Mother liquors, purification

An alternative method of purification consists in dissolving the crude sulphonyl chloride in the minimum volume of boiling chloroform, transferring rapidly to a warm separatory funnel, and separating the lower chloroform layer upon cooling the chloroform solution, the crystalline sulphonyl chloride separates, and is collected by filtration with suction. A further quantity is obtained by concentrating the mother liquor. 

For purification the acid is crystallized from about 150 cc. of glacial acetic acid, using an acid-resistant filter for the hot solution (Note 7). Aconitic acid separates as small, colorless needles weighing 50-60 g., and about 10 g. more can be secured by concentrating the mother liquor under reduced pressure to one-third of its volume. The material is dried in the air and then in a desiccator containing sodium hydroxide in order to remove all traces of acetic acid. One crystallization usually is sufficient to bring the point of decomposition to 198-199° (Note 6). 

Water can be added to the mother liquor, and the mixture extracted with chloroform to increase the diazide recovery to nearly quantitative (95-98%). During the course of any purification method that might be employed the diazide should not be heated above 50°, since decomposition occurs quite noticeably at that temperature. It is best to store the pure product below —5° in the dark, since it undergoes a facile photochemical rearrangement to the cyclopentene-dione. 

The submitters purified the product by the following procedure. The residual pale yellow solid is dissolved in 50 ml of diethyl ether and the remaining solid is filtered off (Note 16). The filtrate is concentrated to a volume of ca. 25 mL, and the solution is allowed to crystallize at 0°C. Once crystallization begins, 50 mL of petroleum ether is added in two portions over 10 hr, and then crystallization is allowed to proceed overnight at 0°C. The white solid is collected by filtration and washed with a mixture of 3 1 petroleum ether-diethyl ether to afford 3.8 g of 4. Chromatographic purification of the mother liquor (5.5 x 18 cm of DSH silica gel 40-63 mm, elution with 1 L of petroleum ether/ethyl acetate 4 1 followed by 1.5 L of 3 1 petroleum ether-ethyl acetate) gives 2.5 g of 4 as a pale yellow solid. All the material is combined and recrystallized from diethyl ether/petrol as above to yield 5.2 g (47%) of 4 in two crops. 

The unwanted erythro isomer of (11) crystallised out at this point, so the synthesis continues with the mother liquors. We must now protect the NH2 and both OH groups during the nitration - this also allows purification of crystalline threo (12). 

About 70-80 per cent of the biacetyl monoxime is recovered on crystallization. Practically all of the monoxime left in the mother liquor can be recovered by steam distillation. The recrystallized and dried compound melts at 76.5°. Purification by distillation is not recommended. 

When making pharmaceuticals, one critical issue is to control and minimize metal impurities in the product, often to less than 10 ppm. Each product requires a different work-up and purification protocol, and it is difficult to describe a general solution. On some occasions washing removes the catalyst, but at other times the product is crystallized and the catalyst remains in the mother liquors occasionally, the product is volatile and can be distilled. Sometimes the catalyst is carried forward to the next stage and is removed at this point. In our experience, residual metal has not been problematic, but if it is then either immobilized or water-soluble catalysts, as described in this chapter, can be employed. 

For further purification the crystallised acid is boiled for a quarter of an hour under reflux with methylated spirit (one part by volume of spirit for each part by weight of acid), left over night without filtering, then collected again at the pump, washed with alcohol, and finally the almost colourless material is recrystallised from spirit, in which it is dissolved by boiling under reflux. The pure cholic acid separates on cooling in the form of transparent tetrahedral crystals. Melting point 196°. A further quantity of pure substance can be obtained from the mother liquor by concentration. If the acid, partially purified as described, is extracted in a thimble with ethyl acetate, a very fine preparation is obtained. The yield of pure acid amounts to fully 50 g. 

Ordinarily the mother liquors from the preparation and purification of 1-ester will be discarded, but a small additional quantity of the 3-acid may be obtained by concentrating these solutions, adding alkali to hydrolyze the ester, adding water, and acidifying. The precipitated material is purified by crystallizing the sodium salt twice, and from this 8 g. (5 per cent) of the pure 3-acid is obtained. 

Crystallisation was one of the earliest methods used for separation of radioactive microcomponents from a mass of inert material. Uranium X, a thorium isotope, is readily concentrated in good yield in the mother liquors of crystallisation of uranyl nitrate (11), (33), (108). A similar method has been used to separate sulphur-35 [produced by the (n, p) reaction on chlorine-35] from pile irradiated sodium ot potassium chloride (54), (133). Advantage is taken of the low solubility of the target materials in concentrated ice-cold hydrochloric acid, when the sulphur-35 as sulphate remains in the mother-liquors. Subsequent purification of the sulphur-35 from small amounts of phosphorus-32 produced by the (n, a) reaction on the chlorine is, of course, required. Other examples are the precipitation of barium chloride containing barium-1 from concentrated hydrochloric acid solution, leaving the daughter product, carrier-free caesium-131, in solution (21) and a similar separation of calcium-45 from added barium carrier has been used (60). 

