Organic Chemistry Stereochemistry

Hi and welcome to Educator.0000

Our next topic is going to be that of stereochemistry; and that is where we take a look at organic molecules in three-dimensions--look at their shapes in space.0002

We've talked about isomers before; our original definition of isomers or the first way we were introduced to it is the idea of having two molecules who are related simply by their molecular formula.0012

They are different compounds, but they have the same formula; the atoms are put together differently--they have a different connectivity; and that is what makes them unique compounds.0023

Of course, they are different compounds because they are not interconvertible; and that is what makes them unique.0034

The original isomers we have our known as structural isomers or constitutional isomers; these are the ones with difference connectivity.0043

For example, these to alcohols are unique compounds; but because they have the same # of carbons, hydrogens, oxygens, they are defined as isomers of one another.0050

What we are going to look at next is the concept of having stereoisomers; stereoisomers again are described as isomers because they are not interconvertible and they are not identical.0060

But they have the same connectivity; all the atoms are put together in the same way and they differ by the arrangement space only.0074

Only when we look at their three-dimensional shape do we see a difference in their structures.0082

Let's take a look at a few examples.0087

For example if we have an alkene, we can have either the cis configuration or the trans configuration.0091

These different arrangements that we can have about the carbon-carbon double bond makes these two alkenes unique compounds; they are not superimposable; they are not identical.0099

Because rotation around this double bond is hindered--is prohibited, then we cannot simply flip them to be one side or the other.0111

We call it trans if they are on opposite sides and cis if they are on the same sides; and these are examples of stereoisomers.0121

They are the same # of carbons, hydrogens, oxygens, and so on--same formula; and they are even put together in the same order.0128

This is a one, two, three, four-carbon chain with a chlorine at carbon 2 and 3; and this is also a one, two, three, four-carbon chain with chlorines at carbon 2 and 3.0135

Only by look at their three-dimensional shape do we find a difference; these are called stereoisomers; sometimes, this is just called cis-trans isomerism.0148

Another example where we can have cis-trans isomerism is in the case of cycloalkanes when we have a ring.0156

Let's say we have two groups on a ring.0162

Here we have two methyl groups in the 1 and 3 position; here we also have two methyl groups in the 1 and 3 position; so both of these molecules will be named as 1,3-dimethylcyclohexane.0163

But again when we look at their three-dimensional shape, we see that they are unique compounds.0176

Because in this case, both methyl groups are pointing down, pointing away; and here we have one pointing down and one pointing up.0181

We use the same terminology here to describe cis and trans; we describe two groups on a ring as being cis to one another if they are on the same side of the ring.0189

If we flatten out the ring, you see that you can either be in the up position or the down position, either above the ring or below the ring.0201

Because these two substituents are on the same side of the ring, we would describe them as being cis to one another.0209

If they are on opposite sides of the ring, one up and one down, we would describe them as being trans to one another.0215

Once again these two molecules are unique compounds; they are not interconvertible.0222

In this case, it is because of the ring that free rotation around the sigma(σ) bonds are prohibited and we cannot interconvert between the two.0226

So cis and trans molecules are examples of stereoisomers.0235

Another interesting example of stereoisomers that we are going to be spending most of our time with in this section deals with a tetrahedral carbon.0242

An sp3 hybridized carbon that has four different groups attached; so four unique groups attached.0250

If I were to build such a carbon and then I were to build another carbon with the exact same four groups and I attached them in the exact same order.0257

In three dimensions I would see that I built two molecules that are identical; they are completely identical.0273

We could draw that on the page as saying: if I draw my tetrahedral carbon--if I have a red up here and a green down here and a blue as a wedge and a yellow as a dash.0279

These two molecules as drawn would be described as being superimposable; every atom on the first structure corresponds exactly with the atom on the second structure when you try and align these two.0293

That is another word for just saying they are identical.0309

But that is the test we are going to use to describe if two stereoisomers are identical--is if we can superimpose them.0312

Let me show you a little trick here: if I swap any two groups on here--let's take the red and the yellow and switch their positions.0319

When I do that and I try this same test and try to align them, all of sudden I find that the two tetrahedral carbons are no longer superimposable; they are no longer identical.0331

If I line up the blue and the green, then the red and the yellow don't match up.0342

If I line up the red and the blue, any two colors that I pick to line up, I will find that the other two colors don't align.0346

Now suddenly by doing this switch, we have come up with a new structure.0356

It doesn't matter which two groups you switch; you could try this at home.0365

Let's switch the red and the green but keep the blue and the yellow in the same position.0368

When we make that swap, we find that these two groups are now non-superimposable; they are unique compounds; they are stereoisomers of one another.0373

This now is going to be a little more challenging to see without working with models.0391

Eventually we are going to have to look at this 3D drawing and this 3D drawing and be able to tell by manipulating in our minds that in fact they are non-superimposable and they are unique compounds.0396

One more thing I want to demonstrate with these two tetrahedral carbons is they do in fact have a relationship you might be able to see.0410

It looks as if I had a mirror placed in between the two molecules; one would be the perfect reflection of the other; we describe these as having a mirror image relationship.0420

That is another relationship that is going to be very important to us in this chapter that we will come back to.0431

What makes a tetrahedral carbon with four unique groups on it have this special relationship of being non-superimposable with this mirror image is the fact that this molecule is a chiral molecule.0440

We need to discuss the term chirality and understand what that means; and then we will test out a few examples.0455

What we have just demonstrated is that stereoisomers are going to be possible for any tetrahedral carbon with four different groups attached; a lot of times we identify that carbon with an asterisk.0465

That carbon can be described as a chiral carbon or an asymmetric carbon or perhaps a chirality center.0478

What we will find is that when we have chiral objects, they are described as chiral because they have no mirror planes of symmetry; no internal planes of symmetry.0486

There are a few rare exceptions of highly symmetrical molecules that have no plane of symmetry but are still not chiral; but we are not going to come across any of those in our introductory lessons.0497

What we are going to look for is a plane of symmetry to describe whether or not something is chiral.0510

If an object does have a plane of symmetry, we are going to describe that molecule as being achiral; as achiral meaning not chiral.0517

Let's take a look at some sample molecules and see if we can determine whether or not they might be chiral or achiral--how about just a plain cyclohexane ring?0526

In cyclohexane, we know that it has various conformations; it can be a chair or a boat or a few different chairs.0539

But when it comes to looking for elements of symmetry, what we are going to do is we are going to totally flatten out these rings.0545

We are going to try and make them as symmetrical as possible before we look for symmetry.0551

Would you describe cyclohexane then as a symmetrical molecule?--does it have an internal plane of symmetry where one half of the molecule reflects on the other half?0555

Yes, in fact, this is a highly symmetrical molecule.0565

We can have a plane of symmetry that cuts straight through this molecule here; these three carbons reflect on these three carbons perfectly.0568

In fact, you can even have a plane of symmetry that slices through carbons and hydrogens; so one-half of this carbon atom reflects on the other half of this carbon.0577

The point is that the left-hand half of the molecule is the exact mirror image of the right-hand half.0587

So one example of an achiral molecule would be just something like a simple cyclohexane ring.0596

Now what if I were to put a substituent somewhere on the ring?--bromine, chlorine, something; now is this still a symmetrical molecule?0603

Clearly we have taken away some of the symmetry, but there is one plane of symmetry that still exists.0613

In fact I forgot to mention that we could even slice through for just cyclohexane, we can slice through all six carbons and that would be a plane of symmetry.0621

It reflects the six top hydrogens on the six bottom hydrogens.0630

So putting a substituent on the ring takes away that plane of symmetry.0636

But we still have one plane of internal symmetry right here; we can slice exactly through that atom and through these two carbons and those hydrogens and reflect this half onto this half.0639

Because it has a plane of symmetry, we describe this as an achiral molecule.0651

Maybe we could draw this as a ring with just either a wedge coming out or even a dash coming out; it doesn't matter how we draw that group.0658

How about looking at a carbon-carbon double bond such as this?--let's look at an alkene a carbon-carbon double bond.0668

Let's put one group on here; maybe again a chlorine or a bromine or maybe a methyl; something like that.0679

This is not a plane of symmetry and this would not be a plane of symmetry; this is not a plane of symmetry because it reflects a white atom onto a hydrogen.0687

But because this molecule is planar, we can use the plane of the molecule as a plane of symmetry slicing through every one of these atoms and reflecting the top half onto the bottom half.0694

So this in fact is also a symmetrical molecule; we describe this as an achiral molecule... so something like this; let's maybe put a CH₃ here for example.0704

And this is planar so the plane of the molecule is going to act as the plane of symmetry.0720

