Why does crystallization fail

Figure 3. The oily acetanilide droplets appear more colored than the solution, indicating a higher quantity of dissolved methyl red impurity. If an oiled out liquid eventually solidifies, it often forms an impure glass-like non-crystalline solid. The reasons for oiling out are several, and it can happen while dissolving the solid and during crystallization.

It may be that the melting point of the solid is naturally low. It may also be that a solid is so impure that its melting point is dramatically lowered as impurities lower the melting point.

If either of these methods fail, recover the crude solid by rotary evaporation and attempt another crystallization. If the failed attempt used a mixed solvent, try a single solvent if possible. Or choose another solvent with similar solubility properties, but with a lower boiling point. For example, if ethanol were used as the solvent the first time, repeat the crystallization using methanol. Methanol has similar solubility properties as ethanol, but its lower boiling point may allow for the solid to come out of solution above its melting point.

Lisa Nichols Butte Community College. Complete text is available online. Crystallization is Too Quick Rapid crystallization is discouraged because impurities tend to become incorporated into the crystal, defeating the purpose of this purification technique. Although more compound will dissolve in the mother liquor, the compound will stay soluble longer once set aside to cool. For example, in the crystallization of trans -cinnamic acid with a mixed solvent of methanol and water, use of the minimum amount of hot solvent to dissolve the solid Figure 3.

To remedy this problem, the solid was placed back on the steam bath, additional methanol soluble solvent was added, brought to a boil to dissolve the solid, and then cooled. The solid then began to crystallize much more slowly Figure 3.

A shallow solvent pool has a high surface area, which leads to fast cooling. Transfer the solution to a smaller flask using some solvent to rinse the flask, and then boil away the same amount of solvent used for rinsing and repeat the crystallization.

Be sure to use a watch glass over the top of the Erlenmeyer flask to trap heat, and set the flask atop some material to insulate the bottom several paper towels, a wood block, or cork ring. An inverted beaker could also be tried to create an insulating atmosphere around the cooling flask. Crystallization Doesn't Happen It can be quite frustrating to set aside the dissolved solution to cool and have no crystals form at all.

The yellow impurities present in the crude compound have been removed, yielding an off-white solid. Based on the identity of the compound and the impurities, the purity of the crystals can be verified by NMR spectroscopy, melting point measurements, or visual inspection.

X-ray crystallography is a powerful characterization technique that identifies the three-dimensional atomic structure of a molecule. This requires a pure single crystal, which is obtained by recrystallization. Some classes of molecules such as proteins are difficult to crystallize, but their structures are extremely important for understanding their chemical functions. With careful selection of recrystallization conditions, even these classes of molecules can be analyzed by X-ray crystallography.

To learn more about this process, see this collection's video on growing crystals for crystallography. Impure reactants can cause unwanted side reactions. Purifying reactants by recrystallization improves product purity and yield. Once a solid product has been isolated and washed, reaction yield can also be increased by removing volatiles from the filtrate and recrystallizing the product from the resulting solid. Antifreeze proteins, or AFPs, are expressed in many organisms that live in icy environments.

AFPs hinder internal ice growth by binding to ice planes, inhibiting recrystallization into larger ice crystals. Different AFPs bind to different types of ice crystal planes. Investigating AFP binding mechanisms involves adsorbing them onto single ice crystals. Proper growth of a single ice crystal is essential for clear and informative results.

These proteins have applications from the engineering of cold-resistant crops to cryosurgery. You've just watched JoVE's introduction to purifying compounds by recrystallization.

You should now be familiar with the principles of the technique, a purification procedure, and some applications of recrystallization in chemistry. An example of the results of recrystallization is shown in Figure 2. The yellow impurities present in the crude compound have been removed, and the pure product is left as an off-white solid. The purity of the recrystallized compound can now be verified by nuclear magnetic resonance NMR spectroscopy or, if it is a compound with a published melting point, by how similar its melting point is to the literature melting point.

