29-8 Chemistry of carbon: racemic mixtures
Uploaded by JUSTANEMONERD on 17.12.2012
Transcript:
PROFESSOR CIMA: Where does racemic mixture come from?
In the late 19th century, there were people quite concerned about this.
And, of course, the person that discovered this was none other than
the famous microbiologist Louis Pasteur. And what he was working on, at the time--
He was a microbiologist and so, microbiologists were primarily working
on, not human health, but winemaking. You have to put things in priorities.
It turns out this chemical in winemaking that is extremely important
is called tartaric acid. And they knew that you had to control the
amount of tartaric acid in winemaking.
I know you you'll recognize these crystals if you open enough bottles of
wine, especially French wine. When you open the bottle, sometimes you'll
see little crystals on the cork.
And those crystals are of this molecule, tartaric acid.
Now they were stumbling about understanding tartaric acid.
Remember, this is in the 19th century. And stumbling because they knew there were
several acids with exactly the same amount of carbon, hydrogen, and oxygen
in them. But they had different properties.
So you can see, one was racemic acid, which, when you crystallized it, had a
melting point of around 206 degrees. Racemic acid here, melting point of 206 degrees.
And then another one that they called tartaric acid, which melted
considerably lower. So it had different properties.
They knew they had to be isomers. And they couldn't figure out what was different
about them. Well, what Pasteur was messing around with,
he was trying to grow crystals of them.
And he stumbled across a very unusual preparation, where he took a solvent
that was a natural oil. And natural is the key thing here.
And what we found was that when he dissolved racemic acid into these, he
heated up, he could then lower the temperature and grow some crystals.
Just like you did with sugar when you were a kid, grow sugar crystals.
And what he found, under certain conditions, when he took racemic acid,
he got crystals that look like this. This one and this one.
And you see that they looked very similar, except that they were mirrors
of one another. And he literally picked them out under the
microscope. He'd pick one, put them in one bucket.
Put the other one in another bucket. And then dissolved them up.
And looked at the rotation. Well, I should write the chemical structure
here. And we use a lot of shorthand here.
I'll do the full structure. You'll see there is C-H O-H here, C-H O-H.
That's the full tartaric acid. And we lots of times simplify the structure
so that we don't show all the hydrogens.
So these hydrogens are not shown there. But what's interesting about tartaric acids
as you look, that this carbon and that carbon are chiral.
Right, so, this carbon has four different groups on it.
And so does this one. Special case though, we have to consider.
And it turns out that if you take tartaric acid it rotates, light
rotation, to left or levo. And if you take racemic acid, it gives you
no rotation, no net rotation. But if he takes these crystals that he grew
from racemic acid solutions, put one in one bucket and one in the other bucket,
he gets two. He gets an L. So an L. Rotation.
And what's the other one? A right rotation.
So he'd pretty much proved that what racemic acid was, was just tartaric
acid, but with the opposite handedness. Racemic acid was a mixture of tartaric acid
and its mirror image. Now, tartaric acid's also an interesting case
because it has an additional symmetry.
While both of these are chiral, you can see there's a mirror plane in the
molecule itself. So you have a couple of possibilities.
Let's say that this moves light to the left, and this one moves light to the
left, that's actually tartaric acid. What if I have this chiral center the moves
light to the left, and this chiral center moves this to the right.
That's called mesotartaric acid. And what do you think it does?
It's not optically active. Not optically active.
Why? Well, because if this one moves to the left
and this one rotates light to the right, I can spin this around and this end
will superimpose on that end. So the two chiral centers cancel each other
out. And then finally, you can have the racemic acid is where they're mixed on
both sites equally. Racemic acid has equal amounts of each handedness
on both of those chiral centers.
Now this is important, these crystals. The fact that we can now resolve a racemic
mixture into two separate solids means there are some interesting phase
diagrams that you can create.
You thought we would forget all about that. No, not at all.
So let's look at the phase diagrams. The simplest phase diagram you can make--
and it turns out that this is what happens with tartaric acid--
is I can put the right handed one on that end of the phase diagram.