A lot of times what we can do is we can draw... you could use a dashed line to indicate where the internal plane of symmetry is on the molecule; so there it is for the substituted cyclohexane.0726

And this one has a few planes of symmetry; we can go across this way or this way; and we can also have the plane of the molecule if we were to flatten it out.0737

How about having a six-membered ring with two groups on it?--does this still have a plane of symmetry?--well, in this case it does.0750

It has a plane of symmetry right here; and this is a plane of symmetry because we have an atom pointing towards you on the left and an atom pointing towards you on the right.0763

This would be as reflected on a mirror; so anything that is a wedge on one side would have to be a wedge on the other side; just like you would expect for a mirror image relationship.0774

So this too would be an example of an achiral molecule.0782

How about if I swapped one of these groups?--instead of looking at the cis disubstituted, how about the trans disubstituted?--now does this molecule still have a plane of symmetry?0794

Well it is a symmetrical molecule and a lot of times what you might recognize is that it has got a rotational symmetry; but that is not what we are looking for for chirality.0807

For chirality, we are looking for a plane of symmetry; an internal plane.0817

When we try and cut the molecule in half this way, we see that here we have a red atom reflecting up on the top and here that is reflecting on hydrogen.0821

This in fact does not have a plane of symmetry; so we would describe this molecule as a chiral molecule... as a chiral molecule.0831

So if we made one a wedge and one a dash, this now would be a chiral molecule.0842

Another example of a chiral molecule was this tetrahedral carbon that we saw, right?--because it has four unique groups0852

There is no plane of symmetry here because each group has no match to reflect onto.0860

We could write that down as an example of something that could be chiral--is a carbon with four different groups on it.0868

Remember we describe that as being a chiral carbon or an asymmetric carbon; and that is because it is an example of something that is chiral.0880

Another interesting example of something that is chiral is your hand; you will see this used in nearly every textbook that you refer to for organic chemistry.0888

Even though it is planar, the top half of your hand is different from the bottom half; your palm looks different and has different texture than the top half of your hand.0899

So this is also something that is described as chiral; and we will see some examples with that.0910

We can look for the symmetry in all sorts of different things besides molecules; like I said you could use your hand; you could also imagine maybe a chair0918

What if you had an ordinary chair with arms on both sides and the seat and the back?0927

That is something that is symmetrical; the left half looks exactly the same as the right half; so we could say that a chair is an example of something that is achiral.0933

How about if we compare that with a student desk that you might find in a classroom?0946

The student desk that has a chair but attached to it is a table, and it is usually attached to one side or the other side, right?--we have some right-handed desks; we have some left-handed desks.0951

That takes away the plane of symmetry; so a student desk is something that is also described as chiral.0962

One thing we want to know when we are studying stereochemistry is not only the definition of what it means to be chiral or achiral but then also to identify a given species as being chiral or achiral.0972

It is simply a matter of identifying internal planes of symmetry.0985

Let me show you something interesting about a molecule that is chiral or achiral.0990

Let's come back to our achiral molecule where we had the two groups pointing up right here; and let me draw its mirror image.0998

I am going to imagine a mirror here; and then I am going to try and draw the same structure and draw what I would see if I had a mirror here.1008

This pointing toward a mirror just like this one would be a wedge; and this one on the third carbon down we have another wedge; this would be the mirror image of this first structure.1017

Now let me ask what is the relationship of those two compounds?--if you had to describe the relationship of these two compounds, how would you describe them?1028

Let me build two of them and we can compare it.1039

Hopefully you see the mirror image relationship here, right?--they are mirror images of one another.1043

Are these two compounds superimposable?--are they identical?1048

Well sure; hopefully you can see that if I just picked this up and moved it over, I would in fact be able to match up every single atom on the first structure with the one on the second.1053

We describe this as being superimposable or identical... in other words, they are identical to one another.1061

Let's do the same thing with this second structure; so right here I have a molecule drawn where the one on the left is a wedge pointing up and the one on the right is a dash pointing down.1081

Then let's draw its mirror image; what does that mirror image look like?1097

We draw another cyclohexane ring; this one is the closest here; and pointing in this direction we have a dash; and then over here we have a wedge.1102

Now let's look at these two molecules again and ask what is their relationship?--what is the relationship?--are these superimposable?1113

This is where it gets to be a little challenging.1123

This is where working with models and getting plenty of practice is going to pay off because we are going to need to be able to see these relationships.1126

Here I have the model of these two; can I get them to superimpose?1137

If I do that same trick as before--if I lift it up and just try to lay them on top of each other.1140

I see they do not superimpose because here we see we have the red atom up and here we have the red atom down.1145

How about if I were to flip it?--can you imagine doing that?--let's try flipping it.1151

When I flip it, the same thing happens; I cannot get these to line up.1158

No matter what manipulations I do... remember you are free to rotate this around; but we are going to flatten it out and make it as symmetrical as possible.1162

These will not superimpose; these are unique compounds; these are non-superimposable.1169

These are called... we have a name for these; when you have a chiral object and you have a pair of non-superimposable mirror images--we call these enantiomers.1186

There is a lot of vocabulary in this stereochemistry unit; a lot of new terms and vocabulary that we will need to become familiar with.1199

A pair of non-superimposable mirror images are called enantiomers.1207

Let's look a little more closely at this and see if we can come up with some generalizations.1213

I've just redrawn what we drew by hand.1218

We said that these two molecules when we build them we confirm that they are in fact superimposable; while these two molecules when we build them we found that they are non-superimposable.1220

This is in fact a generality that we can determine dealing with chiral and a chiral; I am realizing right here that there is a little typo... let's compare a chiral to achiral.1232

If we have chiral objects, all chiral objects have non-superimposable mirror images.1250

Every time you have an object like this that we determine as chiral, it has no planes of symmetry; when we draw its mirror image or build its mirror image, it will always be non-superimposable.1256

In other words, every chiral molecule has an enantiomer; an enantiomer is something that exists for every chiral molecule.1267

All achiral objects, on the other hand, are exactly the same as their mirror image.1275

Because this molecule is achiral--it has this internal plane of symmetry, when we build its mirror image, we will always end up with the exact same molecule.1281

Again we can extend this to not just molecules like this, but we can extend it to the examples we saw on the previous page.1290

Imagine having a regular chair; if you were to build its mirror image and have a second chair sitting right next to it so that they are mirror images of each other. 2151 Would that be a different kind of chair or is it the exact same thing?--of course, it would be the exact same kind of chair.1299

In other words, an achiral molecule does not have an enantiomer; it does not have a unique mirror image; it is the same as its mirror image.1318

But if you had a right-handed student desk and you made its mirror image, that would be a new type of desk.1326

It would be a left-handed student desk; so that would be like the enantiomer of that original student desk.1333

This is where the example of the hand comes into play; and that is why you will always see it in the textbook--is because you have built in with you at all times a beautiful pair of enantiomers.1338

Disregarding any slight imperfections in your hands; imagining these are perfect mirror images of one another, they would in fact be non-superimposable.1349

Your right hand is unique from your left hand; and that is because this is a chiral object; it has no symmetry.1357

So when you built its mirror image which is what you have with your right and left hand... when you build its mirror image, you will end up with a unique compound.1364

Any time you are having trouble remembering what enantiomers are, remember that you have a little cheat sheet attached to your arms all the time.1372

Next let's talk about some nomenclature; how do we tell the world if these two molecules are different molecules?1382

Here we had our original pair of enantiomers that we built; we now know what to call these two molecules--mirror images; non-superimposable mirror images.1390

How do we tell the world that we are referring to this structure and not this structure?--we need some systematic nomenclature rules to describe this three-dimensional shape compared to this one.1400

What we are going to do is we are going to--for every chiral carbon that we find--so every tetrahedral carbon with four unique groups on it, we are going to name that as either an R or an S configuration.1419

Let's talk about the rules on how to determine whether it is R and S; and then we can look at several examples.1430

These are known as the Cahn-Ingold-Prelog rules; and our first step is that we need to assign priorities to the four groups; we need to prioritize them 1, 2, 3, and 4.1437

We are going to do this based on their atomic number; so we can just look at the four atoms attached and rank them 1, 2, 3, and 4; #1 is the highest atomic number; #4 is the lowest atomic number.1449

If you ever have a hydrogen attached to that chiral carbon, that of course would always be #4 because that is the lowest atomic number possible.1460

What if you have a tie--if you have two atoms that are identical that are attached to that tetrahedral carbon?1468

What you are going to do is you are going to move away one atom at a time until you find a difference; so you are going to try and break the tie; we will look at some examples of that.1473

If you encounter a double bond in your structure, you can treat that as if you had two separate single bonds; we will see some examples of that as well.1480

