Extraction with solvents, continuous theory

In a liquid-liquid extraction unit, spherical drops of solvent of uniform size are continuously fed to a continuous phase of lower density which is flowing vertically upwards, and hence countercurrently with respect to the droplets. The resistance to mass transfer may be regarded as lying wholly within the drops and the penetration theory may be applied. The upward velocity of the liquid, which may be taken as uniform over the cross-section of the vessel, is one-half of the terminal falling velocity of the droplets in the still liquid. 

A mixture of 5 mmol each of 80% NaH and 15-crown-5 in 50 ml of absol. toluene is stirred at 20°C under inert gas for 10 min and a solution of 5 mmol of 2-diethoxy-phosphoryl)-butiric acid 3-[(l-methyl-lH-imidazol-5-yl)methyl]-2-oxo-propyl ester in 50 ml of absol. toluene is then added dropwise. Stirring is continued for a further 15 min under inert gas and the mixture is hydrolyzed with a little water until phase separation is detectable. After separating off the organic phase, the aqueous layer is saturated with NaCI and extracted several times with CHCI3. The combined organic phases are the solvent is distilled off at 40°C in vacuo and the residue 3-ethyl-4-[(l-methyl-lH-imidazol-5-yl)methyl]-5H-furan-2-one is purified twice by flash chromatography (silica gel ethyl acetate/CH3OH). Yield 52% of theory virtually colorless oil. 

The reaction is very efficient. If the hydrolysis is continuously titrated to pH 7.8 with sodium hydroxide about 96% of the penicillin G is hydrolysed to 6-AP A. This is close to the equilibrium position for a dilute solution (33 g dm ) of penicillin G. After the hydrolysis the enzyme is removed and the solution is acidified (pH 2.5). The phenylacetic acid released is extracted into a solvent (methylisobutylketone) and is recycled to the penicillin G fermentation (section 6.3.1). The crude solution of 6-APA which remains is then neutralized and concentrated until its concentration is between 120 and 150 g cm " At its isoelectric point (pH 4.3) it precipitates from this concentrate and the crystals are washed and dried. The overall yield of 6-APA is about 90% of theory. 

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