Codeinone from Thebaine
To a 3-litre flask provided with a stirrer, a thermometer, and a gas outlet duct containing calcium chloride, and containing a solution of 150 g of dry hydrobromic acid in 550 ml. of di-n-butylether externally cooled down to -15°C, there was added a solution of 2 g of iodine dissolved in 100 ml. of dry methylene chloride, while the temperature was gradually lowered to -20°C.
Once such a temperature was reached, a solution of 100 g thebaine (purity 92.5%), dissolved in 1000 ml. of methylene chloride previously cooled to -15°C, was added. As a result of this addition, the temperature increased to +10°C. The temperature was then lowered to 0°C in a short time and was maintained at that level for further 7 minutes.
After that length of time, the contents of the flask were poured with vigorous agitation into a 5-litre flask containing a suspension of 180 g of sodium bicarbonate in 1000ml of water and 450 g of ice.
Agitation was continued for an hour and the reaction product separated into two phases. The pH value of the aqueous phase was increased to 8 by addition of diluted soda and extracted three times with 200 ml of methylene chloride. The extract was added to the previous organic phase, washed with water, and dried with anhydrous sodium sulphate. The solvent was then removed from the solution under vacuum until its volume was reduced to 1/leo Codeinone of a clear pure colour was obtained by concentration of the solution, filtration and washing with ethyl ether.
96 g Codeinone having a melting point of 165-167°C and a purity of 90.36% were obtained with a calculated yield of 98%.