Our first goal is to rank the groups 1, 2, 3, 4; we are now going to view this chiral carbon with a very specific point of view.1487

We are going to take the #4 group; let's say this yellow is our lowest priority.1499

We are going to hold the molecule in such a way or view the molecule in such a way that the lowest priority group is pointing away from us; so it is a dashed bond.1503

When it is pointing away from us, we are going to move from group #1 to 2 to 3; 1-2-3, 1-2-3, 1-2-3.1512

Then we are going to look if that rotation in moving from 1-2-3 is a clockwise rotation; then we describe that chiral center as being an R configuration; clockwise meaning right-handed.1522

It is like if you turned a steering wheel clockwise, your car would make a right-hand turn; so clockwise means right-handed; that comes from the Latin Rectus.1537

If the rotation instead is counterclockwise, that is like making a left-hand turn; that configuration is known as S; and that comes from the Latin Sinister for left-handed.1547

So that is how we are going to determine R and S; let's take a look our first example.1558

Do have any chiral carbons or asymmetric carbons on this first molecule?--well, sure; right here this carbon has four different groups on there.1565

We would describe that as a chirality center; and that means we could name this as either having the R configuration or the S configuration.1575

Our first goal is to rank our groups; we have a carbon, oxygen, hydrogen, bromine; our highest priority group is the bromine, #1.1584

Next is oxygen; we could just refer to the periodic table if we need to see who has the higher atomic number.1595

Hydrogen is always going to be #4; and that means this carbon is #3; so we rank our groups 1, 2, 3, 4.1604

Now what we do is we view the molecule with the lowest priority group #4 pointing away from us.1611

If we look at this right here, we see that the hydrogen #4 already is pointing away from us because it is a dashed bond; wo we already are viewing it from the right perspective.1617

We go from 1 to 2 to 3... 1 to 2 to 3; 1-2-3-, 1-2-3, 1-2-3; keep doing that rotation; and how would you describe that rotation?1626

Looks like a counterclockwise rotation; and because it is counterclockwise, we call this the S configuration; so this is the S molecule.1640

Let's try another one; here we have another chiral carbon right here; another asymmetric carbon; and we need to identify the four groups and number them.1654

I only see three groups there; where is the fourth group?--there must be a fourth group.1666

Remember for line drawings, it is common to omit the hydrogen; because we have these two bonds in the plane and the chlorine is a wedge, there must be a hydrogen right here as a dash.1671

This is where we are really going to have a firm understanding of line drawings and three-dimensional shapes.1682

Now I see my four groups; we have a hydrogen, chlorine, carbon, carbon; so that allows me to rank chlorine as #1 and hydrogen is #4; but now we have a tie.1688

We look back at our rules; we say in the case of a tie, we are going to move away just one atom at a time until we find a difference.1702

Let's ask this: what three groups are attached to this carbon?--I know it is attached to the chiral carbon; what are the other three bonds?1709

It is just a CH₃, isn't it?--so we have a hydrogen and a hydrogen and a hydrogen attached.1718

Let's come over to this carbon and ask the same question; what are the three bonds to this carbon?--well, this has a carbon and then a hydrogen and a hydrogen; so now we have broken the tie.1725

Once again we are going to look to the atomic number; which has the highest atomic number?1738

This carbon beats out the hydrogen; so this is going to be group #2 and this is going to be group #3; so ranking the groups 1, 2, 3, 4 sometimes requires a little work here.1742

Next we are going to make sure our lowest priority group is pointing away; it is doing that; it is a dashed bond.1756

What do we do?--we move from 1 to 2 to 3 and we keep doing that; 1-2-3, 1-2-3, 1-2-3; and what does it look like here?1761

Now it looks like we are doing a clockwise rotation so this is going to be the R configuration.1770

Let's see a few more examples; how about this structure?--do we have any chiral centers in this one?--we are looking for a carbon with four different groups on it.1777

Well yeah; it looks like here where we have shown some stereochemistry, this looks like a chiral carbon.1788

We have our dashed hydrogen is missing from the structure so we can add that in to make sure we see all four groups.1794

And what are the atoms of attachment?--we have a carbon, carbon, hydrogen, nitrogen.1802

The first assignment we can make is that nitrogen is #1 and hydrogen is #4; and then we have these two carbons being in a tie; so let's look at them one by one and see what is attached.1810

What do we have on this carbon?--we have an oxygen and then a carbon and a carbon.1823

And what do we have attached to this carbon?--well, now we have a double bond.1831

If we refer back to our Cahn-Ingold-Prelog rules, it says that you can treat a double bond the same as if it were two single bonds to that atom.1836

So what we have for our three bonds is we have an oxygen and another oxygen and a hydrogen.1843

What I want you to be careful of is avoiding the temptation to add these groups up and see which total is higher; we are not doing that; we are simply looking for the highest priority group.1853

They each have an oxygen so that is tie; so then we move to the next highest priority; this has a carbon and this has an oxygen; so the second oxygen wins here.1865

So this is group #2--this carbonyl group; this whole group attached to the chiral carbon is group #2.1876

And this whole group is going to be group #3; so now we have ranked our groups 1, 2, 3, 4.1882

Then what do we do?--we move from 1 to 2 to 3 and we keep doing that; make sure you keep making a complete circle and keep doing the rotation; 1-2-3, 1-2-3, 1-2-3.1890

This looks like a counterclockwise rotation; so this is the S configuration... the S configuration.1900

How about the next one?--this looks like our chiral center; that is the only chiral carbon there is.1911

We have a hydrogen here still a dash; we will look at examples where it is not a dash next; so he is group #4.1921

Now we have a three-way tie--all three of these are carbons; so let's see which one is going to win.1928

Again it might be tempting to say: wow look at this big group; this must be the #1 priority.1934

But again we are not doing that; we are going to have a systematic approach; and that means we are just simply going to move out one atom at a time and decide which one is the higher priority.1939

What does this carbon have attached to it?--what three?--there is only going to be three bonds from that carbon.1950

There are three hydrogens--hydrogen, hydrogen, hydrogen; this carbon has a carbon and then two hydrogens; this carbon has a carbon and a carbon and a hydrogen.1956

Right away just moving out one atom at a time, we've already broken the tie.1973

Who is our #1 priority?--this group up here; and then this group is #2; and then this methyl group over here is #3.1977

Now we go from 1 to 2 to 3; 1-2-3, 1-2-3, 1-2-3; we see that it is clockwise; this is the R configuration; very good.1992

How about the next one?--now we have a case where when we add in our missing hydrogen, we see that this now a wedge instead of a dash; so we need to figure out what to do in that case.2005

Let's rank our groups first; who wins?--we have a carbon, iodine, hydrogen, and chlorine.2015

Iodine has the highest atomic number so that is #1; chlorine and then carbon and then hydrogen.2022

This turns out this oxygen over here--we never were concerned with that because we didn't have a tie; so we just look at the four attached atoms.2031

Now we want to move from 1 to 2 to 3, but this hydrogen--this lowest priority group is in the wrong direction; well, let me show you something.2042

If we are holding this molecule so that the lowest priority group from you is pointing away; let's say we are going in this direction to do 1-2-3; the rotation that you see is counterclockwise.2051

Guess what rotation I see from my point of view?--I see clockwise; so you see the exact opposite.2067

So if your lowest priority group is exactly in the wrong position--the opposite position, all you need to do is reverse the rotation that you are going to do.2075

Let me show you want we are going to do; we are going to go from 1 to 2 to 3 and then we are going to back it up and go backwards; and instead we are going to go from 3 to 2 to 1.2088

#4 is a wedge so we are going to reverse our rotation; in other words, we are going to go from 3 to 2 to 1 and then look at that rotation.2100

From 3 to 2 to 1, this is a clockwise rotation; and clockwise is always the R configuration.2117

If your lowest priority group is a wedge instead of a dash, it is really just as simple to do it.2123

We just have to remember that the correct orientation--the correct point of view is one which has the lowest priority group pointing away; so that is when we are going to reverse it.2130

How about this last group?--how about this last group if we try and assign the configuration R or S?2140

Bromine is #1; hydrogen is #4 as always if you have a hydrogen; and how about the other two groups?--when we go to rank these 1, 2, 3, 4, what do you see?2148

Well this is a tie; this is a carbon and a carbon; and they are both CH₂s; and then when we move out these are both CH₃s; so these two groups are identical.2161

We are not going to be able to number this 1, 2, 3, 4; so what does that do to this chiral center?--does that make this R or S?2174

It is kind of a trick question, isn't it?--because these two groups are identical, that means this carbon atom in this molecule is a plane of symmetry; this is an achiral carbon; so it is not R or S.2182

The R and S configuration is only something that we consider for chiral carbons meaning a carbon with four unique groups attached to it.2200