And I put the left handed one on this end of the phase diagram.
And I mix this. I mix the two and ask, what's the melting
point? Well, each one of these will have its own
melting point. So, let's say it's that one for the positive.
What's the melting point for this one? What's it got to be?
It's got to be exactly the same. Good.
So that's the melting point. What happens in between?
Well, there's a couple of things. So one possibility is that these two enantiomers
don't form a compound. So a compound for an enantiomer is one where
this hand packs with this hand into a regular crystal.
If they don't, you get a eutectic. And so mixtures--
so this'll be liquid up here. This is plus and minus, and this is a plus
plus liquid, and this is liquid plus minus.
You get it. How about if I do it this way.
That looks better. So you get a eutectic.
In fact, most of the time when you crystallize racemic acid
you don't get this. You get what the other possibility is.
So I'll do the same. You get your same melting points.
But instead, there's a 50 50 compound. When you think about it, it's stacking just
my left hand into a crystal. And, of course, I can stack my right hand
into a similar crystal, but there's also the possibility I can stack both
hands together. That's my 50 50 compound.
And in fact, for racemic acid then that compound melts at a higher
temperature than either of the other two. And, of course, between we have eutectics.
So this is liquid up here. This compound I'll call alpha, which is just
the two versions of tartaric acid.
This is liquid plus alpha. This is liquid plus alpha.
This is a plus plus alpha. And this is alpha plus minus.
So, now I mentioned one of the tricks that Pasteur used to resolve these two
chiral compounds was to use a natural oil, natural solvent material.
And the reason why that was significant is that it turns out all
natural products are made with one hand. So in other words, anything that involves
a biochemical synthesis-- it's not really known.
There's lots of theories as to why, but it turns out all biochemical
substrates, foods and things like that, that are have chiral centers are
only the left hand version. And so, the solvent that he was using, because
it was a naturally derived solvent, turned out it was chiral also.
And so the solubilities of each of these two chiral
crystals were different. And so, he could selectively crystallize the
two enantiomers.
In the late 19th century, there were people quite concerned about this.
And, of course, the person that discovered this was none other than
the famous microbiologist Louis Pasteur. And what he was working on, at the time--
He was a microbiologist and so, microbiologists were primarily working
on, not human health, but winemaking. You have to put things in priorities.
It turns out this chemical in winemaking that is extremely important
is called tartaric acid. And they knew that you had to control the
amount of tartaric acid in winemaking.
I know you you'll recognize these crystals if you open enough bottles of
wine, especially French wine. When you open the bottle, sometimes you'll
see little crystals on the cork.
And those crystals are of this molecule, tartaric acid.
Now they were stumbling about understanding tartaric acid.
Remember, this is in the 19th century. And stumbling because they knew there were
several acids with exactly the same amount of carbon, hydrogen, and oxygen
in them. But they had different properties.
So you can see, one was racemic acid, which, when you crystallized it, had a
melting point of around 206 degrees. Racemic acid here, melting point of 206 degrees.
And then another one that they called tartaric acid, which melted
considerably lower. So it had different properties.
They knew they had to be isomers. And they couldn't figure out what was different
about them. Well, what Pasteur was messing around with,
he was trying to grow crystals of them.
And he stumbled across a very unusual preparation, where he took a solvent
that was a natural oil. And natural is the key thing here.
And what we found was that when he dissolved racemic acid into these, he
heated up, he could then lower the temperature and grow some crystals.
Just like you did with sugar when you were a kid, grow sugar crystals.
And what he found, under certain conditions, when he took racemic acid,
he got crystals that look like this. This one and this one.
And you see that they looked very similar, except that they were mirrors
of one another. And he literally picked them out under the
microscope. He'd pick one, put them in one bucket.
Put the other one in another bucket. And then dissolved them up.
And looked at the rotation. Well, I should write the chemical structure
here. And we use a lot of shorthand here.
