The Research On Electroreduction Synthesis Of Dihydro-1-indenamine And Tetrahydro-1-naphthylamine Pharmaceutical Intermediates

Indeneamine and Naphthylamine compounds have attracted much attention as key intermediates in the synthesis of Asagiline,ozanimod,1,2,3,4-tetrahydro-1-naphthylamine derivatives and sertraline drugs.In this paper,ketoxime was prepared from ketone and hydroxylamine hydrochloride,and then reduced to amine compounds by electrochemical method.The process was optimized by linear sweep voltammetry and electrolytic synthesis method.The research contents and results are as follows:（1）The optimization process of electrochemical reduction reaction of indenamine drug intermediate—2,3-dihydro-1-indeneamine was studied:The methanol solvent of 0.06 mol/L2,3-dihydro-1-indanone oxime was added to the cathode electrolyte of 0.2 mol/L KOH,and 5mol/L KOH was used as the anode electrolyte,zinc sheet（2×2 cm²）as the working electrode and platinum sheet（1×1 cm²）as the anode electrode,electrolyzed at 50°C with current density of 150 m A·cm^-2for 6.5 h,the obtained product was salted with HCl（g）,and the desired product 2,3-dihydro-1-indenamine hydrochloride was obtained with a yield of 90.7%.（2）The optimization process of electrochemical reduction reaction of indeneamine drugs intermediate containing cyano group—4-cyano-2,3-dihydro-1-indeneamine was studied:The acetonitrile solvent of 0.04 mol/L 4-cyano-2,3-dihydro-1-indanone oxime was added to the cathode electrolyte of 0.5 mol/L Na₂HPO₄,and 5 mol/L Na OH was used as the anode electrolyte,zinc sheet（2×2 cm²）as the working electrode and platinum sheet（1×1 cm²）as the anode electrode,electrolyzed at 40°C with current density of 6.5 m A·cm^-2for 17 h,the obtained product was salted with HCl（g）,and the desired product 4-cyano-2,3-dihydro-1-indeneamine hydrochloride was obtained with a yield of 90.9%.（3）The optimization process of electrochemical reduction reaction of naphthylamine drugs intermediate—1,2,3,4-tetrahydro-1-naphthylamine was studied:The methanol solution of 0.04 mol/L 1,2,3,4-tetrahydro-1-naphthone oxime was added to the cathode electrolyte of0.2 mol/L KOH,and 5 mol/L KOH was used as the anode electrolyte,zinc sheet（2×2 cm²）as the working electrode and platinum sheet（1×1 cm²）as the anode electrode,electrolyzed at50°C with current density of 200 m A·cm^-2for 4 h,the obtained product was salted with HCl（g）,and the desired product 1,2,3,4-tetrahydro-1-naphthylamine hydrochloride was obtained with a yield of 95.9%.（4）The optimization process of electrochemical reduction reaction of naphthyl-amine dr ugs intermediate containing aromatic group—4-（3,4-dichlorophenyl）-1,2,3,4-tetrahydro-1-nap hthylamine was studied:The ethanol solvent of 0.02 mol/L 4-（3,4-dichlorophenyl）-1,2,3,4-tetr ahydro-1-naphthone oxime was added to the cathode electrolyte of 0.2 mol/L KOH,and 5 mo l/L KOH was used as the anode electrolyte,zinc sheet（2×2 cm²）as the working electrode and platinum sheet（1×1 cm²）as the anode electrode,electrolyzed at 60°C with current density of200 m A·cm^-2for 7 h,the obtained product was salted with HCl（g）,and the desired product 4-（3,4-dichlorophenyl）-1,2,3,4-tetrahydro-1-naphththylamine hydrochloride with a yield of 97.3%.4-（3,4-dichlorophenyl）-1,2,3,4-tetrahydro-1-naphththylamine hydrochloride has ¹H and ¹³C spectra of two groups of diastereomers,and the spectral analysis conform to its characteristcs.