If you ever find that you can't rank them 1, 2, 3, 4, and you have a tie, that means you are maybe looking at the wrong carbon in order to assign your R and S configuration.2207

Let's get some practice drawing stereoisomers; let's say we are asked to draw S-2-bromopentane; how could we do that?2220

We could draw pentane; one, two, three, four, five--so there is pentane.2230

On carbon 2, we have a bromine; and what we are going to need to decide--what are our two choices?2237

That bromine can either be a wedged bond or it can be a dashed bond; and only one of them is going to have the S configuration.2244

You could spend an awful lot of time thinking this through in your head and planning it out and trying it get the right answer right off the bat.2251

But that might turn out to be a pretty big waste of time; my advice is to just guess and pick one of them; let's say we want to have it as a wedge.2256

Then what can we do?--we can check to see if we made the right guess.2268

Bromine would be #1; and between these two carbons, we have a methyl and we have this propyl; this has an extra carbon attached so this is #2; this is #3; and our hydrogen is pointing back.2273

Did we make the right guess?--did we make the right guess?--no, this looks like we drew the R configuration.2287

Guess what we have to do?--all we have to do is just erase it; I'll just cross is out so I can leave my work here.2294

But I just made the wrong guess; and it is just the bromine as a dash instead; you could confirm this if you want but this would in fact be the S configuration.2302

A lot of times it is a lot faster to pick one of the stereoisomers and then confirm it rather than try and guess in your mind what is going to be the appropriate one.2314

So that would be S-2-bromopentane; now what if I asked you to draw the enantiomer of S-2-bromopentane?--we already see what the structure of the S enantiomer looks like.2325

If I wanted to draw the other enantiomer, there is two methods; there are two approaches we can take to this problem.2335

One approach is we could draw the mirror image because we know the definition of an enantiomer is that they are mirror images of each other.2342

We can imagine a mirror to the side or to the bottom and maybe we can draw it like this.2349

Draw the bromine here; this would be the mirror image of this if I had a mirror right here; or if I had a mirror right here you could see it.2356

So that should be the enantiomer; that is one possible way to do it; some students have an easier time drawing mirror images than others.2366

But there is another method we can have; what we can do is we can invert all of our chiral centers; and by invert I mean swap two groups.2376

In this case we are going to keep our carbon chain fixed; but instead of having the bromine be a dash, our bromine is going to be a wedge.2389

That is another way in fact to draw an enantiomer accurately; and so whichever method works for you, they both should result in the right answer.2401

Are these the same answer?--are these the same compound?--you see that?--well, sure.2410

If I take one and I simply flip it over, they should superimpose; if I flip over one, the bromine that was a wedge becomes a dash, and they will line up very nicely.2415

Let's check the configuration here?--we can do it on this one.2426

Here we have bromine is 1, propyl is 2, and methyl is 3; looks like this is the first guess we had up top here, isn't it?--this is 1-2-3; this is the R configuration.2429

How about this one?--if this is the same molecule as this, it should have the same configuration; let's check that.2444

This is #1, this is #2, this is #3; and I go 1-2-3, but where is my lowest priority group?2449

My lowest priority group is actually a wedge so I am going to have to reverse this and go backwards 3-2-1, 3-2-1, 3-2-1; yes, this is in fact also the R configuration.2459

Either one of these got to the right answer; and something that we can observe here is that the enantiomers have opposite configurations... they have opposite configurations.2471

If one enantiomer is the S configuration, the other enantiomer must be the R configuration; that will always be true.2492

Even if you have multiple chiral centers, all of the configurations in the chiral center is one enantiomer; it will be the opposite in the other.2499

I would like to talk about a shorthand notation we can use to draw chiral centers; these are known as Fisher projections.2510

Here is the definition of a Fisher projection; what we are going to do is we are going to view a tetrahedral carbon from a very unique perspective.2518

Usually we draw tetrahedral carbons or we view them in such a way that two bonds are in the plane so it is easier to draw.2527

One is a wedge and one is a dash; that is usually how we draw our drawings.2534

For a Fisher projection, what we are going to do is we are going to hold the chiral center or the tetrahedral carbon this way so that only the carbon atom is in the plane.2538

The two bonds on your right and left are projecting out towards you; it is like you can reach out with your right and left arms and hold on to these atoms on the side; these groups on the side.2546

The top and bottom groups are pointing away from you; they are actually dashed going back into the plane.2556

If we always view the tetrahedral carbon with this exact perspective, then we don't need to use the dashes and wedges.2562

What we do in a Fisher projection is we project the wedges back into the plane and project the dashes forward into the plane; and we draw it simply as a cross.2568

Even though this is drawn all as straight lines, none of these bonds are actually in the plane.2579

This is a very special convention; and it means that the side groups are wedges.2584

Kind of looks like a bowtie, doesn't it?--some of my students tell me that is a way to help that remember what a Fisher projection looks like.2589

These side groups are actually wedges and these top and bottom groups are dashes.2595

By convention the carbon chain is usually drawn in this vertical position; so although you can look at a tetrahedral carbon this way or this way, there is a few different points of view you can have.2601

If this was the carbon chain, usually we put that in the vertical position; we will see lots of examples of this.2616

Here is one example; let's say we are asked to draw this Fisher projection.2623

We have four carbons; we have a chlorine as a wedge here.2634

What we are going to do for the Fisher projection is instead of viewing this molecule from the side.2641

We are going to be tipping the molecule up like this so that we are viewing this tetrahedral carbon as defined by the Fisher projection.2645

As defined the carbon chain is top and bottom pointing away from you; and the two side groups, in this case chlorine and hydrogen, are projecting out toward you and are wedges.2652

In this perspective, where do you see the chlorine?--it is on your left.2664

So when we draw the Fisher projection... let's number our carbons here; let's say 1, 2, 3, 4.2670

Carbon 1--let's put this up here; we have a one-carbon chain up here.2681

Then on the bottom, we have this two-carbon chain CH₂CH₃; so this is 2 and this is 3 and this is 4; so I'm drawing here the backbone of the Fisher projection.2687

What we are going to see is when we view it like this so that the methyl group is up and the ethyl group is down, the chlorine should be on our left; that would be an accurate Fisher projection.2700

That is great if you have a model and you can pick it up and move it.2717

But if we don't have a model, I think another good strategy you can use is rather than taking the model and picking it up and moving it, is we can pick ourselves up and move our point of view.2722

If we were to leave this molecule in the plane as drawn, what would be the perspective that I would need to take to view this molecule so that I see this picture?2734

With the chlorine and hydrogen projecting out toward me and the methyl up top?2744

What I would need to do... how about if I laid down on the bottom here and viewed the molecule like this?2748

If I were to lay down in that position, the methyl group would be aligned with my head; the ethyl group with my feet; and looking up in this direction, where would you see the chlorine?2758

If I am in the plane, the chlorine would be a wedged bond which would be on my left; so we can have this little person saying the chlorine is on my left.2767

Using this stick figure is a nice way to maybe see it from the proper perspective.2782

Another thing you can do if you have some time to check your work is you can check the configuration.2789

If you have drawn the proper Fisher projection, you should still have the same configuration that you had on the line drawing.2793

What was the configuration of this carbon 2 here?--was it R or S?2799

We have #1 here, #2 here, #3 here, #4 here; our lowest priority group is pointing away as it should.2805

So we go from 1 to 2 to 3; 1-2-3, 1-2-3, 1-2-3; this was the R configuration; let's check to see if this is still the R configuration.2816

Same priorities; chlorine is 1, ethyl is 2, methyl is 3, hydrogen is 4; we move from 1 to 2 to 3 and now let's check our lowest priority group.2828

Where is our lowest prioirty group?--is it pointing away like it needs to be?2843

It is in this side position; what is the definition of the side position of the horizontal groups?2847

Remember that bowtie; that side position is like it is coming out towards you; you can grab it with your right and left hands; it is a wedge.2851

What do we do if our lowest priority group is a wedge?--we reverse our direction and we go 3-2-1, 3-2-1, 3-2-1.2859

Sure enough, we did draw the correct configuration here; these both have the R configuration.2866

What is very nice about being able to draw a Fisher projection is that it allows us to draw chiral centers very very quickly because we don't have to worry about dashes and wedges.2874

It also makes it super easy to draw mirror images because now we don't have to worry about dashes and wedges.2883

Nearly everyone, even the most artistically challenged or spatially challenged student, can draw the mirror image of this Fisher projection.2889

We have a hydrogen closest to the mirror; we have a chlorine further from the mirror; we have a methyl up top and we have an ethyl down below.2896

Just like that we drew the mirror image; much much easier to draw it for a Fisher projection than a line drawing.2904

