WEBVTT

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Prof: Okay,
so we were talking last time

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about rotation in ethane,
and the fact that there was a

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barrier,
and that you can measure the

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barrier.

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And one way to measure the
barrier, the first way that the

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barrier was measured,
was remarkably enough,

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by the heat capacity of ethane;
how much heat it takes to warm

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it to a certain temperature.

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So that showed that the barrier
was about three kcal/mole,

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but it didn't say what the
geometry of minimum energy was.

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Was it eclipsed,
as shown by the red line here,

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so that the eclipsed form is
the lowest in energy?

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Or was the favored form
staggered?

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And people differed in their
interpretation of that.

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Ultimately there was some
diffraction study,

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electron diffraction,
that showed that it was

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staggered.

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But now the best word on this
nowadays is probably from really

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high-quality calculations.

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And you can see from this
paper, published in the

01:01.631 --> 01:04.081
Journal of Chemical
Physics in 2003,

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that there's pretty good
agreement.

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All these various abbreviations
are various really high-quality

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computational results.

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You can see at the top,
our experimental results,

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from heat capacity.

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It's about 1000 wavenumbers.

01:20.650 --> 01:25.830
A wavenumber is 2.86 small
calories, not kilocalories,

01:25.825 --> 01:26.895
per mole.

01:26.900 --> 01:30.750
So there's heat capacity from
infrared spectroscopy,

01:30.754 --> 01:33.934
from microwave,
from Raman spectroscopy.

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All these experiments give very
close to 2.9 kcal/mole,

01:37.968 --> 01:40.808
or about 1000 wave numbers --
right?

01:40.810 --> 01:44.750
-- within a couple of percent;
even less than that probably.

01:44.750 --> 01:51.730
And then all these calculations
give about 2.7 kcal/mole.

01:51.730 --> 01:53.560
And it doesn't make very much
difference.

01:53.560 --> 01:56.470
The first one of these -- some
of these aren't such very

01:56.473 --> 01:59.193
high-quality calculations,
but some of them are very,

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very high quality,
the best that can be done.

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And they all agree pretty much.

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So it's clear that the
staggered form is favored over

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the eclipsed;
despite what everyone wrote in

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the nineteenth century,
when they always wrote them

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eclipsed,
and what whoever it was that

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drew the picture for the
American Chemical Society of

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their Molecule of the Week,
last week, drew too.

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He drew it eclipsed;
or she.

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Okay?

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So anyhow, but then there's the
question why?

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Why is it that the staggered
form is lower in energy than the

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eclipsed?

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Why is there a three
kilocalorie barrier?

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Well there's different points
of view on that.

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One is that the eclipsed form
is unstable;

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that for some reason having it
eclipsed makes it unstable.

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The other one is that the
staggered form is unusually

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stable.

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And what does this remind you
of, in terms of a question?

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Students:
Compared to what?

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Prof: Compared to what?

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What's unusual,
right?

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Is what's unusual the eclipsed
form or the staggered form?

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Well from the point of view of
the eclipsed form,

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why would it be unstable?

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Well it could be that the
hydrogens repel one another,

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because just in space;
their van der Waals radii.

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Okay, but if you think about
that, then if you had a methyl

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in place of one of those
hydrogens, it's ever so much

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bigger.

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Therefore you should have a
much bigger barrier to rotation,

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of a methyl group in propane.

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But, in fact,
the barrier is almost exactly

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the same;
3.4, not ten or something like

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that.

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So the size of hydrogen doesn't
seem to be so very important.

03:45.220 --> 03:50.230
Of course, protons repel one
another, and the electrons that

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are in the bonds repel one
another;

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there's electron repulsion.

03:54.740 --> 03:58.600
So that might be why you don't
want to have it eclipsed;

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that you want to rotate it a
little bit to make it staggered.

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But that's not easy to do in
your head,

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because there are also
attractions between a proton on

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one side,
and the electron on the other,

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and it's not clear which of
these is going to dominate.

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So anyhow, there's the
possibility that it has to do

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with the eclipsed form being
unusually destabilized -- right?

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-- because of repulsions;
that could be.

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The other point of view is that
the staggered form is unusually

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stable.

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Now why could that be?

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It's that you have a
σ on one side and a

04:33.343 --> 04:36.873
σ* on the other
side of these C-H bonds;

04:36.870 --> 04:38.030
and vice-versa as well.

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And you can get overlap between
this HOMO and LUMO in this way.

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And it turns out,
surprisingly enough,

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that the overlap is bigger when
they're anti than when they're

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eclipsed.

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You might think,
intuitively,

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that there'd be more overlap
when they're on the same side,

04:59.533 --> 05:01.473
than when they're on the
opposite.

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But it doesn't take too much
work to convince yourself that

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the other is in fact true,
and that this is the better

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overlap.

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So you'll get better HOMO/LUMO
interaction from one side to the

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other;
and not only for these two

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hydrogens,
but for the other two pairs of

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hydrogens as well,
if the thing is staggered,

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so that the opposite ones are
parallel to one another.

05:24.420 --> 05:28.750
So you can get this kind of
mixing, HOMO/LUMO mixing,

05:28.750 --> 05:32.250
among σ bonds,
which is called

05:32.250 --> 05:34.000
hyperconjugation.

05:34.000 --> 05:36.340
Conjugation is when normal
double bonds,

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p orbitals overlap,
from one to the other,

05:39.211 --> 05:41.371
and you get resonance
structure.

05:41.370 --> 05:43.310
The name
"hyperconjugation"

05:43.312 --> 05:46.232
was created to talk about the
same phenomenon when it's

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σ bonds,
rather than π bonds

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that are doing the trick;
and it's usually much,

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much less important.

05:52.160 --> 05:55.000
We'll talk about more examples
of this later on.

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But at any rate,
that's a very different point

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of view from the first one.

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Which is it,
that the eclipsed is

06:01.389 --> 06:04.779
destabilized or that the
staggered is unusually stable?

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Or maybe both.

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And, in fact,
this is a little bit a

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scholastic argument analogous to
how many angels could dance on

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the head of a pin;
and you get people that debate

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about this.

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Right?

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So the point is that
fundamentally there's quantum

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mechanics that controls this,
but it doesn't say which one of

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these things is what.

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It doesn't divide it that way.

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So some people say one,
some people say the other,

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and we'll just say maybe a
little of both.

06:33.370 --> 06:37.890
Okay, now here's a digression
on the question of what's called

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"topicity";
which turns out to be relevant

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in a lot of biochemical
applications.

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So it's worth mentioning at
this point, this aspect of

06:49.232 --> 06:50.162
stereochemistry.

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Topicity relates to,
for example,

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the question:
are two protons equivalent?

06:57.339 --> 07:00.099
Now at first glance,
that's sort of a stupid

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question.

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Obviously a proton is a proton,
so they're equivalent.

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But suppose one is the H of an
OH group in ethanol,

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and the other is an H of the
methyl group.

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Now are they equivalent?

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Well protons clearly still are
equivalent.

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Protons are protons.

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What's different about them?

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What's different is their
environment.

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So it could be that the place
they are is different,

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even though the protons
intrinsically are the same,

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and therefore they could have
different properties.

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Now, that happens to be the
case in ethanol.

07:37.060 --> 07:40.860
An OH group has a pKa of about
16.

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It's not very acidic but it's
possible to dissociate H+ and

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leave O-.

07:45.293 --> 07:45.893
Right?

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But an H that's on a methyl
group doesn't do that.

07:48.519 --> 07:50.329
It has a pKa of about 50.

07:50.329 --> 07:57.459
So it's 10^34th weaker as an
acid, than the OH group.

07:57.459 --> 08:01.179
So there's clearly a difference
between these two hydrogens

08:01.180 --> 08:03.230
because of the place they're in.

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Right?

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So that the OH on the alcohol
group exchanges readily with

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acidic water;
so you can put deuterium in and

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out of that, wash it in,
wash it out;

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and you can't do that in the
case of methane.

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So D+ can come in.

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Low LUMO, attacked by the high
HOMO.

08:21.603 --> 08:22.803
You get that.

08:22.800 --> 08:24.870
And then unzip it the other way.

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The electrons go back on,
H+ comes off.

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So you can do this exchange.

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That doesn't happen over on the
other case because it's so hard

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to get the proton off,
and the carbon has no unshared

08:35.940 --> 08:38.170
pair to pick up the new proton.