I'll do the full structure. You'll see there is C-H O-H here, C-H O-H.
That's the full tartaric acid. And we lots of times simplify the structure
so that we don't show all the hydrogens.
So these hydrogens are not shown there. But what's interesting about tartaric acids
as you look, that this carbon and that carbon are chiral.
Right, so, this carbon has four different groups on it.
And so does this one. Special case though, we have to consider.
And it turns out that if you take tartaric acid it rotates, light
rotation, to left or levo. And if you take racemic acid, it gives you
no rotation, no net rotation. But if he takes these crystals that he grew
from racemic acid solutions, put one in one bucket and one in the other bucket,
he gets two. He gets an L. So an L. Rotation.
And what's the other one? A right rotation.
So he'd pretty much proved that what racemic acid was, was just tartaric
acid, but with the opposite handedness. Racemic acid was a mixture of tartaric acid
and its mirror image. Now, tartaric acid's also an interesting case
because it has an additional symmetry.
While both of these are chiral, you can see there's a mirror plane in the
molecule itself. So you have a couple of possibilities.
Let's say that this moves light to the left, and this one moves light to the
left, that's actually tartaric acid. What if I have this chiral center the moves
light to the left, and this chiral center moves this to the right.
That's called mesotartaric acid. And what do you think it does?
It's not optically active. Not optically active.
Why? Well, because if this one moves to the left
and this one rotates light to the right, I can spin this around and this end
will superimpose on that end. So the two chiral centers cancel each other
out. And then finally, you can have the racemic acid is where they're mixed on
both sites equally. Racemic acid has equal amounts of each handedness
on both of those chiral centers.
Now this is important, these crystals. The fact that we can now resolve a racemic
mixture into two separate solids means there are some interesting phase
diagrams that you can create.
You thought we would forget all about that. No, not at all.
So let's look at the phase diagrams. The simplest phase diagram you can make--
and it turns out that this is what happens with tartaric acid--
is I can put the right handed one on that end of the phase diagram.
And I put the left handed one on this end of the phase diagram.
And I mix this. I mix the two and ask, what's the melting
point? Well, each one of these will have its own
melting point. So, let's say it's that one for the positive.
What's the melting point for this one? What's it got to be?
It's got to be exactly the same. Good.
So that's the melting point. What happens in between?
Well, there's a couple of things. So one possibility is that these two enantiomers
don't form a compound. So a compound for an enantiomer is one where
this hand packs with this hand into a regular crystal.
If they don't, you get a eutectic. And so mixtures--
so this'll be liquid up here. This is plus and minus, and this is a plus
plus liquid, and this is liquid plus minus.
You get it. How about if I do it this way.
That looks better. So you get a eutectic.
In fact, most of the time when you crystallize racemic acid
you don't get this. You get what the other possibility is.
So I'll do the same. You get your same melting points.
But instead, there's a 50 50 compound. When you think about it, it's stacking just
my left hand into a crystal. And, of course, I can stack my right hand
into a similar crystal, but there's also the possibility I can stack both
hands together. That's my 50 50 compound.
And in fact, for racemic acid then that compound melts at a higher
temperature than either of the other two. And, of course, between we have eutectics.
So this is liquid up here. This compound I'll call alpha, which is just
the two versions of tartaric acid.
This is liquid plus alpha. This is liquid plus alpha.
This is a plus plus alpha. And this is alpha plus minus.
So, now I mentioned one of the tricks that Pasteur used to resolve these two
chiral compounds was to use a natural oil, natural solvent material.
And the reason why that was significant is that it turns out all
natural products are made with one hand. So in other words, anything that involves
a biochemical synthesis-- it's not really known.
There's lots of theories as to why, but it turns out all biochemical
substrates, foods and things like that, that are have chiral centers are
only the left hand version. And so, the solvent that he was using, because
it was a naturally derived solvent, turned out it was chiral also.
And so the solubilities of each of these two chiral
crystals were different. And so, he could selectively crystallize the
two enantiomers.