PsycheLogics
Rising Star
Hey all, I found this at the shroomery and thought it would be useful to folks here: [quote:90d74f389e] I decided to make this post because I've seen several posts in my career here regarding extractions and the yielding of impure crystals or dirty looking crystals. Often the suggestion is made by the learned to recrystallize the crystals. I sometimes wonder if those receiving the advice know what to do or how to do it. I often speculate that the person receiving the advice is just dissolving in and evaporating off the solvent and not actually carrying out a recrytsallization. Therefore I'm making this post to clear up any misconceptions one might have. Background Information On both a large and small scale crystallization is the most important method for the purificatino of solid organic compounds. A crystalline organic substance is made up of a three-dimensional array of molecules held together primarily by Van der Waals forces. These intramolecular attractions are fairly weak; most organic solids melt in the range of roomt tmperature to 250C. Crystals can be grown from the molten state just as water is frozen into ice, but it is not easy to remove impurities from crystals made in this way. Most purifications in the laboratory involve dissolving the material to be purified in the appropriate hot solvent. As the solvent cools, the solution becomes saturated with respect to the substance, which then crystallizes. As the perfectly regular array of crystal is formed, foriegn molecules are excluded, and the crystal is thus one pure substance. Soluble impurities remain in solution becuase they are not concentrated enough to saturate the solution. The crystals are collected by filtration, the crystals are washed with cold solvent to remove the adhering impurities, and then the crystals are dried. This process is carried out on an enormous scale in commercial purification of sugar. When working with crystallization you will have to judge the solvent or the solvent pair to used based on knowledge of the compounds that are within your extractiont mix. The Seven Steps of Crystallization * Choosing the Solvent and the solvent pairs. * Dissolving the solute. * Decolorizing the solution. * Filtering suspended solids. * Crystallizing the solute. * Collecting and washing the crystals. * Drying the product 1. Choosing the Solvent and Solvent Pairs In Choosing the solvent the chemist is guided by the dictum "likes dissolve likes." Even the non-chemist knows that oil and water do not mix and that sugar and salt dissolve in water but not in oil. Hydrocarbon solvents such as hexane will dissolve hydrocarbons and other nonpolar compounds, and hydroxylic solvents such as water and ethanol will dissolve polar compounds. Often it is difficult to decide, simply by looking at the structure of a molecule, just how polar or nonpolar it is and which solvent would be best. Therefore, the solvent is often chosen by experimentation. The best crystallization solvent (and none is ideal) will dissolve the solute when the solution is hot but not when the solution is cold; it will either not dissolve the impurities at all or it will dissolve them very well (so they won't crystallize out along with the solute); it will not react with the solute; and will be nonflammable, nontoxic, inexpensive, and very volatile (so it can be removed from the crystals). Some common crystallization solvents are: Water - BP: 100C - The solvent is cheap, nonflammable, and nontoxic and will dissolve a large variety of polar organic molecules. Its high boiling point and high heat of vaporization make it difficult to remove from crystals. Vinegar - BP: 118C - Will react with alcohols and amines. Difficult to remove from crystals. Not a common solvent for recrystallizations, although used as a solvent when carrying out oxidation reactions. Dimethyl Sulfoxide (DMSO) - BP: 189C - Also not a commonly used solvent for crystallization but used for reactions. Methanol - BP 63C - A very good solvent, used often for crystallization. Will dissolve molecules of higher polarity than will the other alcohols. 95% Ethanol - BP: 78C - One of the most commonly used crystallization solvents. It's high boiling point makes it a better solvent for the less polar molecules than methanol. Evaporates readily from the crystals. Esters may undergo interchange of alcohol groups or recrystallize. Acetone - BP: 56C - An excellent solvent, but its low boiling point means there is not much difference in solubility of a compound at its boiling point and at room termperature. Methyl ethyl ketone (MEK) - BP: 80C - An excellent solvent with many of the most desirable properties of a good crystallization solvent. Ethyl acetate - BP: 78C - Another excellent solvent that has about the right combination of moderately high boiling point and yet the volatility needed to remove it from crystals. Dichloromethane (methylene chloride) - BP: 40C - Although a common