7.4,Extraction and Washing Guide
Overview,
This handout describes standard extraction and washing protocols that can be applied to
virtually any crude reaction mixture,Aqueous washings are done to remove water soluble
impurities from organic products since normally the compound that you desire will be dissolved in
the organic layer,
Reference,
For an excellent discussion,read Zubrick pages 127–138,
Standard Aqueous Workup Protocol,
1) Pick an organic solvent,Ether is the most popular because it can be removed easily on
the rotary evaporator,ethyl acetate also works well but is harder to remove,dichloromethane
is a poor choice and should be avoided,if possible,since it often forms nasty emulsions and
complicates matters because it is heavier than water,
2) Pick the size of your separatory (sep.) funnel,You will usually use 125 or 250-mL,
large scale reactions (1–10 g) can require 500-mL or 1-L sizes,Remember that your sep,
funnel will contain the solvent and wash liquid which must be thoroughly mixed,
3) Dilute the crude reaction mixture with your solvent of choice and transfer to
your chosen sep,funnel,Large amounts of material require large amounts of solvent,
Normal reactions (50–500 mg of product) can be diluted with between 25–100 mL of
solvent,
4) Wash the organic layer to remove impurities,The volume of a wash phase is
typically one tenth to one half the volume of the organic phase,It is sometimes best to
repeat a wash two or three times,An acid wash (usually 10% HCl) is used to remove
amines,while a basic wash (usually sat,NaHCO
3
or 10% NaOH) is used to remove
unwanted acids,In most cases,when neither acidic nor basic impurities are an issue,the
solution is washed with distilled water to remove any non-organic compounds,(Note,
When shaking mixtures in a sep,funnel be sure to vent it regularly by holding it upside-
50
WARNING NOTICE,The experiments described in these materials are potentially hazardous and require a high level
ofsafety training,special facilities and equipment,and supervision by appropriate individuals,You bear the sole
responsibility,liability,and risk for the implementation of such safety procedures and measures,MIT shall have no
responsibility,liability,or risk for the content or implementation of any of the material presented,Legal Notices
down,pointing it up and to the back of your hood,then opening the stopcock,This will
release any pressure that has built up during mixing,Additionally,when draining liquids
out of the sep,funnel,be sure to first remove the stopper.)
5) Back-extract to recover lost product,If your compound is somewhat water soluble
(has several polar functional groups),you may need to back-extract the water layers with
ether or ethyl acetate to avoid significant loss of compound in the aqueous phase,TLC can
be used to determine when all of your compound has been removed from the water,
6) Finish with a brine (saturated NaCl solution) wash,This helps disrupt any
emulsions and will "dry" the organic layer by extracting water that may have dissolved in
the organic phase,
7) Dry the organic layer,After removing your solution from the aqueous phase,a drying
agent is added to remove all traces of water,This is usually MgSO
4
,more effective and
faster,but slightly acidic; or Na
2
SO
4
,less effective and slower,but neutral,These
compounds bind to any water remaining in the organic solution,forming clumps when they
react,A decent amount of drying agent should be added,but as long as some solid is not
clumped,no more needs to be added,(This will make sense once you've done this a couple
of times.)
8) While the compound is drying,it is time to flute the filter paper,Refer to
Zubrick page 136-138 for directions,Some chemists prefer to use a Büchner funnel and
unfluted filter paper (or a fritted funnel) under mild vacuum as their standard filtration
method,Their motive is a slightly higher yield of product,
9) Filter the solution into a large round bottom flask using your expertly fluted filter
paper and a large funnel (or the Büchner method),To guard against bumping on the
rotavap,do not fill the flask more than half full,
10) Concentrate the solution on the rotavap,then dissolve the compound in a small
amount of solvent and transfer to a small pre-weighed (tared) flask,
11) Concentrate the solution on the rotavap again,Higher boiling solvents are more
effectively removed by concentrating,adding dichloromethane then repeating once more,
51
12) Use the vacuum pump to remove residual solvent,For non-volatile compounds,
residual solvent is most effectively removed by using the vacuum pump,One useful trick to
speed up this process is the following,evacuate the flask and vent to N
2
,repeat this again,
then pump on the flask for 30 minutes,If your compound is volatile—low molecular
weight and/or low boiling point—obtain a constant weight using the rotavap,not the vacuum
pump,
13) Obtain a constant weight,Weigh the flask after leaving it on the vacuum pump (or
rotavap),then return to the pump (or rotavap) for 15 to 30 minutes and weigh again,Once
two weights in a row are the same,you're ready to take an NMR,
