Today we've got an exotic array of reagents.
In the previous video we tried out a way of converting vanillin, an aldehyde, into the
nitrile.
It didn't work though.
So today we're going to try another approach.
So let's go through the lineup of reactants and explain the theory.
First up, here's our vanillin.
We're using 10 grams of food grade vanillin powder here.
This is our aromatic aldehyde, and our objective is to convert this into the corresponding
nitrile, vanillyl nitrile.
You can see that this comprises removing the oxygen and hydrogen of the aldehyde and
replacing them with nitrogen, forming an organic cyanide.
Otherwise known as a nitrile.
And here's the reagent which is key to our strategy.
Here we've got 5 grams of hydroxylamine hydrochloride crystals, otherwise known as hydroxylammonium
chloride.
Unfortunately this isn't exactly ODC, and it's difficult to make.
But hunt around online and you may be able to find some.
Well you may know that in the presence of a base which can
convert the hydroxylamine salt into free hydroxylamine, the aldehyde and the hydroxylamine
can react together to form a compound known as an oxym.
In fact we've done this in a previous video with exactly these two reagents.
But look closely at the oxym.
What happens if we remove water from this?
So let's move on to the next reagent.
Here we have 22 mL of liquid pyridine.
This is slightly impure and yellow-colored because we've added a little bit of hydrogen.
We can put it in a slightly dirty bottle.
But it's dry which is the important thing.
This is our base, and we've measured out enough here so that there's sufficient to
neutralize not only the hydrochloride part of the hydroxylamine salt, but also acids
such as acetic acid which are going to get produced as a side effect of the reaction.
So there's one component left from our plan.
Something that can suck the water out of the oxym and hopefully form our product.
Here it is, 10 grams of acetic anhydride.
We prepared this in a previous video by reacting sodium acetate and acetyl chloride, so check
that out for details.
As the anhydride reacts with water, it's going to produce acetic acid.
Hence the quantity of pyridine we measured out.
We're going to use a 200 mL beaker for the reaction, equipped with stirring.
So only one thing left, a solvent.
And that's it.
So here we've got 50 mL of acetonitrile.
We've chosen acetonitrile because later on we'll be able to add water to the reaction
mixture and have it mix without forming a separate layer.
We also figured that maybe the presence of nitrile groups in the solvent will coax out
our product.
The nitrile will form because it will see the other happy nitrile groups around it and
figure that they can be a nice safe happy family together.
All right, let's get this set up.
It's pretty simple.
We've got the beaker containing the acetonitrile on a stirrer, and we've got a thermometer
in here as well to record the temperature.
So let's start stirring.
The acetonitrile bottle was in a warm place so we're starting off at 30 degrees C. First
let's get our vanillin dissolved.
It dissolves in the acetonitrile rapidly, and as we often notice when we dissolve vanillin,
there's a considerable temperature drop.
Now down at 20 degrees C. Someone should make cool packs containing vanillin and acetonitrile.
We reckon the customer potential is huge.
Now we'll add the pyridine to the reaction mixture.
Okay.
Remember that the yellow tint is a trace impurity.
Pure pyridine is clear like water.
Okay so now let's add the hydroxylamine hydrochloride.
On adding this we should hopefully see a sign of a reaction as free hydroxylamine is generated
in the mixture.
Not as immediately soluble as the vanillin was.
But after a few minutes of stirring it is dissolving as you can see.
Okay.
And we've got a temperature increase up to 35 degrees C. Which we would expect from an
acid-base neutralization reaction, the hydrochloride reacting with the pyridine.
After a few more minutes the solid has completely dissolved.
We left this stirring for 30 minutes in order to make sure that any reaction in the mixture
had completed.
Remember, at this point we're hoping that we're going to get vanillinoxam being produced.
in the mixture. We partially covered the beaker with some wrap in order to avoid
any nasty pyridine getting out. Ok so 30 minutes later. Now we're going to slowly
add the acetic anhydride to the reaction mixture and see what happens. A little at
a time using a pipette. And there we go, a slight temperature increase. There's no
visible change in the reaction mixture. Let's add some more anhydride. Up again,
about 38 degrees. So let's get this all in now.
And things are hotting up in there. Peak temperature was 50 degrees C. So now we'll
just let this mixture stir and slowly cool back down to room temperature again. We stirred
for 2 hours as the mixture slowly cooled. And here we are 2 hours later. We took the
beaker off.
the stirrer, covered it very tightly in plastic wrap, and then left it for 24 hours. Apparently
the reaction can take some time to complete, so we figured we'd leave it overnight and
then we'd at least given it a decent chance of working. And here we are 24 hours later.
