There crystallization (or recrystallization) is the most important method for the purification of organic compounds. The process of removing crystallization impurities implies that a compound is dissolved in a suitable hot solvent, that the solution is allowed to cool so that it becomes saturated with the so purified compound, that it crystallizes, isolating it by filtration, that its surface is washed with solvent cold to remove residual impurities and let it dry. Here is a detailed step-by-step guide on how to crystallize organic compounds. The whole process is best done in a controlled chemical laboratory, in a well-ventilated area. Note that this procedure has wide applications, including large-scale commercial purification of sugar by crystallization of the crude product, which leaves impurities behind.
Steps
Step 1. Choose the appropriate solvent
Remember the saying "like dissolve with like": Similia similibus solvuntur. For example, sugar and salt are soluble in water, but not in oil - and non-polar compounds such as hydrocarbons dissolve in non-polar hydrocarbon solvents, such as hexane.
-
The ideal solvent has these properties:
- It dissolves the compound when the solution is hot, but not when the solution is cold.
- It does not dissolve impurities at all (so that they can be filtered out when the impure compound is dissolved) or dissolves them very well (so they remain in solution when the desired compound is crystallized).
- It does not react with the compound.
- It is not flammable.
- It is non-toxic.
- Is cheap.
- It is very volatile (so it can be easily removed from crystals).
-
It is often difficult to decide on the best solvent; the solvent is often chosen by experimentation or by using the most available non-polar solvent. Familiarize yourself with the following list of common solvents (most to least polar). Note that the solvents adjacent to each other are miscible (they dissolve each other). Commonly used solvents are in bold.
- Water (H2O): it is non-flammable, non-toxic, cheap and dissolves many polar organic compounds; the drawback is the high boiling point (100 degrees C), which makes it relatively non-volatile and difficult to remove from the crystals.
- Acetic acid (CH3COOH): it is useful for the oxidation reaction, but it reacts with alcohols and amines and is therefore difficult to remove (the boiling point is 118 degrees C).
- Dimethyl sulfoxide (DMSO), methyl sulfoxide (CH3SOCH3): it is mainly used as a solvent for reactions; rarely for crystallizations.
- Methanol (CH3OH): is a useful solvent that dissolves compounds of higher polarity than other alcohols.
- Acetone (CH3COCH3): it is an excellent solvent; the drawback is the low boiling point at 56 degrees C, which allows little difference in a compound's solubility between its boiling point and ambient temperature.
- 2-Butanone, methyl ethyl ketone, MEK (CH3COCH2CH3): it is an excellent solvent with a boiling point at 80 degrees C.
- Ethyl acetate (CH3COOC2H5): is an excellent solvent with a boiling point at 78 degrees C.
- Dichloromethane, methylene chloride (CH2Cl2): It is useful as a solvent pair with ligroin, but its boiling point, 35 degrees C, is too low to make it a good crystallization solvent.
- Diethyl ether (CH3CH2OCH2CH3): It is useful as a solvent pair with ligroin, but its boiling point, 40 degrees C, is too low to make it a good crystallization solvent.
- Methyl-t-butyl ether (CH3OC (CH3) 3): it is an optimal and convenient choice that replaces diethyl ether, given its higher boiling point, 52 degrees centigrade.
- Dioxane (C4H8O2): it is easy to remove from the crystals; slightly carcinogenic; forms peroxides; boiling point at 101 degrees C.
- Toluene (C6H5CH3): it is an excellent solvent for the crystallization of aryls and has replaced benzene (a weak carcinogen), which was once commonly used; a drawback is the high boiling point at 111 degrees C, which makes it difficult to remove it from the crystals.
- Pentane (C5H12): it is widely used for non-polar compounds; often used as a solvent paired with another.
- Hexane (C6H14): it is used for non-polar compounds; inert; often used in a pair of solvents; boiling point at 69 degrees C.
- Cyclohexane (C6H12): it is similar to hexane, but cheaper and has a boiling point of 81 degrees C.
- Petroleum ether is a mixture of saturated hydrocarbons, of which pentane is a main component; cheap and used interchangeably with pentane; boiling point at 30-60 degrees C.
-
Ligroin is a mixture of saturated hydrocarbons with hexane properties.
Steps for choosing the solvent:
- Put a few crystals of the impure compound in a test tube and add a single drop of solvent, letting it flow down the side of the tube.
- If the crystals dissolve immediately at room temperature, do not use the solvent as much of the compound will dissolve at a low temperature - look for another.
- If the crystals do not melt at room temperature, heat the tube on a hot sand bath and observe the crystals. If they don't dissolve, add an extra drop of solvent. If they dissolve at the boiling point of the solvent and then crystallize again when cooled to room temperature, you have found a suitable solvent. If not, try another solvent.
-
If, after a trial and error process, you have not found a satisfactory solvent, you will do well to use a pair of solvents. Dissolve the crystals in the best solvent (the one in which they dissolved readily) and add the poorer solvent to the hot solution until it becomes cloudy (the solution is saturated with solute). The solvent pair must be miscible with each other. Some acceptable solvent pairs are water-acetic acid, ethanol-water, acetone-water, dioxane-water, acetone-ethanol, diethyl ether-ethanol, methanol-2Butanone, cyclohexane-ethyl acetate, acetone-ligroin, ligroin-acetate di ethyl, ethyl ether-ligroin, dichloromethane-ligroin, toluene-ligroin.