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So these two protons,
the red one and the blue one,

08:41.388 --> 08:43.578
the OH and the methyl-H,
are called

08:43.577 --> 08:47.577
"heterotopic";
hetero means different,

08:47.577 --> 08:50.507
and the Greek topos
means place.

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So they're in a different place.

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They have different properties
because they're in a different

08:54.990 --> 08:55.340
place.

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So ‘topicity' comes from
the same root obviously,

08:59.549 --> 09:02.669
and it means the placeness of a
group.

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It could be a hydrogen,
it could be another group,

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two groups, that appear to be
the same but are in different

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places.

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So this is a pretty obvious
case.

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But there are cases that are
less obvious.

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So protons within the blue
group are homotopic,

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and the green protons are
homotopic with one another.

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Right?

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They're in the same kind of
place.

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At least they're in the same
kind of place if we're

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discussing constitution,
what they're bonded to,

09:32.022 --> 09:35.152
and what those things are
bonded to and so on.

09:35.154 --> 09:35.994
Right?

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The nature and sequence of
bonds are obviously the same

09:39.446 --> 09:43.156
between the two green or among
the three blue hydrogens.

09:43.158 --> 09:46.188
And both of those are different
from one another,

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and from the red hydrogen.

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Okay, so from the point of
constitution,

09:50.539 --> 09:54.509
the blue ones are homotopic,
the green ones are homotopic.

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The red one is its own -- right?

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-- but the green is heterotopic
with respect to the red or the

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blue, and so on.

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So that isn't telling you much
that you wouldn't already have

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realized easily.

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But if you get into
stereochemical topicity,

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it gets more subtle.

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So let's look at stereotopic
relationships among these

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protons.

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First, we said that the blue
ones were homotopic.

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But are they really homotopic?

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Let's consider those two
hydrogens.

10:27.048 --> 10:30.248
Do they have the same
environment?

10:30.250 --> 10:33.580
They're clearly the same with
respect to constitution,

10:33.576 --> 10:35.706
what they're linked to --
right?

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-- but are they the same
stereochemically?

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Are their environments
superimposable,

10:42.292 --> 10:44.972
exactly on one another?

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Yes or no?

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So are they stereochemically
homotopic?

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Corey, what do you say?

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Student:  I'd say yes.

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Prof: You say they are?

11:00.399 --> 11:01.489
Student:  Yes.

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Prof: If you took the
top hydrogen away,

11:05.610 --> 11:08.710
and looked at everything else,
and then made another model

11:08.706 --> 11:10.766
where you took the bottom one
away,

11:10.769 --> 11:15.429
and looked at everything else,
are those everything elses,

11:15.429 --> 11:18.819
the places, superimposable?

11:18.820 --> 11:22.330
No, they're not,
because one has a hydrogen down

11:22.326 --> 11:25.006
here missing,
and the other one has a

11:25.010 --> 11:27.250
hydrogen up there missing.

11:27.250 --> 11:31.760
You can't superimpose those
unless you do a rotation.

11:31.755 --> 11:32.445
Right?

11:32.450 --> 11:35.410
So that's a question of
conformation,

11:35.412 --> 11:37.142
of rotation,
right?

11:37.139 --> 11:43.889
Okay, so those are
diastereotopic from the point of

11:43.889 --> 11:46.469
--
that is, different places --

11:46.471 --> 11:49.461
from the point of view of
conformation,

11:49.460 --> 11:54.520
but not from the point of view
of >

11:54.517 --> 11:55.707
constitution.

11:55.711 --> 11:56.541
Right?

11:56.538 --> 11:58.398
Sorry, I'm getting my c's
confused.

11:58.399 --> 12:02.529
It's a long run,
from the beginning of September

12:02.528 --> 12:04.108
to Thanksgiving.

12:04.110 --> 12:08.280
You'll find that this will have
been the longest period,

12:08.283 --> 12:11.473
unrelieved period,
of your time at Yale.

12:11.470 --> 12:13.270
It gets easier after this.

12:13.269 --> 12:16.879
Okay, so anyhow they're
diastereotopic from the point of

12:16.878 --> 12:20.288
view of conformation,
but homotopic from the point of

12:20.288 --> 12:21.928
view of constitution.

12:21.929 --> 12:23.979
How about those two?

12:23.980 --> 12:29.740
Do they have the same
environment, those two

12:29.740 --> 12:31.350
hydrogens?

12:31.350 --> 12:39.090


12:39.090 --> 12:40.690
Cathy, what do you say?

12:40.690 --> 12:41.620
Student:  Yes.

12:41.620 --> 12:43.650
Prof: They're
superimposable;

12:43.649 --> 12:47.379
that is, if you took the H in
front away, you'd have a certain

12:47.375 --> 12:50.245
bunch of stuff left;
that's its environment.

12:50.250 --> 12:55.340
And if you took the H in back
away, and looked at the rest of

12:55.336 --> 13:00.336
the stuff, are those two
remainders absolutely identical;

13:00.340 --> 13:01.750
superimposable?

13:01.750 --> 13:03.820
Student:  No.

13:03.820 --> 13:06.820
Prof: What is the
relationship between them?

13:06.820 --> 13:08.700
Obviously that was sort of a
leading question.

13:08.700 --> 13:10.820
Student:  They're mirror
images.

13:10.820 --> 13:12.050
Prof: They're mirror
images.

13:12.048 --> 13:14.218
So what would you call those
two protons?

13:14.220 --> 13:16.390
Student:  Enantiomers.

13:16.389 --> 13:18.769
Prof: Not enantiomers.

13:18.769 --> 13:21.189
It's their places that are
different.

13:21.190 --> 13:22.280
Enantio-what?

13:22.279 --> 13:23.599
Student:  Enantiotopic.

13:23.600 --> 13:24.650
Prof: Enantiotopic.

13:24.649 --> 13:27.829
So the ones at the top are
enantiotopic,

13:27.827 --> 13:31.987
and the first ones we looked at
were diastereotopic.

13:31.985 --> 13:32.795
Right?

13:32.799 --> 13:34.379
Now, do you care?

13:34.379 --> 13:36.599
Is that going to make a
difference in chemistry?

13:36.600 --> 13:42.940
I say no, and the reason I say
no is that it rotates so fast

13:42.942 --> 13:49.072
around a single bond -- we
talked about that last time;

13:49.070 --> 13:50.700
10^10th per second.

13:50.700 --> 13:54.330
And when you rotate,
you exchange one -- one takes

13:54.333 --> 13:56.563
the place of another,
right?

13:56.558 --> 13:59.668
So they exchange places among
themselves faster than almost

13:59.672 --> 14:02.662
anything could happen;
10^10th^( )per second.

14:02.659 --> 14:05.289
So who cares? Right?

14:05.288 --> 14:08.588
So in truth they're
conformationally diastereotopic,

14:08.585 --> 14:10.975
but you don't care about
conformation,

14:10.976 --> 14:13.626
in this case,
because they would rotate so

14:13.625 --> 14:14.525
quickly.

14:14.528 --> 14:18.548
So they're not going to have
experimentally distinguishable

14:18.551 --> 14:21.811
properties, probably,
unless you can look pretty

14:21.809 --> 14:22.229
quick.

14:22.226 --> 14:22.916
Okay?

14:22.918 --> 14:27.038
Now, so these distinctions are
only conformational and erased

14:27.038 --> 14:29.978
by rotation;
in 10^-12 seconds I said here.

14:29.975 --> 14:30.365
Okay?

14:30.370 --> 14:31.450
Yeah, that's more like it.

14:31.450 --> 14:33.750
Okay, now how about the two
green ones?

14:33.750 --> 14:35.880
What's the relationship between
them?

14:35.879 --> 14:39.359
Pat, what do you say?

14:39.360 --> 14:40.670
What's the relationship?

14:40.668 --> 14:44.548
Student:  They're
enantiotopic.

14:44.548 --> 14:46.438
Prof: They're
enantiotopic.

14:46.440 --> 14:51.040
Now, are they enantiotopic with
respect to conformation?

14:51.038 --> 14:54.798
Can you rotate one and give it
exactly the same place as the

14:54.796 --> 14:55.556
other one?

14:55.559 --> 14:56.359
Student:  No.

14:56.360 --> 14:57.420
Prof: Why not?

