This article is about the technique I call ‘exhaustive digestion’. This is a phrase that I used in my blog entitled, Getting Better Recovery from Crystallization. In this blog, I make the point that chemists scaling up a laboratory process often fail to do adequate preliminary purification of a solid and as a consequence get a lower recovery from their crystallization than is possible if a preliminary treatment were done. I proposed digestion or trituration as pretreatments before crystallization. I don’t know whether there are any widely accepted differences in meaning between the words digestion and trituration but, when used in my blogs, ‘trituration’ can be understood to apply equally to oils or solids while ‘digestion’ will only be applied to solids. Second, ‘trituration’ can be done with either hot or cold solvent while ‘digestion’ and particularly ‘exhaustive digestion’ as described hereunder is to be done with hot, boiling liquid, usually a rather poor solvent for the desired product.
Exhaustive digestion is related to swish trituration about which I have written earlier. The difference is that the swish trituration employs its anti-solvent system at ambient temperature and does not measure the boiling point depression of the liquid to assess the extent of purification.
In the old literature, the progress of purification by digestion on the laboratory scale was followed by observing the change in the boiling point of the digesting solvent or solvent mixture using a Beckmann thermometer, which is a thermometer that can measure differences as small as one-tenth of one Centigrade degree. I don’t know how long it has been since I have seen anyone use a Beckmann thermometer but, at least in my undergraduate Phys. Chem., (over 50 years ago) it was done quite often. The scale on a Beckmann thermometer is only 10-20 degrees but its range can be adjusted by removing or adding mercury to the column of mercury used for measurement by moving mercury back and forth from an attached mercury reservoir. Today a digital thermometer is more likely to easily achieve the same or better precision of measurement without managing liquid mercury.
I will illustrate exhaustive digestion by quoting from an experiment taken from Laboratory Technique in Organic Chemistry by Avery Adrian Morton, First Edition, McGraw-Hill, 1938, pg. 128-229.
“The apparatus consists of a tube or flask of such size that a large part of the bulb is covered by the solid material being extracted, a thermometer graduated in tenths of a degree, a reflux condenser, and a water or oil bath. Place the sample in the container, insert the thermometer so the bulb is immersed in or covered by the sample, and add solvent to cover the solid and the thermometer bulb. The solvent is usually one that will dissolve impurities without appreciable quantities of the desired material. Petroleum ether or ligroin is often suitable. A mixture of solvents may be employed without affecting their utility in this experiment, as long as the composition of the mixture is not varied. Reflux the solution [I think slurry is intended] using a water or oil bath as a source of heat. After about 20 minutes the temperature has reached a constant level. Usually, no trouble will be experienced from superheating as long as a solid phase is present, although a little agitation with the thermometer is sometimes needed. Filter either by pouring into a Buchner funnel or by using a filter stick. Add more of the same solvent, reflux once more, and observe the temperature after equilibrium conditions have been reached. Continue the operation until the temperature of two or more successive operations is identical. The more soluble impurities have now been removed, and the solution contains only the pure compound or the compound with [less soluble type] impurities that have not been entirely removed…. The operation may be continued if desired until all the product has been dissolved. A change of solvent [may be implemented at some point for further purification]….. Constancy in the boiling points of successive portions constitutes further evidence of the purity of the material, whereas a drop in the boiling point is evidence of the exhaustion of still another component. Usually, the final portions of exhaustive digestion are pure materials.”
Continuously measuring and recording the changes, in real-time, of the boiling point without any actual sampling makes this an early application of Process Analytical Technology (PAT). The improvements in the size and sensitivity of temperature measuring devices for following small changes in boiling point under conditions where superheating does not occur deserve more frequent consideration.
Exhaustive digestion if used at scale would require a more rugged method for measuring small changes in the boiling point of the slurry than the old Beckmann thermometer. Fortunately, modern digital thermometers meet that need.
Exhaustive digestion, similar to swish trituration, may profit from using either water-rich or hydrocarbon-rich binary azeotropes, as the anti-solvents, as the desired product’s solubility dictates. Some are suggested in the following list:
97.0% water 3.0% acetic acid azeotrope bp 76.6ºC
91.0% water 9.0% benzyl alcohol azeotrope bp 99.9ºC
87.1% heptane 12.9% water azeotrope bp 79.2ºC
94.4% hexane 5.6% water azeotrope bp 61.6ºC
95.5% hexane 4.5% allyl alcohol azeotrope bp 65.5ºC
97.0% hexane 3.0% 1-butanol azeotrope bp 67.0ºC
91.5% cyclohexane 8.5% water azeotrope bp 69.8ºC
83.7% acetonitrile 16.3% water azeotrope bp 76.5 C
72.9% allyl alcohol 27.1% water azeotrope bp 88.2ºC
66.0% allyl cyanide 34.0% water azeotrope bp 89.4ºC
77.5% formic acid 22.5% water azeotrope bp 107.1ºC
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