Warning: Sulfuric and propionic acids are corrosive.
Wear gloves when handling them.
Ethanol is highly flammable.
Fire safety protocols must be in place.
Greetings fellow nerds.
I wanted to make more ethyl propionate so i'd have a good stock available in case i made more mistakes in my synthesis of pyrimethamine.
Now in a previous video we made ethyl propionate by the classic process of acid catalyzed fischer esterification between ethanol and propionic acid.
If you want to review that video you can check the video description.
The drawback of that method was that our raw yield was about 40% and that was likely inflated since we hadn't purified by distillation yet.
The reason why the yield was low was because the reaction is reversible.
The water can react with the ethyl propionate and produce propionic acid and ethanol again.
If we could remove the water we could drive the reaction forward.
Unfortunately we can't just distill the water out because the ethanol and the ethyl propionate azeotropes have even lower boiling points.
We'd never be able to selectively remove just the water.
We'd also carry out too much of our reactants and stop the reaction.
Now in a previous video i showed that we could use molecular sieves to dry alcohol
and some have asked if that could be used for fischer esterification.
Unfortunately we can't add the molecular sieves directly because the acids in the reaction would destroy them.
Luckily, for us, there is a workaround.
In a previous video I showed this apparatus, the soxhlet extractor.
For further information about it you can check the video description.
But briefly it allows us to condense vapor, dissolve or expose something to that condensate,
and then return the dissolved substance to the boiling flask.
In this video we're going to use it instead to selectively remove water with molecular sieves.
First we start with a erlenmeyer flask and add in 80 mL of propionic acid.
Then we add to that 100 mL of ethanol.
Normally you would remove any dissolved water first but in this case we don't have to as we'll be removing the water during our reaction.
Finally we need an acid catalyst and we’ll use 4 mL of concentrated sulfuric acid.
The process so far is just like regular fischer esterification.
Now for the important difference, instead of a simple reflux apparatus,
we set up a soxhlet apparatus filled with molecular sieves 3A.
I have about 80 grams worth.
Mine is bagged with filter paper to prevent the beads from being sucked through the siphon tube and falling into the boiling flask.
The molecular sieves were previously dried on a hot plate at 250 celsius for three hours.
Now the amount of molecular sieves you have limits the size of your reaction.
Molecular sieves can hold about 22% of their mass in water.
So you have to calculate how much mass water that is and size your reaction to produce a roughly equal amount.
You also have to ensure you have enough volatile solvents to fill your soxhlet extractor.
If it doesn't fill high enough to activate the soxhlet siphon then the solvents won't properly return when they are dried.
I sized the quantity of chemicals earlier to match what i'm using here.
Okay once the apparatus is all assembled and the cooling water running, turn on the hotplate.
Gradually raise the temperature until it starts to reflux and condense into the soxhlet extractor.
You don't need a very high turnover rate.
What’s happening is we’re reacting the propionic acid with ethanol to form ethyl propionate and water.
The sulfuric acid acts as a catalyst.
Now as said before, the reaction is reversible so we can never get a good yield just at equilibrium.
The water reacts with the ethyl propionate and goes back to ethanol and propionic acid.
The soxhlet extractor helps us get around this.
The boiling mixture of ethanol, propionic acid, ethyl propionate and water forms low boiling azeotropes that rise up and condense into the soxhlet apparatus.
For those of you that don't know, or missed my video on fractional distillation, azeotropes are mixtures that boil together.
They behave almost like pure chemicals in that they boil and condense with the same composition.
You can't separate them by distillation alone.
Now i don't exactly know what azeotrope compositions form here.
Water and ethanol make one azeotrope but i found no data on ethyl propionate and the azeotropes it forms.
Whatever it is, I'm betting the the lowest boiling azeotrope between all three contains water.
Even if it's just a few percent water that's tremendously advantageous to us.