14:57.418 --> 15:01.258
What would happen if you tried
to rotate, to put the back green

15:01.259 --> 15:03.859
one in the place of the front
green one?

15:03.860 --> 15:05.780
Student:  It'd change
the location of the OH.

15:05.778 --> 15:07.768
Prof: It would change
the location of the OH.

15:07.768 --> 15:08.078
Right?

15:08.080 --> 15:11.340
So how could you exchange their
environments?

15:11.340 --> 15:13.400
The only way,
we'd have to break a bond and

15:13.403 --> 15:15.373
put the other hydrogen someplace
else.

15:15.370 --> 15:18.620
So what kind of enantiotopic
are these?

15:18.620 --> 15:23.670
Is it configuration,
conformation,

15:23.673 --> 15:30.263
or constitution,
that you have to change?

15:30.259 --> 15:31.459
Can you do it just by rotation?

15:31.460 --> 15:34.140
Is it just conformation? No.

15:34.139 --> 15:37.889
Do you have to change what's
bonded to what,

15:37.889 --> 15:38.939
to make one?

15:38.936 --> 15:39.456
No.

15:39.460 --> 15:42.320
So it's not -- so it's
configuration,

15:42.315 --> 15:42.945
right?

15:42.950 --> 15:46.270
But the important thing is you
have to break a bond to change

15:46.274 --> 15:46.554
them.

15:46.551 --> 15:47.051
Right?

15:47.048 --> 15:49.168
So that's not going to happen
easily.

15:49.168 --> 15:52.948
So the difference between those
two -- those are also

15:52.946 --> 15:55.406
enantiotopic,
but configurationally

15:55.414 --> 15:56.654
enantiotopic.

15:56.649 --> 15:59.149
So that will last,
that distinction,

15:59.148 --> 16:02.288
in principle,
as long as the bonds endure.

16:02.289 --> 16:04.769
So there's quite a difference.

16:04.769 --> 16:06.159
Those two could be different.

16:06.158 --> 16:08.188
Now let's see if we can see a
case where they're different.

16:08.190 --> 16:13.570
Now that carbon is not a
stereogenic center.

16:13.570 --> 16:17.060
Why is it not a -- how do you
recognized a stereogenic center?

16:17.059 --> 16:18.209
Nate?

16:18.210 --> 16:21.200
Student:  By what it's
attached to -- it's bonded to

16:21.201 --> 16:22.441
four different things.

16:22.440 --> 16:23.550
Prof: You guys shouldn't
sit next to each other.

16:23.549 --> 16:25.919
I was talking to the other Nate.

16:25.918 --> 16:27.238
Student:  It's got two
H's on it.

16:27.240 --> 16:27.790
Prof: Can't hear.

16:27.788 --> 16:28.958
Student:  It's got two
hydrogens on it.

16:28.960 --> 16:30.170
Prof: It's got two
hydrogens.

16:30.173 --> 16:31.493
It has four different things,
right?

16:31.490 --> 16:32.940
And this has two of the same.

16:32.940 --> 16:36.620
But it's called,
for this purpose of topicity

16:36.624 --> 16:41.344
stuff, "prochiral";
that is, it will become chiral

16:41.344 --> 16:45.384
if two of the things that are
the same become different.

16:45.379 --> 16:47.109
For example,
if one of them,

16:47.114 --> 16:49.234
instead of an H,
were a deuterium,

16:49.232 --> 16:51.612
then it would be a chiral
center.

16:51.610 --> 16:54.110
So that thing is called
prochiral.

16:54.110 --> 16:56.580
It would be chiral if the
enantiotopic atoms,

16:56.580 --> 16:59.670
or groups -- it could be
chlorines or it could be methyl

16:59.668 --> 17:02.418
groups or whatever;
if they were made different

17:02.419 --> 17:04.259
somehow, then it would be
chiral.

17:04.259 --> 17:09.979
Now, so in ethanol,
those two green groups are

17:09.978 --> 17:14.678
enantiotopic and
configurationally.

17:14.680 --> 17:20.190
So now "toponymy"
-- that's names of places;

17:20.190 --> 17:22.540
how do we name them?

17:22.538 --> 17:27.218
So we have things -- we have
groups that are constitutionally

17:27.222 --> 17:28.162
homotopic.

17:28.160 --> 17:30.190
They have the same
constitution,

17:30.193 --> 17:32.233
connected to the same things.

17:32.230 --> 17:35.740
Okay, so consider those,
the green hydrogen there,

17:35.744 --> 17:39.394
the light green one in front;
and I'm drawing a Newman

17:39.385 --> 17:41.035
projection also to show it.

17:41.038 --> 17:44.478
We have to be able to give it a
name so people will know what

17:44.476 --> 17:47.396
we're talking about,
when we're -- if this turns out

17:47.396 --> 17:49.456
to be important for some reason.

17:49.460 --> 17:53.450
Okay, so the way we do it is to
assign priority,

17:53.449 --> 17:56.079
if the hydrogens were
different.

17:56.080 --> 17:56.930
Right?

17:56.930 --> 17:59.510
Then we'll be able to call it
R or S,

17:59.507 --> 17:59.917
right?

17:59.920 --> 18:01.620
Because we already have a
scheme for that.

18:01.618 --> 18:03.828
But the two hydrogens would
have to be different.

18:03.829 --> 18:07.229
So let's look at the priority.

18:07.230 --> 18:10.700
OH at that carbon -- the
prochiral carbon -- is obviously

18:10.700 --> 18:13.670
top, and the methyl,
the carbon group attached to

18:13.673 --> 18:16.263
it, is second;
but the two hydrogens come

18:16.255 --> 18:17.265
third and fourth.

18:17.269 --> 18:19.739
But which one should be third
and which one should be fourth?

18:19.740 --> 18:21.360
Now here's the rule.

18:21.358 --> 18:28.078
You give higher priority to the
one that you're naming.

18:28.083 --> 18:29.083
Right?

18:29.078 --> 18:32.888
So if we want to name this one,
we'd give it higher priority

18:32.894 --> 18:33.934
than this one.

18:33.930 --> 18:37.340
So this one will be three and
this one will be four.

18:37.339 --> 18:39.179
So here's the lowest priority.

18:39.180 --> 18:41.860
You can run one to four,
in either direction,

18:41.862 --> 18:43.632
high to low or low to high.

18:43.630 --> 18:45.520
You get the same sense of
handedness.

18:45.519 --> 18:47.549
So let's think about this.

18:47.548 --> 18:52.598
Here we have -- so if I put my
left thumb coming out where this

18:52.596 --> 18:56.586
hydrogen is, the number four,
and curl my fingers,

18:56.585 --> 18:58.285
I go one, two,
three,.

18:58.294 --> 18:59.194
Okay?

18:59.190 --> 19:03.710
So this one would be
left-handed, if it were higher

19:03.713 --> 19:04.713
priority.

19:04.710 --> 19:05.870
Everybody with me on that?

19:05.868 --> 19:08.498
So we'll call that,
not S,

19:08.502 --> 19:11.552
we'll call that hydrogen
pro-S,

19:11.548 --> 19:15.168
because it will become S
-- okay?

19:15.170 --> 19:18.160
-- if we make this -- for
purposes of naming,

19:18.163 --> 19:20.413
when we give it a higher
priority.

19:20.406 --> 19:21.016
Okay?

19:21.019 --> 19:23.669
Now, suppose we look at the
other hydrogen,

19:23.666 --> 19:26.186
that I've shown in the darker
arrow here.

19:26.189 --> 19:26.819
Right?

19:26.818 --> 19:28.318
It obviously is going to be
pro-R,

19:28.319 --> 19:30.609
because the same thing would
run in the opposite direction.

19:30.608 --> 19:34.748
Okay, so pro-R and
pro-S are the name that

19:34.753 --> 19:39.203
you can give to distinguish
groups that are enantiotopic.

19:39.200 --> 19:43.220
Now, is there a reactivity
difference that we would care

19:43.220 --> 19:45.340
about between these groups?

19:45.338 --> 19:48.998
Suppose you bring up a chlorine
atom, and it can attack one or

19:49.000 --> 19:50.560
it can attack the other.

19:50.558 --> 19:52.768
So suppose it attacks the one
on the left.

19:52.768 --> 19:53.198
Right?

19:53.200 --> 19:56.880
Its SOMO mixes with one of the
electrons of the H,

19:56.875 --> 20:00.625
and the other electron on the H
goes on the carbon,

20:00.627 --> 20:03.477
and we break the bond and get
HCl.

