Brucine recovery

Sastry et al. [50] estimated primaquine in its tablet formulation. Powdered tablets equivalent to 100 mg of primaquine phosphate were dissolved in water, filtered, and filtrate was diluted to 100 mL with water. Portions of the solution were shaken with 3 mL of 5 mM brucine-0.16 M sulfuric acid, 1.5 mL of 5 mM sodium periodate and 2 mL of 1.2 M sulfuric acid and diluted to 9 mL with water. The solution was set aside for 20 min in a boiling water bath, cooled, and diluted to 10 mL with water. The absorbance was measured at 510 nm versus a reagent blank. Beer s law was obeyed from 20 to 140 pg/mL of primaquine phosphate. The coefficient of variation was 1.56% (n = 8). Recovery was 99.2%. 

Pasteur s original chemical method of resolution, which is still widely used at the present time, involves the formation of diastereoisomeric salts from racemic acids or bases by neutralisation with available optically pure bases or acids respectively. The required optically pure reactants are often available from natural sources and include tartaric, malic and mandelic acids, and alkaloids such as brucine, strychnine, morphine and quinine. Ideally, by appropriate choice of the resolving reagent, the diastereoisomeric salts are crystalline and have solubilities sufficiently different to permit the separation and ready purification of the less soluble salt by fractional crystallisation from a suitable solvent. The regeneration of the optically pure enantiomorph, and incidentally the recovery of the resolving reagent, normally presents no problems. 

Crude d-octyl hydrogen phthalate is obtained similarly from the crystalline brucine salt. This is first dissolved in the minimum amount of hot ethanol, and the solution is poured into the dilute acid. The aqueous solutions containing brucine hydrochloride are retained for the recovery of brucine. 

Initial results on the attempted resolution screen of racemic UK-350,926 with our in-house collection of chiral amines were not encouraging due to the propensity of the highly crystalhne racemic free acid to preferentially precipitate from solution. The only success in the initial screen was with the chiral amine brucine hydrate 19. Crystalhzation of a stoichiometric brucine salt from hot acetone gave the desired diastereoisomer in 92% recovery and 40% d.e (Scheme 10.5). 

The recovery of 0.2 mg./liter NO3-N from waters varying in chlo-rosity from 10 mg./liter to 16 grams/liter was quantitative using brucine... 

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