Solvents recrystallization

Suppose, after all this, you still haven t found a solvent. Look again. Perhaps your compound completely dissolved in ethanol at room temperature, and would not dissolve in water. AHA Ethanol and water are miscible (i.e., they mix in all proportions) as well. You will have to perform a mixed-solvent recrystallization (see Working with a Mixed-Solvent System ). 

From this, you should get the idea that it would be good to use a mixed solvent to recrystallize compounds that are soluble in alcohol yet insoluble in water. You see, each solvent alone cannot be used. If the material is soluble in the alcohol, not many crystals come back from alcohol alone. If the material is insoluble in water, you cannot even begin to dissolve it. So, you have a mixed solvent, with the best properties of both solvents. To actually perform a mixed-solvent recrystallization you... 

Polymorphism is also a common phenomenon in Pcs. Among them, CuPc has been the most studied compound because of its stability and its extensive use in the dye industry. Five polymorphs, namely the a-, fi-, y-, S- and s-forms of CuPc are known. /1-CuPc is the thermodynamically stable polymorph while the a-, y-, S- and g-CuPc modifications are metastable and can be converted to j6-CuPc upon heating or solvent recrystallization. 

Micronization with supercritical fluids - Crystallization - Rapid expansion - Gas anti-solvent Recrystallization - Precipitation with compressed anti-solvent - Solution-enhanced dispersion - Particles from gas-saturated solutions 80 - 300 fine particles and powders from various products and of designed properties... 

Gas anti-solvent processes (GASR, gas anti-solvent recrystallization GASP, gas antisolvent precipitation SAS, supercritical anti-solvent fractionation PCA, precipitation with a compressed fluid anti-solvent SEDS, solution-enhanced dispersion of solids) differ in the way the contact between solution and anti-solvent is achieved. This may be by spraying the solution in a supercritical gas, spraying the gas into the liquid solution. 

To a THF (15 mL) soln of (l-pyrenyl)methanol (3.07 g, 13.2 mmol) and 4-nitrophenyl chloroformate (3.21 g, 16.0 mmol), pyridine (1.3 mL) was added dropwise at 0 °C. The mixture was stirred at 0 °C for 1 h and then at rt for 2 h. The solvent was distilled off and the residue dissolved in CH2C12, washed successively with 1M HC1, 4% NaHC03, H20, and sat. NaCl, then dried (Na2S04). After removal of the solvent, recrystallization of the crude product from CHCI s/hexanes gave 4-nitrophenyl 1-pyrenylmethyl carbonate yield 4.79 g (91%) mp 130 °C. 

Another problem arises from brominated aromatic species derived from inoiganic bromides used as oxidation cocatalysts. As a result, the cmde NDA is converted to its dimethyl ester, DMNDA [840-65-3], and solvent recrystallized to give a high purity diester (36—38). A process for purifying NDA directly by hydrogenation (pure TA process) has also been described (39). 

The product is poured into ice water, thoroughly extracted yith benzene, and the benzene solution washed with water. Benzene is then removed by distillation until a volume of 25-50 cc. is reached and the resulting deep-red solution is passed through a 12 by 2 cm. column of aluminum oxide. The column is developed with ordinary, undried benzene, and that portion of the eluate which runs through before the strawberry-red zone reaches the bottom of the tube is discarded. The solution that follows is collected, and a pale yellow crystalline mass is obtained upon removal of the solvent. Recrystallization from ethanol gives 1.24-1.37 g. (60-65%) of pale yellow crystals that sinter at 119° and melt at 122.7-123.2° (cor.). 

Information concerning the method of manufacture may be presented in the form of a flow chart. Supply a brief description of the methods of isolation (e.g., synthetic process, fermentation, extraction, recombinant deoxyribonucleic acid [DNA] procedure) and purification (solvent recrystallization, column chromatography, distillation). Include all synthetic pathways that have been adequately characterized during the investigational stages of drug development. 

Gallagher P., Coffey M, Krukonis V., Gas Anti-Solvent Recrystallization of RDX Formation of Ultra-fine Particles of a Difficult to Comminute Explosive, The Journal of Supercritical Fluids, No. 5, pp. 130-142, 1992... 

The miscibility of solvents with each other must be taken into account when attempting mixed-solvent recrystallizations (see p. 95) the properties of some common recrystallization solvents, which you are likely to encounter in your laboratory work, are shown in Table 13.1. Remember that this is only a general list of solvents further information on solvent properties can be found in standard textbooks such as Harwood et al. (2000, p. 133), Loewenthal (1990, p. 146) and Furniss et al. (1989, p. 137). 

To carry out a single-solvent recrystallization (Box 13.3) you must get the compound into solution and this is achieved by suspending it in the appropriate cold solvent, found in the solvent selection process, and then heating the mixture to dissolve the soUd. The equipment used will depend on the boiling point of the solvent, its flammability and toxicity. Some general systems are shown in Table 13.2. 

Detailed procedures for single-solvent and mixed-solvent recrystallizations are shown in Box 13.3 and Box 13.4 respectively and the modifications necessary for the use of other solvent systems can be worked out from the information in Table 13.2. 

