1. Isolation of Caffeine Overview
Liquid/Liquid Extraction of Caffeine from Vivaran, an over-the-counter energy & stimulant drug
An aqueous Vivarin/Sodium Carbonate mixture is extracted with Dichloromethane (Methylene Chloride)
The solution is evaporated to dryness and the mass and % recovery of the product are determined.
Confirmation of product is verified by Melting Point
References:
Pavia: pp. 24, 73 – 84
Note: These pages are not in the GMU version of the Pavia text sold in the book, only in the primary text that we do not use anymore.
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2.  Isolation of Caffeine Background
Caffeine is a bitter, white crystalline alkaloid (derivative of Xanthine) that acts as a stimulant drug
Caffeine is synthesized in plants from the purine nucleotides AMP, GMP, and IMP. These in turn are transformed into xanthosine and then theobromine, the latter being the penultimate precursor of caffeine 
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3. Isolation of Caffeine
The two Amide groups exist as zwitterionic resonance structures where the Nitrogen and Carbon atoms are double bonded to each other so that both of the Nitrogen atoms are essentially planer (in sp2 orbital hybridization)
A zwitterion is a neutral molecule with a positive and a negative electrical charge (not dipoles) at different locations within that molecule
Zwitterions are sometimes also called inner salts
The fused ring system therefore contains a total of ten pi () electrons and hence according to Huckel’s rule is aromatic
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4. Isolation of Caffeine
Zwitterionic Resonance
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5. Isolation of Caffeine Chemical Properties
Caffeine acts as a general nervous system stimulant, warding off drowsiness
Caffeine is considered a “psycho active” substance, but is generally legal and unregulated
Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, acting as a natural pesticide by paralyzing and killing insects
Sources for human use include coffee plants, tea leaves, and kola nuts
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6. Isolation of Caffeine Procedure
Obtain 2 Vivarin tablets noting % of active ingredient
Determine the mass of the tablets
Obtain and determine mass of approximately 8 g of Sodium Carbonate
Crush the tablets with a pestal & mortor
Add the crushed sample to a 150 mL beaker
Add 60 mL of Distilled Water
Add the Sodium Carbonate (Na2CO3) to the solution
Add a Teflon boiling chip
Heat solution to boiling on a hot plate – maintain boiling point for 2 minutes
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7. Isolation of Caffeine Procedure (Cont’d)
Allow the hot mixture to settle slightly - some solid particles will remain undissolved
Obtain a glass funnel and lightly pack glass wool in the form of a boat into the upper part of the stem
Place glass funnel through a clay triangle sitting on an iron ring attached to a ring stand
Obtain a 125 mL Separatory funnel and secure the stopcock by tightening
Place the end of the Separatory funnel through a clay triangle sitting on another iron ring attached to the ring stand below the glass funnel
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8. Isolation of Caffeine Procedure (con’t)
Decant the sample solution into the glass funnel allowing the liquid to drain into the 125 mL Separatory Funnel
Rinse the beaker with a small amount of distilled water and pass the water through the glass funnel to the separatory funnel
Allow the filtrate in the Separatory Funnel to cool to room temperature
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9. Isolation of Caffeine
Liquid–liquid Extraction, also known as solvent extraction and partitioning, is a method to separate two immiscible liquids, usually an aqueous component and an organic solvent component
The process involves the extraction of a substance from one liquid phase into the other liquid phase utilizing a separatory funnel
Use the following steps to extract the Caffeine from the aqueous phase into the organic phase consisting of Methylene Chloride solvent (density – 1.33 g/ml)
You will do three (3) extractions
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10. Isolation of Caffeine Procedure (Cont’d)
Add 8.0 mL of Dichloroethane (Methylene Chloride) to the mixture in the separatory funnel
Place the stopper in the top opening and make sure it is secure, i.e. won’t leak
Invert the funnel pointing the stopcock end away from your face
Use “gentle” swirling (avoids formation of an emulsion) for seconds
Slowly open the stopcock to relieve any pressure
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11. Isolation of Caffeine
Close the stopcock and continuing swirling with venting every 15 seconds until no more gas is released (two or three times should be sufficient)
Continue the swirling for a total of 5 minutes
Replace the separatory funnel in the ring stand and allow the mixture to settle for a few minutes
Remove the stopper from the Separatory Funnel
Open the stopcock slowly and collect the clear bottom (organic) layer into a clean 150 mL beaker
Repeat the extraction process two more times with new 8.0 mL aliquots of Methylene Chloride, but reduce the total swirling time to 2 minutes
Each time, add the clear bottom layer to the mL beaker
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12. Isolation of Caffeine Procedure (Cont’d)
With the help of the instructor, add Anhydrous Sodium Sulfate as a drying agent
Leaving the particles settled on the bottom of the beaker, slowly pour (decant) the liquid into a clean, dry, 50 mL beaker
Rinse the beaker containing the drying agent particles on the bottom with one additional small portion of Dichloromethane and add to the sample beaker
Evaporate the mixture to dryness in the hood
Note: Set hot plate setting to about 3
Note: Crude yield at this point is roughly 90%
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13. Isolation of Caffeine Procedure (Cont’d) Recrystallization Process
Dissolve the dried product in mL cold Acetone (from ice/water bath)
Heat solution gently on hot plate
If solution is incomplete, remove beaker from hot plate and add more Acetone in 2 mL increments
Up to 20 mL of additional Acetone may be required until a clear pale-yellow solution is obtained
Remove solution from hot plate and allow to cool slightly
Add Petroleum Ether, drop by drop, with swirling from a full plastic pipet until the first appearance of pervasive cloudiness throughout the solution
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14. Isolation of Caffeine Procedure (Cont’d)
Continue cooling until crystallization is complete
Note: Maximum yield is obtained when the addition of Petroleum Ether is stopped at the first appearance of a pervasive cloudiness throughout the solution
Separate the crystals from the solution by Vacuum Filtration rinsing the beaker and crystals in the funnel with small amounts of Petroleum Ether
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15. Isolation of Caffeine
Air-dry the sample from the evaporation procedure or the vacuum filtration procedure on a pre-weighed weighing tray for one week
Compute the mass of the purified sample
Compute the percent recovery from the original mass of the tablets
If available, use the percentage of active ingredient from the tablet bottle to compare your experimentally determined content with the actual content
Determine melting point -  236 oC
Note: Decomposition of this crude material occurs beginning at 236oC over a range of 5oC or so
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