extraction solvent, dichloromethane boils too low to make a good crystallization solvent. It is useful in a solvent pair with ligroin Diethyl ether (ether) - BP: 35C - Its boiling point is too low for crystallization, although it is an extremely good solvent and fairly inert. Used in solvent pair with ligroin. Toluene - BP: 111C - An excellent solvent that has replaced the formerly widely used benzene (A weak carcinogen) for crystallization of aryl compounds. Because of its boiling point it is not easily removed from crystals. Pentane - BP: 46C - A widely used solvent for nonpolar substances. not often used alone for crystallization, but good in combination with a number of other solvents as part of a solvent pair. Hexane - BP: 69C - Frequently used to crystallize nonpolar substances. It is inert and has the correct balance between boiling point and volatility. Often used as part of a solvent pair. See ligroin. Cyclohexane - BP: 81C - Similar in all respects to hexane. See ligroin. Petroleum ether BP: 30 - 60C - A mixture of hydrocarbons in which pentane is a cheif component. Used interchangeable with pentane because it is cheap. Unlike diethyl ether or t-butyl methyl ether, it is not an ether in the modern chemical sense. Ligroin - BP: 60 - 90C - A mixture of hydrocarbons with the properties of hexane and cyclohexane. A very commonly used crystallization solvent. Also sold as "hexanes." * Ordered in decreasing polarity Each solvent that is similar in chemical structure will be miscible with each other. These solvents are used both for crystallization and as solvents in which reactions are carried out. How to Do it: To choose a solvent for crystallization, place a few crystals of the impure solute in a small test tube, and add a very small drop of the solvent. Allow it to flow down the side of the tube and onto the crystals. If the crystals dissolve instantly at room temperature, the solvent cannot be used for crystallization because too much of the solute will remain in solution at low temperatures. If the crystals do not dissolve at room temperature, warm the tube on a hot sand bath, and observe the crystals. If the do not go into solution, add a drop more solvent. If the crystals go into solution at the boiling point of the solvent and then crystallize when the tube is cooled, you have found a good crystallization solvent. If not remove the solvent by evaporation, and try a different solvent. In this trial and error process it is easiest to try low-boiling solvent first, because they can be removed most easily. Ocassionally no single satisfactory solvent can be found, so mixed solvents or solvent pairs, are used. 2. Dissolving the Solute Once a crystallization solvent has been found, the impure crystals are placed in an Erlenmeyer flask (never use a beaker), add enough solvent to cover the crystals, and then heat the flask on a steam bath (if the solvent boils below 90C) or a hot plate/sand bath until the solvent boils. Stir the mixture or, better, swirl it to promote dissolution. Add solvent gradually, keeping it at the boil, until all of the solute dissolves. Addition of a boiling stick or a boiling chip to the solution once most of the solid is gone will promote even boiling. It is not difficult to superheat the solution (therefore use the boiling stick/chip!). Never add the boiling chip or stick to a hot solution. A glass rod with a flattened end can sometimes be of use in crushing large particles of solute to speed up the dissolving process. Do not work with nearby flames when using flammable solvents. Becareful not to add too much solvent. Note how rapidly most of the material dissolves, and then stop adding solvent when you suspect that almost all of the desired material has dissolved. It is best to err on the side of too little solvent rather than too much. Undissolved material noted at this point could be an insoluble impurity that never will dissolve. Allow the solvent to boil, and if on further material dissolves, proceed to Step 4 to remove suspended solids from the solution by filtration, or if the solution is colored go to Step 3 to carry out the decolorizing process. If the solution is clear proceed to Step 5, Crystallizing the Solute. 