20:03.480 --> 20:06.240
This is the first step,
remember, in free radical

20:06.238 --> 20:07.098
substitution.

20:07.098 --> 20:10.258
Or we could do it with the
other one.

20:10.259 --> 20:16.119
What's the relationship between
those two pathways?

20:16.119 --> 20:18.949
Can you see?

20:18.950 --> 20:22.530
The pathway that happens on the
left and the pathway that

20:22.527 --> 20:25.207
happens on the right,
are they the same?

20:25.210 --> 20:26.710
Student:
>.

20:26.710 --> 20:30.590
Prof: Well they're not
superimposable,

20:30.592 --> 20:31.212
okay?

20:31.210 --> 20:32.870
So they're not precisely the
same.

20:32.869 --> 20:34.319
But what are they?

20:34.319 --> 20:36.469
Sophie?

20:36.470 --> 20:37.660
Student:  They're mirror
images.

20:37.660 --> 20:38.940
Prof: They're mirror
images of one another.

20:38.940 --> 20:40.730
Therefore they have the same
energy.

20:40.730 --> 20:43.330
So one will be just as --
remember,

20:43.328 --> 20:47.258
we talked last time about how
fast a reaction goes has to do

20:47.259 --> 20:51.119
with how high an energy you have
to go to, along that path.

20:51.123 --> 20:51.793
Right?

20:51.788 --> 20:53.068
And these are going to be the
same.

20:53.068 --> 20:55.228
So they'll have precisely the
same rates.

20:55.230 --> 20:58.340
So who cares? Okay?

20:58.338 --> 21:01.728
So attacked by a reagent like a
chlorine atom,

21:01.734 --> 21:05.584
those two versions of the
attack, are mirror images,

21:05.584 --> 21:08.984
and thus they're identical in
their rate.

21:08.980 --> 21:11.440
So who cares?

21:11.440 --> 21:18.820
But suppose that you use
something that's handed,

21:18.816 --> 21:23.886
like a right hand,
to pull it off?

21:23.885 --> 21:25.265
Okay?

21:25.269 --> 21:29.339
Now suppose you use the same
right hand to pull the other one

21:29.342 --> 21:29.752
off?

21:29.750 --> 21:34.750
Those aren't mirror images of
one another anymore.

21:34.752 --> 21:35.572
Right?

21:35.568 --> 21:39.048
What do you call -- what's the
relationship between these two

21:39.053 --> 21:39.753
reactions?

21:39.750 --> 21:41.540


21:41.538 --> 21:45.598
What would you call the
relationship between them?

21:45.599 --> 21:46.599
Angela?

21:46.598 --> 21:49.208
Student:  They come out
completely different.

21:49.210 --> 21:49.490
Prof: Can't hear.

21:49.490 --> 21:51.060
Student:  They come out
completely different.

21:51.059 --> 21:54.559
So they're diastereomers.

21:54.558 --> 21:56.478
Prof: Right,
they're diastereomeric paths.

21:56.480 --> 21:57.790
So they're different in energy.

21:57.788 --> 21:59.228
So one will be faster than the
other.

21:59.230 --> 22:04.630
What does that tell you about
the metabolism of ethanol?

22:04.630 --> 22:08.750
If you've got ethanol inside
you, there are things that pull

22:08.753 --> 22:12.043
the hydrogen off and make
aldehyde out of it.

22:12.038 --> 22:17.158
In fact, that's where the name
"aldehyde"

22:17.159 --> 22:18.489
comes from.

22:18.490 --> 22:24.480
Aldehyde is an alcohol that's
been dehydrogenated;

22:24.480 --> 22:25.890
al-de-hyde.

22:25.890 --> 22:27.830
It's interesting, isn't it?

22:27.828 --> 22:31.538
But anyhow, this can be --
would your body,

22:31.544 --> 22:35.524
if your body was trying to
metabolize ethanol,

22:35.522 --> 22:40.212
could it distinguish between
those two hydrogens?

22:40.210 --> 22:41.590
Student:  Yes.

22:41.589 --> 22:42.639
Prof: Why?

22:42.640 --> 22:44.050
Who said yes?

22:44.049 --> 22:45.729
Sam?

22:45.730 --> 22:48.040
Student:  Because
whatever enzyme is doing that is

22:48.035 --> 22:48.895
going to be a hand.

22:48.900 --> 22:51.980
Prof: Because the enzyme
that does it is a hand,

22:51.984 --> 22:52.794
a single hand.

22:52.785 --> 22:53.295
Right?

22:53.298 --> 22:55.178
So it will be able to
distinguish between those.

22:55.180 --> 22:58.220
Now, can we prove that? Okay?

22:58.220 --> 23:01.890
So attacks by a resolved chiral
reagent, like an enzyme,

23:01.891 --> 23:05.431
are diastereomeric and should
have different rates.

23:05.430 --> 23:10.500
So horse liver alcohol
dehydrogenase removes only the

23:10.500 --> 23:14.110
pro-R hydrogen from
ethanol.

23:14.108 --> 23:20.068
Pardon me, if it removes only
the pro-R hydrogen in

23:20.073 --> 23:25.253
this deuteroethanol,
it should remove the hydrogen

23:25.249 --> 23:28.509
and never deuterium,
in the case that it's

23:28.512 --> 23:29.682
deuterated like this.

23:29.675 --> 23:30.115
Right?

23:30.118 --> 23:33.798
Messed that up saying it,
but you can read it better than

23:33.798 --> 23:34.188
I can.

23:34.193 --> 23:34.723
Okay?

23:34.720 --> 23:37.510
Now, so that would be a great
experiment.

23:37.509 --> 23:41.559
If you had this compound,
(S)-1-deuteroethanol,

23:41.558 --> 23:43.998
and you reacted it with this
enzyme,

23:44.000 --> 23:49.620
if you always pulled off the H
and left deuteroacetaldehyde,

23:49.619 --> 23:51.829
that would show it was specific.

23:51.828 --> 23:54.108
But if it weren't specific,
then you'd sometimes get one

23:54.113 --> 23:56.523
and sometimes the other coming
off, and you'd get different

23:56.521 --> 23:57.271
acetaldehydes.

23:57.269 --> 24:00.469
Some would have deuterium and
some wouldn't,

24:00.471 --> 24:01.361
left behind.

24:01.364 --> 24:01.964
Okay?

24:01.960 --> 24:05.370
Now what's the problem in doing
this experiment?

24:05.369 --> 24:07.629
Zack?

24:07.630 --> 24:09.350
Student:  How do you
know that deuterium's right

24:09.345 --> 24:09.595
there?

24:09.598 --> 24:12.298
Prof: How do you get the
compound with the deuterium on

24:12.296 --> 24:14.506
only one side in the first
place, so you can do the

24:14.506 --> 24:15.166
experiment?

24:15.170 --> 24:18.280
And this is where there's a
clever way of doing it.

24:18.281 --> 24:18.781
Right?

24:18.778 --> 24:21.648
That would be the reaction,
and you'd get only the

24:21.648 --> 24:23.868
deuterium left and never
hydrogen left,

24:23.874 --> 24:25.284
if it were specific.

24:25.278 --> 24:27.878
So that's a good test,
but where do you get the

24:27.878 --> 24:29.008
starting material?

24:29.009 --> 24:34.439
Now actually,
the alcohol dehydrogenase is a

24:34.443 --> 24:36.723
catalyst, right?

24:36.720 --> 24:40.240
And a catalyst lowers the
energy of the barrier you have

24:40.236 --> 24:43.636
to go through to go across;
lowers the barrier.

24:43.640 --> 24:48.110
But that means it lowers the
barrier in either direction;

24:48.108 --> 24:51.078
because you can go either
direction across this.

24:51.083 --> 24:51.593
Right?

24:51.588 --> 24:56.248
So that means that you can --
this is an oxidation;

24:56.250 --> 24:58.220
removing hydrogen is an
oxidation.

24:58.220 --> 25:01.010
But you could also do the
reverse reaction;

25:01.009 --> 25:01.939
a reduction.

25:01.940 --> 25:05.120
That is, you could start with
this.

25:05.118 --> 25:09.788
So what really does the
oxidation -- LAD is a catalyst

25:09.788 --> 25:13.488
-- what does it is this NAD+
becoming NADH,

25:13.489 --> 25:14.809
taking H- away.

