Study On The Synthesis Of Optically Active N-methyl-β -hydroxyl-phenylethylamine

N-methyl-β-hydroxyl-phenylethylamine is a kind of important organic chemical intermediate, which can be used widely in the field of medicine and other fine chemicals industry. Because of the low productivity of synthesis route reported on the literature and the strict conditions, it does not suit in the industrial production. Therefore, it is very important to improve in synthesis technology of N-methyl-β-hydroxyl-phenylethylamine and to realize its commercial process. Presently, most of N-methyl-β-hydroxyl -phenylethylamine which are sold in the market are mainly made from methods of synthesis which is used the synthesis route of styrene oxide– methylamine. However, there are some shortcomings, such as serious waste of raw materials, reaction yield unstable and low product yield. The thesis is to make some improvements in the craft of preparation, and use the existing conditions to optimize the conditions of the synthesis craft, to provide a basis for industrial production.In this research, single factor experiments and orthogonal L₉(3⁴) experiment were applied to selected the optimum technology, and fixing the yield of N-methyl-β-hydroxyl-phenylethylamine as index. In the single factor experiments, we examined the effect of relevant factors on the yield of N-methyl-β-hydroxyl-phenylethylamine, such as adding amount(styrene oxide and methylamine), reaction time , reaction temperature and solvent. The optimum condition were, respectively, the molar ration: n(styrene oxide)∶n(methylamine)=1∶6. The reaction temperature was 3℃. The reaction time was about 6 days. Based on the single factor experiments, the optimum technology was selected by using of orthogonal L₉(3⁴) experiment. The optimal technology were the molar ration: n(styrene oxide)∶n(methylamine)=1∶6, The reaction temperature was 9℃. The reaction time was about 9 days. The yield of N-methyl-β-hydroxyl-phenylethylamine was between59.5% and 65.5%.We also explored preliminary the catalyst on the yield in the reaction. In the thesis, Zincperchlorate Hexahydrate and Phosphomolybdic acid hydrate-Neutral alumina were selected to study in the reaction. The results showed that the reaction time was shorten and the reaction was more moderate than which was at room temperature. It is suitable for industrial production. However, the ultimate yield of target product do not meet expectations.Finally, preparation of optically active N-methyl-β-hydroxyl-phenylethylamine was by chrial resolution. On the basis of getting racemic modification N-methyl-β- hydroxyl-phenylethylamine, we were split it. Through related references and tests, chiral reagent D-(+)- dibenzoyl -tartaric acid and L-(-)- dibenzoyl -tartaric acid were successful applied in chemical resolution ofβ-hydroxyl-phenylethylamine to get R-products and S-products with yield of about 78%.