Abstract
Micronization processes involving supercritical carbon dioxide are rapid methods to produce fine particles. They also might offer the possibility of using less organic solvent than conventional crystallization methods leading to an environmentally friendlier processing. The separation capabilities of such processes are now demonstrated on the diastereomeric resolution of mandelic acid using (R)-1-phenylethanamine as a resolving agent, utilizing the batch type gas antisolvent fractionation as the separation method. A detailed study was conducted on the effects of the operational parameters pressure (12-20 MPa), temperature (35-55 °C) and co-solvent concentration (33-99 mg/ml). At 12 MPa, 35 °C and 99 mg/ml methanol concentration, a selectivity of 0.52 and a diastereomeric excess of 62% was reached. The same operational parameters were applied during the investigation of the recrystallization-based further purification of the diastereomeric salts, applying the resolving agent in molar equivalent quantity to a non-racemic mixture of mandelic acid. It has been found that the more stable (R)-1-phenylethylammonium-(R)-mandelate salt can be purified to de>98% through four additional recrystallization steps following the initial, half-molar equivalent resolution step.
Highlights
Separation techniques involved in almost every chemical manufacturing process are often solvent- and energy-intensive
Our aim is to show the effects of the operational parameters (i.e. pressure (p [MPa]), temperature (T [°C]) and organic solvent concentration in depth on the optical resolution of mandelic acid with (R)-1phenylethanamine carried out using gas antisolvent fractionation (GASF) as a separation method
Starting from non-racemic mandelic acid, the latter simulates the recrystallization of diastereomeric salts obtained from an initial resolution
Summary
Separation techniques involved in almost every chemical manufacturing process are often solvent- and energy-intensive. [1] antisolvent processes carried out using supercritical carbon dioxide are not yet widely applied in the industry, but they are intensively researched crystallization methods offering solvent-free, highly crystalline products in the (maximum) micrometer particle size range or even micronized composites having special properties. During the formation of the above-mentioned mixture, the polarity of the solvent drops significantly the solubility of polar components is sharply decreased too. These effects allow the dissolved material to form solid (mostly highly crystalline) particles (Fig. 1 b). The organic solvent is still present in the high-pressure precipitation vessel, so an extractive washing step has to be applied using pure supercritical carbon dioxide (Fig. 1 c). Antisolvent processes (mostly scaled up variants like the semi-continuous supercritical antisolvent precipitation) allow controlling the main particle size
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