I have a feeling that as you get comfortable with Fisher projections, you will very likely prefer to use them if you have a choice on how to draw your chiral centers.2910

What should the configuration of this mirror image be?--since this is a chiral molecule and we just drew its enantiomer, I think this better have the S configuration.2921

I just inverted my chiral center; look if you compare these two, we just swapped the position of the hydrogen and the chlorine.2932

Sure enough, we go from 1 to 2 to 3, but then we back it up again 3-2-1, 3-2-1, 3-2-1; this is in fact the S configuration.2939

We just drew the Fisher projection of this molecule and then drew its enantiomer very quickly.2949

One other very nice use of Fisher projections is if we have to assign the configuration where if our #4 group is in the plane of the page.2954

Let me redraw this in case it is a little too low to the bottom of the screen.2963

If we were given this molecule and we were asked to assign it as the R or S configuration, we would have a hard time doing it.2968

Because our lowest priority group is not a wedge projecting out toward you; it is not a dash pointing away from you.2976

It is in the plane which means it is parallel to the plane; and we don't have any rules for that.2983

In that case, I think one of the quickest and easiest strategies is to view this molecule as a tetrahedral carbon with this orientation so that you can convert it to a Fisher Projection.2990

What do you think?--if I do this; if I view it from this angle.3005

Here is the tetrahedral carbon as I see it; what groups do I have on the top and bottom from this perspective?3010

Looks like I have a hydrogen aligned with my head and a methyl group aligned with my feet.3017

Here is the tricky part: I have two groups on my right and left; they are both coming out toward me; and where is this OH?3024

If I am in the plane of the board, the OH is going to be on my left-hand side.3032

Very good; if you can do that with a little practice, you've got Fisher projections down; piece of cake.3038

What is nice about a Fisher projection is by definition every group is either a dash or a wedge so it is always a simple exercise to assign the configurations.3047

Now all we do is we assign our priorities; oxygen is #1; hydrogen is #4; and for these two carbons, since this one has an oxygen attached, he is a higher priority than the methyl.3055

We rank our groups 1, 2, 3, 4; we move from 1 to 2 to 3; and then we check our lowest priority group; where is it?--it is in the up position.3069

And what does that mean?--that means it is pointing away from us just like it should be; so we keep our configuration.3080

1-2-3, 1-2-3, 1-2-3, and what do we have here?--we have the R configuration.3086

This is a very simple rapid way to assign configurations if your molecule is drawn in such a way with the lowest priority group in the plane.3091

Another example where picking up your body and moving it is going to be a good strategy in getting the proper perspective.3101

Let's take a look at some molecules that have two chiral centers and see what we can do with those.3111

Here we have an example of 2-bromo-3-chloropentane; I've drawn them both here as wedges.3119

Because this molecule has two chiral centers, each of them can be described as being the R or S configuration; so I've put some parentheses out here in anticipation of that.3126

Let's complete the name of this molecule because the stereochemistry, the configuration, is going to be a part of the complete name of a molecule whose three-dimensional shape is given.3137

Here On carbon 2, we have a bromine; let's determine that configuration.3149

This is group #1; let's write them without making too big of a mess; group #2, group #3; so we go from 1 to 2 to 3; and our lowest priority group is a dashed hydrogen.3154

So we go 1-2-3, 1-2-3, 1-2-3; so at carbon 2 we have the R configuration; so we are going to call that 2R out front because we have to say which carbon we are describing.3168

Then on carbon 3, we have a chlorine; and this chlorine has group #1 and group #2 and group #3; our lowest priority group is pointing away like it should; looks like this is also the R configuration.3180

This stereoisomer that is drawn is described as (2R,3R)-2-bromo-3-chloropentane.3192

It is simply put out in the very front of the name; in parentheses is where we put all our stereochemical information.3200

How about if I wanted to draw the enantiomer of A?--we will call this molecule A; for short, the enantiomer of A.3207

Remember there are two ways we can do it; we can either draw the mirror image; 5338 As our molecules get more complex, you might imagine the mirror images are going to be a little more challenging to draw.3214

I would recommend or personally what I think would be the easiest way to draw the enantiomer is to keep my carbon chain the same.3224

So bromine is still on 2 and chlorine is still on 3; but I would invert the chiral centers; so they were both wedges; they are now going to be both dashes.3232

I automatically know that this is now the enantiomer of A.3243

Let's call this molecule B; and what do you think the configuration is going to be for B?3246

It must be the opposite now of A; so it is going to be 2S,3S; of course you can check all that later; go back; that is some very good practice that you can get.3254

How about the Fisher projection of A?--if I wanted to do the Fisher projection, now we have again our carbon chain.3266

Let's number it so we can get oriented; one, two, three, four, five carbons.3272

We have a methyl group; and then carbons 2 and 3 are both chiral centers; so our Fisher projection has now two horizontal lines.3276

In fact, Fisher projections are ideal for drawing molecules with multiple chiral centers because it is greatly simplified in this form.3284

What we have to decide then to draw an accurate Fisher projection for A is where do we locate the bromine and the chlorine?--are they going to be on the right or left on each carbon?3294

We have to get the proper perspective; and let's see if we can do that using our line drawings or stick figures.3302

For carbon 2, what would be the proper point of view to view carbon 2 so that the methyl group is pointing up and away from me?3313

And then the two groups on carbon 2, the hydrogen and the bromine, are both projecting out toward me as wedges?3320

We are going to have to come up from above the molecule looking down; and now that is exactly what we see.3327

We see our bromine and our hydrogen on carbon 2 both coming toward me; carbon 1 and carbon 3 are both pointing away from me; and where is that bromine?3335

If I am lined up in this perspective and I am in the plane, the bromine is going to be on my left... the bromine is going to be on my left.3346

On carbon 2, I am going to draw the bromine on the left and hydrogen on the right.3364

How about for the chlorine?--I can't stay up here with this same perspective and view down at the chlorine because now the chlorine isn't coming toward me.3369

It is pointing away from me; so that is the improper perspective.3377

The easiest thing for me to do is pick myself up and move myself down here and view in this direction; now I am looking at it from underneath the plane of the molecule and looking up.3382

When I do that, again carbon 1 always need to be aligned with my head; where is that chlorine?3394

If I am in the board, that chlorine is coming down to my right... the chlorine is on my right.3398

When I come up to carbon 3 here, that is what I see; and there is my Fisher projection of A.3410

We can confirm that we've done it correctly; this should still be 2R,3R; in fact it is.3416

Let me show you this molecule... seeing I think I have it built here.3422

Here we have the bromine and the chlorine as both wedges on my five-carbon chain; and let's take a look at what that Fisher projection is.3428

The Fisher projection is actually viewing the molecule like this so that the bromine and hydrogen here are coming out towards you.3435

But then this carbon also comes out towards you so what we've done is we have rotated the molecule to have this conformation for a Fisher projection.3444

In a Fisher projection, all the chiral centers have the two groups pointing out towards you; so the molecule wraps itself around like this.3455

The methyl group is at the very top; ethyl group is the very bottom; we see that the bromine is on our left and the chlorine is on our right.3463

What we did over here was instead of having the model because we didn't have the model to pick up.3470

What we did is we viewed the molecule from the top looking down over here; and that is how we saw the bromine on our left.3477

Then we came down here and we viewed the molecule like this looking up; when I do that, now I see that the chlorine is on my right.3485

A little practice with models again will really pay off here; ultimately though we need to be able to work just on paper and with these three-dimensional drawings.3494

A little practice with both gets you up to speed very quickly.3507

How about if I wanted to draw B?--again, once I have the Fisher projection of A, the Fisher projection of B is very straightforward; we just draw its mirror image.3511

Methyl at the top; methyl at the bottom; and on the top carbon, we have a hydrogen on the inside and a bromine on the outside.3522

On the next carbon, we have a chlorine on the inside and a hydrogen on the outside.3532

There it is; we just drew the mirror image of B; this must be 2S,3S; we can confirm that if we wanted to.3536

What is the relationship between A and B?--because A is chiral and because B is its mirror image, A and B are enantiomers... non-superimposable mirror images.3544

Are there any other stereoisomers that exist for 2-bromo-3-chloropentane?3563

We have one example here in this line drawing where they are both wedges; we have one where they are both dashes3569

Are there any other arrangements we can have?--well sure; we can have one as a wedge and one as a dash.3574

So here are the other possibilities we can have; we have already seen A and B where we have wedges and dashes.3582

What if we were to have one wedge and one dash?--this now would be another unique stereoisomer; let's call this molecule C.3589

Just by referencing it to the structures A and B we've already drawn, we even know the configuration.3602

