Crystallization solids purification

Crystalline materials are commonly associated with purity, but recent demands lead to almost suprapure materials, and it is common to ask for an impurity profile. Crystallization epitomizes purification at the molecular level and the technology exploits the ability of a crystal surface to reject molecules that it does not recognize (Davey, 1994). This is essentially a supramolecular process. Two types of approaches are possible, viz. the use of eutectic and solid solutions. In the eutectic approach there is efficient rejection, whereas in solid solutions molecular level discrimination is difficult. 

To a synthetic chemist the concept of a polymer is rather different. The term is often used to describe molecules formed from quite small numbers of monomers units but which resist crystallization and purification owing to the range of chain lengths present. Such materials will normally form brittle solids which are either amorphous or have a low level of crystalline order. 

While evaporation is used for the concentration and removal of solvents, usually the reaction by-products are not volatile. Similarly, filtration of precipitated or crystallized solids is not likely to be applicable to all the members of a library, and furthermore the automation of these processes is not straightforward an interesting example of general precipitation of library members from an organic medium due to the presence of a basic ionizable group has been recently reported by Perrier and Labelle (87). Extraction procedures possess the desired separation properties and have been used for the purification of several solution-phase libraries we will cover this subject in more depth in this section. An excellent review (88) has recently been published in which the interested reader will find a description of available strategies for separation and purification of single compounds and arrays. 

A mixture of CuCN (5.0 g, 55 mmol) and dry pyridine (100 mL) was heated under reflux until all the CuCN dissolved. The solution was cooled to rt as 6-iodo-9-( -D-ribofuranosyl)purin-2-amine (5.0 g, 12.7 mmol) was added, and the mixture was heated at 130-135 °C for 10 min. The mixture was evaporated to dryness, and the black residue was extracted with hot MeCN (3x250mL). The combined MeCN extracts were evaporated, and the residual solid was reextracted with hot i-PrOH (3 x 200 raL). The i-PrOH extract was evaporated to yield 6.0 g of tan solid. Purification by column chromatography (silica gel) gave a pure sample yield 2.6 g (70%). Crystallization (EiOH) gave light yellow crystals mp 131 -132 C. 

The alkali metal cyantrimethylsilylamides may be prepared in an inert organic solvent like n-hexane or toluene. Alternatively, an excess of the liquid BTSC can be used. In all cases the alkali metal compound is obtained as a white solid. Purification was performed by washing with hexane, drying in vacuum, and/or re-crystallization fl om THF or pyridine. 

Liquid-liquid extraction (LLX) proved to be a highly attractive separation method for many of these applications due to low consumption of energy and of reagents, operation at about ambient temperature, avoidance of solid crystallization and purification, and reduction of the formation and treatment of by-products. 

Solid and vapor Preferential condensation (desublimation) preferential participation in crystal structure Purification of phthalic anhydride 18, 22, 23... 

For purification, transfer the acid to a 150 ml. flask containing 60 ml. of water, boil the mixture under reflux, and then add acetic acid in 5 ml. portions down the condenser until almost all the solid has dissolved avoid an excess of acetic acid by ensuring that the solvent action of each addition is complete before the next portion is added. A small suspension of insoluble impurity may remain. Add 2 g. of animal charcoal, boil the solution again for 10-15 minutes, and then filter it through a preheated Buchner funnel. Cool and stir the filtrate, which will deposit pale cream-coloured crystals of the acid. Collect as before and if necessary repeat the recrystallisation. Yield of pure acid, 9 g. m.p. 227-229°. 

Solid organic compounds when isolated from organic reactions are seldom pure they are usually contaminated with small amounts of other compounds ( impurities ) which are produced along with the desired product. Tlie purification of impure crystalline compounds is usually effected by crystallisation from a suitable solvent or mixture of solvents. Attention must, however, be drawn to the fact that direct crystallisation of a crude reaction product is not always advisable as certain impurities may retard the rate of crystallisation and, in some cases, may even prevent the formation of crystals entirely furthermore, considerable loss of... 

Purification of the Methylamine HCI is in order now, so transfer all of the crude product to a 500mL flask and add either 250mL of absolute Ethanol (see end of FAQ for preparing this) or, ideally, n-Butyl Alcohol (see Footnote 4). Heat at reflux with a Calcium Chloride guard tube for 30 minutes. Allow the undissolved solids to settle (Ammonium Chloride) then decant the clear solution and cool quickly to precipitate out Methylamine HCI. Filter rapidly on the vacuum Buchner funnel and transfer crystals to a dessicator (see Footnote 3). Repeat the reflux-settle-cool-filter process four... 