3. Decolorizing the Solution The vast majority of pure organic chemicals are colorless or a light shade of yellow and consequently this step is not often required. Occasionally a chemical reaction will produce high molecular weight by-products that are highly colored. The impurities can be adsorbed onto the surface of activated charcoal by simply boiling the solution with charcoal. Activated charcoal has an extremely large surface area per gram (several hundred square meters) and can bind a large number of molecules to this surface. On an extremely large commercial scale such as the refining of sugar, activated charcoal is used to adsorb the impurities and color from brown sugar in the refining process of sugar. Powdered activated charcoal is often used to decolorize the solution. However it can only be separated from the solution through filtration with filter paper and it often obscures the color of the solution making determining how much charcoal to use impossible, the users of powdered activated charcoal often have to repeat this step twice to get all the color. Pelletized activated charcoal is best. It is often sold as .8 x 3mm cylindrical pieces. The most popular brand is Norit. It works just as well as finely divided powder, and it doe snot obscure the color of the solution. It can be added in small portions until the solution is decolorized and the size of the pieces makes it easy to remove them from solution (just pick them out). To decolorize add a small amount (about .1% of the total solute weight is sufficient) of the charcoal to solution and then boil the solution for a few minutes. Be careful not to add the charcoal pieces to a superheated solution, it will cause the solution to boil over. Remove the charcoal either by picking it out or by filtration. 4. Filtering Suspended Solids The filtration of a hot, saturated solution to remove solid impurities or charcoal can be performed in a number of ways. Processes incloude gravity filtration, pressure filtration, decantation, or removal of the solvent using a pastuer pipette. Vacuum filtration is not used because hot solvent will cool during the process and the product will crystallize in the filter. This can be one of the most frustrating processes if during the filtration process the desired compound crystallizes. Test the solution or a small portion of it before filtration to ensure that no crystals form at room temperature. Like decolorization with charcoal the removal of solid impurities by filtration is usually not necessary. Though one may find it neccessary if the desired product is the result of an extraction from plant matter. 5. Crystallizing the Solute The crystallization process should normally start from a solution that is saturated with the solute at the boiling point. If it has been necessary to remove impurities or charcoal by filtration, the solution has been diluted. To concentrate the solution, simply boil off the solvent or blow off the solvent using a gentle stream of air. Be sure to have a boiling chip/stick in place during the process but do not forget to remove it before initiating crystallization. Once it's been ascertained that the hot solution is saturated with the compound just below the boiling point of the solvent, it is allowed to cool slowly to room temperature. Crystallization shold begin immediately. If it does not, add a seed crystal or scratch the inside of the vessel with a glass rod at the liquid-air interface. Crystallization must start on some nucleation center. A minute crystal of the desired compound saved from the crude material will suffice. If a seed crystal is not available, crystallization can be started on the rough surface of a fresh scratch on the inside of the container. Once it is ascertained that crystallization has started, the soloution must be cooled slowly without disturbing the container so that large crystals can form. It's best to insulate the hot flask with bath towels. Slow cooling will guarantee the formation of large crystals, which are easily separated by filtration and easily washed free of adhering impure solvent. Cooling maximizes the amount of solute that crytsallizes out of solution. 6. Collecting and Washing the Crystals Once crystallization is complete, the crytsals must be separated from the-ice cold mother liquor, washed with ice-cold solvent, and dried. The best way to separate and dry somewhat, is to do it under vacuum filtration. This can be done with either a Buchner Funnel or Hirsch Funnel, or just a Gravity Filter with a fluted filter paper and a watch glass on which to dry the crystals. 7. Drying the Product Once the crystals have been washed on the funnels, press them down with a clean cork or other flat object and allow air to pass through them until they are substantially dry. Final drying can be done under reduced pressure (crytsals in flask with rubber stopper with glass tubing port connected to vacuum). The crystals can then be turned out of the funnel and squeezed between sheets of filter paper to remove the last trace of solvent before final drying on a watch glass. Extra Considerations:Crystallization Problems and Their Solutions * No Crystals Form: Induction of Crystallization Occasionally a sample will not crystallize from solution on cooling, even though the solutoin is saturated with the solute at elevated temperature. The easiest method for inducing crystallization is to add to the supersaturated solution a seed crystal that has been saved from the crude material (if it was crystalline before recyrstallization was attemped). There is a sort of old wive's tale about the great sugar chemist Emil Fischer who merely had to wave his beard over a recalicitrant