The configuration matches A here so it is 2R, but then it is the opposite for the next one so it would be 3S; so we have this molecule.3608

And instead we can make the bromine the dash and chlorine the wedge; and this too would be a unique compound; this molecule we can call D; and this has 2S,3R.3623

We could draw the Fisher projections of these as well; and these would be good to practice with; in drawing these Fisher projections, you can use the stick figures or you can use models.3644

But just in comparing it to the Fisher projections we already have for A and B, we can see that for C, it is going to have the bromine and the chlorine both on the left.3658

Then for D, it is going to have the bromine and the chlorine both on the right.3672

What is the relationship then between these next two stereoisomers that we've drawn?3686

Looks like their configurations have change; we've gone from R,S, to S,R; looks like they are mirror images of each other that are non-superimposable.3692

And yes, you might guess that these are also enantiomers; so we have another pair of enantiomers; so these are all the stereoisomers of 2-bromo-3-chloropentane.3701

The question that you might be asking is then what is the relationship between A and C?3713

A and B are enantiomers of each other; A and C are clearly stereoisomers because they are both 2-bromo-3-chloropentane; they have the same connectivity; they only differ by their stereochemistry.3728

The way we describe those two structures is we call them diastereomers... they are called diastereomers.3741

Pretty much, the definition of a diastereomer is a stereoisomer that is not an enantiomer.3752

If you have two molecules that you decided are stereoisomers that are non-superimposable and they have the same connectivity, you only really have two choices.3767

They are either going to be enantiomers or diastereomers.3776

Do we have any other diastereomer pairs?--when we look at these four structures, what other compounds can be described as diastereomers of each other?3780

A and C are diastereomers, but A and D are also diastereomers; and the relationship of B to either C or D would also be a diastereomer.3792

So A and D, or B and C, or B and D; so any other combination other than the enantiomers, we describe as diastereomers.3806

In other words, all stereoisomers are either enantiomers, which we describe as non-superimposable mirror images.3817

Whether you can see that or not, they will always have that relationship.3844

Or we are going to describe them--all other possibilities are called diastereomers; they have the relationship of being diastereomers; so they are non-mirror images.3847

Another way that we can distinguish between enantiomers and diasteroemers--if you compare structures A and B, you see that all of our chiral centers have been inverted.3859

All our wedges have been turned to dashes; and for C and D, every wedge is now a dash and every dash is now a wedge.3868

Another thing we can look at for enantiomers is that all chiral centers are inverted.3875

Where for diastereomers, if you have multiple chiral centers and if you invert some but not all, then you would be diastereomers; not all chiral centers inverted; only some have been inverted.3888

Let's say you have ten chiral centers; if you invert all ten chiral centers, that structure would be the enantiomer of the original.3907

Any other combination, if you just inverted one or two or five or eight, then all those structures that you could draw would be diastereomers.3914

We will find that you can have many diastereomers but only one enantiomer; only one molecule would be the exact mirror image and with all the chiral centers being inverted.3922

It turns out the possibility for the # of stereoisomers is you could have 2ⁿ stereoisomers possible where n equals the # of stereocenters.3935

The term stereocenters can refer to chirality centers; chirality centers like chiral carbons.3955

You could have an R and S possibility; but another possibility for stereoisomerism is if you have a double bond, you can have cis and trans isomerism.3961

Maybe double bonds or rings, groups being cis or trans on a ring, cis or trans on a double bond; all those stereoisomers we can have 2ⁿ possible.3974

Because 2-bromo-3-chloropentane has two chiral centers; that is why we had four possible stereoisomers that are shown here.3984

Let's take a look at another example--how about if we wanted to draw all stereoisomers of 2-3-dichlorobutane?--now what would be a systematic way of doing that?3995

We could draw a four-carbon chain; there is butane; and we have a chlorine.4007

Let's draw them both as wedges to start off with; that would be one possible stereoisomer.4012

It turns out that this is 2R,3R; I'll let you check that on your own; and we can call this structure A.4017

We could draw it as a line drawing or we could draw it as a Fisher projection.4026

Again, I am just going to draw the Fisher projection; and you can confirm that on your own later and try it.4029

One chlorine is going to be on the left; the other is going to be on the right; this would still be A.4037

What would be another stereoisomer we could draw?--how about the enantiomer of A?4045

We could draw the mirror image of A either as the Fisher projection... either as the Fisher projection; this is now a unique compound; we will call it B.4050

Or as the line drawing; the line drawing would have instead of both chlorines as wedges, it would have both chlorines as dashes.4069

This would be 2S,3S; and that would be structure B; that would be the enantiomer.4081

This is a pretty systematic approach; we could draw both as wedges and then both as dashes.4090

What would be another possibility?--well, we could draw one as a wedge and the other as a dash; so this is a clearly unique compound; we would call this 2R,3S.4096

Our top carbon here stayed the same and the chlorine on the left; but now the bottom carbon moved the chlorine over to be on the right; so this is structure C.4114

Now we could draw its mirror image; so it is useful to draw stereoisomers as pairs of enantiomers; pairs of mirror images with inverted chiral centers.4127

Hydrogens on the inside; chlorines on the outside; and that would be the same structure; but instead of a wedge and then a dash, we could have a dash and then a wedge; and we would call this structure D.4137

But there is a problem with this analysis; there is a problem here.4155

I want you to compare these two Fisher projections or even these two line drawings; are these in fact unique structure?4159

Can we take this line drawing and just rotate it in the plane and turn it over like this and have it aligned with this first structure?4171

The same thing with this Fisher projection; I could take one Fisher projection and just rotate it 180 degrees to line up with the other?4182

You can in fact do this; so what we are observing is that this molecule is not a unique compound; these two are superimposable.4190

These are not structures D as you might have guessed; even though we drew the mirror image, we still drew the same molecule; we had a repeat of a structure we had already drawn.4204

What is going on here?--why do we not have four possible stereoisomers here?--well, let's take a look closer at this structure C.4218

Again, I've just redrawn; we have it as the line drawing that are superimposable or the Fisher projections that are superimposable.4226

What is happening--the reason our images are superimposable and identical is because we have a plane of symmetry in C.4233

Anytime you have a symmetrical molecule, remember the mirror image is identical as to the original structure.4245

What we have is a very special case here where the carbon has a plane of symmetry which reflects one chiral center onto another.4253

That is a very special kind of symmetrical molecule; it is called a meso compound.4260

In other words, it does have chiral centers; it does have two chiral centers; we can name those as R or S.4268

But the molecule as a whole has a plane of symmetry that reflects one chiral center onto the other chiral center; and for those unique compounds, we call them meso compounds.4275

Because it has a plane of symmetry, C is achiral; it is no longer chiral if it has a plane of symmetry.4288

If it is achiral, C does not have an enantiomer; of course, it has a mirror image; everything has a mirror image.4299

But what makes it not its enantiomer is the fact that the mirror image is superimposable; it is identical with the original structure.4313

In this case what we see is that there are only three stereoisomers possible for 2,3-dichlorobutane.4321

There are not 2ⁿ as we just said that we can have as a maximum; 2ⁿ represents a maximum number; what we said is actually there is 2ⁿ that are possible.4330

But in a case of a molecule that is symmetrically substituted, any three-dimensional arrangement that gives symmetry from one half to the other through an internal plane of symmetry.4345

It means that we are no longer going to have them occurring in pairs because that symmetrical molecule is not going to have an enantiomer.4358

If we take a look at this molecule, here we have 2,3-dichlorobutane; we have a chlorine as a wedge and a chlorine as a dash.4367

This looks like an asymmetric molecule; but if we rotate this around so that we try and make it symmetrical.4380

In fact, remember that is what the Fisher projection does for us--is that it makes it a symmetrical molecule.4390

We see that in fact this can be cut in half; the top half reflects on the bottom half.4397

What we can do here is we can even see this in the line drawing if we rotate this about this single carbon-carbon bond.4403

If we were to look at this molecule in this conformation it would be a little easier to see how in fact that it is a symmetrical molecule and it would not have an enantiomer.4413

If I drew these both as wedges or I drew these both as dashes, it would be the same molecule; I just flipped it over.4424

If I draw them both as wedges, it is the same exact molecule as if I draw them both as dashes.4430

Keep in mind when you are looking for symmetry, when you are looking to determine if something is chiral or achiral.4435

Make sure you rotate it around and get in it in the most symmetrical conformation possible so that you don't miss any potential planes of symmetry.4440

One more thing that we should talk about that is important for stereochemistry is the concept of optical activity.4453

This is one of the physical properties that we can discuss for stereoisomers.4460

What is known is that chiral molecules... so again, molecules that do not have an internal plane of symmetry.4467

Chiral molecules rotate a plane and polarize light; for that reason, chiral molecules are called optically active.4473

