Surfactant-free air bubble flotation-coagulation for the rapid purification of chloroquine

A simple and rapid separation method based on surfactant-free air bubble flotation and coagulation was designed for the purification of chloroquine (CQ) from its crude product. An open glass column having a sintered glass filter (for column chromatography) was used as a flotation vessel. The flotation was conducted by pouring the crude CQ into the aqueous solution containing 0.1% (v/v) of 2-propanol followed by feeding air through the glass filter to generate air bubbles. At pH 12, CQ was enriched into the foam temporary generating on the surface of water to form the coagulates within 90 s after the start of the air bubble flotation. On the other hand, reactants; 4,7-dichloroquinoline and 4-amino-1-diethylaminopentane, as well as generated impurities remained in the bulk aqueous solution. The result of dynamic surface tension measurement indicated that CQ molecules selectively adsorbed on the air-water interface and the coagulates more strongly adsorbed the interface. Adsorption and coagulation of CQ molecules on the air-water interface were also reproduced in the calculation results of a molecular dynamic simulation. The coagulates were collected from the surface of water by suction and then poured into another flotation vessel for conducting repeated separation. The time required for the respective separation process including air bubble flotation and collection by suction was within 5 min. After three-times separation, highly purified (> 99.0%) CQ was obtained with a yield of 72 ± 8%. The amounts of reactants and other impurities reduced into undetectable levels.