Warning: This experiment uses highly corrosive sulfuric acid and chlorinated solvents.
Wear gloves when handling them.
This experiment also generates sulfur dioxide.
Work outside or in a fume hood.
Greetings fellow nerds.
In a previous video I made chlorotoluene by reacting toluene
and a chlorine source like chlorine gas or trichloroisocyanuric acid.
While this worked very well and gave better than eighty percent yield,
the resulting chlorotoluene consisted of a mixture of para and ortho isomers.
Since different experiments require different isomers we'll need a way to separate them.
Now ortho and para chlorotoluene have slightly different boiling points
and so they can be separated industrially by fractional distillation.
Unfortunately the overlap of their vapors is so great
that you need a huge column of 200 theoretical plates or more.
One of the patents i read called for a column 13 meters long.
Yeah my puny little vigreux column is not going to cut it.
We're going to have to use a chemical approach rather than physical.
So here is our mixture of chlorotoluene isomers.
About 450 grams worth.
Now chlorotoluene is clear but my sample is a cloudy due to tiny amounts of water.
This is not a problem though.
Now add in about 65 mL of concentrated sulfuric acid.
This corresponds to a one third molar equivalent.
My acid is red because it's low grade drain cleaner acid.
High quality acid will work better but isn't strictly necessary.
Now set up a dean stark apparatus around the flask operating in heavy return mode.
I've shown how to make these in a previous video.
A traditional apparatus cannot be used because it only returns the lighter fraction but we
want to return the heavy fraction.
Now chlorotoluene boils at around 160 degrees celsius.
To minimize heat loss and makes this reaction go faster i'm insulating the hot portions
of the dean stark apparatus with foil.
Normally I'd insulate more of this but i'm leaving some parts open so you can see the
progress of the reaction.
Now turn on the heating to three hundred degrees celsius and let it boil.
What we're doing is sulfonating the chlorotoluene and releasing water.
By turning up the heat high enough to boil the mixture,
the water boils out along with chlorotoluene.
The dean-stark trap allows us to conveniently separate
and return the chlorotoluene and keep just the water.
By removing the water from the reaction we drive it forward.
Now an interesting thing happens with the isomers of chlorotoluene.
Ortho-chlorotoluene reacts faster and is more stable than para-chlorotoluene.
This is because the sulfonate group is quite bulky
and thus is more stable on positions far away from any other substituent.
On ortho-chlorotoluene this is easy since there are two positions
it can react with that aren't beside another substituent.
But on para-chlorotoluene wherever it goes it will bump against another substituent.
So para chlorotoluene sulfonation is less favored than ortho-chlorotoluene.
This effect of the physical crowding affecting reactivity is called the steric effect
and allows us to fine-tune a lot of chemical reactions that way.
In this case we're using it to resolve ortho and para chlorotoluene.
Now even though some of the para chlorotoluene is reacting,
this isn't a problem because the reaction is reversible.
So the sulfuric acid regenerated can go to react with the ortho isomer.
If we use equal or less sulfuric acid than the ortho isomer we can get almost exclusive
ortho sulfonation.
Unfortunately this is rather slow.
So keep running the reaction until the water content in the dean-stark trap stops increasing
and then run an extra hour to ensure an equilibrium is reached.
Now you're probably wondering if i know this mixture has 60% ortho-chlorotoluenes which
i want to remove,
why did i only about one third equivalent of sulfuric acid which is not enough to remove
it all.
Well I did try adding a stoichiometric equivalent
but i then notice a large amount of decomposition happening.
The chlorotoluene sulfonic acid decomposes at high temperatures
and concentrations to chlorocresols and sulfur dioxide.
By limiting the sulfuric acid to less one third we limit the concentration of chlorotoluene
sulfonic acids
and thus limit decomposition.
The drawback is that we'll have to repeat the process to convert more of the o-chlorotoluene.
Okay looks like we're done.
Now turn off the heating and let it cool.
So here we are.
Now while some of our chlorotoluenes is in the dean stark trap.
Most of it is here as a mixture of chlorotoluenes, chlorotoluene sulfonic acid and decomposition
products.
Now if you look very closely there is a small amount of separation of the components.
But there is still a lot of contamination
and it's very difficult to get clean recovery of just the chlorotoluenes this way.
So we're going to use steam distillation.
To the mixture add an equal amount of water.
Since i have about 500 mL total i'm going to add another 500 mL of water.
Stir it up until thoroughly mixed.
Now assemble the dean stark apparatus around it and set it up for light return mode.
You'll also notice that rather than a graduated cylinder for our trap we're using a much larger
500 mL flask.
This is because we're going to collect all our chlorotoluenes there.
Now simply heat up the mixture until boiling and start collecting the heavier components.
What we're doing is taking advantage of the fact that water
and chlorotoluenes form a low boiling azeotrope.
This carries our chlorotoluenes out of the mixture
and separates them from our chlorotoluene sulfonates and decomposition products.
This is much cleaner than trying to decant the mixture from earlier.
The dean-stark apparatus lets us remove the water
and return it to the mixture to continuously carry out the chlorotoluenes.
Now you might be wondering if we originally made the chlorotoluene sulfonate by sulfonation
and removing water,
wouldn't adding the water back in hydrolyze it
and thus reverse process destroying our progress.
You're absolutely right and this would happen at higher temperatures.
But since we added so much water the mixture is boiling
and thus maintaining a lower temperature at about the boiling point of water.
At this lower temperature we can take advantage of azeotropic distillation
without worrying about the reverse reaction.
