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kilomentor | 17 January, 2008 20:16
Today’s Kilomentor blog pertains to a laboratory technique, which is particularly appropriate at a scale of 5-10 litres where it becomes problematic to pick them up and pour from them. It is sometimes necessary either to filter a solution without sucking the solvent dry and exposing the slurried solid or to draw away the liquid phase from a reactor flask to leave behind the solid phase. This can be particularly useful if the solid is sensitive to the air or moisture in the atmosphere. it can also be used when the slurry material would block the filter, make the flow impractical, and prevent a filtration from being completed. Removing a liquid phase from a vessel to leave the solid inside is called inverted filtration.
An apparatus for inverted filtration is described in Organic Synthesis Coll. Vol. 2 1966. A figure is printed on pg. 610. The solution is drawn up from the bottom of the reactor through a tube using gentle suction and carried over through the tube to a second vessel. A filter entirely encloses the end of the tube that is inserted into the reaction mixture. The filter is prepared from an extraction thimble and a rubber stopper, which has a single hole drilled through the top to accommodate the glass tube. The thimble is stuffed with glass wool to hold the thimble centered around the glass tube.
During the reaction the filtering assemblage is held above the reaction solution but inside the reactor. When the time for the inverted filtration arrives, the assemblage is pressed down by pressing the glass tube into the solution sliding it further down on the stopper which blocks a neck of the reactor flask. When the filter assembly is at least partially dipping into the solution, clear liquid will pass through the extraction thimble By the application of pressure to the reactor or gentle suction on the tube (by way of the filtrate receiving flask) the liquid which has been filtered through the extraction thimble will be forced up the tube and over into the receiving flask. Thus only liquid, which passes through the filter is transferred.
kilomentor | 10 January, 2008 10:04
A reaction may proceed quite well to give an 80% yield of the desired product but still be very difficult to work up when it is a mixture of neutral compounds. In this situation acid-base extraction cannot help to obtain some partitioning between organic and aqueous phases. Furthermore, most often the two compounds making up the reaction mixture are both essentially insoluble in water. When there is 20% by weight of an impurity, even when you can find a solvent which gets the major compound to selectively crystallize, the recovery is usually quite poor simply because by the time you have crystallized 60% of the product, the mother liquors are a 1:1 mixture of desired and undesired compounds. At this point the rate of crystallization normally becomes impractically slow and for practical purposes the crystallization has stopped.
Usually thin layer chromatography in more than one solvent system can quickly tell you whether the main impurity, which most probably is the one blocking the crystallization, is, by-and-large, less polar or more polar than the desired major component. When the minor component is the more polar, what we intuitively would like to do is triturate with water, modified so that it can dissolve more of the mixture, hoping that the additional material dissolved into the water rich phase will be disproportionately the more polar impurity component.
A cosolvent for water to be effective must prefer to mix with the water rather than forming an oil phase with the products. Only experimentally can we find something guaranteed to work, but perhaps kilomentor can propose a rule of thumb, which could increase the likelihood of success. This aqueous phase modifier should be completely miscible in all proportions with water. If a diluent is only partially miscible with water it is more likely that when mixed with the neat reaction oil it will simply migrate into the oil.
The most lipophilic solvents that are completely miscible in all proportions with water are: acetone, methyl ethyl ether, methyl acetate,and t-butanol. The lower homologues of each of these function group types will also be completely miscible. That is: methanol, ethanol, propanol, isopropanol are also completely miscible and could be used as diluents. For esters, ethyl formate is not completely stable in water so it cannot be used. Acetonitrile is completely miscible but propionitrile is not. Nitromethane is not completely miscible, while Dimethylformamide, N-methylformamide, formamide, DMSO, pyridine, and acetic acid are.
In addition to adding small quantities of these solvents to a large excess of water to increase the leaching power of the polar phase, recrystallization from the less polar of these at least: acetone, t-butanol, pyridine or methyl acetate by the gradual addition of water could be fruitful.
Once the level of the impurity is reduce below 10% from the 20% range, crystallization in general can be expected to give a superior recovery. From a mixture containing just 10% impurity one could crystallize 80% before the mother liquors would be 50:50 product : impurity.
Even on scale a reaction mixture can be freed of organic solvent by concentration in the presence of a water phase to give a reaction product oil as an oil in water. The aqueous phase modifier could be added into this mixture.
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