Molecular sieves are extremely good at extracting water from organic solvents
so any ethanol or ethyl propionate that condensed would be thoroughly dried and then returned to the boiling flask.
Where it reboils along with a bit more water.
By cycling the water, alcohols and esters around with the extractor,
we can gradually remove all the water and only the water,
without losing our alcohol or esters as we would if we just went with straight distillation.
It's a great trick, the only drawback is that it won't work if none of the low boiling azeotropes contain water.
Now at this point you might be wondering what happens with the acids.
Propionic acid and sulfuric acid are too polar and too high boiling so they don't vaporize and condense into the soxhlet apparatus.
This is very convenient for us as molecular sieves are destroyed by acids.
Thanks to the soxhlet extractor we can use them for the reaction without actually using them in the reaction.
In a way, we've built a mini chemical plant where we have two separate processes running.
Fischer esterification here, and water removal over here.
Anyway, I'll let this run overnight.
While molecular sieves are very effective they are also very slow and need time to work.
Okay here we are the next day and i've already turned off the heating.
Once it's cooled, we pour 100 ml of cold water into the soxhlet extractor.
This is to wash out the alcohol and ethyl propionate from the sieves for greater recovery.
Now give it a stir.
The water will now dissolve most of the components in our reaction mixture except ethyl propionate
which has very low solubility in water.
The ethyl propionate will then float on top like an oil allowing for convenient separation.
To do this we use a separatory funnel.
You can see the layer of ethyl propionate floating on top of the water.
Drain away the water first and then collect the ethyl propionate.
Now you might be wondering why i'm washing with water when i said water destroys ethyl propionate.
While the mixture is cold the reaction of water and ethyl propionate is very slow.
It's only when it's hot that the reverse reaction becomes a problem.
Nonetheless, when i store this i'll be sure to remove all traces of water.
And there it is, crude ethyl propionate.
The mass of this is 103g for a crude yield of 93%.
This is a tremendous improvement over the direct method that only gave 40%.
Now granted, this 93% is grossly impure, but so was the 40% of the original method so we can still compare them.
To improve purity somewhat i'm going to wash it again with 100mL of cold water.
The most likely impurity is ethanol which, while soluble in water is also soluble in ethyl propionate
and usually doesn't wash out in a single run.
Let me separate them out again.
And there we go.
This is 90g or about 81% yield.
We're still ahead of the original method.
Now i'm going to store my crude ethyl propionate over molecular sieves to remove the water.
In my future experiments i'll need it water free.
There is likely still a few percent ethanol remaining but that isn't an issue for what i want it for.
If you want to remove the ethanol you can fractionally distill the ethyl propionate.
In anycase i'm actually quite pleased with how well the soxhlet extractor with molecular sieves worked.
My bet that water was in the low boiling azeotrope paid off.
And this procedure wasn't even optimized yet.
I used twice as much ethanol as necessary because i was roughly copying the old method.
If the water is so effectively removed then we don't need an excess of ethanol.
A stoichiometric amount might work better and give even higher recoverable yield.
Yet another option would be to use an excess of propionic acid and have complete conversion of ethanol.
With no water or ethanol present one could directly fractionally distill pure ethyl propionate from the mixture.
No need for water washing and additional molecular sieve drying.
So many options are available.
This procedure doesn't waste any new chemicals either, the molecular sieves used in the soxhlet extractor can be dried and reused.
This is what i love about having a new tool for chemistry.
The tool itself might change just a single step.
But it can radically change your procedures in ways that open up whole new pathways.
I wish i had more time to try out all these new pathways but i need to move on to my next experiment.
Anyway, so that was how you use a soxhlet extractor and molecular sieves to drive forward the fischer esterification of ethanol and propionic acid.
Thanks for watching.
Special thank you to all of my supporters on patreon for making these science videos possible
with their donations and their direction.
If you are not currently a patron, but like to support the continued production of science videos like this one,
then check out my patreon page here or in the video description.
I really appreciate any and all support.