Reduced absolute melting point

Other purification procedures include the formation of the picrate, prepared in benzene soln and crystd to constant melting point, then decomposed with warm 10% NaOH and extracted into ether the extract was washed with water, and distd under reduced pressure. The oxalate has also been used. The base has been fractionally crystd by partial freezing and also from aq 80% EtOH then from absolute EtOH. It has been distd from zinc dust, under nitrogen. 

To a refluxing solution of 9.73 gm (0.047 mole) of l-phenyl-3-(2-cyanoethyl)-thiourea in 75 ml of absolute methanol is added dropwise 7.4 gm (0.052 mole) of methyl iodide over a 5 min period. After refluxing for 3 hr the solution is evaporated to dryness under reduced pressure to give an oil. The oil is triturated with 50 ml of acetone to afford 15.1 gm (93%). Three recrystallizations from 3 1 absolute ethanol-ether solution raised the melting point from 152°-159°C to 165°-167°C (picrate derivative, m.p. 139°-141°C). 

The residual crude crystalline ip-D-ribofuranosyl-4-methoxy-l,2-dihydro-l,3,5-triazin-2-one is dissolved in a 10% solution of dry ammonia in absolute methanol (4 ml) and the whole reaction mixture is allowed to stand in a stoppered flask for 30 min at room temperature (the product begins to deposit in the course of 5 min) and for 12 h in a refrigerator at -10°C. The resulting 5-azacytidine is collected with suction, washed with methanol and dried under reduced pressure. A yield of 0.216 g (88.6%) of 5-azacytidine, that is [l-p-D-ribofuranosyl-4-amino-l,3,5-triazin-2(lH)-one], melting point 232°-234°C (dec.), is obtained. 

Codeine (boiling point 250°C at 22 mmHg, melting point 157°C, density 1.32) can be isolated from opium and morphine (also obtained from opium). To direct this alkylation to the phenolic hydroxyl and to reduce alkylation of the tertiary nitrogen, a quaternary nitrogen-alkylating agent, phenyltrimethylammonium hydroxide, is employed. This results in yields of 90 to 93 percent codeine and some recovery of unalkylated morphine. The alkylation is carried out with the morphine dissolved in absolute alcohol in the presence of potassium ethylate. The dimethyl aniline and solvents are recovered and reused. 

Methylbenzyltrimethylammonium bromide is not noticeably hygroscopic. The crude product, after it has been dried at 80° under reduced pressure over phosphorus pentoxide, melts at 197-199°. RecrystaUization from absolute ethanol followed by similar drying gives crystals melting at 199-200°. Less thoroughly dried samples show lower and erratic melting points. 

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