Hydrochloric Acid → Mitoguazone

Participants

Reaction Conditions

Reaction Steps

Aminoguanidine bicarbonate (Aldrich 98.5%) was slurried in DI water at 35°-40° C. for about 30 minutes, the suspension was filtered to remove diaminoguanidine and other impurities amounting to about 1% w/w. 505 g, 3.8 mol of the filtered aminoguanidine bicarbonate was suspended in 200 g DI water and 300 g (156 mL) isopropanol to give a heavy, but stirrable mixture. Concentrated HCl (376 g, 37.8%) was cautiously added dropwise over a 1.5 hr period to prevent excessive foaming (Note 1). The mixture stirred readily after 5% of the HCl had been added. The reaction was endothermic and the temperature was maintained at between 19° C. and 28° C. At the end of the addition a clear colorless solution was obtained (Note 2). It was warmed to 32° C. and stirred for 20 minutes (Note 3). The methyl glyoxal dimethylacetal (212 g, 1.79 mol) (Fluka, 98%) was next added over 1.5 hours at a temperature of 30°-35° ) (Note 4). The suspension was stirred overnight at ambient temperature. The next morning isopropanol (2.0 kg) was added over 15-20 minutes. The suspension was cooled to about 10° C. and stirring was continued for 1.5 hours. The solids were collected by filtration and rinsed with 2×200 mL isopropanol. After drying overnight in a vacuum oven at 30°-35° C., 463 g (47%) of the crude MGBG was obtained. TLC [acetone 90, water 5, NH4OH 5]; HPLC (ETI~0.79%); nmr (dmsod6).

Provenance & Evidence