They are described as being optically active because they rotate a plane of polarized light.4486

This angle of rotation called alpha (α); the angle that it rotates is measured by an instrument called a polarimeter.4492

Let's see what it means to be polarized light and how that plane might be rotated.4498

This is kind of a cartoon of what polarized light looks like; imagine if you were looking directly at a beam of light; let's see what ordinary light looks like.4504

Ordinary light if you are looking straight at it... light oscillates; so if you are looking straight at it, it is going to be coming as a wave toward you.4516

You are going to see it oscillating; but it is going to be going in every direction; so ordinary light has oscillating waves of radiation going in every direction.4526

What a polarimeter does is it filters that out so that all you see is a single plane of oscillation of the electromagnetic field; so you can show it like this.4541

If you take this polarized light and you pass it through a chiral object--a chiral sample, that plane is going to rotate; and it is going to rotate one way or the other.4552

If it rotates in this direction, we describe that as having a positive angle; so maybe a +10 degrees or 20 degrees or 90 degrees.4563

We describe those molecules as being dextrorotatory; they have a right-handed clockwise rotation.4573

If the molecule rotates in the opposite direction, we describe that angle as being a negative angle; and we describe those molecules as being levorotatory.4581

We use the little l or d to describe these molecules; and that is how we describe it when we see a counterclockwise rotation.4591

Chiral molecules are going to optically active; and we can measure their α.4603

An achiral species, something that is not chiral, are not optically active.4607

In other words, if you put them in a polarimeter and you pass a beam of polarized light through it, that beam is going to pass through unchanged.4612

In other words, α= 0 degrees for an optically inactive species such as something that is achiral.4620

What are some other physical properties of stereoisomers that we can take a look at?4633

It turns out that if we are comparing enantiomers and the relationship of enantiomers, we will see that they have identical physical property.4642

Every physical property that you want to measure--things like its boiling point or melting point or solubility or its NMR or its IR spectra; those sorts of things.4649

They are going to be exactly the same; they will be completely indistinguishable except for this optical activity; it turns out they have equal and opposite optical rotation.4657

If one enantiomer rotates it clockwise, the other enantiomer is going to rotate it counterclockwise; one will have a + angle and the other will have a ? angle of the exact same magnitude.4669

When we are comparing diastereomers, stereoisomers that that are not enantiomeric and that are not mirror images of each other, they just have different physical properties.4682

Again, anything you can imagine--boiling point, melting point, their optical rotations, their NMR, their solubilities; everything you can imagine.4690

They may be coincidentally be similar, but they are not going to be identical.4702

Let's take a look at some examples; here we have some sugar molecules.4707

Sugar molecules are definitely well suited for these Fisher projections because sugar molecules often have multiple chiral centers.4712

We can draw them very easily showing the configuration about each of these polyalcohols.4720

Here is an example of ribose; and this is the 2R,3R,4R version of ribose.4730

Over here, it looks like we've drawn the mirror image; so this is the enantiomer of ribose.4737

It is still called ribose because it is the same molecule; exact same connectivity; it is just the mirror image; so this will be 2S,3S,4S.4744

In short, we could just call this (+)-ribose; sometimes this is called the specific rotation.4752

Once we measure the α angle in the polarimeter and we adjusted for the concentration and the path length and that sort of thing.4773

We report it in something that looks like this; we call it the specific rotation.4781

This shows it was the D line of a sodium light that was used; it was 20 degrees; so this is what it looks like when you report it.4788

What is found is that (?)-ribose, the 2R,3R,4R, has an optical rotation of -19 degrees; so it rotates the plane of polarized light in a counterclockwise direction for 19 degrees.4796

The other enantiomer is also going to rotate at 19 degrees, but it is going to go in the other direction; it is going to go in a clockwise direction.4812

Sometimes, we refer to the different enantiomers as the (+) enantiomer or the (-) enantiomer and that will be a way to distinguish between the two.4820

Every other physical property that you can imagine--melting point, solubility, spectroscopy--are going to be exactly the same.4831

For example, the melting point here for both enantiomers is 88 degrees.4838

Let's compare that too; so here we have two molecules which are enantiomers of one another.4843

Every stereocenter has been inverted and we now have its mirror image.4852

If we compare this structure to the next structure, you see that one of the chiral centers has been inverted but the others haven't.4856

Now we are comparing molecules that are diastereomers of each other; if they are no longer enantiomers, they are diastereomers.4864

This is a different sugar; this is called arabinose; this is the (-)-arabinose.4874

What would we predict its rotation to be?--that is not something we can predict; we can't predict it; we have to take the measurement.4881

We have to put it in a polarimeter and measure the optical rotation; there is no way to predict it; we can't say that if it is an R, it goes one way; or if it is an S, it goes another way.4897

The only way we can ever predict an optical rotation is if we know the optical rotation of one enantiomer; then we know the optical rotation of the other enantiomer. 8156 Otherwise, it is just something we have to measure.4907

Here it is a very similar molecule; and this rotation for arabinose has 104 degree rotation; and this enantiomer has it in the levorotatory direction; so -104.4919

What is a melting point?--well, again, not something we can predict; we would have to measure that.4931

You might think, well gee, they have the exact same functional group so I would expect them to be pretty similar.4937

But there is actually quite a big difference; instead of 88 degrees, we have a melting point of 162; it is almost twice the melting point.4942

The difference there reflects this stereochemical shape of the sugar; because remember the temperature of a melting point has to do with how tightly the crystals pack together.4948

The arabinose molecules because of their 3D shape must have a better packing in their crystal structure; and that is what account for their higher melting point.4965

No way we would be able to predict that; but it is just a nice illustration on how the physical properties between diastereomers are totally different, but between enantiomers they are the same.4973

So when do enantiomers behave differently?--it is possible for two enantiomers to behave differently; and that is going to be when they interact with other chiral objects; another chiral thing.4988

For example, if we take our favorite pair of enantiomers, our right and left hand, when do they behave differently?5000

If you try to pick up a water bottle or a coffee mug, something that is a symmetrical object.5007

You would be able to do it equally effectively with your right hand or your left hand in terms of how it fits with the coffee mug.5015

In this case, we would find that there is no difference on how they fit.5025

But what if I had my right and my left hand, and I had a right-handed glove that I was trying to interact with.5033

Of course my right hand would fit perfectly into my right-handed glove, but my left hand would not fit at all.5039

In this case, we observe a difference between the two enantiomers; so why is that?--what is the difference?5047

Why is one going to be indistinguishable and the other going to find a difference?--well, that is because a coffee mug is a symmetrical thing; it is achiral.5057

Because it is symmetrical, my right hand and left hand are going to see the same thing when they try and interact and dock with that mug if you will.5068

But a right-handed glove is something that is chiral; and so when you bring in a chiral molecule with another chiral molecule, they are going to interact differently.5077

That is exactly an example of that.5087

We just saw that the two enantiomers are going to interact differently with polarized light, right?5090

There is a difference there; one is going to be dextrorotatory, and one is going to be levorotatory.5097

What does that tell us about polarized light?--it tells use polarized light must be chiral in order for there to be a difference; and it is.5104

It is because it's a helix; it is actually helical, and you can have a right-handed helix or a left-handed helix; there is chirality to it.5113

That is why a polarimeter is able to distinguish between enantiomers.5120

Let me show you one other interesting example; here is another enantiomer pair; this molecule is called carvone.5125

You could call this S-carvone and R-carvone because there is a single chiral center there.5132

That would be some nice practice to confirm that you can come up with S and R.5137

Or you could call this (+)-carvone and (-)-carvone; because that is their optical rotation; you could see that they are equal and opposite.5141

But there is something else that is very interesting about carvone.5150

S-carvone, the dextrorotatory enantiomer, tastes and smells like caraway seeds; those are the little bitter seeds that you have in rye bread.5152

While R-carvone tastes and smells like spearmint; that is the minty flavor you might have in chewing gum or something like that.5165

Exact same molecule, exact same three-dimensional shape; we simply have this mirror image relationship; but a huge difference in how we perceive it in our bodies in terms of its taste and its odor.5174

What does that tell you about the receptors that must be in our noses and in our mouths?--they must be chiral.5186

Our odor receptors and our taste receptors must be chiral in that they can distinguish between enantiomers.5194

If we have an odor receptor here, one enantiomer is going to fit differently than another enantiomer; and that is going to send different signals to our brain.5202

We are going to interpret that differently as a different odor or a different smell.5209

The whole world of stereochemistry suddenly takes on a whole new light of importance.5213

Because when you think about naturally-occurring compounds, things like amino acids or sugars or enzymes, these are all chiral molecules; they exist in nature typically as just a single enantiomer.5217

