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 liter absolute ethanol and 1.6 liter benzene. This reaction mixture is heated to the reflux temperature and 3.5 liter 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 liter) benzene. Then 2 liter 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 which washings are added to the filtrate. The volume of the combined filtrate and absolute ethanol washings is reduced to 5 liter 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 liter 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. customis removed by distillation
2. additionof a 25 percent solution of sodium methoxide in methanol is slowly added over an interval of five minutes
3. additionThat addition
4. additionis followed by the addition of 820 gm
5. temperatureThis reaction mixture is heated at the reflux temperature for three (3) hours, whereupon the solution
6. temperatureis cooled to 38° C.
7. additionconcentrated hydrochloric acid is added slowly until the pH of the solution
8. additionTo the acidified solution is added more (3.4 liter) benzene
9. customThen 2 liter of the solvent medium is removed by distillation under reduced pressure and 50° C
10. temperatureThe mixture is then heated to 75° C.
11. filtrationfiltered in order
12. customto remove the sodium chloride
13. customproduced by the reaction
14. washThe filter cake of salt is washed with hot absolute ethanol which washings
15. additionare added to the filtrate
16. customThe volume of the combined filtrate and absolute ethanol washings is reduced to 5 liter by evaporation under reduced pressure at 50° C
17. concentrationThe resulting concentrate
18. temperatureis cooled at 5° C. for 18 hours while crystals
19. customform
20. customThe crystals are collected on
21. filtrationa filter
22. washwashed with cold (5°) ethanol
23. customThe washed crystals are dried in an oven under reduced pressure at 50° C. for 18 hours
24. customat 137° to 139° C
25. customA further purification
26. dissolutionby dissolving the 408 gm
27. temperaturein 4 liter methanol at reflux temperature
28. concentrationThis solution is concentrated
29. customto evaporate to a volume of 2 l
30. temperaturewhile being heated on a steam bath
31. temperatureto cool slowly to 25° C
32. temperatureIt is then chilled to 5° C. for two hours
33. customThe crystals that form are collected on
34. filtrationa filter
35. washthe filter cake is washed with ice-cold methanol
36. customAfter drying there
37. customis obtained 389 gm

ORD record

ord-c9612fa259d34413bb0f11479c61aa7c

Source dataset

uspto-grants-1979_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04171431