No visible change. We'll work this up by firstly pouring it onto ice and diluting the solvent
down.
And now the reaction mixture.
There's a milky suspension formed, but even as the ice melted and the mixture was then
chilled for a few hours, no crystals of a nitrile product formed. Instead we got a yellow
colored viscous oil appearing in the bottom of the beaker. And after a few hours the suspension
had cleared. With the ice melting, we then added the soda. And here we are, no visible
all the tiny oil droplets going into this bottom layer.
We figured we'd extract this using 25 ml of dichloromethane.
We also adjusted the pH of the mixture using 50% sulfuric acid in order to ensure that
all pyridine was dissolved in the aqueous layer.
We placed the mixture into a separating funnel, separated the bottom DCM layer, and then washed
it.
We dried it using magnesium sulfate, and then evaporated down the DCM to see what we were
left with.
And here it is.
A fairly viscous slightly yellow colored oil.
Which resisted all attempts to crystallize, and interestingly when fresh didn't have any
acetic acid aroma, but on standing overnight started to dissolve.
And that's the giveaway.
What we've got here is probably a mixture of compounds, but contains a large quantity
of O-acetyl vanillin oxym.
In other words the phenol group of the vanillin was too acidic and it reacted preferentially
with the anhydride before it got a chance to dehydrate.
Even freezing didn't produce any crystals.
So this first test is a failure.
But it got us thinking.
Maybe if we start using pure vanillin.
And then use a stronger but less reactive dehydrating agent perhaps we can get this
to work?
So here's another experiment.
This time we're going to do things a bit differently.
On the left we've got 7 grams of pure vanillin oxym which we prepared as per our previous
video.
And on the right, covered with wrap to protect it from moisture, we've got 5 grams of phosphorus
pentoxide.
In theory just under 4 grams should be needed to dehydrate the oxym completely, so this
is a 20% excess.
Here's a 200 ml beaker equipped with stirring, and as a solvent for the reaction we're going
to use 50 ml of dichloromethane.
In goes the oxym.
In.
Actually doesn't dissolve that well in DCM.
So we're going to add a little bit of oxym.
So we'll have to leave it as a suspension.
Let's protect this from atmospheric moisture ready.
And we slowly add the phosphorus pentoxide.
Nothing happens to start with, but after a few additions the mixture starts to gum up
and form lumps.
We complete the addition and then leave the mixture stirring.
We left this for two hours, and during this time the lumps seemed to break up and form
a finer powder in the mixture with a slightly brown-gray colour.
Here we are after two hours.
Well something looks like it's happened but we won't know what until we work this up.
It's done.
We'll start by getting this back on stirring, and we'll add ice cubes which should slowly
and gently hydrolyze any remaining pentoxide.
At one point the mixture bubbles slightly, but not by much.
Another ice cube.
We let this stir away for about 30 minutes and then set up to filter the mixture.
There's some more cool 60s psychedelic stuff going on in there.
Oh.
Next we get the filtrate into a separating funnel.
We separate off the bottom DCM layer, dry it using magnesium sulfate again, and then
evaporate down in order to see what's left behind.
Here we go.
A kind of splodgy mess.
But some did react and has come through here.
And here's an oily liquid with some solids starting to form.
So what is it.
Well it's not the nitrile.
Again it's probably a mixture of things, but the overwhelming characteristic is the strong
aroma of vanillin.
Yes we've ended up back at vanillin again.
What's happened is that the phosphorus pentoxide or perhaps the phosphoric acid generated,
being strongly acidic, have hydrolyzed the oxym rather than sucking water out of it.
This has just taken us back.
back to where we started. Back to vanillin. So this didn't work either.
Well we're not giving up hope yet. We think there must be a convenient way to get from the aldehyde
to the nitrile. We just need to try some more ideas. What it does show though is how synthetic
chemistry is a game. Some reactions you want to do but you can't because they'll mess up other
functional groups. In the end you've got to find your way through the maze and to the path that
works. We're kind of surprised that no one has written a computer algorithm with every known
reaction in it which does a search tree analysis, rather like analyzing a chess game, and can tell
you how to get from A to B. Perhaps they have and we just don't know. We'll be taking another short
break for a week and a half now. Unfortunately although chemistry beats economics in terms of
logic and predictability, economics trumps chemistry in the real world and so we need to
go.
Stay tuned for more reactions soon.