Recrystallization

Since most reactions do not go to completion or afford byproducts, the crude product is more or less contaminated with other compounds. If the product is a solid, recrystallization is common way to purify the crude product. The main problem is to find a good solvent for this task.

T (°C)	Solubility (mg/mL)
0	1.0
20	1.5
40	2.0
60	2.5
80	3.0
100	4.0

In order to dissolve 100 mg of the compound, 25 mL of solvent are required at 100 ^oC. Upon cooling to 0 ^oC, 75 mg of the compound will precipitate and 25 mg will stay in solution. Conclusions for this solvent:

1. 25 % of the compound will be lost in solution, 75 % of the compound recovered as precipitate. Not a good recovery!

2. A relatively large amount of solvent was used which raises the cost for this purification step significantly. In addition, a lot of waste is produced as well!

In order to dissolve 100 mg of the compound, ~1.7 mL of solvent are required at 100 ^oC. Upon cooling to 0 ^oC, 17 mg of the compound will precipitate and 85 mg stay in solution. Conclusions for this solvent:

1. Approximately 85 % of the compound stays in solution and will be lost, only 15 mg are recovered. That is a a VERY poor recovery rate.

2. The solvent quantity is much lower because the overall solubility of the compound is much higher, but due to the low slope of the curve, the recovery is very poor.

c. The compound displays a high solubility at high temperature and a low solubility at low temperature.

Temp. (°C)	Solubility (mg/mL)
00	1.7
10	2.1
20	2.9
25	3.4
30	4.2
40	6.0
50	9.5
60	12.0
70	17.7
80	27.2
90	45.5
95	68.0

In order to dissolve 100 mg of benzoic acid, ~1.5 mL of water are needed at 95 ^oC. Upon cooling to 0 ^oC, 97.5 mg of benzoic acid precipitate and 2.5 mg stay in solution. Conclusions:

2. The majority of the purified sample is recovered (here: 97.5 %) which is highly desirable

Although in theory there always should be a good single solvent to perform a recrystallization, the question is also if it is readily available and reasonably priced. In many cases, one can also resource to a mixture of two solvent in order to accomplish the same task. The boiling points of these two solvents should be very similar and the polarity difference not too extreme to avoid phase separation if a compound is added. Of course, the two solvents have to be miscible in the first place and possess different polarities. The table below shows commonly used solvent mixtures.

More-polar solvent	bp.(C)	Less-polar solvent	bp.(C)
Benzene	80	Cyclohexane	81
Ethanol	78	Hexane	69
Ethyl acetate	77	Cyclohexane	81
Ethanol	78	Acetone	56
Chloroform	61	Petroleum ether	~50
Water	100	Ethanol	78
Water		Acetone	56

However, the solvent mixture should not be boiled excessively to prevent a significant change in composition, which can cause problems during the dissolution or the precipitation part of the procedure.

There are different ways described how to perform a recrystallization. Which one is the right one for you depends on certain factors i/e. quantity, amount of solvent required, equipment available for the task and last but not least how similar the compounds are.

Dissolve the the compound and remove the impurity by filtration. Strictly speaking, this is not a recrystallization, much more of an extraction.

Suspend the crude product in a suitable solvent (like-dissolves-like) and filter the mixture afterwards. Strictly speaking, this is not really a recrystallization, much more of an extraction.

The key to a pure sample here is to really dissolve everything. This should be done in a suitable solvent (as determined in part 1) and at high temperature (boiling point of the solvent). In many cases, it takes some time to dissolve all the crude product. A watch glass with some ice cubes on top of the Erlenmeyer flask allows you to gently reflux the mixture (less solvent evaporates away during the heating phase). Do not forget to add a boiling stick, boiling stone or a spin bar (that of course should spin) while heating.

The resulting mixture can be filtered hot if necessary with a short stem funnel, and then allowed to cool down slowly in order to obtain clean crystals. The faster the precipitate forms, the more impurties are usually trapped in the solid. A slow crystallization allows the compound to arrange its molecules properly in the solid phase and leave the impurties in solution.

In case the compound does not crystallize again from solution there might be several things that you can do:

Problem	Question	Fix
Samples does not dissolve	Right solvent or solvent mixture (correct ratio if mixed solvent?)	Double-check solvent
	Did you heat the mixture to a boil to dissolve the sample?	If not, then you probably will have to much solvent. Boil a significant amount off.
Sample does not crystallize	Did you use a too much solvent (see above)?	If so, boil some of the solvent off
	Solution is supersaturated	Use a seed crystal or scratch the insides of the flask with a glass rod.