25:14.809 --> 25:15.779
Right?

25:15.778 --> 25:18.508
So if you ran this reaction
backwards,

25:18.509 --> 25:20.529
and started with a deuterium
there,

25:20.528 --> 25:23.938
then if the thing were
specific, you'd put hydrogen

25:23.943 --> 25:26.303
only there,
when you run it backwards;

25:26.298 --> 25:31.738
if it's specific taking it off,
it'll be specific putting it

25:31.741 --> 25:32.021
on.

25:32.019 --> 25:32.849
Right?

25:32.848 --> 25:37.168
Now how would you know if it's
specific, putting it on?

25:37.170 --> 25:41.090
How would you know if it did
that?

25:41.088 --> 25:47.648
How would you know whether,
when it does this reaction,

25:47.650 --> 25:50.670
it scrambles and puts it in
both positions,

25:50.670 --> 25:53.380
and then when you run it
backwards it scrambles and takes

25:53.380 --> 25:55.490
it off both positions,
sometimes one,

25:55.490 --> 25:59.090
sometimes the other;
or whether it's specific going

25:59.088 --> 26:01.188
on and specific coming off?

26:01.190 --> 26:04.960
Lucas, you got an idea?

26:04.960 --> 26:07.280
Student:  You can pull
it off and check optical

26:07.278 --> 26:07.758
activity.

26:07.759 --> 26:09.699
Prof: Ah,
if you could measure the

26:09.698 --> 26:12.508
optical activity of this stuff,
that would be a good way of

26:12.509 --> 26:13.139
doing it.

26:13.140 --> 26:15.350
But it doesn't have very much
optical activity,

26:15.352 --> 26:18.192
if the only difference is
between deuterium and hydrogen;

26:18.190 --> 26:19.520
not very much.

26:19.519 --> 26:21.669
Student:  This is just
kind of guess,

26:21.673 --> 26:24.383
but if they did it to both
things, wouldn't you get one

26:24.376 --> 26:26.426
with both and then one with only
one?

26:26.430 --> 26:29.950
And then if it only went to one
side, you'd only get one with

26:29.948 --> 26:30.298
one.

26:30.298 --> 26:33.518
Prof: I think you said
it.

26:33.519 --> 26:34.619
Student:  Probably not
right.

26:34.618 --> 26:36.298
Prof: But I don't know
that everyone understood what

26:36.300 --> 26:36.620
you said.

26:36.619 --> 26:38.979
The idea is do both.

26:38.980 --> 26:45.630
Put on, and then take that
product and take it off again.

26:45.630 --> 26:48.480
If it's specific going on,
and specific going off,

26:48.483 --> 26:51.983
when you go through the whole
cycle you'll get back where you

26:51.979 --> 26:52.969
started from.

26:52.970 --> 26:56.560
But if it mixes up going on and
coming off, then sometimes it

26:56.557 --> 27:00.137
will put it on the wrong place,
sometimes it will take it off

27:00.144 --> 27:01.344
the wrong place.

27:01.338 --> 27:04.368
And when you come back,
sometimes you'll have H and

27:04.366 --> 27:07.386
sometimes you'll have D,
in that starting material.

27:07.394 --> 27:08.004
Right?

27:08.000 --> 27:09.540
So you go both ways and see.

27:09.539 --> 27:11.219
And that works, right?

27:11.220 --> 27:15.170
By starting with the same
catalyst and excess deuteride,

27:15.172 --> 27:17.112
you do that,
to go that way.

27:17.113 --> 27:17.763
Okay?

27:17.759 --> 27:20.559
So if you do a full cycle,
like that, then you come back

27:20.557 --> 27:23.507
-- pardon me -- you come back
exactly where you started.

27:23.509 --> 27:26.359
But, this proves the
specificity;

27:26.358 --> 27:28.918
but it doesn't say which one,
it doesn't say whether it was

27:28.921 --> 27:30.291
pro-R or pro-S.

27:30.288 --> 27:33.398
For that you need to do other
kinds of experiments that we

27:33.396 --> 27:35.026
don't have time to talk about.

27:35.032 --> 27:35.472
Okay?

27:35.470 --> 27:37.190
So that's really a neat
experiment,

27:37.190 --> 27:39.660
that shows that topicity makes
a difference,

27:39.660 --> 27:45.190
and that enzymes discriminate
between stereotopic,

27:45.190 --> 27:48.250
enantiotopic groups, or atoms.

27:48.250 --> 27:52.320
Okay, next subject is Baeyer
Strain Theory,

27:52.318 --> 27:55.128
which was proposed in 1885.

27:55.130 --> 27:58.750
So that's ten years after van't
Hoff.

27:58.746 --> 27:59.446
Okay?

27:59.450 --> 28:03.410
So here's the group in Munich,
in 1893, and here,

28:03.411 --> 28:06.881
front and center,
is the boss of the group,

28:06.876 --> 28:08.606
Adolf von Baeyer.

28:08.608 --> 28:11.208
And this picture hangs in the
hallway out there,

28:11.208 --> 28:12.478
the original picture.

28:12.480 --> 28:13.430
You can look at it.

28:13.430 --> 28:18.600
And the reason it does is that
this guy here is Henry Lord

28:18.602 --> 28:19.512
Wheeler.

28:19.509 --> 28:20.879
Did you ever see his name?

28:20.880 --> 28:27.480
Student:
>.

28:27.480 --> 28:31.440
Prof: See how observant
you are.

28:31.440 --> 28:32.390
Student:
>.

28:32.390 --> 28:33.870
Prof: Pardon?

28:33.869 --> 28:35.339
Lexy, did you -- Pat?

28:35.338 --> 28:37.278
Student:  Is it down in
the foyer to this building?

28:37.279 --> 28:38.459
Prof: Yeah,
when you come in,

28:38.464 --> 28:39.994
there are these names carved on
the walls,

28:39.990 --> 28:42.750
which were the people who were,
in the nineteenth,

28:42.750 --> 28:44.520
early-twentieth century,
professors.

28:44.519 --> 28:47.399
So he was the first organic
chemist at Yale,

28:47.397 --> 28:50.807
and he went to Munich,
where a lot of people went to

28:50.811 --> 28:53.491
learn organic chemistry from
Baeyer.

28:53.490 --> 28:56.590
Baeyer, remember,
was the guy who fiddled with

28:56.594 --> 28:59.214
the bread rolls,
together with Fischer,

28:59.214 --> 29:00.944
to make these models.

29:00.940 --> 29:04.160
He was also the guy that did
experiments on arsenic in

29:07.068 --> 29:11.108
So Baeyer was the leading
organic chemist of the time.

29:11.108 --> 29:14.988
Now, in 1885 he -- that's
earlier than this picture;

29:14.990 --> 29:19.000
that picture was 1893,
when Henry Lord Wheeler was

29:19.003 --> 29:19.663
there.

29:19.660 --> 29:24.430
Notice that he died at what;
at thirty-seven,

29:24.428 --> 29:26.408
the age of thirty-seven.

29:26.410 --> 29:30.760
I don't know what he died of,
in 1911.

29:30.759 --> 29:32.309
So he wasn't a professor very
long.

29:32.308 --> 29:36.998
Okay, so this paper,
eight years earlier,

29:36.999 --> 29:41.219
was about polyacetylene
compounds;

29:41.220 --> 29:43.940
so a bunch of triple bonds
arranged in a row.

29:43.940 --> 29:45.910
We've talked about double bonds
in a row;

29:45.910 --> 29:47.850
you can have triple bonds in a
row too.

29:47.848 --> 29:50.998
But you don't have them for
very long because,

29:51.000 --> 29:54.430
as Baeyer reported in this
paper, they explode.

29:54.430 --> 29:57.100
He had a collaborator named
Dr. Homolka,

29:57.104 --> 30:01.634
who he thanks for doing some of
the experiments in this paper.

30:01.630 --> 30:06.280
Dr. Homolka does not appear
in the 1893 picture.

30:06.278 --> 30:07.268
>

30:07.266 --> 30:09.356
I suspect that he just
graduated, got his degree and

30:09.362 --> 30:11.132
went to be gainfully employed
someplace.

30:11.130 --> 30:11.940
But who knows?

30:11.940 --> 30:14.700
Anyhow, polyacetylenes are
explosive.

