[MUSIC - CLAUDE DEBUSSY, "DEUX ARABESQUES"]
PROFESSOR: Reaction work-up 1--
extracting, washing, and drying.
As all chemists quickly learn, it
is very rare for a chemical reaction
to provide only the one compound that you're looking for.
Even highly selective reactions generate the desired product
as a crude mixture, containing byproducts and underreacted
starting materials and reagents.
Liquid-liquid extraction is the most common technique
for separating a compound from a complex mixture.
In an extraction, you can take advantage
of differing solubilities to selectively separate
the different components.
By carefully planning out an extraction
and washing sequence, otherwise known as a work-up,
the desired product can usually be separated
from the unwanted impurities.
This video will illustrate the proper technique involved
in working up a reaction.
In an ideal world, each chemical reaction in the laboratory
would provide only the desired product in its pure form.
In reality, the product is almost always generated
as part of a messy mixture of byproducts and side products.
In short, garbage.
Liquid-liquid extraction is a useful technique
used to isolate the desired compound
from a complex mixture.
In an extraction, the mixture is partitioned
between two immiscible solvents in a separatory funnel,
otherwise known as a "sep" funnel.
The key is that the two solvents are mutually insoluble,
so they form two distinct layers.
One of the solvents is almost always water,
and the other is an organic solvent of your choice.
The different components of the mixture
are selectively distributed in one solvent or the other,
depending on their different solubilities.
In this way, you can take advantage
of differing solubilities to selectively transport solutes
from one layer to another.
In most cases, but not all, neutral organic molecules
prefer the organic phase, while charged
molecules and inorganic salts prefer the aqueous layer.
By carefully planning out an extraction
and washing sequence, otherwise known as a reaction work-up,
the desired compound can usually be separated from most
of the unwanted impurities.
This brings up an important point.
What is the difference between an extraction and a wash?
These terms describe similar, but fundamentally different,
operations.
An extraction involves pulling the desired compound
out of a mixture of compounds.
Whereas, in a wash, you are pulling unwanted impurities
away from the desired product.
In other words, you always keep the extracts,
and trash the washes.
This might sound confusing, but it will hopefully
become clear as we continue.
The first step in an extraction and washing sequence--
once you have decided on the appropriate solvents,
of course--
is filling the sep funnel.
It is a good idea to use an iron ring and a nice, cushy cork
ring to safely support the sep funnel.
Before you add any solvent, close the stopcock,
and place a clean, dry flask under the sep funnel.
This will prevent you from dumping precious material
all over the dirty bench.
The flask will save you if the funnel leaks, or the stopcock
somehow opened itself.
When the stopcock is safely closed,
and the flask is in place, pour your two solvents
into the sep funnel.
Use a sep funnel large enough that you don't
fill it more than 3/4 full.
If it is too full, you won't be able to efficiently mix
the solvents.
This brings us to the next step--
mixing and venting.
It is important to mix the two solvents very well.
This increases the contact surface area
and allows the distribution of solutes to occur very rapidly.
But use caution-- mixing will frequently
cause pressure to build up inside of the sep funnel.
Pressure buildup is especially common
when you are using particularly volatile solvents,
like diethyl ether, or compounds that can generate gas,
like sodium bicarbonate.
Under acidic conditions, sodium bicarbonate
will release gaseous carbon dioxide.
Before any vigorous mixing, it is a good idea
to gently swirl and invert the sep funnel.
Then, invert the sep funnel, holding the stopper tightly.
Allow the liquid to drain away from the stopcock,
and point the tip of the sep funnel away
from yourself and other people.
Slowly open the stopcock to allow venting.
Now, you're ready to really mix it up.
Hold the sep funnel firmly, and shake it vigorously
for several seconds.
Once again, invert the funnel and vent it carefully.
Repeat the shaking and venting until you no longer hear
gas escape when you open the stopcock.
Then, set your funnel down, and let the layers settle.
Ideally, two layers with a nice, clean interface
should form very quickly.
Unfortunately, things don't always go so smoothly.
A thick, cloudy layer, called an emulsion,
can sometimes form between the two solvent layers.
An emulsion is a colloidal mixture of the two solvents,
and is frequently caused by the presence of fine particles
in the solution.
Getting rid of an emulsion can take some time,
so if you know that you are likely to generate one,
your best bet is to take pains to prevent it ahead of time.
For example, gently swirling and inverting your sep funnel
will rarely cause an emulsion to form.
You will have to spend more time mixing because swirling is not
as efficient as shaking, but it may be worth it.
Don't worry, if you unwittingly generated a monster emulsion,
you still have a few options.
First, you can just sit and wait.
It might clear itself up, even if it takes a few hours.
If you don't have all day to finish your extraction,
try swirling the mixture gently, and stirring the emulsion
with a glass rod.
If this doesn't work, add several milliliters
of saturated sodium chloride solution
to the funnel, and swirl to mix.
The sodium chloride increases the ionic strength
of the aqueous layer and decreases
the solubility of the organic solvent in the water.
As a last resort, you may need to use vacuum filtration
to filter your entire mixture through a pad of Celite.
When you are carrying out an extraction
and washing sequence, it is very important
that you keep track of which layer is which,
and what compounds are dissolved in each layer.
This means that you constantly need to be asking yourself,
which layer is on the top?
Which layer is on the bottom?
One way to keep track of this is to know something
about the densities of the solvents you are using.
In every case, the solvent with the lowest
density will be on top.
And the solvent with the highest density will be on the bottom.
This is helpful because you can generally
assume that dilute aqueous solutions have
a density around 1 gram per milliliter, similar to water.
The organic solvent will be in the top layer
if it has a density less than 1 gram per milliliter,
such as hexane, diethyl ether, or ethyl acetate.
