Prodine is a analgesic opioid that is a analog of pethidine. Alpha-prodine is 97% more powerful than morphine (subcuteneous), and Beta-prodine is 550% more powerful than morphine SC.
Reagents:
76 parts by weight of aqueous 37% formaldehyde solution is slowly added to 84 parts by weight of 40% methylamine solution with stirring and cooling, temperature kept below 10C/50F. Solid caustic soda is added in small increments until 2 layers form and seperate. Upper layer is taken. The lower layer is extracted with benzene and extracts are added to the upper layer (this is skippable, but you will have a lower yield).
The resulting solution is dried over anhydrous potassium carbonate and distilled. At 65-75C (149-167F) / 35mm, there is obtained a fraction of practically pure N,N',N"-trimethyltrimethylenetriamine (hexahydro-1,3,5-trimethyl-1,3,5-triazine) in an amount of at least 36 parts by weight.
Prodine Synthesis
Note: Phosphoric Acid is not required, as it is used as a catalyst. As propionic anhydride is only used to bind water in the phosphoric acid, it can be substituted for propionic acid. The use of propionic anhydride can be avoided at the price of a lower yield of 20-25%.
Mix the acid and the styrene, slowly add the amine. Apply heat for 4 hours, let stand for 2 days, then continue.
To a stirred, cooled mixture of 298 parts of propionic acid and 175 parts of propionic anhydride, 85% phosphoric acid is added to a total of 150 parts. When heat is no longer liberated, there are slowly added 103 parts of hexahydro-1,3,5-trimethyl-1,3,5-triazine and 104 parts of 2-phenyl-1-butene. The mixture is stirred at 125C for 18 hours, cooled, and poured into 3000 parts of water. Aqueous mixture is extracted with benzene.
The benzene solution is dried over potassium carbonate, and distilled. Fractionation under reduced pressure gave a fraction of 7 parts distilling at 30-80C/1.5mm, a fraction of 27 parts distilling at 80-120C/1.5mm, a fraction of 31 parts distilling at 120-160C/1.5mm, and 16 parts residue. The third fraction is redistilled at 120-135C/1.5mm.
The product thus contains Prodine. Yield approx 30%
Reagents:
- N,N',N"-trimethyltrimethylenetriamine (hexahydro-1,3,5-trimethyl-1,3,5-triazine)
- 2-phenyl-1-butene
- propionic acid, propionic anhydride
- phosphoric acid [optional]
- benzene
- potassium carbonate
- water
76 parts by weight of aqueous 37% formaldehyde solution is slowly added to 84 parts by weight of 40% methylamine solution with stirring and cooling, temperature kept below 10C/50F. Solid caustic soda is added in small increments until 2 layers form and seperate. Upper layer is taken. The lower layer is extracted with benzene and extracts are added to the upper layer (this is skippable, but you will have a lower yield).
The resulting solution is dried over anhydrous potassium carbonate and distilled. At 65-75C (149-167F) / 35mm, there is obtained a fraction of practically pure N,N',N"-trimethyltrimethylenetriamine (hexahydro-1,3,5-trimethyl-1,3,5-triazine) in an amount of at least 36 parts by weight.
Prodine Synthesis
Note: Phosphoric Acid is not required, as it is used as a catalyst. As propionic anhydride is only used to bind water in the phosphoric acid, it can be substituted for propionic acid. The use of propionic anhydride can be avoided at the price of a lower yield of 20-25%.
Mix the acid and the styrene, slowly add the amine. Apply heat for 4 hours, let stand for 2 days, then continue.
To a stirred, cooled mixture of 298 parts of propionic acid and 175 parts of propionic anhydride, 85% phosphoric acid is added to a total of 150 parts. When heat is no longer liberated, there are slowly added 103 parts of hexahydro-1,3,5-trimethyl-1,3,5-triazine and 104 parts of 2-phenyl-1-butene. The mixture is stirred at 125C for 18 hours, cooled, and poured into 3000 parts of water. Aqueous mixture is extracted with benzene.
The benzene solution is dried over potassium carbonate, and distilled. Fractionation under reduced pressure gave a fraction of 7 parts distilling at 30-80C/1.5mm, a fraction of 27 parts distilling at 80-120C/1.5mm, a fraction of 31 parts distilling at 120-160C/1.5mm, and 16 parts residue. The third fraction is redistilled at 120-135C/1.5mm.
The product thus contains Prodine. Yield approx 30%