Crystallization
in the laboratory is rarely performed under an inert atmosphere.
Most commonly, crystal filtration is done in the open air on a Buchner filter
followed by washing with ice-cold wash liquid and then partially dried by sucking air through the filter cake using water-aspirator vacuum.
Because lab filtrations are most commonly conducted in this fashion, the final crystallization temperature and the temperature of the wash liquid are rarely taken below zero degrees Centigrade. If lower temperatures could be used, recoveries could be higher but this would cause moisture from the air to contaminate the solvents used and/or to condense on the porcelain or glass filter funnel. Furthermore, if the Buchner filter is not sufficiently cold, it becomes more difficult to draw off the mother liquors and the wash solvent without partially redissolving the filtrand. Thus, laboratory filtration in the air has upper and lower temperature bounds. This limitation does not exist at-scale. In the plant, both the solution and the solid crystalline cake are always inerted and since water vapor can't get into the reactor to condense, the clarified solution can be cooled to -20 C to force out more crystals. In the same way, wash liquid to wash the material on the filter is conveniently cooled to a sub-zero temperature while excluding moisture throughout.
Black's Rule [F.L. Muller, M. Fielding and S.N. Black, Org. Process Res. Dev. 2009, 13, 1315-13231] states that solubility doubles every 20 C°. Sometimes struggles to find a suitable solvent system for recrystallization that depends upon the difference in solubility between two different temperatures can be replaced with a low-temperature recrystallization from hexane, pentane or other hydrocarbon liquid. The larger temperature ranges between these liquids' boiling points and -20°C diminishes the need for a dramatic difference in solubility between some refluxing hot solvent and that same solvent at 0°C.
However, special laboratory equipment for the laboratory is necessary to explore such an approach. Roger Giese described such an apparatus and its mode of use in Journal of Chemical Education, 45, 610 (1968). Step by step instruction is provided. The apparatus is sufficiently simple that it can be put together by modifying a chromatography column that has a fritted glass disc as the plug. Because it operates with its own jury-rigged cold bath made from a plastic bottle, it does not need to fit in a Dewar for cooling, unlike the apparatus described by C. Frank Shaw, III and A. L. Alfred in Journal of Chemical Education, 47, 165 (1970).
Using Giese's apparatus it would be interesting to see what kind of improvements in yield and purity could be achieved in important crystallizations.
Because lab filtrations are most commonly conducted in this fashion, the final crystallization temperature and the temperature of the wash liquid are rarely taken below zero degrees Centigrade. If lower temperatures could be used, recoveries could be higher but this would cause moisture from the air to contaminate the solvents used and/or to condense on the porcelain or glass filter funnel. Furthermore, if the Buchner filter is not sufficiently cold, it becomes more difficult to draw off the mother liquors and the wash solvent without partially redissolving the filtrand. Thus, laboratory filtration in the air has upper and lower temperature bounds. This limitation does not exist at-scale. In the plant, both the solution and the solid crystalline cake are always inerted and since water vapor can't get into the reactor to condense, the clarified solution can be cooled to -20 C to force out more crystals. In the same way, wash liquid to wash the material on the filter is conveniently cooled to a sub-zero temperature while excluding moisture throughout.
Black's Rule [F.L. Muller, M. Fielding and S.N. Black, Org. Process Res. Dev. 2009, 13, 1315-13231] states that solubility doubles every 20 C°. Sometimes struggles to find a suitable solvent system for recrystallization that depends upon the difference in solubility between two different temperatures can be replaced with a low-temperature recrystallization from hexane, pentane or other hydrocarbon liquid. The larger temperature ranges between these liquids' boiling points and -20°C diminishes the need for a dramatic difference in solubility between some refluxing hot solvent and that same solvent at 0°C.
However, special laboratory equipment for the laboratory is necessary to explore such an approach. Roger Giese described such an apparatus and its mode of use in Journal of Chemical Education, 45, 610 (1968). Step by step instruction is provided. The apparatus is sufficiently simple that it can be put together by modifying a chromatography column that has a fritted glass disc as the plug. Because it operates with its own jury-rigged cold bath made from a plastic bottle, it does not need to fit in a Dewar for cooling, unlike the apparatus described by C. Frank Shaw, III and A. L. Alfred in Journal of Chemical Education, 47, 165 (1970).
Using Giese's apparatus it would be interesting to see what kind of improvements in yield and purity could be achieved in important crystallizations.
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