Crystallize Organic Compounds Step 2 Step 2. Dissolve the impure mixture:
to do this, put it in a test tube. Crush the large crystals with a rod to help dissolve. Add the solvent drop by drop. To remove solid, non-soluble impurities, use the excess solvent to dilute the solution and filter the solid impurities at room temperature (see step 4 for the filtration procedure), then evaporate the solvent. Before heating, put a wooden stick in the tube to prevent overheating (the solution will be heated above the boiling point of the solvent without actually being boiling). The air trapped in the wood will come out in the form of cores to also allow boiling. Alternatively, hot porous porcelain shards can be used. Once the solid impurities have been removed and the solvent evaporated, add a little, drop by drop, mixing the crystals with a glass rod and heating the tube on a steam or sand bath, until the mixture is completely dissolved with the minimum amount of solvent.
Crystallize Organic Compounds Step 3 Step 3. Decolor the solution
Skip this step if the solution is colorless or has only a slight shade of yellow. If the solution is colored (resulting from the production of byproducts of high molecular weight chemical reactions), add excess solvent and activated carbon (carbon) and boil the solution for a few minutes. The colored impurities adsorb on the surface of the activated carbon, due to its high microporosity. Remove the charcoal with the adsorbed impurities by filtration, as described in the next step.
Crystallize Organic Compounds Step 4 Step 4. Remove solids by filtration
Filtration can be done by gravity filtration, decantation or solvent removal using a pipette. In general, do not use vacuum filtration, as the hot solvent cools during the process, allowing the product to crystallize in the filter.
- Gravity Filtration: This is the method of choice for removing fine carbon, lint, dust, etc. Take three Erlenmeyer flasks heated on a steam bath or hot plate: one containing the solution to be filtered, another containing a few milliliters of solvent and a stemless funnel, and the last with several milliliters of crystallization solvent to use for rinsing. Place a fluted paper filter (useful since the aspirator is not used) in a stemless funnel (to prevent the saturated solution from cooling and clogging the stem with crystals) above the second flask. Bring the solution to be filtered to a boil, grab it in a napkin and pour the solution into the paper filter. Add boiling solvent from the third flask to the crystals formed on the filter paper and rinse the flask that contained the filtered solution, adding the rinse for the filter paper. Remove excess solvent by boiling the filtered solution.
- Decanting: it is used for large solid impurities. You simply have to pour (decant) the hot solvent, leaving out the insoluble solids.
- Removal of solvent using a pipette: is used for a small amount of solution and if the solid impurities are large enough. Insert a square-tipped pipette into the bottom of the tube (rounded bottom) and remove the liquid by aspiration, leaving solid impurities.
Crystallize Organic Compounds Step 5 Step 5. Crystallize the compound that interests you
This step assumes that any colored and insoluble impurities have been removed with the previous processes. Remove any excess boiling solvent or blow with a gentle stream of air. Start with a solution saturated with a boiling solute. Let it cool slowly to room temperature. Crystallization should begin. Otherwise, start the process by adding a crystal seed or scrape the inside of the tube with a glass rod in the air-liquid area. Once crystallization has begun, be careful not to move the container to allow the formation of large crystals. To facilitate slow cooling (which allows the formation of larger crystals), the container can be insulated with cotton or absorbent paper. Larger crystals are easier to separate from impurities. Once the container is completely cooled to room temperature, place it on ice for about five minutes to maximize the amount of crystals.
Crystallize Organic Compounds Step 6 Step 6. Collect and wash the crystals:
to do this, separate them from the freezing solvent by filtration. This can be done using the Hirsch funnel, the Buchner funnel or by removing some solvent using a pipette.
- Filtration using the Hirsch funnel: Place the Hirsch funnel with non-grooved filter paper in a tightly mounted isothermal aspirator container. Put the filter flask on ice to keep the solvent cold. Wet the filter paper with the crystallization solvent. Hook the flask to a vacuum cleaner, start it up and make sure the filter paper is drawn into the funnel. Pour and scrape the crystals on the funnel and stop aspiration as soon as all the liquid is removed from the crystals. Use a few drops of frozen solvent to rinse the crystallization flask and put it back on the funnel while reapplying the suction; stop it as soon as all the liquid is removed from the crystals. Wash them a couple of times with freezing solvent to remove any residual impurities. At the end of the wash, leave the aspirator running to dry the crystals.
- Filtration using the Buchner funnel: Insert a piece of non-grooved filter paper into the bottom of the Buchner funnel and wet it with solvent. Insert the funnel tightly against an isothermal filter vessel via a rubber or synthetic rubber adapter to allow for vacuum suction. Pour and scrape the crystals on the funnel, and stop aspiration as soon as the liquid is removed from the flask, when the crystals are left on the paper. Rinse the crystallization flask with frozen solvent, adding it to the washed crystals, reapply the aspirator and stop it when the liquid is removed from the crystals. Repeat and wash the crystals as many times as necessary. Leave the aspirator on to dry the crystals at the end.
- Wash using a pipette: it is used to wash small amounts of crystals. Insert a square-tipped pipette into the bottom of the tube (rounded bottom) and remove the liquid, leaving the washed solids behind.
Crystallize Organic Compounds Step 7 Step 7. Dry the washed product:
the final drying of a small amount of crystallized product can be done by pressing the crystals between sheets of filter paper and allowing them to dry on a watch glass.
Advice
- If too little solvent is used, crystallization can occur too quickly when the solution is cooled. When crystallization occurs too quickly, impurities can become trapped in the crystals, which thwarts the purpose of crystallization purification. On the other hand, if too much solvent is used, crystallization may not occur at all. It is best to add just a little more solvent beyond the saturation at the boiling point. Finding the right balance takes practice.
- When trying to find the ideal solvent by trial and error, start with the more volatile, low-boiling solvents in the first place, because they can be removed more easily.
- If you add too much solvent and small crystals form during cooling, you need to evaporate some solvent by heating and repeating the cooling.
- Perhaps the most important step is to wait for the boiling solution to slowly cool and allow the crystals to form. It is extremely important to be patient and let the solution cool down undisturbed.