A common procedure in the use of crystallization for purification is shown schematically in Figure 1. As shown, product is recovered in an initial crystallization step, redissolved, and then recrystallized. Given enough of these steps, the purity of the final recovered crystals can be expected to meet demanding standards. Unfortunately, redissolution and recrystallization usually means loss of product, and caution must be exerdsed in using mother liquor recycle because of the potential for accumulation of impurities. 

The third crop generally weighs about 100 g. and is about 80% pure the fourth crop weighs about 75 g., and is about 60% pure (Note 11). For purification, the third crop is recrystallized from the mother liquor resulting from the recrystallization of the combined first and second crops the fourth crop is recrystallized from the third-crop mother liquor. An additional recrystallization from water is usually required to obtain material of 95 + % purity. 

Formerly all the iodine was made from the ash of seaweed, and potash was a remunerative appendix to the iodine industry but just as the Stassfurt salts killed those industries which extracted potash from other sources, so did the separation of iodine from the caliche mother-liquors threaten the industrial extraction of iodine from seaweed with extinction. Iodine in a very crude form was exported from Chili in 1874—e.g. a sample was reported with iodine 52-5 per cent. iodine chloride, 3-3 sodium iodate, 13 potassium and sodium nitrate and sulphate, 15 9 magnesium chloride, 0 4 insoluble matter, 1 5 water, 25-2 per cent. About that time much of the iodine was imported as cuprous iodide. This rendered necessary the purification of the Chilian product but now the iodine is purified in Chili before it is exported. The capacity of the Chilian nitre works for the extraction of iodine is greater than the world s demand. It is said that the existing Chilian factories could produce about 5100 tons of iodine per annum whereas the... 

Precipitate with aq. ammonia. Evaporate the soln. down to about 100 c.c., and filter the ot liquid so as to remove calcium sulphate. The cone. soln. is sat. with ammonium alum and allowed to stand for some time. The mixed crystals of potassium, rubidium, and oeesium alums and of lithium salt are dissolved in 100 c.c. of distilled water and recrystal-lized. The recrystallization is repeated until the crystals show no spectroscopic reaction for potassium or lithium. The yield naturally depends on the variety of lepidolite employed. 100. grms of an average sample gives about 10 grms. of crude crystals and about 3 grms. of the purified caesium and rubidium alums. For the purification of caesium and rubidium salts, see the chlorides. The mother-liquors are treated with an excess of barium carbonate, boiled, and filtered. The filtrate is acidified with hydrochloric acid, and evaporated to dryness. The residue is extracted with absolute alcohol in which lithium chloride is soluble, and the other alkali chlorides are sparingly soluble. 

Simple Recrystallization.—In the simplest procedure of recrystallization, the salt is dissolved in some appropriate hot solvent, and the solution is then allowed to cool to room temperature. All the salt in excess of the weight soluble at the lower temperature crystallizes and may be filtered from the mother liquor. Insoluble impurities remain undissolved and may be removed by filtering the hot solution before crystallization begins soluble impurities remain in the solution from which the crystals separate. It is evident that this simplest process applies to the purification of salts that have a decided difference of solubility at different temperatures to cases in which the soluble impurity is not too abundant, or too sparingly soluble and to cases in which... 

In a 500-cc. round-bottomed, three-necked flask fitted with a reflux condenser, dropping funnel, and a mercury-sealed stirrer (Note 1) is placed a solution of 46 g. (0.5 mole) of dry aniline in 125 cc. of pure dry benzene. Stirring is started, and a solution of 42 g. (0.5 mole) of ketene dimer (p. 64) in 75 cc. of pure dry benzene is added dropwise over a period of half an hour. The reaction mixture is then heated under reflux on the steam bath for one hbur. After the major portion of the benzene has been removed by distillation from the steam bath, the remainder is removed under reduced pressure. The residue is dissolved in 500 cc. of hot 50 per cent aqueous alcohol from which the aceto-acetanilide separates on cooling. The mixture is cooled to 0° before filtration. A second crop of crystals can be obtained by adding 250 cc. of water to the mother liquor and cooling again (Note 2). The total yield of product, m.p. 82-83.5°, is 65 g. (74 per cent of the theoretical amount). Further purification by recrystallization from 300 cc. of 50 per cent alcohol yields 55 g. of a product which melts at 84-85°. 

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