Formaldehyde → HCID 86596996, compound

Participants

Reaction Conditions

Reaction Steps

A 2-liter, 3-neck round bottom flask equipped with a nitrogen blanket, addition funnel, mechanical stirrer and thermocouple was charged with isopropylamine (425 mL, 5.0 mol). The addition funnel was charged with a pre-dissolved mixture of tris(hydroxymethyl)nitromethane (TN®)(377.75 g, 2.5 mol) in 37% aqueous formaldehyde (202.9 g, 2.5 mol) and the reactor contents cooled to 15 C with a cold water bath. The TN/formaldehyde solution was added dropwise to the isopropylamine over a period of 1.5 hours while maintaining an internal reaction temperature of 15-19° C. After the addition was complete, the cooling bath was removed. The mixture changed from a clear solution to a water/oil emulsion and slowly warmed to 34° C. over 40 minutes. A heating mantle was then used to warm the mixture to 70° C. for 5 hours. The reaction mass was then allowed to cool back to room temperature overnight. The reaction product had partially solidified to a yellow paste. Hexane (750 mL) was then added and the water was azeotropically removed. As the last of the water was removed, a white solid precipitated. The slurry was placed in the freezer overnight to complete crystallization. The white, crystalline hexahydropyrimidine product was recovered via filtration, 245 g, 39.9% of theory. The hexane layer was concentrated on a rotary evaporation to yield the oxazine (IPA-OZ) as a yellow oil (approximately 370 g, 60% of theory). Note: Over a period of weeks, the oxazine will slowly convert to the hexahydropyrimidine as evidenced by its crystallization from the oil.

Provenance & Evidence