Crystalhzation is important as an industrial process because of the number of materials that are and can be marketed in the form of crystals. Its wide use is probably due to the highly purified and attractive form of a chemical solid which can be obtained from relatively impure solutions in a single processing step. In terms of energy requirements, crystallization requires much less energy for separation than do distillation and other commonly used methods of purification. In addition, it can be performed at relatively low temperatures and on a scale which varies from a few grams up to thousands of tons per day. 

Purification of a chemical species by solidification from a liquid mixture can be termed either solution crystallization or ciystallization from the melt. The distinction between these two operations is somewhat subtle. The term melt crystallization has been defined as the separation of components of a binaiy mixture without addition of solvent, but this definition is somewhat restrictive. In solution crystallization a diluent solvent is added to the mixture the solution is then directly or indirec tly cooled, and/or solvent is evaporated to effect ciystallization. The solid phase is formed and maintained somewhat below its pure-component freezing-point temperature. In melt ciystallization no diluent solvent is added to the reaction mixture, and the solid phase is formed by cooling of the melt. Product is frequently maintained near or above its pure-component freezing point in the refining sec tion of the apparatus. 

Disodium 4-nitrophenylphosphate (6H2O) [4264-83-9] M 371.1 Dissolve in hot aqueous MeOH, filter and ppte by adding Me2CO. Wash the solid with Me2CO and repeat the purification. Aq MeOH and Et20 can also be used as solvents. The white fibrous crystals contain less than 1% of free 4-nitrophenol [assay J Biol Chem 167 57 1947]. 

Solid sulfonyl cyanides now show a melting point not more than 1-2 below that of recrystallized material. They may be used with t further purification. Analytically pure samples are obtained by r crystallization from dry benzene, diy petroleum ether, or a mixture or the two. 

The chloropyruvic acid prepared in this manner is satisfactory for use in the next reaction without purification. It often crystallizes to form a waxy solid or semisolid which is quite hygroscopic. I hc pure anhydrous material is rei)orted to melt at 45°, while the inonohydrate obtained l)y other melhods melts at 57 58°. The chloropyruvic acid is normally uscci immediately,... 

At the alumina plant, the bauxite ore is further crushed to the correct particle size for efficient extraction of the alumina through digestion by hot sodium hydroxide liquor. After removal of "red mud" (the insoluble part of the bauxite) and fine solids from the process liquor, aluminum trihydrate crystals are precipitated and calcined in rotary kilns or fluidized bed calciners to produce alumina (AljOj). Some alumina processes include a liquor purification step. 

Similarly, different unit operations are available to accomplish the same processing objective. For example, a filter, a centrifuge, or a decanter could be used to separate a solid from a liquid. Crystallization or distillation could also be used for purification. 

The reaction mixture is diluted with 250 ml of water, the mixture is transferred to a 2 liter flask using methanol as a wash liquid, and the organic solvents are distilled at 20-25 mm using a rotary vacuum evaporator. The product separates as a solid and distillation is continued until most of the residual toluene has been removed. The solid is collected on a 90 cm, medium porosity, fritted glass Buchner funnel and washed well with cold water. After the material has been sucked dry, it is covered with a little cold methanol, the mixture is stirred to break up lumps, and the slurry is kept for 5 min. The vacuum is reapplied, the solid is rinsed with a little methanol followed by ether, and the material is air-dried to give 9.1 g (85%), mp 207-213° after sintering at ca. 198°. Reported mp 212-213°. The crude material contains 1.0-1.5% of unreduced starting material as shown by the UV spectrum. Further purification may be effected by crystallization from methanol. 

B. 2-Methylcyclopenlane-l,3,5-trione hydrate. A mixture of 200 g. (0.89 mole) of the keto ester prepared above, 910 ml. of water, and 100 ml. of 85% phosphoric acid is healed under reflux for 4 hours and then cooled in an ice-salt bath to —5°. The trione mixed with oxalic acid separates and is collected by filtration and dried under reduced pressure. The dried material is extracted with boiling ether (250-300 ml.) under reflux, and the ethereal extract is separated from the undissolved oxalic acid. The original aqueous filtrate is also extracted with ether in a continuous extractor. The two extracts are combined, and ether is removed by distillation. The crude trione separates as a dark brown solid and is crystallized from ca. 250 ml. of hot water. The once-crystallized, faintly yellow product weighs 95-105 g. (74-82%), m.p. 70-74°. This product is used in the next step without further purification. A better specimen, m.p. 77-78°, which is almost colorless, can be obtained by recrystallization from hot water after treatment with Norit activated carbon. 

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