This is also why we didn't directly distill the mixture.
As said before, chlorotoluenes boil at about 160 celsius which is hot enough to begin decomposing
the chlorotoluene sulfonates.
Okay, looks like the level of chlorotoluene is no longer increasing, we can turn off the
heating and let it cool.
Here is our chlorotoluenes and I've decanted most of the water.
This mixture is enriched in para-chlorotoluene isomers and depleted in ortho-chlorotoluenes.
The residue back here contains our ortho-chlorotoluene sulfonate and some water.
Now we can convert this into pure ortho-chlorotoluene
but first i'm going to set it aside and focus on further purifying the para-chlorotoluene.
Now this mixture has an unknown ratio of para and ortho-chlorotoluenes.
We know it's been para-chlorotoluene enriched, we just don't know if it's pure.
We could use nuclear magnetic resonance spectroscopy.
But if you had access to that you wouldn't be trying to make para-chlorotoluene in your
basement
and would just buy it directly from a chemical supply company.
Fortunately there is a simple test we can perform.
Ortho-chlorotolene has a much lower freezing point than para-chlorotoluene
so we can roughly figure out our purity based on that.
This is because para-chlorotoluene has a melting point of 7 celsius while ortho-chlorotoluene
has a melting point of -35 celsius.
Take a small sample of your chlorotoluene mixture and put it in the freezer.
If it doesn't freeze at all then it has too much ortho-chlorotoluene.
If it freezes then make a mixture of ice water and place the sample vial in that.
If it melts again then it's richer in para-chlorotoluene but not quite pure enough.
If it stays frozen then it's highly pure para-chlorotoluene.
Now we didn't simply drop our sample into ice water because chlorotoluenes have a strong
tendency to supercool
so starting from a liquid state and lowering the temperature to find the freezing point
is terribly inaccurate.
It's much more accurate to start from a solid state and warm upward to find the melting
point.
Anyway, in our first run back here the melting point test showed it remained liquid even
in the freezer,
so we still have a lot of ortho-chlorotoluene that we need to separate.
So we'll need to do our sulfonation again.
Make a note of how much chlorotoluene you have now
and calculate how much sulfuric acid you'll need to equal a one third mole equivalent.
I have about 300 mL of chlorotoluenes and this corresponds to about 40 mL of sulfuric
acid.
There is some water in my chlorotoluenes from earlier.
But i'm not bothering to remove it since we'll be running the dean-stark trap in heavy return
mode and removing the water anyway.
So run the sulfonation as before and then perform the azeotropic separation.
Then run the freezing and melting point test to see how pure the chlorotoluenes are.
Keep saving the ortho-chlorotoluene sulfonates
if the freezing and melting point test shows the chlorotoluenes to be impure.
If however the test shows the chlorotoluenes to be pure para-chlorotoluene,
do not save the ortho-chlorotoluene sulfonates from that run.
This is because that particular run was when the sulfonation reaction finally exhausted
all the ortho-chlorotoluene
and is now consuming para-chlorotoluene.
The sulfonates from that run now contain a mixture of chlorotoluene sulfonates
rather than pure ortho-chlorotoluene sulfonate.
Anyway.
Here is the purified para-chlorotoluene.
It took a lot of work.
And from 450 mL of mixed chlorotoluenes we only recovered about 70 mL of para-chlorotoluenes.
Most of the loss was from the fact the para-chlorotoluene was only present in about 40%,
and the rest of the loss was from handling losses since this is such a complicated and
laborious process.
Nonetheless by amatuer means we have produced essentially a pure para-chlorotoluene isomer.
To be absolutely sure i sent off a sample for NMR analysis.
As you can see the clean spectrum shows we have indeed produced pure para-chlorotoluene.
Now for storage i recommend adding some molecular sieves to remove the cloudiness that comes
from suspended water droplets.
As for the ortho-chlototoluene sulfonates, we can now convert it back into ortho-chlorotoluene.
The process is actually quite simple.
Just gradually heat the mixture and distill off the water and ortho-chlorotoluene.
The water from the original separation of chlorotoluenes should still be there so we
don't have to add more.
What's happening is that at first the excess water boils off at lower temperatures.
As the temperature rises the water remaining reacts with the ortho-chlototoluene sulfonates
to produce sulfuric acid and ortho-chlorotoluene.
The ortho-chlototoluene boils off and distills over.
Unfortunately there is also a large amount of decomposition at these temperatures to
chloro cresols
and sulfur dioxide so our yield is severely affected.
Try and maintain a temperature of about 175 to 180 celsius in the mixture to reduce decomposition.
Now if you don't actually need ortho-chlorotoluene for anything then i say don't bother and just
dispose of sulfonates.
This hydrolysis is prone to boiling over and ruining your reaction.
Even worse is that once the hot sulfonates get stuck in your condenser they solidify
and it takes hours of cleaning to get them out again.
Anyway.
After many aggravating days of work i eventually got some ortho-chlorotoluene.
I was actually expecting a lot more than this
but a lot of the ortho-chlorotoluene sulfonates decomposed and thus reduced our yield.
I think the fact that i used drain cleaner grade sulfuric acid with whatever impurities
are in it may have accelerated decomposition.
Oh well.
NMR analysis shows i have reasonably pure ortho-chlorotoluene so at least this wasn't
a total loss.
Anyway, that is how you use steric effects and sulfonation to separate ortho and para
chlorotoluene isomers.
This is another step in our synthesis of the antiprotozoal drug pyrimethamine.
Thanks for watching.
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