How to Crystallize Organic Compounds: 11 Steps (with Pictures)

2024 Author: Jason Gerald | [email protected]. Last modified: 2023-12-16 10:50

Crystallization (or recrystallization) is the most important method for the purification of organic compounds. The process of removing impurities by crystallization includes dissolving the compound in a suitable hot solvent, cooling the solution and saturating it with the compound being purified, crystallizing the solution, isolating it by filtration, washing its surface with cold solvent to remove residual impurities, and drying.

This procedure is best performed in a controlled chemistry laboratory, in a well-ventilated area. Note that this procedure has a wide range of applications, including large-scale commercial purification of sugar by crystallizing the raw sugar product and leaving the impurities behind.

Step

Step 1. Choose a suitable solvent

Remember the term "like dissolves like" or Similia similibus solvuntur, which means substances with similar structures will dissolve in each other. For example, sugars and salts are soluble in water, not in oil -- and nonpolar compounds such as hydrocarbons will dissolve in nonpolar hydrocarbon solvents such as hexane.

• An ideal solvent has the following properties:

  • Soluble compounds when hot, but do not dissolve when cold.
  • Not dissolving any impurities at all (so that they can be filtered out when an impure compound is dissolved), or dissolving all impurities (so that they remain in solution when the desired compound is crystallized).
  • Will not react with compounds.
  • Cannot burn.
  • Non-toxic.
  • Inexpensive.
  • Very volatile (so it can be easily separated from crystals).

• It is often difficult to determine the best solvent, which is often obtained experimentally, or by using the most nonpolar solvent available. Familiarize yourself with the following list of the most common solvents (from most polar to least polar). Note that solvents that are close together will mix (dissolve each other). The most frequently used solvents are in bold.

  • Water (H₂O) is a non-flammable, non-toxic solvent, and will dissolve many polar organic compounds. The drawback is its high boiling point (100 degrees Celsius), making it relatively nonvolatile and difficult to separate from crystals.
  • Acetic acid (CH₃COOH) is a useful substance for oxidation reactions, but reacts with alcohols and amines, and is therefore difficult to separate (boiling point is 118 degrees Celsius).
  • Dimethyl sulfoxide (DMSO), methyl sulfoxide (CH₃SOCH₃) mainly used as a solvent for reactions, rarely for crystallization. This substance boils at 189 degrees Celsius, and is difficult to separate.
  • Methanol (CH₃OH) is a useful solvent for dissolving various compounds with a higher polarity than other alcohols. Boiling point: 65 degrees Celsius. C.
  • Acetone (CH3COCH3) is a very good solvent, the disadvantage is that it has a low boiling point of 56 degrees Celsius, so the difference in temperature is small in the solubility of the compound at boiling point and room temperature.
  • 2-Butanone, methyl ethyl ketone, MEK (CH₃COCH₂CH₃) is a perfect solvent with a boiling point of 80 degrees Celsius.
  • Ethyl acetate (CH₃COOC₂H₅) is a perfect solvent with a boiling point of 78 degrees Celsius.
  • Dichloromethane, methylene chloride (CH₂Cl₂) useful as a solvent partner with ligroin, but its boiling point of only 35 degrees Celsius is too low to make a good crystallization solvent. However. its freezing point is -78 degrees Celsius. using ice or acetone soap,
  • Diethyl ether (CH₃CH₂OCH₂CH₃) useful as a solvent pair with ligroin, but its boiling point of 40 degrees Celsius is too low to make a good crystallization solvent.
  • Methyl t -Butyl ether (CH₃OC(CH₃)₃) is an inexpensive solvent, a good substitute for diethyl ether due to its higher boiling point, 52 degrees Celsius.
  • Dioxane (C₄H₈O₂) is a substance that is easily separated from crystals, is a mild carcinogen, forms peroxides, and has a boiling point of 101 degrees Celsius.
  • Toluene (C₆H₅CH₃) is a good solvent for crystallization of aryl compounds and has replaced the previously most commonly used benzene compounds (weak carcinogens). The drawback is its high boiling point, 111 degrees Celsius, making it difficult to separate from crystals.
  • Pentane (C₅H₁₂) It is widely used for non-polar compounds, often as a pairing solvent with other solvents. Its low boiling point means this solvent is more useful when used in conjunction with ice or acetone.
  • Hexane (C₆H₁₄) used for non-polar compounds, inert, often used as a solvent pair, boiling point 69 degrees Celsius.
  • Cyclohexane (C₆H₁₂) similar to hexane, but cheaper and has a boiling point of 81 degrees Celsius.
  • Petroleum ether is a saturated hydrocarbon mixture whose main component is pentane, is inexpensive, and can be used interchangeably with pentane. The boiling point is 30-60 degrees Celsius.

