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

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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.

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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Isolation of Caffeine

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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

Isolation of Caffeine

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Zwitterionic Resonance

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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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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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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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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Isolation of CaffeineLiquid–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) extractions04/18/23 9

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 10-15 seconds

Slowly open the stopcock to relieve any pressure

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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 150 mL beaker

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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%04/18/23 12

Isolation of Caffeine Procedure (Cont’d)

Recrystallization Process Dissolve the dried product in 12-15 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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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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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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