Things to look up before lab
1. Chemical structure of caffeine
Separation of Benadryl and Caffeine
Experiment 5
2. Chemical structure of the active ingredient in benadryl
3. Composition of brine
See also http://www.wfu.edu/chemistry/courses/organic/extract/extraction.htm
(extraction) http://www.wfu.edu/chemistry/courses/organic/TLC/TLC.htm
(TLC)
Introduction
In this lab you will use chemically active extraction to separate caffeine from the active ingredient in Benadryl. Extraction is a technique that involves partitioning a substance between two immiscible liquids. Compounds tend to display preferential solubilities in different solvents. Thus, one can usually dissolve an ionic substance in water easier than in a less polar organic solvent.
Conversely, a non-polar, neutral molecule will usually be more soluble in the organic solvent than in water.
In chemically active extraction, one changes the characteristics of the two immiscible solvents in such a way that one or more of the substances to be separated changes form from ionic to neutral or neutral to ionic. For example, benzoic acid is a neutral organic compound that shows higher solubility in ethyl acetate than water. So, imagine that you added 5 grams of benzoic acid to a mixture of 100 mL of water and 100 mL of ethyl acetate. Most of the benzoic acid, say 4.7 grams, would dissolve in the ethyl acetate with the rest remaining in the water. You can then physically separate the two solvent layers using a separatory funnel (see link above).
Questions: 1) which liquid would form the top layer (i.e. float on the other)? Why?
2) How can you get the remaining 0.3 grams of benzoic acid out of the water layer?
Now, imagine that you add NaOH to the water layer in the example above. The hydroxide will react with benzoic acid to produce water and sodium benzoate. Sodium benzoate is an ionic salt and is preferentially soluble in water. When 5 grams of benzoic acid is added to a biphasic mixture of 100 mL ethyl acetate and 100 mL 0.1 M aqueous NaOH, most of the material, say 4.5 grams, dissolves in the aqueous layer. (Again, how would you get the 0.5 grams of sodium benzoate out of the ethyl acetate?)
In order to recover the sodium benzoate from the water, you can acidify the aqueous layer – the acid protonates the benzoate producing benzoic acid. If you have separated the water and ethyl acetate, the benzoic acid, not soluble in water, will precipitate from solution and can be collected by filtration. If the water layer is still in contact with the ethyl acetate when you acidify, the benzoic acid will dissolve in the ethyl acetate.
Objective
Devise a method, using chemically active extraction, to separate caffeine from the active component of Benadryl. You will use acid/base chemistry, a separatory funnel and rotary evaporation

to effect the separation. You will be given 100 mg of a mixture of the two components. Keep approximately 5 mg (a spatula tip amount) for use in TLC and separate the remaining amount.
After the separation, TLC the original mixture against the two separated components to determine how effective your technique was. For the TLC, use silica gel plates and an eluent of between 5 and 10% EtOH in CH
2
Cl
2
. Visualize the TLC plate using a UV lamp.
Questions
1. Which component is most polar?
2. Did you achieve good separation? If so, how do you know? If not, what could you change to improve the technique?
3. If your mixture also contained benzoic acid, how might you separate it from the other two components??
4. Predict the 1H NMR of the active component of Benadryl.