Synthesis And Structural Characterization Of 3-(Dimethylamino)-1-(3-methoxyphenyl)-2-methylpropan-1-one

Isoquinoline and its derivatives are an important class of pharmaceutical and chemical intermediate, by which many compounds are synthesized. These compounds have lots of pharmacological effects, which include blood pressure, anti-arrhythmia, anti-inflammatory, blood sugar lowering and even can replace morphine as an analgesic drugs. The research of isoquinoline is the hot topic both at home and abroad. The intent of this paper is to provide a synthesis method of intermediate of isoquinoline derivatives. First of all, propiophenone is selected as the starting material, then the target products, 3-(dimethylamino)-1-(3-methoxyphenyl)-2-methylpropan-1 -one, can be synthesized by six steps which include nitration, reduction, diazotization, hydrolysis, Williamson reaction, Mannich reaction.1. Some experimental improvement has been used for the nitration. The low temperature and common pressure condition have been explored to instead of high temperature and high pressure condition for the nitration. Such is where the innovation of this paper. From the condition experiment, the optimum reaction temperature and the optimum ratio of mixture acid [n(Sulfuric acid)/n(Nitrate)] are obtained. that is, the temperature is lower than -5℃, the molar ratio of mixture acid is greater than 5, the yield will up to 85 %.2. Reduction condition of 1-(3-nitrophenyl)propan-1-one have been discussed firstly, then sodium sulfide has been chosen for reductive reagent. From the condition experiment, the optimum reducing conditions are founded. that is, the molar ratio of sodium sulfide to 1-(3-nitrophenyl)propan-1-one is 2:1, the reaction time is greater than 4 h, the yield of 1-(3-aminophenyl)propan-1-one will up to 73 %.3. The diazotization of 1-(3-aminophenyl)propan-1-one is carried out in the water. The diazonium salt which is produced from diazotization should not be separated from the water, and can be decomposed directly to the 1-(3-hydroxyphenyl)propan-1-one with heating. From the condition experiment, the optimum diazotizating conditions are achieved. That is, the temperature is maintained at 0℃, the molar ratio of sulfuric acid to 1-(3-hydroxyphenyl)propan-1-one is 4:1, the yield will up to 84 %.4. 1-(3-methoxyphenyl)propan-1-one can be got from Williamson reaction. From the condition experiment, the optimum Williamson reaction conditions are acquired. That is, the reaction temperature is maintained at 70~75℃, the reaction time is greater than 3 h and the reaction solvent is DMSO, the yield will up to 82 %.5. The traget compounds of 3-(dimethylamino)-1-(3-methoxyphenyl)-2- methylpropan-1-one (T·M·) can be produced by Mannich reaction. From the condition experiment, the optimum Mannich reaction conditions are attained. That is, the temperature is maintained at 70℃, the molar ratio of reactants [n(1-(3-methoxyphenyl)propan-1-one):n(formaldehyde):n(dimethylamine hydrochlo- ride)] is 1:1:1, the reaction time is greater than 16 h, the use level of hydrochloric acid is six times than T·M·, the yield will up to 86 %.