06%yield with the mol ratios of 4-chloro-3-sulfamoylbenzoylchloride/ 2-Methylindolin-1-amine hydrochloride (mol/mol) =1.5:1.0, and react at 20℃ for 4 hours.Tetrahydrofuran (THF) is a fine organic solvent and the precursor of polymers, more over was an important solvent of indapamide synthesis. The adsorption equilibrium and kinetics of tetrahydrofuran + water solution mixture on molecular sieve 3A and 4A have not been reported in the literature. The adsorption equilibrium of tetrahydrofuran + water solution mixture on molecular sieve 3A and 4A was carried out: The equilibrium behaviour was shown to fit a Langmuir isotherm;The adsorption kinetics of tetrahydrofuran + water solution mixture in a batch system on molecular sieve 3A and 4A was carried out: A surface diffusion model, coupled with the Langmuir isotherm equation, was used to interpret the observed experimental adsorption kinetic curves with different initial concentrations, temperatures and particle sizes. The surface diffusivity D_s can be extracted;The adsorption kinetics of tetrahydrofuran + water solution mixture in fixed bed on molecular sieve 3A and 4A was carried out: It came to the result that the mixture of tetrahydrofuran and water can be commendably separated by fixed-bed adsorption, as theconcentration of tetrahydrofuran got from the bed can be higher than 99.9%. A Homogeneous Surface Diffusion Model (HSDM) was proposed to predict the adsorption breakthrough curves. The experimental results on the adsorption of tetrahydrofuran + water mixture on molecular sieve 4A columns proved that the HSDM can predict the column performance satisfactorily and therefore can be used in the design of fixed bed. Some important operation parameters such as Va, Za, NF,HF ,Kfav and so on were extracted.The above result of adsorption provide important foundation data for design and magnify the tetrahydrofuran + water solution mixture in on molecular sieve.