Purifying an organic compound

Why purify at all?

Suppose you make aspirin in a lab. The solid you scrape from the flask holds aspirin, but also leftover starting material, a little solvent and some by-products. To study aspirin, or to sell it as a medicine, you must separate it from all this.

Chemists choose a method by asking one question. How does the compound differ from its impurities?

It may differ in how easily it turns to vapour. It may differ in how well it dissolves in hot and cold solvent. Or it may differ in how strongly it clings to a surface.

A pure solid melts sharply, at one fixed temperature. A pure liquid boils at one fixed temperature. If a solid melts over a wide range, it is still impure.

Sublimation

Some solids turn straight into vapour on heating, without becoming liquid. On cooling, the vapour turns straight back into a solid. This is sublimation.

Camphor, naphthalene, benzoic acid and ammonium chloride all sublime. Their usual impurities, such as common salt or sand, do not.

• Put the impure solid in a china dish and cover it with an inverted funnel. Plug the stem with cotton wool.
• Heat gently. The pure solid sublimes, rises, and settles as crystals on the cool inside of the funnel.
• The impurities stay behind in the dish.

Crystallisation

Most solids dissolve better in a hot solvent than in a cold one. Crystallisation uses this.

1. Dissolve the impure solid in the smallest amount of hot solvent, to make a saturated solution.
2. Filter the hot solution to remove any insoluble impurity. A pinch of animal charcoal first can adsorb coloured impurities.
3. Let the filtrate cool slowly. The pure compound crystallises, because the cold solvent cannot hold as much.
4. Filter off the crystals, wash them with a little cold solvent, and dry them.

The impurities are present in small amounts, so they stay dissolved in the leftover liquid, called the mother liquor. Sugar from hot water and benzoic acid from hot water are classic examples.

If two compounds are both present in large amounts, but dissolve differently, you can crystallise one, then the other. This is fractional crystallisation.

Distillation

Distillation separates liquids by their boiling points. The liquid is boiled, the vapour is cooled, and the liquid that condenses is the distillate. There are four kinds. Which one you pick depends on the liquids.

Simple distillation. It works for a liquid that boils without decomposing, mixed with a non-volatile impurity, or with another liquid whose boiling point is clearly different. Chloroform (boils at $334\ \text{K}$) and aniline (boils at $457\ \text{K}$) separate this way. The chloroform boils first, and is collected.

Fractional distillation. When two liquids have close boiling points, simple distillation leaves a mixture in the distillate. A fractionating column is fitted between the flask and the condenser. In the column, the vapour condenses and boils again and again, and each round enriches it in the more volatile liquid. Petroleum is separated into petrol, kerosene and diesel this way.

Distillation under reduced pressure. A liquid boils when its vapour pressure equals the pressure above it. Lowering the pressure lowers the boiling point. Some liquids would decompose at their normal boiling point. Glycerol is one. It is distilled at low pressure, so it boils well below its normal boiling point and stays whole.

Steam distillation. It suits a liquid that does not mix with water and has a high boiling point, such as aniline or the oil in an orange peel. Steam is passed through the mixture. The mixture boils when the vapour pressures of the water and of the liquid add up to the atmospheric pressure. This happens below $373\ \text{K}$, so the liquid never gets hot enough to decompose.

For the two liquids in the distillate, the masses follow the vapour pressures $p$ and the molar masses $M$:

• $\dfrac{w_1}{w_2} = \dfrac{p_1 M_1}{p_2 M_2}$

Differential extraction

A compound dissolved in water can often be moved into an organic solvent, such as ether, that does not mix with water.

• Shake the aqueous solution with the solvent in a separating funnel.
• The compound is more soluble in the organic solvent, so most of it moves there.
• Let the layers settle, and run the lower layer out through the tap.
• Distil off the solvent to recover the compound.

Several small portions of solvent extract more than one large portion of the same total volume.

Chromatography

The word comes from the Greek for colour and write, because it was first used to separate coloured plant pigments. A mixture is carried by a mobile phase, a liquid or gas, over a stationary phase. Each compound clings to the stationary phase a different amount, so each travels at its own speed.

• Column chromatography. A glass tube is packed with alumina or silica gel. The mixture is poured on top, and a solvent runs through. The compounds come out of the bottom at different times, and each is collected in its own flask.
• Thin layer chromatography (TLC). A thin layer of adsorbent, such as silica, is spread on a glass plate. A drop of the mixture is placed on a starting line, and the plate stands in a little solvent. The solvent rises, and carries each compound a different distance.
• Paper chromatography. The paper holds water in its fibres, and that water is the stationary phase. The solvent rises through the paper.

Colourless spots are shown by ultraviolet light, by iodine vapour, or by a spray such as ninhydrin for amino acids.

The Rf value

For each spot, measure from the starting line.

• $R_f = \dfrac{d_s}{d_f}$, where $d_s$ is the distance moved by the substance and $d_f$ the distance moved by the solvent front.

The Rf is a pure number, and it is never more than 1. Under the same conditions, the same compound gives the same Rf. So you can name a spot by comparing its Rf with the Rf of known compounds run on the same plate.

Practise with new numbers

Try it in Python

The program turns the spot distances on a plate into Rf values, and compares each with three known dyes.

Common mistakes

• Putting the solvent front on top of the Rf fraction. An Rf is below 1, so the spot is on top.
• Measuring from the bottom of the plate. Measure from the starting line, for the spot and for the front.
• Using too much solvent in crystallisation. Too much of the compound stays dissolved when the solution cools, and the yield is poor.
• Mixing up the two low-pressure ideas. Reduced pressure lowers the boiling point of one liquid. Steam distillation works because two liquids share the pressure.

Remember these

• Sublimation: a solid goes to vapour and back, leaving impurities behind.
• Crystallisation: hot saturated solution, then cooling.
• Simple, fractional, reduced pressure and steam distillation: each suits its own kind of liquid.
• Extraction moves a compound into a solvent that does not mix with water.
• Chromatography separates by different clinging to a stationary phase. $R_f$ is the spot distance over the front distance.

Check yourself

Try each one on your own first. If you are stuck, open a hint. Then check with Show the answer.

1. Which method would you use to get pure camphor from a mixture of camphor and sand?

2. Why is glycerol distilled under reduced pressure and not at its normal boiling point?

3. A liquid does not mix with water and decomposes near its boiling point. Which distillation suits it?

4. Can a spot on a TLC plate have an $R_f$ of 1.3?