  • Ligroin is a saturated hydrocarbon mixture that has the properties of hexane.

    Steps for choosing a solvent:

1. Put a small amount of crystals of the impurity compound in a test tube and add one drop of each solvent, so that it can flow down the side of the test tube.
2. If the crystals in the test tube dissolve immediately at room temperature, reject the solvent because large amounts of the compound will remain soluble at low temperatures. Try a different solvent.
3. If the crystals do not dissolve at room temperature, heat the test tube in a hot sand bath and observe the crystals. Add another drop of solvent if the crystals have not dissolved. If the crystals dissolve at the boiling point of the solvent and crystallize again when cooled to room temperature, you've found the right solvent. If not, try another solvent.

4. If, after the solvent testing process, no satisfactory single solvent is found, use a solvent pair. Dissolve the crystals in the better solvent (a solvent that has been proven to dissolve the crystals), then add the less favorable solvent to the hot solution until it becomes cloudy (the solution is saturated with the solute). Solvent pairs must be mixed with each other. Some useful solvent pairs are acetic acid - water, ethanol - water, dioxane - water, acetone - ethanol, ethanol - diethyl ether, methanol - 2-butanone, ethyl acetate - cyclohexane, acetone - ligroin, ethyl acetate - ligroin, diethyl ether - ligroin, dichloromethane - ligroin, toluene - ligroin.

   

   Step 2. Dissolve the impurity compound

   To perform this procedure, put the compound in a test tube. Crush large crystals with a stirring rod to speed up dissolution. Add the solvent drop by drop. To separate insoluble solid impurities, use excess solvent to dissolve the solution and filter the solid impurities at room temperature (see filtration procedure in step 4), then evaporate the solvent. Before heating, insert the applicator wood into the test tube to avoid superheating (heating the solution above the boiling point of the solution without actually boiling). The air trapped in the wood will come out to form nuclei so that the solution can boil even more. Alternatively, use a perforated porcelain boiling chip. After the solid impurities have been removed and the solvent has evaporated, add the solvent drop by drop while stirring the crystals with a glass stirrer and heating the test tube in steam or sand until the compound is completely dissolved with minimal solvent.

   

   Step 3. Remove the color of the solution

   Skip this step if the solution is colorless or only slightly yellow. If the solution is colored (as a result of the formation of high molecular weight by-products in the chemical reaction), add excess solvent and activated charcoal (carbon), and boil the solution for a few minutes. Colored impurities will be adsorbed onto the activated charcoal surface due to its high degree of microporosity. Separate the charcoal which already contains the adsorbed impurities by filtration, as will be explained in the next step.

   

   Step 4. Separate solids by filtration

   Filtration can be done by gravity filtration, decantation, or separation of the solution using a pipette. In general, do not use vacuum filtration as the solvent will cool down in the process, so the product will crystallize in the filter.

