New improved PPA Akabori Synthese

Improvement in the yield of racemic PPA*HCl via Akabori reaction (35 % molar) Here is an improved synthesis of PPA. Work is done here with the Akabori synthesis. Process: It is basically on those last two points that I believe my work-up of the reaction is superior, cleaner and brings a better yield of clean racemic PPA*HCl. HERES THE PROTOCOL: In a 1 L RBF, 358 g of benzaldehyde (3.36 moles) and 50 g of finely crushed DL-alanine (0.56 moles) were mixed together with magnetic stirring. It was attached to a simple distillation setup and heated on an oil bath at 140 celsius for 3 hours (Figure-1). No more CO2 was evolved from the flask at this point and the color of the mixture was a deep burgundy (almost black). The flask was removed from the oil bath and let cool on its own for 20 minutes. Afterwards, 100 mL of 20 % AcOH in Toluene were added to the flask and the latter was stirred, at RT, for 20 minutes. When this induction period was over, 400 mL of 15 % HCl (aq) was added to the flask and the whole mixture was refluxed gently on the oil bath for 3 hours. Afterwards, the pH of the mixture was verified to be strongly acidic. If not, small portions of concentrated HCl (aq) were added until it was and the mixture was refluxed for another 30 minutes. The flask was then removed from the oil bath, the mixture left to cool for a bit and then rapidly separated with a separation funnel while still warm (Figure-2). An orange/red aqueous phase and a dark black organic phase were obtained (Figure-3). The aqueous phase was washed 3 times with 150 mL of DCM (Figure-4). Then the volume of the aqueous phase was reduced, with gentle heating and stirring, until half of the volume was vaporized (Figure-5). The remaining aqueous phase was washed 3 other times with 75 mL DCM. The aqueous phase was then treated with small portions of NaHCO3 until fizzing becomes less violent (Figure-6), then small portions of NaOH were added until pH was strongly alkaline. A light brown-yellow oily layer with a strong and biting amine smell separated from the aqueous phase (Figure-7). The latter was separated and the aqueous phase was extracted 4 times with 200 mL DCM. All the NP fractions were pooled together, washed 2 times with 100 mL BRINE and the DCM was stripped off to afford a viscous brown oil that partially turns to a solid once cooled. The oil was dissolved in 5 times its volume of dry acetone. Small portions of an 1:3 HCl (muriatic)-isopropanol solution were added until pH 4 was reached. Large amounts of crystalline material precipitated during the addition (Figure-8 and 9). The flask was put in the freezer overnight, the crystalline material was vacuum filtered and washed with small portions of cold and dry acetone. 33.2 g of racemic PPA*HCl were obtained (Figure-10). Evaporation of the acetone liquor afforded another 3 g after appropriate washing and drying. Melting point, after 1 week in the dessicator, was 131-136 0C . The product gave a positive test to Chen’s reagent and to the nitrous acid test . It has a very distinctive smell reminding of crude benzoic acid . Figure-1

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