The organic solvent will be the bottom layer
if it has a density greater than 1
gram per milliliter, such as methylene chloride
or chloroform.
But be careful-- high concentrations of solutes
can sometimes drastically affect the density of a solvent.
If you're having trouble figuring out
which layer is which, you may need
to perform a quick solubility test.
Take a couple of drops of the layer in question,
and add them to a small amount of water in a test tube.
If the drops dissolve without turning the water cloudy,
then the drops were from the aqueous layer.
If the solution turns cloudy, or the drops
form an insoluble layer on the bottom,
or an insoluble layer on the top,
then the drops are from the organic layer.
But even if you think you know which layer is which,
do not discard any of the layers until you
are absolutely sure that you have
isolated all of the material.
Once you have a good idea of where your material is,
it's time to separate the layers.
Before you do anything, place a clean, dry labeled beaker
under the sep funnel, and remove the stopper.
If you don't do this, you'll have some trouble
getting any liquid to drain.
With the stopper off, open the stopcock,
and allow the bottom layer to drain into the beaker.
Take it slow when you get near the interface,
so that you can close the valve precisely in between the two
layers.
Once you have drained the bottom layer, you have a few options.
If you still need to perform a wash or an extraction
with the top layer, then leave it in the funnel.
Pour in the second solvent, and proceed to mix and vent.
If you are done with the top layer, then pick up the funnel,
and pour it into a second clean, dry labeled beaker.
Here is a little bit of sep funnel etiquette to follow.
When you are separating the layers,
always drain the bottom layer through the stopcock,
and pour the top layer through the top.
This will minimize recontamination
of your material.
Before we move on to proper post extraction procedures,
let's walk through a sample reaction
work-up, similar to one you might use in the laboratory.
Let's say that you performed an acylation reaction
to generate phenyl acetate.
At the end of the reaction, you were
left with a solution containing a lot more than the material
you were looking for.
So what do you do?
First, you know that phenyl acetate
is soluble in diethyl ether, and that diethyl ether
is insoluble in water.
Therefore, in your work-up, you will use diethyl ether
as the organic layer, and wash it
with different aqueous solutions to remove the impurities.
Now, it is time to plan out the washes.
It is important that you use what
you know about the impurities to decide on appropriate aqueous
washes for your mixture.
Keep in mind that the washes should only be 10% to 50%
of the volume of the solution that you are washing.
And make sure to repeat each wash two or three times
to wash away as much of the impurities, as possible.
Your crude mixture contains acetic acid, a fairly strong
acid, and two weak bases--
triethylamine and DMAP.
To get rid of the acetic acid, you
need to wash the solution with a mild base that
will deprotonate the acid and pull the charged acetate
ion into the aqueous layer.
Saturated sodium bicarbonate works very well
for this purpose.
Add the sodium bicarbonate solution and mix well.
Make sure that you vent frequently
to release the carbon dioxide gas that is generated.
Finally, drain away the aqueous solution
that now contains the sodium acetate,
and repeat the wash two more times.
To get rid of the weak bases--
triethylamine and DMAP-- you need
to wash with a dilute solution of a strong acid that
will protonate the bases and pull them
into the aqueous layer.
A 10% aqueous solution of HCL works well for this.
Once again, add the wash, and mix and vent well.
Drain the aqueous layer containing
the protonated amines, and repeat two more times.
So far, this looks like a pretty effective reaction work-up.
But there is one more thing to keep in mind.
Water is slightly soluble in ether--
not to a large extent, but there is some water hanging around
in the organic layer.
One way to pull some of the water
out is to wash it with saturated sodium chloride, otherwise
known as brine.
The high ionic strength of the salt solution
decreases the solubility of the aqueous layer in the ether,
effectively washing away some of the water.
Voila.
Now that you have done all you can with your sep funnel,
it's time to dry your organic layer even more
with the drying agent.
Magnesium sulfate is one popular drying agent
because it is quick and effective.
It is also a very fine powder, so take care
that you don't leave any of your desired material absorbed
onto the surface when you discard it.
Keep in mind that magnesium sulfate is also
slightly acidic.
So it may not be suitable for use
with compounds that are sensitive to acid.
To dry the organic layer with magnesium sulfate,
add a small amount of the powder and swirl.
Incrementally add more drying agent, and swirl until you
get the snow globe effect.
There should be free, unclumped powder in the flask,
even after letting it sit for a few minutes.
Sodium sulfate is another common drying agent.
Although it is slower than magnesium sulfate,
it is effectively neutral.
And, in its granular form, will absorb less of your desired
material onto its surface.
Drying the organic layer with sodium sulfate
is similar to using magnesium sulfate,
except you may need to look a bit closer
to see whether there is free, unclumped drying agent
in the flask.
It is also a good idea to let the solution dry for 5 or 10
minutes before removing the drying agent.
To remove the drying agent, perform a gravity filtration
with fluted filter paper.
Once you have filtered the entire solution,
be sure to rinse the drying agent very well
so that you don't leave any product stuck to the surface.
It is a good idea to rinse the drying agent three times
with clean, dry solvent, adding each of these rinses
to the flask.
Once you are confident that you have transferred
all of the desired material to the round-bottom flask,
you are ready to proceed to the rotavap,
and concentrate the solution in vacuo.
For detailed information on proper use of the rotavap,
you can watch the second reaction work-up video.
[CHIMING]
Remember, this video is intended to help
you prepare for lab by providing a demonstration
of the proper experimental technique.
It is not intended as a replacement
for reading your lab manual or the supplementary material.
In order to become a great experimentalist,
it is important that you understand both theory
and technique.
Now it's your turn.
Good luck.
[MUSIC - CLAUDE DEBUSSY, "CLAIR DE LUNE"]