The Study On Electrochemical Synthesis Of Methyl 4-methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylate

Telmisartan is a typical Angiotensin II-receptor antagonists.Compared with other antihypertensive drugs,telmisartan has the advantages of lipid solubility,high affinity,long half-life and so on.Telmisartan is one of the best-selling drugs in the treatment of hypertension.In this thesis,two electrochemical methods were used to research the synthesis of methyl 4-methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylate,which is the key intermediate of telmisartan.(1)Methyl 4-methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylate was synthesized from 3-methyl-4-nitrobenzoic acid via esterification,electroreduction,acylation,nitration and one-pot cyclization by electroreduction.The reduction of methyl 3-methyl-4-butylamino-5-nitrobenzoate was studied by electrochemical method and the optimal conditions for electroreduction to synthesize methyl4-(butyrylamino)-5-methyl-3-aminobenzoate were as follows:The electrolysis was performed with 1.0 M ammonium sulfate as electrolyte and 13 mol%zinc sulfate as catalyst,employing copper sheet(1.0×1.5 cm~2)as cathode and platinum mesh(1.0×1.0 cm~2)as the anode at a constant current of 0.6 A at 40℃for 3 h,and the yield was 98.0%.(2)The optimal conditions for one-pot cyclization to synthesize methyl4-methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylate were as follows:The electrolysis was performed with 0.017 M substrate and ethanol as solvent,0.1 M sulfuric acid as electrolyte,titanium trichloride as catalyst,employing copper sheet(1.0×1.5 cm~2)as cathode and platinum mesh(1.0×1.0 cm~2)as anode at a constant current of 0.3 A at 60℃for 2 h,and the yield was 97.0%.(3)Methyl 4-methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylate was synthesized from methyl 3-methyl-4-aminobenzoate via amidineization and electrocatalytic oxidation.Square wave voltammetry and electrolytic preparation were adopted to optimize the synthesis conditions:The electrolysis was performed with platinum sheet(1.0×1.0 cm~2)as electrode,employing 4%sodium chloride as the electrolyte and the ratio of acetonitrile to the electrolyte solution was 1:3 at a constant current of 0.2 A at 20℃for 0.5 h,and the yield was 51.7%.