When we look at biochemistry, the field of organic chemistry in living systems, we will find that stereochemistry is hugely important and those stereocenters give rise to a particular behavior.5232

In fact, the other thing to keep in mind is that drugs that we take, pharmeceuticals, are often chiral; so many of them are chiral molecules.5248

For example, ibuprofen the pain reliever is a chiral molecule; and we will talk about how that is sold in just a minute.5258

Thalidomide is a chiral molecule; and it was discovered years ago that one enantiomer was something that had very good benefits.5268

But the other enantiomer was something that had devastating effects; it was teratogenic and caused birth defects.5278

So hugely important to consider the stereochemistries of your molecules when you are dealing with things that are going to be entering the body, especially like pharmaceuticals.5286

Because the different enantiomers might behave differently.5294

Let's talk about something called racemic mixtures; that by definition is what we call it when we have an exactly 1:1 mixture of enantiomers.5302

If we had equal amounts of two enantiomers combined into a single mixture, this is now something that is going to be optically inactive; in other words, the α is going to be zero.5310

Think about it; if you have a certain amount of levorotatory enantiomer and you have that exact same amount of the dextrorotatory enantiomer, those are going to cancel each other out.5321

A net result is going to have no rotation whatsoever; so these are optically inactive.5333

In fact, most of the chiral drugs that are in the market such as ibuprofen, those are sold as racemic mixtures.5340

You have both the (+) and the (-) enantiomer in the tablet that you are taking; and again that has very important ramifications for the pharmaceutical industry.5349

Perhaps just a single one of the enantiomers is stronger acting or will last longer.5358

Maybe the other enantiomer is responsible for some side effect or that sort of thing--causing nausea or upsetting your stomach or what have you.5365

Because many of them are sold as racemic mixtures, a lot of research is going into, well, what if we had just a single enantiomer?--would that be more potent?--would it be longer lasting?5379

Do we need a different patent for that?--all sorts of interesting ramifications go on for that.5387

As you might imagine if I had a racemic mixture of ibuprofen and I wanted to separate that mixture into the two different enantiomers.5393

That is going to be quite a challenge since enantiomers have identical physical properties.5401

I can't just do a distillation; I can't do a crystallization; I can't separate them the ways that I would normally separate organic compounds because they behave so similarly.5407

There is a process though that exists that can be used; and this is used very often in the pharmaceutical industry; it is called a resolution--the process for separating enantiomers.5420

Let me just show you how in general that process would work.5430

Let's assume that we have a racemic mixture here; so this is represented by an equal mixture of (+) enantiomers and (-) enantiomers.5434

What we are going to do is we are going to take that racemate or racemic mixture, and we are going to treat it with some kind of chiral resolving agent.5443

This has just a (+) rotation or a (-) rotation; it is some chiral agent that we can get from nature or that is commercially available.5452

We are going to react it with the racemate and form some kind of interaction that is temporary; that is reversible.5463

We are going to have our (+) resolving agent now associated with both our (+) and our (-) racemate components.5471

When we compare the resulting structures, we see that these are in fact now diastereomers.5482

When you compare a structure that has a (+/+) to a structure that has a (+/-), those are no longer enantiomers.5491

They can't be mirror images; one part of the molecule is the same configuration; the other part of it is the opposite; that is our definition of diastereomers.5500

Because they are diastereomers, they have different physical properties; and if they have different physical properties, now we can separate them.5508

We can do something like recrystallize them or do a chromatography; something like that; recrystallization is a very common method here.5521

We can effectively separate the (+/+) diastereomers from the (+/-) diastereomers.5535

Then all we have to do is we can remove and hopefully recover, so we can reuse it, our chiral resolving agent; thus freeing up our enantiomers; and now we have these in two separate containers.5541

We have a container of just our (+) enantiomer and a container of our (-) enantiomer; and we've effectively separated the two enantiomers; this process is called a resolution of a racemic mixture.5561

A racemic mixture is what we call it when we have an exactly 1:1 mixture of two enantiomers.5577

But it is also possible to have unequal mixtures of enantiomers; those mixtures are described by what is known as an enantiomeric excess or ee for short.5582

This is a measure of optical purity; it is another way we can describe it; how pure is it in terms of being just a single enantiomer?5594

ee is defined by comparing the measured optical rotation and dividing that by the pure optical rotation.5607

When we take that and convert it to a percentage, that # is what we describe as the ee, the enantiomeric excess.5615

Another way to describe ee is to say that the ee is the difference between the percentage of the major enantiomer and the percentage of the minor enantiomer.5622

For example, if you had a 100% ee, 100% enantiomeric excess means you have pure enantiomer; 100% in excess of a single enantiomer; your ee is 100% of one minus 0% of the other.5633

A 0% ee means you have no excess of either enantiomer so that means you have exactly 1:1; you have a racemate or a racemic mixture.5649

In other words, 50% of one enantiomer and 50% of the other enantiomer gives you an ee of 0.5661

So 100% means I have pure enantiomer; 0% means I have exactly 1:1 mixture; and any ee percentage in between there means I have some kind of mixture of the two enantiomers.5668

et's take a look at some examples; here we have an alcohol that is the S-alcohol.5681

It is known that this pure S-alcohol has an optical rotation of +20 degrees.5691

Just like other physical properties like melting point or boiling point, this is something that can be measured; support in the literature; and you can look that up.5698

Do we know what the pure R enantiomer would have as an optical rotation or as a specific rotation?5709

If we had a pure R with none of the S in it, we would expect that it would have the same magnitude but the opposite sign; so it would be -20 degrees.5714

What if we had the racemic alcohol?--in other words, an equal mixture of the S-alcohol where this is a dash and the R-alcohol where this is a wedge.5727

We could describe that as a (+/-); this is a way to abbreviate a racemic mixture; what would the optical rotation be there?5736

If we had exactly equal amounts, we would expect it to be optically inactive; it would be a 0 degree rotation; that is what we expect for our racemic mixture.5743

What if we had any other mixture of the R and S enantiomer; any other combination of those, where would you expect the α optical rotations to be?5756

We would expect that they would be somewhere between -20 degrees and +20 degrees; so the -20 and the +20 are the extreme rotations you can have if you had pure R or pure S.5768

The presence of the other enantiomer is going to lower that optical purity and reduce that rotation and bring it closer to 0.5787

For example--if you had a sample of this alcohol; it was pure alcohol; you took an NMR and you saw no other piece in here so it is not contaminated with any other molecule.5799

But its optical rotation is +10 degrees; then what is the ee for this sample?5808

Remember ee is defined as the observed optical rotation divided by the pure or the literature optical rotation; so we see that our sample has a +10 degrees.5817

And the pure--because this is a (+), that means I have an excess of which enantiomer?--what do I have more of?5838

I must have more of the one with the (+) rotation; so I have an excess of S.5847

But there is some R mixed in there; that is why our optical rotation isn't the maximum that it should be.5856

So I have +10 divided by +20; that means that I have a 50%; we are multiplying it by 100% to convert it to a percentage; we have a 50% ee for this sample; a 50% ee.5861

What does that mean for the percentage breakdown? How much of each molecule do we have?5879

Remember that the other way to describe ee is the major percent minus the minor percent.5884

We could do a simple algebra problem to solve this so that it comes out x; we could set the major percent as x and the minor percent would be 100-x.5893

We could do this and solve for x; and what we would find is that we have 75% of the (+) enantiomer and 25% of the (-) enantiomer.5908

Again, 75 minus 25 would come up to 50%; so you can see we have a 50% excess of the (+) enantiomer.5923

You can imagine that of this 75%, we have 50% that is our excess and 25% is going to combine with this 25% to be racemic.5937

It is like half of our mixture is a racemic mixture with (+) and (-), 25% of each; the other half of the mix is pure (+); so that is why our optical rotation is only half of what we are expecting.5951

Let's say we have a 100g sample, only 50% of it is the pure (+) that is going to be giving the optical rotation; the other 50% of it is a racemic mixture that has no optical rotation.5968

I just want to give you a feel for how to work with the ee's.5979

One more example; what is the percent composition of a sample with 90% ee?5987

Again, that means we have 90% of one enantiomer plus 10% of the racemic.5992

We have 5% and 5%; so that means we have 95% of one enantiomer plus 5% of the other enantiomer.6003

This is just one way to think about it again; you could solve it algebraically like this to set one to be x and one to be 100-x; and then the difference now would be 90%.6016

But the difference between 95% and 5% is 90% ee; so 90% ee equals 95% minus 5%.6027

If you have a 95:5 mixture of two enantiomers, it would be described as having a 90% ee.6039

You would expect the optical rotation to be 90% of the maximum or the literature value for that sample.6048