30:14.700 --> 30:18.530
And this got Baeyer thinking,
why should just a regular old

30:18.528 --> 30:20.308
hydrocarbon be explosive?

30:20.308 --> 30:25.758
So he branched out in this
paper, and the very first topic

30:25.757 --> 30:30.537
was "The Theory of Ring
Closure and the Double

30:30.536 --> 30:31.966
Bond."

30:31.970 --> 30:33.890
Now that seems a funny thing to
talk about;

30:33.890 --> 30:35.910
when you're talking about
triple bonds,

30:35.907 --> 30:38.987
to talk about making rings,
and talk about double bonds.

30:38.990 --> 30:42.780
But what he says is:
"Ring closure"

30:42.778 --> 30:46.048
which was a popular synthetic
goal,

30:46.048 --> 30:48.628
at that time,
to make new kinds of compounds,

30:48.630 --> 30:49.770
was to try to make rings.

30:49.769 --> 30:51.829
They could make six-membered
rings, they could make

30:51.825 --> 30:52.725
five-membered rings.

30:52.730 --> 30:56.670
In Bayer's lab they actually
made four-membered rings and

30:56.669 --> 30:58.779
three-membered rings,
right?

30:58.779 --> 31:00.649
Although that was quite a chore.

31:00.650 --> 31:04.570
Okay, so "Ring closure is
apparently the only phenomenon

31:04.567 --> 31:08.287
that can supply information
about the arrangement of atoms

31:08.288 --> 31:09.528
in space."

31:09.528 --> 31:11.728
This is ten years after van't
Hoff.

31:11.730 --> 31:15.230
"Since a chain of five or
six members can be closed

31:15.232 --> 31:17.712
easily,
while one of more or fewer

31:17.713 --> 31:20.343
members is difficult or
impossible,

31:20.338 --> 31:23.578
spatial factors are apparently
involved."

31:23.578 --> 31:25.898
And you know,
we already talked about a case

31:25.902 --> 31:28.872
like this, where you tell
something about arrangement in

31:28.872 --> 31:31.142
space from the ability to form a
ring.

31:31.140 --> 31:32.540
Do you remember what that is?

31:32.539 --> 31:34.399
Anybody? Yeah?

31:34.400 --> 31:35.500
Student:  Synthesis of
mesitylene.

31:35.500 --> 31:36.200
Prof: Can't hear very
well.

31:36.200 --> 31:38.170
Student:  Synthesis of
mesitylene.

31:38.170 --> 31:40.040
Prof: Oh,
the synthesis of mesitylene

31:40.035 --> 31:40.725
formed a ring.

31:40.730 --> 31:44.350
But that doesn't -- so he used
that to say where the methyl

31:44.347 --> 31:45.967
groups were on the ring.

31:45.970 --> 31:48.140
And that's actually a good
example, but it's not the one I

31:48.140 --> 31:48.940
was thinking about.

31:48.940 --> 31:51.670
Student: Cyclopropane.

31:51.670 --> 31:53.320
Student:  Cyclopropane?

31:53.319 --> 31:55.619
Prof: Dichloropropane?

31:55.619 --> 31:56.539
Student:  No.

31:56.538 --> 31:57.658
Prof: Is that what you
said?

31:57.660 --> 31:59.600
Student:  No,
I said cyclopropane with the

31:59.597 --> 32:00.727
>.

32:00.730 --> 32:02.610
Prof: It's not
cyclopropane that I had in mind;

32:02.608 --> 32:05.288
although that was one of the
compounds that was synthesized

32:05.288 --> 32:08.198
in Baeyer's lab for the first
time, and found to be reactive.

32:08.200 --> 32:10.800
But there was another occasion.

32:10.798 --> 32:13.378
Remember maleic and fumaric
acid;

32:13.380 --> 32:15.420
one was cis and one was
trans?

32:15.420 --> 32:19.840
And the one that was cis
could lose water to form a ring.

32:19.837 --> 32:20.397
Right?

32:20.400 --> 32:22.920
So that was what he's referring
to here.

32:22.920 --> 32:26.090
Okay, so then he goes on to
say: "The previously --

32:26.090 --> 32:29.610
" (So there's a website you
can click on to see this.)

32:29.608 --> 32:32.708
"The previously proposed
general rules on the nature of

32:32.713 --> 32:35.083
carbon atoms are the following:
I.***Carbon is

32:35.082 --> 32:36.242
tetravalent."

32:36.240 --> 32:37.380
Who did that?

32:41.683 --> 32:42.253
right?

32:42.250 --> 32:46.380
"The four valences are
equivalent, shown by the fact

32:46.384 --> 32:49.564
there's only one
monosubstitution product of

32:49.559 --> 32:50.889
methane."

32:50.890 --> 32:52.030
(We've talked about that.)

32:52.029 --> 32:52.539
"III.

32:52.538 --> 32:55.648
The valences are equivalently
arranged in space to the corners

32:55.646 --> 32:57.376
of a regular tetrahedron."

32:57.380 --> 32:59.760
Who says that carbon is
tetrahedral?

32:59.759 --> 33:00.799
Student:  van't Hoff.

33:00.799 --> 33:01.689
Prof: van't Hoff.

33:01.690 --> 33:04.790
Also, incidentally,
there was a Frenchman who did

33:04.792 --> 33:06.802
it simultaneously,
called LeBel.

33:06.798 --> 33:07.378
Okay?

33:07.380 --> 33:07.920
"IV.

33:07.917 --> 33:11.207
The atoms or groups attached to
the four valences cannot

33:11.211 --> 33:12.711
exchange places."

33:12.710 --> 33:16.470
(So you can't -- you have to
break bonds to make new isomers,

33:16.468 --> 33:16.968
right?

33:16.970 --> 33:18.990
So if you get them one way,
they'll stay.)

33:18.990 --> 33:21.950
"The evidence is that
there are two tetrasubstitution

33:21.945 --> 33:23.705
products, abcd of methane."

33:23.710 --> 33:28.440
(So van't Hoff and LeBel's
rule, that you can have

33:28.442 --> 33:32.792
configurational enantiomers,
we would say.)

33:32.788 --> 33:33.258
"V.

33:33.256 --> 33:35.876
Carbon atoms can bond to one
another with one,

33:35.882 --> 33:37.752
two, or three valences."

33:37.750 --> 33:39.750
(That is, you have single,
double, triple bonds.)

33:39.750 --> 33:40.670
"VI.

33:40.666 --> 33:46.576
The compounds can form either
open chains or rings."

33:46.578 --> 33:48.278
(That's what he's talking about
here.)

33:48.279 --> 33:52.389
"I should like to add the
following, to these generally

33:52.385 --> 33:53.565
accepted rules.

33:53.568 --> 33:57.098
So he's adding a new property,
to the models,

33:57.101 --> 34:01.371
the same way van't Hoff did;
van't Hoff added arrangement in

34:01.365 --> 34:04.175
space, to the models that people
already drew.

34:04.180 --> 34:07.010
What Baeyer is adding is VII.)

34:07.009 --> 34:09.509
"The four valences of the
carbon atom point to the

34:09.514 --> 34:12.444
directions connecting the center
of the sphere to the corners of

34:12.436 --> 34:13.546
a tetrahedron."

34:13.550 --> 34:17.440
(That's what van't Hoff also
said -- already said.)

34:21.442 --> 34:22.752
another."

34:22.750 --> 34:25.280
(That's very quantitative and
precise.

34:25.280 --> 34:30.110
That's the angle between the
center and two vertices in a

34:30.112 --> 34:32.702
geometric regular tetrahedron.

34:32.702 --> 34:33.482
Okay?)

34:33.480 --> 34:36.610
But then this is what's
interesting: "The direction

34:36.614 --> 34:38.954
of attachment can undergo
alteration"

34:38.951 --> 34:41.971
(It doesn't have to be exactly
that angle) "but a

34:41.972 --> 34:45.532
strain is generated,
increasing with the size of the

34:45.534 --> 34:46.484
deflection."

34:50.105 --> 34:55.145
then there's going to be higher
energy associated with strain;

34:55.150 --> 34:59.140
or, what he's actually talking
about is not higher energy,

34:59.139 --> 35:00.329
but reactivity.

35:00.329 --> 35:05.799
Okay, so he drew this picture,
showing how much the angles are

35:08.309 --> 35:12.509
So if you consider ethylene to
be a two-membered ring,

35:12.505 --> 35:16.375
with two bent bonds,
the angle the bonds are going

35:16.384 --> 35:19.634
at is where it should be
tetrahedral;

35:19.630 --> 35:21.190
and in fact they're collinear.