A few comments concerning the crystallization of carbanions are in order. These comments are based upon the personal experience developed in our own laboratory and also upon observations noted in the literature in the course of crystallizing enolate anions. Although alkali metal enolate anions are relatively unstable compounds, they have been prepared in the solid state, isolated, and characterized by IR and UV spectroscopy in the 1970s. Thus the ot-lithiated esters of a number of simple esters of isobutyric acid are prepared by metallation of the esters with lithium diisopropylamide in benzene or toluene solution. The soluble lithiated esters are quite stable at room temperature in aliphatic or aromatic hydrocarbon solvents and are crystallized out of solution at low temperature (e.g. -70 °C.). Alternatively the less soluble enolates tend to precipitate out of solution and are isolated by centrifugation and subsequent removal of the solvent. Recrystallization from a suitable solvent can then be attempted. The thermal stability of the lithiated ester enolates is dramatically decreased in the presence of a solvent with a donor atom such as tetrahydrofuran. 

Supercritical fluids have been shown to be excellent recrystallization agents for a variety of materials, and their use in recrystallizing an explosive, nitroguanidine (NQ), is presented. A new process, GAS (gas anti-solvent) Recrystallization, is described. 

Equations 1 and 2 are strictly applicable only to the homogeneous condensation of a vapor to liquid droplets. In a two or three component system such as anti-solvent recrystallization, for example, or for recrystallization from a melt, other factors such as viscosity of the medium, the mode of nucleation, i.e., whether homogeneous or heterogeneous, etc., come into play, and the equations are modified by these other factors. Equations 1 and 2 are, nevertheless, of pedagogical value in predicting some general effects of these other systems. 

In an anti-solvent recrystallization process, then, particle size and particle size distribution is determined by the interaction between the nucleation rate and the growth rate of crystals, on one hand, and by the rate of creation of supersaturation, on the other hand all three are influenced by the manner of addition of the anti-solvent. Figure 5 is a qualitative picture of simultaneous events that occur when an anti-solvent is added to a solution of a solute that is to be recrystallized. The three zones shown in Figure 5, designated I, II, and III, denote three areas of supersaturation. Zone I is for a supersaturation less than 1, i.e., for actual solute concentrations less than saturation. No growth of particles will occur in this zone (and in fact if there are any particles that are "somehow" present, they will dissolve). In Zone II, the supersaturation is less than the critical value discussed earlier, but "some" nucleation can occur particles that are present in this... 

Krukonls, V. J., Coffey, M. P., Gallagher, P. M. Exploratory Development on a New Process to Produce Improved RDX Crvstsls L Supercritical Fluid Anti-Solvent Recrystallization. Phasex Corp. Final Rept. to U.S. Army Ballistics Research Laboratory, 1988, Contr. DAAA15-86-C-007. 

Gallagher PM, Coffey MP, Krukonis VJ, Klasutis N. Gas anti-solvent recrystallization new process to recrystallize compounds insoluble in supercritical fluids. In Johnston KP, Penniger JML, eds. Supercritical Fluid Science and Technology. Washington, DC American Chemical Society, 1989 334-354. Dixon D, Johnston KP, Bodmeier R. Polymeric materials formed by precipitation with a compressed fluid antisolvent. AIChE J 1993 39 127-136. Chattopadhyay P, Gupta RB. Production of griseofulvin nanoparticles using supercritical CO2 antisolvent with enhanced mass transfer. Int J Pharm 2001 228 19-31. 

If you have not found a suitable solvent, then you will need to carry out a mixed-solvent recrystallization and you must find out which combination of solvents will be suitable (see Box 13.2). 

Various substituted aromatic compounds can be converted into sulfonyl chlorides by dissolution in five parts of chloroform, dropwise addition of five parts of chlorosulfuric acid at 0°, and keeping for 20 minutes at room temperature. The products are isolated by decomposition with ice, washing of the chloroform layer with water, removal of the solvent, recrystallization of the residue from dry low-boiling light petroleum or from chloroform, and drying in a vacuum over concentrated sulfuric acid. The following benzene-and naphthalene-sulfonyl chlorides were obtained in this way 217... 

At faster rates, the previously reported aL-mosaic formed. Figure 3 shows a field with both forms cocrystallized. The a L-mosaic and airspherulite were identical in DTA and DLI behavior to the solvent-recrystallized crystals. Figure 4 shows the transformation of aL-spherulites into dull ft l-spherulites. On further heating, the (3l phase forms and the crystals brighten somewhat. The extinctions of these crystals correspond to those... 

In Fig. 2, three crystalline modifications of thalidomide are illustrated. These were obtained by solvent recrystallization techniques and differ both in crystal habit and in crystal structure. Two of the forms were obtained from a single solvent, and one from a binary mixture. 

Three crystalline modifications of thalidomide obtained by solvent recrystallization. (A) Form 1 obtained as bipyramids by slow crystallization of thalidomide in 1 1 dimethylformamide ethanol at room temperatnre. 

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