solution and the appropriate seed crystals would drop out, causing crystallization to occur. In the absence of seed crystals, crystallization can often be induced by scratching the inside of the flask with a stirring rod at the air/liquid interface. One theory is that part of the freshly scratched glass surface has angles and planes corresponding to the crystal structure, and crystals start growing on these spots. Crystallization is often very slow to begin. Placing the sample in a refrigerator overnight will bring success. Other expedients are to change the solvent (usually to a poorer one) and to place the sample in an open container where slow evaporation and dust from the air may help induce crystallization. * If your solution separates as an oil: Oils and "Oiling Out" Some saturated solutions - especially those containing water- when cooled deposit not crystals but small droplets referred to as oils. "Oiling out" occurs, of necessity, when the temperature of the solution is above the melting point of the crystals. If these droplets solidfy and are collected they will be found to be quite impure. Ths simplest remedy for this problem is to lower the temperature at which the solution becomes saturated with the solute by simply adding more solvent. In extreme cases it maybe necessary to lower this temperature bell below room temperature by cooling the solution with dry ice. If oiling out persists use another solvent (N,N-DMT and 5-MeO-DMT melt at temperatures below 100C [the BP of Water], thus water can't be used as a solvent for DMT and 5-MeO-DMT recrystallization). However! In fitting with the context of this forum. Oiling out is most likely the result of adhesion of base to the impure crystals. This is quite common and happens quite frequently with acid/base extraction seeking alkaloids, as the last step of the actual chemical extraction is adding base. Thus for the purposes assumed oiling out can be remedied in the final steps of the Acid/Base Extraction.. To avoid this:There will be some left over base adhering to the crude product, this is because it is nearly impossible to accurately titrate the solution completely. Thus the last step is finished with the adding of base slowly and alkaloid crystals fall out of solution. The crude crystals should be washed a few times with cold distilled water when filtered to remove any adhering base. This prevents the separation as an oil. To remedy this: Try to obtain a seed crystal. This can be done two ways: * Scratch the inside of the vessel at the air/solvent interface with a stirring rod. * Save a crystal from the crude material (if it was crystalline) and add it to solution to induce crystallization. Once a seed crystal is obtained, heat the solution to dissolve the oil, and add the seed crystal as the solution cools. If it continues to oil out, add a bit more solvent. Crystallization Summary 1. Choosing the solvent. "Like dissolves like." Some common solvents are water, methanol, ethanol, ligroin, and toluene. When using a solvent pair dissolve the solute in the better solvent, and add the poorer solvent to the hot solution until saturation occurs. Some common solvent pairs are ethanol-water, ether-ligroin, and toluene-ligroin. 2. Dissolving the solute. In an Erlenmeyer flask or reaction tube, add solvent to the crushed or ground solute and heat the mixture to boiling. Add more solvent as necessary to obtain a hot saturated solution. 3. Decolorizing the solution. If necessary to remove colored impurities, cool the solution to near room temperature and add more solvent to prevent crystallization from occuring. Add decolorizing charcoal in the form of pelletized Norit to the cooled solution, then heat it to boiling for a few minutes, taking care to swirl the solution to prevent bumping. remove the norit by filtration, then concentrate the filtrate. 4. Filtering suspended solids. If it is necessary to remove suspended solids, dilute the hot solution slightly to prevent crystallization from occuring during filtration. Filter the hot solution. Add solvent if crystallization begins in the funnel. Concentrate the filtrate to obtain a saturated solution. 5. Crystallizing the solute. Let the hot saturated solution cool to room temperature spontaneously. Do not disturb the solutoin. Then cool it in ice. If crystallization does not occur, scratch the inside of the container or add seed crystals. 6. Collecting and washing the crystals. Collect the crytsals using some filtration method (vacuum filtration is best). Wash crystals with ice cold solvent until the crystals are clean and the filtrate comes through clear. 7. Drying the product. Press the product on the filter to remove solvent. Then remove it from the filter, squeeze it between sheets of filter paper to remove more solvent and spread it on a watch glass to dry. [/quote:90d74f389e] you can see the orginal post at http://www.shroomery.org/forums/showflat.php?Cat=&Board=Garden&Number=2533363