Recrystallization mixed solvent

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 ). 

If, after sufficient agony, you cannot find a single solvent to recrystallize your product from, you may just give up and try a mixed-solvent system. Yes, it does mean you mix more than one solvent, and recrystallize using the mixture. It should only be so easy. Sometimes, you are told what the mixture is and the correct proportions. Then it is easy. 

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... 

Every silver lining has a cloud. More often than not, compounds recrystallized from a mixed-solvent system don t form crystals. Your compound may form an oil instead. 

Preparation of various enantiomerically pure sulfoxides by oxidation of sulfides seems feasible in the cases where asymmetric synthesis occurs with ee s in the range of 90% giving crystalline products which can usually be recrystallized up to 100% ee. Aryl methyl sulfides usually give excellent enantioselectivity during oxidation and are good candidates for the present procedure. For example, we have shown on a 10-mmol scale that optically pure (S)-(-)-methyl phenyl sulfoxide [a]p -146 (acetone, o 1) could be obtained in 76% yield after oxidation with cumene hydroperoxide followed by flash chromatographic purification on silica gel and recrystallizations at low temperature in a mixed solvent (ether-pentane). Similarly (S)-(-)-methyl o-methoxyphenyl sulfoxide, [a]p -339 (acetone, o 1.5 100% ee measured by HPLC), was obtained in 80% yield by recrystallizations from hexane. 

A solution of sodium hydroxide (173 g) dissolved in water (867 g) was treated with the dropwise addition of e-caprolactone (150 g) and then stirred at ambient temperature for 5 hours. The mixture was then neutralized with 6M hydrochloric acid, extracted with ethyl acetate, and the organic layer washed with water. The organic layer was dried using MgS04 and concentrated. The residue was recrystallized from mixed solvents consisting of tetrahydrofuran (TH) and heptane and 106.47 g of product isolated. 

The reaction flask is removed from the oil bath, and the solution is poured into a 250-ml. beaker to crystallize 10 ml. of benzene is used to rinse out the flask. When crystallization sets in, 50 ml. of petroleum ether (b.p. 35-55°) is added to the warm mixture with manual stirring. After the mixture has been chilled in an ice bath, the product is filtered by suction and washed with 100 ml. of a 1 1 petroleum ether-benzene mixture. It is then removed from the funnel, stirred into a slurry with 100 ml. of the mixed solvent, filtered, and again washed with 50 ml. of the solvent. These washings remove the bulk of the color, and a powdery white product remains. After standing overnight in a warm place, the product weighs 35.5-36.5 g. (74-76%) and melts at 104-105°. It may be purified further by recrystallization from benzene (3.7 ml. per g.). The yield of colorless benzoylacetanilide melting at 106-106.5° cor. is 32-34 g. 

Purification of complexes is most easily achieved by recrystallization. Most workers have used the mixed solvent approach. The compound is dissolved in one solvent and a second solvent, in which the complex is insoluble but which is miscible with the first, is added. Success depends on a number of factors, one being how badly the product is contaminated. Several repetitions may be necessary. While chromatography has been used in a number of instances, we generally prefer recrystallization as being less time consuming. 

A mixture of 2.0 g of l-(2-nitro-3-chlorophenyl)-l,3-butanedione, 1.9 g of diethyl aminomalonate, 1.5 ml of absolute ethyl alcohol and two drops of piperidine was refiuxed for 5 hours. After cooling, the reaction mixture was allowed to stand and then crystals were separated. The crystals were collected by filtration and then dried to obtain 2.5 g of colorless crystals. The crystals were recrystallized from a mixed solvent of benzene and ether to obtain diethyl N-[ 1-methyl-3-(2-nitro-3-chlorophenyl)-3-... 

HC1. The aqueous extracts were pooled, washed with CH2CI2, and made basic by the addition of 25% NaOH. The precipitate that formed was extracted into several small portions of CH2CI2 which were pooled and dried with anhydrous Na2S04. After removal of the drying agent, the solvent was removed under vacuum. To the residue there was added a 1.0 M solution of HC1 in anhydrous Et20 until the mixture was neutral, as determined by external, damp pH paper. The resulting solid was removed by filtration and twice recrystallized from aMeOH/acetone mixed solvent. There was thus obtained N,N-diethyl-2-methyltryptamine hydrochloride (2-Me-DET) as white crystals with a mp 214-216 °C. 

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). 

Usin mixed solvents for recrystallization - never assume that a mixed solvent system is a mixture of equal volumes of the two solvents.-The ratio of the two solvents is established practically during the recrystallization experiment. 

When no single solvent is found to be suitable for recrystallization, then a mixed solvent system must be used. There are three essential properties required for a pair of solvents to be used in a mixed-solvent system ... 

Suitable common solvent pairs from the solvents given in Table 13.1 are water/ethanol and dichloromethane/light petroleum (b.pt. 40-60 °C), but many other combinations are possible. One of the most frequently encountered mixed solvent systems is aqueous ethanol (water/ethanol) in which the compound to be recrystallized is insoluble in water and very soluble in ethanol. 

Box 13.2 How to carry out a mixed-solvent selection for recrystallization of an unknown compound... 

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. 

To recrystallize the caffeine dissolve it in 5 mL of hot acetone, transfer it with a Pasteur pipette to a small Erlenmeyer flask, and, while it is hot, add ligroin to the solution until afaint cloudiness appears. Set the flask aside and allow it to cool slowly to room temperature. This mixed solvent method of recrystallization depends on the fact that caffeine is much more soluble in acetone than ligroin, so a combination of the two solvents can be found where the solution is saturated in caffeine (the cloud point). Cool the solution containing the crystals and remove them by vacuum filtration, employing the Hirsch funnel or a very small Buchner funnel. Use a few drops of ligroin to transfer the crystals and wash the crystals. If you wish to obtain a second crop of crystals, collect the filtrate in a test tube, concentrate it to the cloud point using the aspirator tube (Fig. 5 in Chapter 3), and repeat the crystallization process. 

If the unknown substance is not pure or is mixed with other components, separation of the compound from the matrix may be required. However, in many cases mixtures may be characterized. The compound can be purified by recrystallization, distillation, solvent-partitioning, pH manipulation, or chromatographic separation. Once the appropriate separation procedures have been completed, the purified unknown can undergo the structural characterization steps described above. 

Briefly, several methods have proved successful in providing X-ray-grade organomagnesium crystals. These methods include slow sublimation, recrystallization from nonpolar solvents (alkanes or toluene), and mixed solvent systems in which a nonpolar... 

The syrupy 33 was dissolved in a mixed solvent of diethyl ether and ethyl acetate (lO.T), and the solution was kept at -70 °C for about 5 h. In this case, no seed crystals of optically pure (8aI )-(-)-33 were needed. Crystals deposited were collected by filtration to yield enantiomerically enriched 33 [a]o -95.8° (c 1.10, benzene). The crystals obtained were further enantiomerically purified by two additional recrystallizations, to give optically pure (8a/ )-(-)-33 mp 50.5-51.0 °C, [a]o -98.96° (c 1.039, benzene). We carried out the preparation of optically pure (8a/f)-(-)-33 with this procedure three times, and all gave satisfactory results. 

Purification and characterization The crude NHS esters were recrystallized to a constant melting from either chloroform-hexane or chloroform-acetone mixed solvents. Product purity was confirmed by proton nuclear magnetic resonance using a GE QE 300 spectrometer. 

The crude product from step 10 above is purified by dry column flash chromatography. cf gnj then by recrystallization from a mixed solvent of petroleum ether and ethyl acetate (1 1 ) to yield colourless crystals (m.p. SY-eOT). 

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). 

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