Warning: Chlorine gas is toxic.
P-chlorobenzyl chloride is a lachrymator and carcinogenic.
This experiment must be performed outside or in a fume hood.
Greetings fellow nerds.
In this video we're going to make p-chlorobenzyl chloride, also known as 4-chlorobenzyl chloride.
This is the next step in making the anti-protozoal drug pyrimethamine
after we made the para-chlorotoluene in a previous video.
So let's get started.
First we have our sample of p-chlorotoluene in the erlenmeyer flask.
I've got about 61g. We're going to boil that until it refluxes.
Now over here is our chlorine generator and drying flask.
Now i've already shown how to make these
and what chemicals to use in another video so i won't discuss it here.
Suffice it to say this generator is loaded with enough chemicals
to produce one mole equivalent to p-chlorotoluene of diatomic chlorine gas.
Now after the gas is dried by the sulfuric acid,
it passes up here and down this condenser column into the claisen adapter.
There it will meet the p-chlorotoluene vapor that's boiling up from the erlenmeyer flask.
Once those two gases are mixed, the fun part happens over here
when it pases over the ultraviolet light emitting diode chip, or UV LED chip.
These LEDs are pretty easy to get online
and i'm using a 50 watt version that i've clipped to this spare intel CPU heatsink i happened to have.
It's being powered by a power supply off camera. The wavelength is about 400 nm.
Now the UV light initiates the reaction between the gases
and the heavier products will condense in this exit column and drip back down into the boiling flask.
The lighter byproducts will not condense and exit out the top.
So let's begin.
I'm going to put some aluminum foil around the flask to insulate it so it boils easier.
I'm also going to put some foil on the inlet column to protect it from UV light.
To be honest this was a useless move so don't bother when you do your reaction.
Anyway. Turning on the heating, the cooling water and wait until the p-chlorotoluene starts to reflux.
Now turn on the UV Light and start generating the chlorine and admitting it to the reaction.
Now i have to apologize at this point for excessive
and annoying number of flies you're going to see around the apparatus.
They seem to be attracted to the UV light and clustering around it.
I know it makes my lab look like a terrible third world ghetto with them in the video like that.
Totally unprofessional and amateurish.
Okay moving on.
What's happening is the ultraviolet light is initiating free radical chlorination.
The light breaks up the chlorine into chlorine radicals.
These chlorine radicals attack the methyl group on the p-chlorotoluene
to form p-chlorobenzyl chloride as well as hydrogen chloride.
The hydrogen chloride gas escapes out the top of the column
but the high boiling p-chlorobenzyl chloride condenses and drips down into the flask.
Since it has a higher boiling point than p-chlorotoluene it should stay in the flask and not get over chlorinated.
Now what's interesting about this reaction is that it only chlorinates the methyl group, not the ring.
In contrast when we were making chlorotoluenes we also used chlorine gas
but by using an iron chloride catalyst rather than UV light we chlorinated just the ring.
This demonstrates the importance of selecting the right reaction conditions to influence the mechanism you want.
Now you'll notice the claisen adapter being filled with black soot.
This is because we're having small chlorine fires.
And you can see them as tiny little orange flashes.
Did you miss it? Let me freeze frame on one of the flashes.
That orange streak is a chlorine fire.
I'm adding too much chlorine too fast and that's creating a mixture rich enough to burn.
Now all the oxygen has been purged out by the continual reaction
but chlorine itself is a powerful oxidizer and thus it can also support combustion in some instances.
The UV light is initiating the reaction.
Now for our product we don't want this to happen so we'll need to stop it.
The process is similar stopping combustion with a regular fire.
We just slow down the rate of chlorine addition to create a mixture too rich in fuel to burn.
Here we go, looks like the burning has been reduced.
Let's see what was happening beneath this foil.
All the black soot shows that a good amount of my chemicals burned in here.
Now looking back, this apparatus was badly designed.
I would have had much better performance if i used a long glass tube
and lead the chlorine deep into the flask first rather than through the top of the claisen adapter.
I would have had better mixing and less burning.
Ah well. This is my first ever photochemically initiated free-radical chlorination reaction.
I had to make a mistake somewhere.
At least now i know how to do better next time.
Okay, the reaction looks stable, i'm going to skip ahead until i use up all the chlorine.
And here we are. The reaction is finished and i've allowed it to cool.
The flask should now contain p-chlorobenzyl chloride
as well as unreacted p-chlorotoluene.
Now rearrange the apparatus and set up for fractional distillation.
Our target p-chlorobenzyl chloride has a boiling point between 216 and 222 celsius
so discard everything below 200 degree celsius.
Then start collecting the fractions between 200 and 230 celsius.
You may have to insulate your apparatus with foil since 200 celsius
and greater tends to be difficult for simple hotplates and bare equipment.
And there we have it, p-chlorobenzyl chloride.
Here is the NMR spectrum proving we have a relatively pure product.
My yield was 50g or about 65%.
I think if i just slowed down the chlorine addition to prevent burning
and better mixed the chlorine i would have better yield.
Ah well. For a first time, that was still a great success.
This is yet another step in making pyrimethamine.
In an upcoming video i'll try and add a nitrile group using cyanide.
Thanks for watching.