| 摘要 |
FIELD: chemistry.SUBSTANCE: invention relates to method for synthesis of 7-methoxy-4-nitro-3-(p-methoxyphenyl)isoquinolinone derivatives, containing: first stage of producing amide, involving preparation of mixture with thionyl chloride 5-methoxy-2-toluic acid under nitrogen, which is mixed and dephlegmated for 3 hours, then excess thionyl chloride is removed at pressure of 20 mBar, residue is dissolved in methylene chloride, and then 40 % aqueous solution is added in droplets while cooling on ice, produced mixture is stirred at 0 °C for 24 hours, then reaction solution is extracted with ethyl acetate, washed with saturated solution of NaCl, dried over NaSOand evaporated at pressure of 100 mBar, obtained residue is purified by column chromatography with silica gel to obtain 5-methoxy-2,N-dimethyl benzamide; second condensation step, involving addition to solution of 1,8M of lithium diisopropylamide, in tetrahydrofuran (THF) at -78 °C under nitrogen solution 5-methoxy-2,N-dimethyl benzamide in tetrahydrofolic acid in droplets and then solution of 4-methoxy benzonitrile in tetrahydrofuran, obtained mixture is stirred at -78 °C for 3 hours, then reaction mixture is allowed to be heated at room temperature, adding NHCl saturated with water, tetrahydrofuran is removed at pressure of 20 mBar, obtained mixture is extracted in ethyl acetate and washed with saturated solution NaCl, organic layer is dried over NaSOand evaporated at 20 mBar, obtained residue undergoes purification by column chromatography with silica gel to obtain 7-methoxy-3-(p-methoxyphenyl)isoquinolinone derivatives; third stage of nitration including cooling to 10 °C while stirring solution of 7-methoxy-3-(p-methoxyphenyl)isoquinolinone derivatives in ethyl acetate and acetic acid, then mixture is added in droplets at temperature below 15 °C with nitric acid solution in ethyl acetate, mixture is stirred at room temperature for 2 hours, then water is added, and produced solid substance is collected, dried in air and recrystallised from toluene or ethyl acetate to produce 7-methoxy-4-nitro-3-(p-methoxyphenyl)isoquinolinone derivatives.EFFECT: novel method for synthesis of 7-methoxy-4-nitro-3-(p-methoxyphenyl)isoquinolinone derivatives on industrial scale, characterised by reduced explosion hazard of synthesis and fewer harmful emissions.1 cl, 3 dwg |
