Ethanol → 1-ethyl-1,3,5-triazine-2,4-dione

Temperature

60 °C

The ethylbiuret prepared in Part A, above, [592 gm., 4.7 mole] is dispersed in 24 l. absolute ethanol and 1.6 l. benzene. This reaction mixture is heated to the reflux temperature and 3.5 l. of solvent medium is removed by distillation. The solution is cooled to 60° C. and 2090 gm. of a 25 percent solution of sodium methoxide in methanol is slowly added over an interval of five minutes. That addition is followed by the addition of 820 gm. of ethylformate. This reaction mixture is heated at the reflux temperature for three (3) hours, whereupon the solution is cooled to 38° C. and concentrated hydrochloric acid is added slowly until the pH of the solution is 2. To the acidified solution is added more (3.4 l.) benzene. Then 2 l. of the solvent medium is removed by distillation under reduced pressure and 50° C. The mixture is then heated to 75° C. and filtered in order to remove the sodium chloride produced by the reaction. The filter cake of salt is washed with hot absolute ethanol and the washings are added to the filtrate. The volume of the combined filtrate and absolute ethanol washings is reduced to 5 l. by evaporation under reduced pressure at 50° C. The resulting concentrate is cooled at 5° C. for 18 hours while crystals form. The crystals are collected on a filter and washed with cold (5° ) ethanol. The washed crystals are dried in an oven under reduced pressure at 50° C. for 18 hours. There is thus obtained 408 gm. of crude product having a melting point at 137° to 139° C. A further purification is achieved by dissolving the 408 gm in 4 l. methanol at reflux temperature. This solution is concentrated by allowing the methanol to evaporate to a volume of 2 l. while being heated on a steam bath. The concentrated solution is allowed to cool slowly to 25° C. It is then chilled to 5° C. for two hours. The crystals that form are collected on a filter and the filter cake is washed with ice-cold methanol. After drying there is obtained 389 gm. (58.7 percent yield) of 1-ethyl-5-azauracil having a melting point of 141° to 142° C. A second crop of crystals is recovered from the mother liquor after further concentration and cooling.

1. additionabove, [592 gm., 4.7 mole] is dispersed in 24 l
2. temperatureThis reaction mixture is heated to the reflux temperature and 3.5 l
3. customof solvent medium is removed by distillation
4. additionof a 25 percent solution of sodium methoxide in methanol is slowly added over an interval of five minutes
5. additionThat addition
6. additionis followed by the addition of 820 gm
7. temperatureThis reaction mixture is heated at the reflux temperature for three (3) hours, whereupon the solution
8. temperatureis cooled to 38° C.
9. additionconcentrated hydrochloric acid is added slowly until the pH of the solution
10. additionTo the acidified solution is added more (3.4 l.) benzene
11. customof the solvent medium is removed by distillation under reduced pressure and 50° C
12. temperatureThe mixture is then heated to 75° C.
13. filtrationfiltered in order
14. customto remove the sodium chloride
15. customproduced by the reaction
16. washThe filter cake of salt is washed with hot absolute ethanol
17. additionthe washings are added to the filtrate
18. customby evaporation under reduced pressure at 50° C
19. concentrationThe resulting concentrate
20. temperatureis cooled at 5° C. for 18 hours while crystals
21. customform
22. customThe crystals are collected on
23. filtrationa filter
24. washwashed with cold (5° ) ethanol
25. customThe washed crystals are dried in an oven under reduced pressure at 50° C. for 18 hours
26. customat 137° to 139° C
27. customA further purification
28. dissolutionby dissolving the 408 gm in 4 l
29. temperaturemethanol at reflux temperature
30. concentrationThis solution is concentrated
31. customto evaporate to a volume of 2 l
32. temperaturewhile being heated on a steam bath
33. temperatureto cool slowly to 25° C
34. temperatureIt is then chilled to 5° C. for two hours
35. customThe crystals that form are collected on
36. filtrationa filter
37. washthe filter cake is washed with ice-cold methanol
38. customAfter drying there
39. customis obtained 389 gm

ORD record

ord-97cfe56859874e17ad4ee7d7285632aa

Source dataset

uspto-grants-1980_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04239753