How Crystallisation Purifies a Solid

When a soluble solid is added to a solvent, its particles separate and spread through the liquid. There is a limit to how much can dissolve under a particular set of conditions. Once that limit is reached, the solution is saturated.

For many solid solutes, more can dissolve at a higher temperature than at a lower one. Heating can therefore allow a concentrated solution to contain a large amount of dissolved material. As the solution later cools, the solvent may no longer be able to keep all of that solute dissolved.

The excess solute begins to leave the solution and form a solid crystal structure. This change is physical rather than the creation of a new chemical substance.

In a typical purification, an impure solid is dissolved in a suitable hot solvent. Insoluble impurities can be removed by filtration while the solution remains warm. The filtered solution is then allowed to cool so the desired substance crystallises.

As crystals form, particles of the desired substance fit into an ordered lattice. Many dissolved impurities do not fit easily into that structure and remain in the solution around the crystals, called the mother liquor.

Cooling too quickly can trap more impurities or produce very small crystals. Slow cooling often gives particles more time to arrange themselves properly. After crystallisation, the solid is filtered, washed with a small amount of cold solvent and dried.

Using too much solvent can reduce the amount of solid recovered because more product remains dissolved after cooling. Using too little may prevent the sample from dissolving properly. The aim is to use enough hot solvent to dissolve the desired substance without leaving a large unnecessary volume.

A careful sequence is:

• •Choose a solvent in which solubility changes usefully with temperature.
• •Dissolve the solid using a small amount of hot solvent.
• •Remove insoluble material while the solution is hot.
• •Cool the solution so crystals can form.
• •Filter, wash and dry the crystals.

Purity and yield can pull in different directions. Washing crystals thoroughly can remove more contaminated solution, but some product may dissolve and be lost. Good technique aims for a useful balance, producing crystals that are clean without throwing away more material than necessary.

Sometimes a cooled solution holds more dissolved solid than it normally could at that temperature, yet no crystals form. This state is called supersaturation. Crystals need a starting point, called a nucleation site, where particles can begin to assemble into a lattice. A very clean, smooth flask may offer few such sites. Chemists often encourage crystals by gently scratching the inside of the glass with a glass rod or by adding a tiny seed crystal of the pure substance.

The same ideas appear in the kitchen. Rock sugar sweets are grown by suspending a string in a strong sugar solution, where the string provides surfaces for crystals to start growing. Honey often becomes grainy in the cupboard because it contains more dissolved sugar than water can comfortably hold, and glucose slowly crystallises out. Warming the jar gently in hot water redissolves the crystals, which shows that the change is physical and reversible rather than a sign the honey has spoiled.

After crystallising a product, chemists need evidence that it is purer than before. One of the simplest tests is the melting point. A pure crystalline substance melts sharply at a fixed temperature, often within a degree or so. Impurities disrupt the regular lattice, so an impure sample usually starts melting at a lower temperature and melts gradually over a wider range. If your recrystallised sample melts higher and more sharply than the crude material, the purification has probably worked.

A useful extension is the mixed melting point. If you suspect your crystals are a known compound, you grind them with a pure sample of that compound and melt the mixture. If they are the same substance, the melting point stays sharp and unchanged. If they are different, each acts as an impurity in the other and the melting point drops. Chemists often add a quick chromatography check as well, looking for a single spot on the plate rather than several, since separate spots suggest more than one substance.

Potassium nitrate shows the idea clearly. About 110 grams of it dissolve in 100 grams of water at 60 degrees Celsius, but only about 32 grams at 20 degrees. Suppose you have 100 grams of potassium nitrate contaminated with 5 grams of sodium chloride, and you dissolve the mixture in 100 grams of hot water. On cooling to 20 degrees, the water can hold only about 32 grams of potassium nitrate, so roughly 68 grams crystallise out. The sodium chloride stays dissolved, because 5 grams is far below the 36 or so grams that the water can hold.

Notice that about a third of the product is lost to the mother liquor, which is the trade-off between purity and yield expressed in numbers. Cooling also works well only when solubility changes a lot with temperature. Sodium chloride is the classic exception: its solubility barely changes between cold and hot water, so cooling a salt solution produces very few crystals. Salt is instead recovered by evaporating the water, which is why sea salt has long been made in shallow pans and ponds where sun and wind slowly remove the water until crystals form.

The same molecules can sometimes pack into more than one crystal arrangement, a property called polymorphism, and the conditions of crystallisation decide which form appears. Chocolate is a delicious example. Cocoa butter can crystallise in six different forms, and only one of them, usually called form V, gives the glossy surface and clean snap of good chocolate. Chocolatiers temper chocolate by melting it, cooling it while stirring and then warming it slightly, or by adding seed chocolate, so that form V crystals dominate. Badly stored chocolate can develop a dull, whitish bloom as its fat recrystallises or moves to the surface.

In medicine the stakes are higher, because different crystal forms can dissolve at different rates. In 1998 the makers of ritonavir, a drug used to treat HIV, discovered that a new and previously unknown crystal form had begun appearing in their production. It was much less soluble than the original, so capsules no longer dissolved properly, and once the new form had appeared it proved very difficult to make the old one again. The company had to withdraw the capsules and reformulate the medicine. Drug makers now screen carefully for alternative crystal forms before a product reaches patients.

Crystallisation purifies a solid by taking advantage of changes in solubility. The substance dissolves under one set of conditions and forms an ordered solid again as the solution cools or becomes more concentrated. Control the solvent amount, temperature and cooling rate, and you can separate useful crystals from many unwanted impurities.