If necessary, multiple recrystallizations can be performed until the purity is acceptably high. Figure 2. Recrystallization is a method of purifying a compound by removing any impurities that might be mixed with it. It works best when the compound is very soluble in a hot solvent, but very insoluble in the cold version of the same solvent.

The compound must be a solid at room temperature. Recrystallization is often used as a final clean-up step, after other methods such as extraction or column chromatography that are effective at removing larger amounts of impurities, but that do not raise the purity of the final compound to a sufficiently high level.

Recrystallization is the only technique that can produce absolutely pure, perfect single crystals of a compound. These crystals can be used for X-ray analysis, which is the ultimate authority in determining the structure and three-dimensional shape of a molecule.

In these cases, the recrystallization is allowed to proceed very slowly, over the course of weeks to months, to allow the crystal lattice to form without the inclusion of any impurities. Special glassware is needed to allow the solvent to evaporate as slowly as possible during this time, or to allow the solvent to very slowly mix with another solvent in which the compound is insoluble called antisolvent addition. The pharmaceutical industry also makes heavy use of recrystallization, since it is a means of purification more easily scaled up than column chromatography.

These different crystal forms might have different biological properties or be absorbed into the body at different rates. A more common use of recrystallization is in making rock candy. Rock candy is made by dissolving sugar in hot water to the point of saturation. Wooden sticks are placed into the solution and the solution is allowed to cool and evaporate slowly. After several days, large crystals of sugar have grown all over the wooden sticks.

Mayo, D. Armarego, W. Ray, P. Google Patents: Hightower, T. Journal of Chemical Education 83 11 , Rohani, S. Organic Chemistry. Purifying Compounds by Recrystallization. To learn more about our GDPR policies click here. If you want more info regarding data storage, please contact gdpr jove. Your access has now expired. Provide feedback to your librarian.

If you have any questions, please do not hesitate to reach out to our customer success team. Login processing Previous Video Next Video. Overview Source: Laboratory of Dr. Jimmy Franco - Merrimack College Recrystallization is a technique used to purify solid compounds.

Perform all steps in a fume hood to prevent exposure to solvent fumes. Selecting a Solvent Place 50 mg of the sample N-bromosuccinimide in an Erlenmeyer flask. If the sample dissolves completely, the solubility in the cold solvent is too high to be a good recrystallization solvent. If the sample does not dissolve in the cold solvent, heat the test tube until the solvent boils. If the sample has not completely dissolved at this point, add more boiling solvent drop-wise, until all of the solid dissolves.

If it takes more than 3 mL to dissolve the sample in the hot solvent, the solubility in this solvent is probably too low to make it a good recrystallization solvent.

If the first choice of solvent is not a good recrystallization solvent, try others. If a single solvent that works cannot be found, try a two solvent system. If you cannot find a suitable single solvent system, then a solvent pair may be necessary. When identifying a solvent pair, there are several key considerations 1 The first solvent should readily dissolve the solid. See Figure 2. Obtain the crystals from the solute : The purer crystals precipitated from the solute are the desirable part of the mixture, and so they must be removed from the solvent.

The process used for isolating the crystals that remain in the beaker still is called vacuum filtration. Suction is created using an aspirator, and whatever remains in the beaker is poured though a Buchner funnel. If for some reason there are no crystals visible, a gravity filtration can be performed. Activated carbon is added to the solution, the mixture is boiled, and a funnel system is used to transfer the new mixture to a new beaker of boiling solvent.

Filter paper is used in the funnel to remove excess carbon. After this mixture cools slowly there should be large crystals present. Dry the resulting crystals: The crystals are dried by leaving them in the aspirator and then by removing them to a glass dish to wait a while longer. The purity of the crystals can be tested by performing a "melting point determination". Introduction An impure compound is dissolved the impurities must also be soluble in the solvent , to prepare a highly concentrated solution at a high temperature.

Note Recrystallization works best when the quantity of impurities is small the solubility curve of the desired solute rises rapidly with temperature. Procedure These are the important steps to the recrsytallization process. See Figure 1 Cool the Solution: The solution is cooled in open air first, and then cooled in an ice bath.