35:26.221 --> 35:30.021
for three, four;
five is perfect, right?

35:30.019 --> 35:32.179
It only deviates by 44'.

35:32.179 --> 35:36.319
But the six-membered ring is
stretched a little bit the other

35:36.324 --> 35:36.744
way.

35:36.739 --> 35:39.749
It has to go out,
rather than sharper.

35:39.750 --> 35:40.320
Okay.

35:40.320 --> 35:42.070
So he says:
"Dimethylene…"

35:42.072 --> 35:43.312
--
that's ethylene,

35:43.309 --> 35:46.179
the first one --
"…is indeed the

35:46.182 --> 35:49.552
weakest ring,
which can be opened by HBr,

35:49.552 --> 35:52.162
bromine,
or even iodine."

35:52.159 --> 35:56.319
(We talked about bromine,
or chlorine attacking the

35:56.324 --> 35:57.994
ethylene already.)

35:57.989 --> 36:00.229
"Trimethyle
ne…"

36:00.226 --> 36:04.556
(cyclopropane) "…is
broken only by hydrogen bromide

36:04.561 --> 36:06.591
but not by bromine."

36:06.590 --> 36:08.840
(So it's not as reactive as the
two-membered ring.)

36:08.840 --> 36:10.530
"Finally,
tetramethylene and

36:10.527 --> 36:13.637
hexamethylene are difficult or
impossible to break."

36:13.639 --> 36:15.079
They're pretty stable.

36:15.079 --> 36:18.909
So this strain causes
reactivity, if the bond angles

36:18.905 --> 36:20.025
aren't right.

36:20.030 --> 36:22.050
So he's becoming more
quantitative;

36:22.050 --> 36:26.550
unusually quantitative for an
organic chemist at this period.

36:26.550 --> 36:29.330
Remember, the physical chemists
-- this is just at the period

36:29.327 --> 36:31.687
when physical chemistry is
coming into its own --

36:31.690 --> 36:35.690
and they were the ones who did
heat and energy and so on.

36:35.690 --> 36:38.510
All Baeyer is talking about is
whether things will react or

36:38.507 --> 36:38.797
not.

36:38.800 --> 36:42.640
But he's using geometric
precision.

36:42.639 --> 36:43.429
Okay?

36:43.429 --> 36:47.739
So the question is,
are six-membered rings,

36:47.739 --> 36:51.639
like this, cyclohexane,
they should be,

36:51.637 --> 36:55.947
according to Baeyer,
a little bit strained.

36:55.947 --> 36:57.177
Right?

36:57.179 --> 37:00.939
Because the angles should be --
you'd think the angles would be

37:02.518 --> 37:04.008
So they're opened up a little
bit too much.

37:04.010 --> 37:08.170
But Sachse, a young
privatdocent -- that is,

37:08.170 --> 37:12.070
essentially,
between a graduate student and

37:12.065 --> 37:15.885
a professor --
in 1890 published a paper that

37:15.889 --> 37:19.059
had this very funny picture,
A,B,C,D,E,F,

37:19.059 --> 37:20.509
up on the top there.

37:20.510 --> 37:24.390
And people didn't understand
what it was.

37:24.389 --> 37:27.639
But what it is,
is a thing that if you trace it

37:27.635 --> 37:31.795
on cardboard and fold along the
diagonals, you get this blue

37:31.797 --> 37:34.507
thing -- right?;
if you fold it along the

37:34.512 --> 37:36.522
diagonals and paste the ends
together.

37:36.521 --> 37:37.011
Right?

37:37.010 --> 37:41.900
And then if you paste van't
Hoff tetrahedra on it,

37:41.896 --> 37:43.986
you get this thing.

37:43.989 --> 37:47.959
And you'll see that this is
just like this.

37:47.960 --> 37:50.980
Everybody see that?

37:50.980 --> 37:56.270
It's using -- but this is a
base on which to build such

37:56.266 --> 38:01.356
tetrahedral carbons,
so as to make this structure.

38:01.360 --> 38:05.980
And what's interesting about it
is that these angles are the

38:05.978 --> 38:08.008
normal tetrahedral angles.

38:08.014 --> 38:08.724
Right?

38:08.719 --> 38:11.089
They're not strained. Right?

38:14.159 --> 38:18.639
Because the ring isn't flat,
it's puckered.

38:18.641 --> 38:19.391
Okay?

38:19.389 --> 38:21.729
So that's what Sachse said.

38:21.730 --> 38:25.240
And he gave people this thing
so they could make their own

38:25.244 --> 38:26.364
models and see it.

38:26.355 --> 38:26.905
Right?

38:26.909 --> 38:32.339
And he gave the directions for
building this more complicated

38:32.344 --> 38:37.154
base, where you put it on and
have a different form of

38:37.146 --> 38:38.226
cyclohexane.

38:38.233 --> 38:39.143
Okay?

38:39.139 --> 38:52.959
And that one,
as you see, looks like this.

38:52.960 --> 38:55.320
Okay?

38:55.320 --> 38:59.280
So in 1890 he knew exactly the
score that we would know -- that

38:59.279 --> 39:02.089
we would get with our own models
nowadays.

39:02.090 --> 39:05.810
Now, when this was abstracted
in the journal that published

39:05.809 --> 39:09.269
abstracts of all chemical
literature so people could go

39:09.271 --> 39:12.801
there and find out what was
going on in chemistry,

39:12.800 --> 39:14.830
Julius Wagner,
who abstracted it,

39:14.833 --> 39:18.523
said: "It is not possible
to write an abstract of this

39:18.519 --> 39:20.899
paper,
especially since the author's

39:20.902 --> 39:23.282
explanations are hardly
understandable,

39:23.280 --> 39:24.210
without models."

39:24.210 --> 39:27.140
Now, one conclusion from that
should be therefore go and build

39:27.143 --> 39:29.643
his models and look at them,
and you'll see what he's

39:29.643 --> 39:30.513
talking about.

39:30.510 --> 39:33.290
But that's not what Wagner
said, and it's not what people

39:33.291 --> 39:33.591
did.

39:33.590 --> 39:36.020
He said, "Forget that,
it's nonsense"

39:36.018 --> 39:36.598
-- right?

39:36.599 --> 39:39.879
-- "you can't understand
it." Okay.

39:39.880 --> 39:45.570
So Baeyer wasn't happy with
this, disputing his theory.

39:45.570 --> 39:47.520
So he wrote,
in the same year,

39:47.523 --> 39:50.643
1890 --
Sachse wasn't too smart about

39:50.643 --> 39:56.023
this because he published that
paper just as they were having a

39:56.016 --> 40:00.516
big celebration of Baeyer's
contributions to aromatic

40:00.523 --> 40:03.563
chemistry in Berlin;
there was this big,

40:03.557 --> 40:06.347
fabulous dinner with eighteen
courses, or something like that,

40:06.347 --> 40:08.677
and all -- everybody,
chemists from all over Germany

40:08.679 --> 40:09.319
gathered.

40:09.320 --> 40:12.170
And Sachse, this nobody,
publishes a paper and says

40:12.170 --> 40:13.710
Baeyer's theory is wrong.

40:13.710 --> 40:15.340
Bad timing.

40:15.340 --> 40:19.010
So Baeyer published a response
quickly.

40:19.010 --> 40:22.020
He said: "A further
proposal is that the atoms in

40:22.016 --> 40:24.736
hexamethylene…"
(six-CH_2 groups,

40:24.739 --> 40:27.339
cyclohexane) "…are
arranged as in Kekulé's

40:27.342 --> 40:27.952
model."

40:31.768 --> 40:35.458
fact a tetrahedron;
which is what Sachse showed how

40:35.463 --> 40:36.633
you could do it.

40:36.632 --> 40:37.292
Right?)

40:37.289 --> 40:40.209
But he says,
"…as in

40:43.876 --> 40:46.026
atoms in space is one with
minimum distortion of the

40:46.027 --> 40:47.207
valence directions."

40:47.210 --> 40:48.780
(That sounds like Sachse.)

40:48.780 --> 40:52.040
But what he says is:
"Thus, the six carbon

40:52.039 --> 40:54.589
atoms must lie on one
plane."

