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4.3 Distillation

4.3.1 Definition

Distillation is the most useful method for purifying liquids, and is used routinely for purifying solvents and reagents. Using appropriate apparatus, and some care it can be possible to separate liquids whose boiling points are less than 5ºC apart.

4.3.2 Safety rules

• Remember that most organic liquids are extremely flammable so great care must be taken to ensure that the vapour does not come into contact with flames, sources of sparks (electrical motors), or very hot surfaces (hot plates).
• Never allow a distillation pot to boil dry. The residues may ignite or explode with great violence.
• Beware of the possibility that ethers and hydrocarbons may be contaminated with peroxides. Be particularly careful when distilling compounds prepared by peroxide and peracid oxidations and always take precautions to remove peroxide residues prior to distillation.
• Carry out a safety audit on the compound you plan to distill to check that it is not thermally unstable. Some types of compounds, e.g. azides, should never be distilled.
• Make sure that all joints are secured very tightly. If any vapor escapes at the connection points, it may come into direct contact with the heat source and ignite.
• Never heat a closed system, the increasing pressure will cause the glass to explode. If the distillation flask has a tapered neck, the thermometer may be placed in such a way as to block to flow of vapors up the neck of the flask; in effect creating a closed system; make sure that if using a tapered neck flask, the thermometer is not resting in the lowest portion of the neck.

4.3.3 Simple distillation

Simple distillation is a procedure by which two liquids with different boiling points can be separated. Simple distillation (the procedure outlined below) can be used effectively to separate liquids that have at least 50ºC difference in their boiling points. As the liquid being distilled is heated, the vapors that form will be richest in the component of the mixture that boils at the lowest temperature. Purified compounds will boil, and thus turn into vapors, over a relatively small temperature range (2 or 3°C); by carefully watching the temperature in the distillation flask, it is possible to affect a reasonably good separation. As distillation progresses, the concentration of the lowest boiling component will steadily decrease. Eventually the temperature within the apparatus will begin to change; a pure compound is no longer being distilled. The temperature will continue to increase until the boiling point of the next-lowest-boiling compound is approached. When the temperature again stabilizes, another pure fraction of the distillate can be collected. This fraction of distillate will be primarily the compound that boils at the second lowest temperature. This process can be repeated until all the fractions of the original mixture have been separated.

Procedure:

1. Check the calibration of the thermometer that is to be used. This can be accomplished by placing the thermometer in an ice bath of distilled water. After the thermometer has been allowed to reach thermal equilibrium, place it in a beaker of boiling distilled water and again allow it to reach thermal equilibrium. If the temperatures measured deviate from the expected values by more than two degrees, obtain a new thermometer and check its calibration.
2. Fill the distillation flask. The flask should be no more than two thirds full because there needs to be sufficient clearance above the surface of the liquid so that when boiling commences the liquid is not propelled into the condenser, compromising the purity of the distillate. Boiling chips should be placed in the distillation flask for two reasons: they will prevent superheating of the liquid being distilled and they will cause a more controlled boil, eliminating the possibility that the liquid in the distillation flask will bump into the condenser.

3. Heat the distillation flask slowly until the liquid begins to boil (see Figure 4). Vapors will begin to rise through the neck of the distillation flask. As the vapors pass through the condenser, they will condense and drip into the collection receiver (see Figure 5). An appropriate rate of distillation is approximately 20 drops per minute. Distillation must occur slowly enough that all the vapors condense to liquid in the condenser. Many organic compounds are flammable and if vapors pass through the condenser without condensing, they may ignite as they come in contact with the heat source.

4. As the distillate begins to drop from the condenser, the temperature observed on the thermometer should be changing steadily. When the temperature stabilizes, use a new receiver to collect all the drops that form over a two to three degree range of temperature. As the temperature begins to rise again, switch to a third collection container to collect the distillate that now is formed. This process should be repeated; using a new receiver any time the temperature stabilizes or begins changing, until all of the distillate has been collected in discrete fractions.
• Note: All fractions of the distillate should be saved until it is shown that the desired compound has been effectively separated by distillation.
5. Remove the heat source from the distillation flask before all of the liquid is vaporized. If all of the liquid is distilled away, there is a danger that peroxides, which can ignite or explode, may be present in the residue left behind. Also, when all of the liquid has evaporated, the temperature of the glass of the filtration flask will rise very rapidly, possibly igniting whatever vapors may still be present in the distillation flask.

Simple distillation is effective only when separating a volatile liquid from a nonvolatile substance or when separating two liquids that differ in boiling point by 50 degrees or more. If the liquids comprising the mixture that is being distilled have boiling points that are closer than 50 degrees to one another, the distillate collected will be richer in the more volatile compound but not to the degree necessary for complete separation of the individual compounds.

4.3.4 Distillation under inert atmosphere

If the distillation is being used to dry a reagent, the process must be carried out under an inert atmosphere.

Procedure:

• Dry all the glass apparatus in the oven, or with a heat gun under vacuum, and purge with inert gas whilst cooling. Most easily accomplished by connecting the apparatus to a double manifold/bubbler system.
• When the glassware has cooled, increase the inert gas flow, quickly disconnect the distillation flask, add any drying agent required, a few anti-bumping granules and the liquid to be distilled, then reassemble the system.
• Heat the distillation flask in an oil bath (do not carry out distillations using a heating mantle) and collect the distillate which comes over at the required temperature.
• When the distillation is complete, remove the collector and seal it quickly with a septum. Most reagents can simply be poured into a reagent bottle before sealing, provided you are quick. However, if the reagent is particularly sensitive to air or moisture a cannulation technique should be used to transfer it.