52
Overview,
This handout describes standard extraction and washing protocols that can be applied to
virtually any crude reaction mixture,Aqueous washings are done to remove water soluble
impurities from organic products since normally the compound that you desire will be dissolved in
the organic layer,
Reference,
For an excellent discussion,read Zubrick pages 127–138,
Standard Aqueous Workup Protocol,
1) Pick an organic solvent,Ether is the most popular because it can be removed easily on
the rotary evaporator,ethyl acetate also works well but is harder to remove,dichloromethane
is a poor choice and should be avoided,if possible,since it often forms nasty emulsions and
complicates matters because it is heavier than water,
2) Pick the size of your separatory (sep.) funnel,You will usually use 125 or 250-mL,
large scale reactions (1–10 g) can require 500-mL or 1-L sizes,Remember that your sep,
funnel will contain the solvent and wash liquid which must be thoroughly mixed,
3) Dilute the crude reaction mixture with your solvent of choice and transfer to
your chosen sep,funnel,Large amounts of material require large amounts of solvent,
Normal reactions (50–500 mg of product) can be diluted with between 25–100 mL of
solvent,
4) Wash the organic layer to remove impurities,The volume of a wash phase is
typically one tenth to one half the volume of the organic phase,It is sometimes best to
repeat a wash two or three times,An acid wash (usually 10% HCl) is used to remove
amines,while a basic wash (usually sat,NaHCO
3
or 10% NaOH) is used to remove
unwanted acids,In most cases,when neither acidic nor basic impurities are an issue,the
solution is washed with distilled water to remove any non-organic compounds,(Note,
When shaking mixtures in a sep,funnel be sure to vent it regularly by holding it upside-
50
WARNING NOTICE,The experiments described in these materials are potentially hazardous and require a high level
ofsafety training,special facilities and equipment,and supervision by appropriate individuals,You bear the sole
responsibility,liability,and risk for the implementation of such safety procedures and measures,MIT shall have no
responsibility,liability,or risk for the content or implementation of any of the material presented,Legal Notices
down,pointing it up and to the back of your hood,then opening the stopcock,This will
release any pressure that has built up during mixing,Additionally,when draining liquids
out of the sep,funnel,be sure to first remove the stopper.)
5) Back-extract to recover lost product,If your compound is somewhat water soluble
(has several polar functional groups),you may need to back-extract the water layers with
ether or ethyl acetate to avoid significant loss of compound in the aqueous phase,TLC can
be used to determine when all of your compound has been removed from the water,
6) Finish with a brine (saturated NaCl solution) wash,This helps disrupt any
emulsions and will "dry" the organic layer by extracting water that may have dissolved in
the organic phase,
7) Dry the organic layer,After removing your solution from the aqueous phase,a drying
agent is added to remove all traces of water,This is usually MgSO
4
,more effective and
faster,but slightly acidic; or Na
2
SO
4
,less effective and slower,but neutral,These
compounds bind to any water remaining in the organic solution,forming clumps when they
react,A decent amount of drying agent should be added,but as long as some solid is not
clumped,no more needs to be added,(This will make sense once you've done this a couple
of times.)
8) While the compound is drying,it is time to flute the filter paper,Refer to
Zubrick page 136-138 for directions,Some chemists prefer to use a Büchner funnel and
unfluted filter paper (or a fritted funnel) under mild vacuum as their standard filtration
method,Their motive is a slightly higher yield of product,
9) Filter the solution into a large round bottom flask using your expertly fluted filter
paper and a large funnel (or the Büchner method),To guard against bumping on the
rotavap,do not fill the flask more than half full,
10) Concentrate the solution on the rotavap,then dissolve the compound in a small
amount of solvent and transfer to a small pre-weighed (tared) flask,
11) Concentrate the solution on the rotavap again,Higher boiling solvents are more
effectively removed by concentrating,adding dichloromethane then repeating once more,
51
12) Use the vacuum pump to remove residual solvent,For non-volatile compounds,
residual solvent is most effectively removed by using the vacuum pump,One useful trick to
speed up this process is the following,evacuate the flask and vent to N
2
,repeat this again,
then pump on the flask for 30 minutes,If your compound is volatile—low molecular
weight and/or low boiling point—obtain a constant weight using the rotavap,not the vacuum
pump,
13) Obtain a constant weight,Weigh the flask after leaving it on the vacuum pump (or
rotavap),then return to the pump (or rotavap) for 15 to 30 minutes and weigh again,Once
two weights in a row are the same,you're ready to take an NMR,
52