   • Gravity filtration: this is the method of choice for separating fine charcoal, dust, lint, and so on. Take three Erlenmeyer flasks heated on hot steam or on a hot plate: the first contains the solution to be filtered, the second contains several milliliters of solvent and a stemless funnel, while the third contains several milliliters of the crystallizing solution to be used for washing. Place fluted filter paper (used because you are not using a vacuum) on a stemless funnel (no stem so that the saturated solution does not cool and clog the funnel stem with crystals) in the second Erlenmeyer flask. Bring the solution to be filtered to a boil, remove it with a towel, then pour the solution onto the filter paper. Add the boiling solvent from the third Erlenmeyer flask to the crystals formed on the filter paper and to wash the first Erlenmeyer flask containing the filtered solution, add the washer to the filter paper. Remove excess solvent by boiling the filtered solution.
   • Decantation: This method is used for large solid impurities. Pour in the hot solvent, so that the insoluble solids are left behind.
   • Solvent separation by pipette: This method is used for small amount of solution if the solid impurity is large enough. Insert a pipette with a square tip into the bottom of the test tube (circular bottom), then separate the liquid by sucking it in with the pipette. Solid impurities will be left behind.

   

   Step 5. Crystallize the desired compound

   This step is carried out with the assumption that all colored and insoluble impurities have been separated by the appropriate steps described above. Remove any excess solvent by boiling it or gently flowing air. Start with a solution that is saturated with the solute at the boiling point. Let cool slowly to room temperature. Crystallization will begin. Otherwise, start the process by inserting the seed crystals or start in a tube with a glass stirrer at the liquid-air interface. Once the crystallization process has started, do not disturb the container to form large crystals. For slow cooling (to allow larger crystals to form), you can insulate the container with cotton or tissue paper. Larger crystals are easier to separate from impurities. Once the container is fully at room temperature, chill on ice for about five minutes to maximize the number of crystals.

   

   Step 6. Take and wash the crystals

   To perform this procedure, separate the crystals from the ice-cold solvent by filtration. Filtration can be carried out with a Hirsch funnel, a Buchner funnel, or by separating the solvent using a pipette.

   • Filtration with a Hirsch funnel: Place a Hirsh funnel with unflushed filter paper in a tightly closed vacuum flask. Place the filter flask on ice to keep the solvent cool. Wet the filter paper with the crystallizing solvent. Connect the flask to the aspirator, turn on the aspirator, and ensure that the filter paper is pulled down by the vacuum into the funnel. Pour and scrape the crystals into the funnel, and remove the vacuum as soon as the liquid is separated from the crystals. Use a few drops of ice-cold solvent to wash the crystallization flask and pour it into the funnel while reinserting the vacuum, and remove the vacuum as soon as all the liquid has been separated from the crystals. Wash the crystals several times with an ice-cold solvent to remove any remaining impurities. When you're done washing, leave the vacuum on to dry the crystals.
   • Filtration using a Buchner funnel: Place a piece of unflushed filter paper at the bottom of the Buchner funnel and moisten it with solvent. Secure the funnel to the filter flask with a rubber or synthetic rubber matcher to allow vacuum suction. Pour and scrape the crystals into the funnel, then remove the vacuum as soon as the liquid is separated into the flask and the crystals remain on the paper. Wash the crystallization flask with an ice-cold solvent, add to the washed crystals, re-install the vacuum, and remove when the liquid has separated from the crystals. Repeat and wash as many crystals as needed. Leave the vacuum to dry the crystals at the end.
   • Wash using a pipette, this method is used to wash crystals in small quantities. Insert a pipette with a square tip into the bottom of a test tube (rounded bottom), and separate the liquid so that only the washed solid remains.

   

   Step 7. Dry the washed product

   Final drying of small amounts of crystallized product can be accomplished by squeezing the crystals between two pieces of filter paper and drying them on a watch glass.

   Tips

   • If too little solvent is used, crystallization may occur too quickly when the solution is cooled. If the crystallization is too fast, the impurities can be trapped in the crystal, so that the purpose of purification by crystallization is not achieved. On the other hand, if too much solvent is used, crystallization may not occur at all. It's best if you add a little more solvent once it's saturated at the boiling point. Finding the right balance takes practice.
   • When trying to find the ideal solvent through several experiments, start with the lower boiling and more volatile solvents first, as they are easier to separate.
   • Perhaps the most important step is to wait for the hot solution to cool slowly and allow crystals to form. It is very important to be patient and not to touch the solution being cooled.
   • If too much solvent is added so that very few crystals are formed, evaporate some of the solvent by heating and repeat cooling.