Study On The Synthesis Of Pharmaceutical Intermediate 5-methoxy-2-tetralone

5-Methoxy-2-tetralone(5M2T) is an important pharmaceutical intermediate. In this paper, 1,6-dimethoxynaphthalene(1,6-OCH₃) was prepared from 1,6-dihydroxy- naphthalene(1,6-OH) by methylation, then through Birch reduction, 5M2T was synthesized . Main results are as follows:The synthesis process of 1,6-OCH₃ was studied with dimethyl sulfate as methylation reagents. Water and organic solvents (methanol, ethanol, acetone, petroleum ether) as a reaction medium were investigated, respectively. NaOH solution was added or anti-added to the reaction solution. It was inspected that the factors influencing the results of experiment to obtain the better synthesis process included the volume of dimethyl sulfate, temperature, reaction time, NaOH concentration, reductant addition, etc.Anti-addition of NaOH solution was better in the method of water solvents, the better conditions are: 20.0g 1,6-OH, 0.5mL 80% of hydrazine hydrate, 35mL Me₂SO₄, 75mL 30% NaOH solution, 3h reaction time, 55℃, the yield and purity of product is 98.7% and 94.06%.Anti-addition of NaOH solution also was better in the method of organic solvents, the good conditions are: 50mL methanol, 20.0g 1,6-OH, 1.0g sodium hyposulfite, 30mL Me 2 SO4, 35mL 40% NaOH solution, 4h reaction time, 65℃, the yield and purity of product is:96.0% and 97.65%The experiment of synthesizing 1,6-OCH₃ is studied with dimethyl carbonate(DMC) as methylation reagents, water solvents and DMC solvents as a reaction medium, respectively, in the presence of catalysts in atmospheric pressure and high pressure. The results of the yield (purity) of 15.7% (62.02%) are not good for industrilization.The synthesis process of 5M2T was studied with 1,6-OCH₃ as raw material, which was reduced with sodium in alcohol, and then hydrolyzed in thin hydrochloric acid. The crude 5M2T was obtained by this way;Saturated sodium hydrogen sulfite solution was then added to the product, and then decomposed in water by addition of sodium carbonate. The higher purity 5M2T was isolated from the decomposition water. The related react conditions influencing the yield were analyzed, for example, temperature, time, dosage and extraction, in order to get the superior technical conditions. The crude yield and purity of product is 82.7% and 95.06%.