40:54.590 --> 40:56.160
(It's got to be planar.)

40:56.159 --> 40:59.229
"and six hydrogen atoms
lie in equidistant parallel

40:59.231 --> 41:00.071
planes."

41:00.070 --> 41:01.390
(Six above, six below.

41:01.389 --> 41:04.419
All the CH_2s are just like
this around the ring.

41:04.420 --> 41:04.990
Right?)

41:04.989 --> 41:06.899
"Further,
each of the twelve hydrogen

41:06.896 --> 41:09.406
atoms must have the same
position relative to the other

41:09.409 --> 41:10.339
seventeen."

41:10.340 --> 41:13.160
(That is, they're homotopic;
you can rotate it,

41:13.161 --> 41:14.681
if the plane is flat.

41:14.679 --> 41:16.369
Now how can he say this?

41:19.972 --> 41:20.662
Okay?)

41:20.659 --> 41:24.629
"The experimental test of
the correctness of this

41:24.630 --> 41:29.590
assumption is relatively easy;
for example sufficient evidence

41:29.592 --> 41:34.972
is that there is a single isomer
of hexahydrobenzoic acid."

41:34.969 --> 41:38.949
That this, only one cyclohexane
carboxylic acid.

41:38.949 --> 41:43.839
That is, if you had this,
and put a COOH group here,

41:43.836 --> 41:48.716
or a COOH group here,
what would be the relationship

41:48.724 --> 41:50.454
between those?

41:50.449 --> 41:55.259
This place and this place,
what would you call -- are they

41:55.257 --> 41:56.267
homotopic?

41:56.268 --> 42:02.998
Are they enantiotopic,
this place and this place?

42:03.000 --> 42:05.080
Mirror images?

42:05.079 --> 42:06.519
No, they're just different.

42:06.519 --> 42:09.069
They're diastereotopic, right?

42:09.070 --> 42:11.350
Now, but you could do a neat
trick.

42:11.349 --> 42:12.709
So that's what he says.

42:12.710 --> 42:16.790
If it were like Sachse,
then you'd have two isomers of

42:16.793 --> 42:19.263
a monosubstituted cyclohexane.

42:19.260 --> 42:22.220
But what he didn't take into
account was this.

42:22.219 --> 42:24.149
This one is sticking up like
that.

42:24.150 --> 42:25.230
Watch this.

42:25.230 --> 42:27.430
Notice the black one is
sticking out,

42:27.429 --> 42:30.239
down at an angle,
and the white one is sticking

42:30.242 --> 42:31.222
straight up.

42:31.219 --> 42:32.139
But watch this.

42:32.139 --> 42:38.989
Now this one's down at an angle
and the black one's straight up.

42:38.989 --> 42:43.479
Did I break any bonds?

42:43.480 --> 42:44.620
What did I do?

42:44.619 --> 42:45.969
Student:  Rotated.

42:45.969 --> 42:47.919
Prof: I just rotated
about bonds.

42:47.920 --> 42:55.330
They're conformational;
conformationally diastereotopic.

42:55.329 --> 42:56.629
Not configurationally.

42:56.630 --> 43:00.100
So they're different but they
can interconvert easily.

43:00.096 --> 43:00.616
Right?

43:00.619 --> 43:04.389
So Baeyer says he's right
because there's only one isomer,

43:04.391 --> 43:07.901
so you have to regard it as
flat, even if it isn't;

43:07.900 --> 43:09.450
although he didn't say that.

43:09.449 --> 43:12.519
"Meanwhile,
as long as our knowledge in the

43:12.521 --> 43:16.021
field is so incomplete,
we must be satisfied that the

43:16.016 --> 43:18.366
above assumption is the most
likely,

43:18.369 --> 43:23.669
and no known fact contradicts
it." Okay?

43:23.670 --> 43:26.550
Now, Sachse didn't take this
lying down either.

43:26.550 --> 43:30.720
So he publishes a forty-one
page paper in Zeitschrift

43:33.530 --> 43:36.210
which is published by Ostwald,
who hates Baeyer,

43:36.210 --> 43:39.320
and vice-versa;
the physical chemists and the

43:39.324 --> 43:41.194
organic chemists didn't get
along.

43:41.190 --> 43:44.570
So he publishes a paper in this
other one where he gives all

43:44.570 --> 43:48.180
this trigonometry to explain
what he means by this structure.

43:48.179 --> 43:52.319
Is this something calculated to
appeal to organic chemists?

43:52.320 --> 43:57.380
Not very likely. Okay?

43:57.380 --> 44:00.730
So this is edited by Ostwald,
who didn't even believe in

44:00.731 --> 44:02.551
atoms,
remember, and wrote

44:02.548 --> 44:05.288
disparagingly of his successor
in Riga,

44:05.289 --> 44:08.399
who had been an organic
chemist: "Scientifically,

44:08.400 --> 44:11.300
he had been brought up in the
narrow circle of contemporary

44:11.300 --> 44:13.970
organic chemistry,
and to him the arrangement in

44:13.974 --> 44:17.224
space of the atoms of organic
compounds was the foremost of

44:17.224 --> 44:19.134
all conceivable problems."

44:19.130 --> 44:22.530
That wasn't what Ostwald
thought was the best problem.

44:22.530 --> 44:24.030
So Sachse published again.

44:24.030 --> 44:27.310
Nobody responded to that first
one, so he publishes again,

44:27.309 --> 44:29.669
the next year,
thirty-four pages again.

44:29.670 --> 44:33.340
And here he gives more formulas;
again, things that didn't

44:33.336 --> 44:36.416
appeal at all to anybody who was
actually interested in the

44:36.416 --> 44:38.166
arrangement of atoms in space.

44:38.170 --> 44:42.430
And then he died at the age of
thirty-one, in that year,

44:42.425 --> 44:46.835
and that was the end of Sachse,
and the end of his theory.

44:46.835 --> 44:47.605
Right?

44:47.610 --> 44:51.250
And Baeyer wrote in 1905 -- so
twelve years later:

44:51.253 --> 44:55.643
"Sachse disagreed with my
opinion that larger rings are

44:55.641 --> 44:56.461
planar.

44:56.460 --> 44:59.250
He is certainly right from a
mathematical point of

44:59.248 --> 45:01.728
view;"
(Although I sort of doubt that

45:01.726 --> 45:04.616
Baeyer went through every line
of this to check it.

45:04.621 --> 45:05.201
Right?)

45:05.199 --> 45:07.659
"Yet, in reality,
strangely enough,

45:07.657 --> 45:09.797
my theory appears to be
correct.

45:09.800 --> 45:12.820
The reason is not clear."

45:12.815 --> 45:13.415
Okay?

45:13.420 --> 45:16.200
So that was -- remember,
Sachse was 1890.

45:16.199 --> 45:23.099
So what important lesson should
we take from the tale of poor

45:23.103 --> 45:24.143
Sachse?

45:24.139 --> 45:26.649
Do you want me to give you that
as a problem to think about over

45:26.650 --> 45:27.250
Thanksgiving?

45:27.250 --> 45:29.250
Fine.

45:29.250 --> 45:32.290
Okay, so this,
remember is what Sachse wrote,

45:32.293 --> 45:34.443
and he drew models like this.

45:34.440 --> 45:37.750
And -- I'll just conclude the
punch line here --

45:37.750 --> 45:41.360
in 1913 Bragg and Bragg
determined the diamond

45:41.356 --> 45:43.996
structure,
by X-ray diffraction of a

45:44.003 --> 45:45.293
crystalline diamond.

45:45.286 --> 45:45.796
Right?

45:45.800 --> 45:51.480
And five years later,
Ernst Mohr published a diagram

45:51.478 --> 45:56.378
he drew of -- from that diamond
structure.

45:56.380 --> 45:59.630
Braggs didn't draw the
structure, but Mohr did five

45:59.630 --> 46:00.540
years later.

46:00.539 --> 46:04.419
And here's what he drew,
and that is exactly what Sachse

46:04.420 --> 46:04.840
meant.

46:04.844 --> 46:05.484
Right?

46:05.480 --> 46:09.070
So the arrangement of the
carbons in a six-membered ring,

46:09.068 --> 46:11.758
in diamond, is exactly what
Sachse said;

46:11.760 --> 46:13.750
but he got nothing for it.

46:13.750 --> 46:16.130
Okay, have a good Thanksgiving.

46:16.130 --> 46:22.000