4.3.5 Fractional distillation

Separation of liquids whose boiling points are between 5ºC and 50ºC apart requires the use of an apparatus which gives better contact between the vapour and liquid phases in the distillation column. Efficient separation of compounds with a boiling point difference of 10-30ºC can be achieved using a long glass tube packed with glass rings or helices, or for high efficiency, wire mesh rings. They key to getting good results from a fractional distillation is to raise the temperature very gradually, and collect the distillate very slowly.
Since the procedures of simple distillation are so similar to those involved in fractional distillation, the apparatus that are used in the procedures are also very similar. The only difference between the equipment used in fractional distillation and that used in simple distillation is that with fractional distillation, a packed fractionating column is attached to the top of the distillation flask and beneath the condenser. This provides the surface area on which rising vapors condense, and subsequently revaporize.
The fractionating column is used to supply a temperature gradient over which the distillation can occur. In an ideal situation, the temperature in the distillation flask would be equal to the boiling point of the mixture of liquids and the temperature at the top of the fractionating column would be equal to the boiling point of the lower boiling compound; all of the lower boiling compound would be distilled away before any of the higher boiling compound. In reality, fractions of the distillate must be collected because as the distillation proceeds, the concentration of the higher boiling compound in the distillate being collected steadily increases. Fractions of the distillate, which are collected over a small temperature range, will be essentially purified; several fractions should be collected as the temperature changes and these portions of the distillate should be distilled again to amplify the purification that has already occurred.

4.3.6 Distillation under reduced pressure

Many compounds decompose when heated to their boiling points so they cannot be distilled at atmospheric pressure. In this situation it may be possible to avoid thermal decomposition by carrying out the distillation at the reduced pressure. The reduction in the boiling point will depend on the reduction in pressure and it can be estimated from a pressure-temperature nomograph. To find the approximate boiling point at any pressure simply place a ruler on the central line at the atmospheric boiling point of the compound, pivot it to line up with the appropriate pressure marking on the right-hand line, and read off the predicted boiling point from the left-hand line.

Procedure:

• Place the sample in the distillation flask (no more than 2/3 full) and add a stirring bar. Note: Anti-bumping granules are not effective at reduced pressure and so an alternative must be used. A very narrow capillary which allows a slow stream of air or nitrogen bubbles to pass through is effective, but brisk stirring using a magnetic follower is much more convenient.
• Assembled the (oven-dried) apparatus, putting a little high vacuum grease on the outer edge of each joint. Ensure that the receiver adapter and the collection flasks are secured using clips, and connect the assembly to a vacuum pump. One convenient method of doing this is to connect it to a vacuum/inert gas double manifold. The pump must be protected with a cold finger trap and the line should incorporate a vacuum gauge for monitoring the pressure.
• Stir the liquid rapidly and carefully open the apparatus to the vacuum. Some bumping and frothing may occur as air and volatile components are evacuated. If necessary adjust the pressure to the required value by allowing inert gas into the system via a needle valve.
• Heat the flask slowly to drive off any volatile impurities and then to distil the product. Monitor the stillhead temperature and collect a forerun and a main fraction, which should distil at a fairly constant temperature. If fractionation is required you may have to collect several fractions and it is very important to distil the mixture slowly and steadily.
• Stop the distillation when the level of liquid in the pot is running low, by removing the heat bath.
• Isolate the apparatus from the vacuum and carefully fill with inert gas. If you are using a double manifold, this can be done by simply turning the vacuum/inert gas tap. The flask containing the distillate will be under a dry, inert atmosphere and should be quickly removed and fitted with a tightly fitting septum.
• Switch off the pump and clean the cold trap.
  
  

4.3.7 Small scale distillation

The chief difficulty with small scale distillations is that a significant proportion of the sample may be lost in “wetting” the surface of the column and the condenser. This problem is reduced by using very compact one piece short-path designs, but this reduces the fractionating efficiency of the columns, leading to less effective separation.

Procedure:

• Place the sample in the end bulb using a Pasteur pipette. If necessary wash the sample into the bulb and then evaporate the solvent on a rotary evaporator.
• Add 2 more bulbs and connects them to the straight length of tubing from the motor assembly.
• Slide the end bulb into the oven and gently close the iris type seal around the connecting joint.
• Set the bulbs rotating (to prevent bumping and speed up the distillation)
• Apply the vacuum gradually to prevent frothing and raise the oven temperature gradually until distillation begins (usually indicated by a mist appearing in the first bulb). Adjust the temperature so that distillation continues at a steady rate.
• When distillation is complete allow the flaks to cool under an inert atmosphere and then remove the bulbs from the apparatus and recover the distillate. If you do not want to wash the collection bulb with solvent, simple clamp it in a vertical position and allow the contents to drain into a flask or sample vial.

Fractionation of compounds with a 20-30ºC boiling point difference can be achieved by inserting all the bubs except one into the oven, distilling the most volatile component into that bulb, withdrawing the next bulb from the oven and distilling the next fraction into that, and so on.

Next - 4.4 Recrystallization