Today on ScienceSketch we are going to dive into stereochemistry and how to assign R and
S descriptors to stereocenters. If you have a chemical structure of, say, adrenaline,
is it R or S? First, let s define some terms Two compounds are stereoisomers if they have
the same atoms and bond types but have a different arrangement of substituents in 3D space. If
we have a carbon with 4 substituents, we can have two configurations. We see that these
two molecules cannot be overlaid. If we align the yellow and red spheres, the blue and magenta
ones do not line up. If we align the blue and magenta spheres, the yellow and red ones
do not line up. They are different. In fact, they are mirror images of one another. We
call mirror image stereoisomers enantiomers and use R or S to describe which is which.
When we draw structures on a piece of paper, we use wedges and hashes to show the orientation
of the substituents. A wedge bond is sticking out at you, and a hash bond is facing away
from you. It is important to get in the habit of visualizing wedge and hash structures as
actual three-dimensional shapes. Nobody was born with this ability. You have to practice
it. Why is stereochemistry important? It is critical
to have an unambiguous way to describe stereochemistry because two stereoisomers can have different
properties. One stereoisomer may be a life-saving medicine, and the other may have no effect
or may even be harmful. Thalidomide is a notorious example. R-thalidomide is a life-saving and
effective sedative. S-thalidomide is a teratogen. That is, it causes birth defects. Tragically,
it was a mixture of the R and S enantiomers (also called a racemic mixture) which was
sold in the 1950 s as a treatment for morning sickness and caused birth defects in thousands
of infants. Picking the correct stereoisomer is important
in the flavor and fragrance industry too. R-carvone is found in spearmint leaves and
has a sweet and minty scent. Its mirror image, S-carvone, found in caraway seeds, has a spicy,
earthy smell and is added to rye bread and other baked goods.
R-limonene, found in lemon and orange peels, has a citrus smell while its enantiomer, S-limonene,
has a pine or turpentine smell. We use the CIP rules to assign R or S stereochemistry
based on the chemical structure. Keep in mind that the R or S descriptor has no basis in
physical laws or chemical properties. It is simply a universally accepted method establish
the orientation of substituents in three-dimensional space. Let's see how it works.
To determine R or S stereochemistry, all you do is assign priority to each substituent.
Orient the molecule so that the lowest priority 4 is facing away from you and then simply
count one two three. If the rotation spins to the left (counter-clockwise), then it's
S (sinister, Latin for left). If it spins to the right (clockwise), then it's R (rectus,
Latin for right). The priority is based on the atomic number of the atom bonded to the
stereocenter, with H being 1, Carbon being 6, Nitrogen 7, oxygen 8 and so on. If there's
a tie, say there are two carbons bonded to the same stereocenter, then you go out one
more bond and keep going out until there's a difference. Let's look at an example.
Here's one of the 20 amino acids that make up proteins: Alanine. Sometimes you will see
structures drawn without all the hydrogens showing. The amino substituent and the carboxylate
are in the plane of the central carbon. The methyl is pointing out of the plane, and therefore
the hydrogen is pointing backward. The carboxylate carbon, because it's bonded to oxygen, is
higher priority than the carbon that s bonded only to hydrogens. With the H placed in back
and counting the other substituents, 1,2,3, we see that it spins to the left. Therefore,
it's S. All the natural amino acids have the same stereochemistry except for glycine, which
is symmetrical and has no stereocenter. The R and S rules work the same in cyclic
molecules. Place the lowest priority substituent in the back. For the structure on the left,
there are two methylenes bonded to the stereocenter. Moving out one more bond, we see that the
carbon bonded to the oxygen is higher priority than the carbon bonded to another carbon.
So, the order is 1,2,3 making it R. Just because an organic compound is drawn
with wedges and hashes doesn't make it chiral. The molecule on the right has a plane of symmetry.
It is identical on each side of the structure. You cannot assign R or S stereochemistry to
a symmetrical molecule. This compound has two asymmetric centers.
Starting with the one on the left, H is facing away from you. So, 1,2,3 It is R. The other
stereocenter has the H sticking out toward us. It's backward! You could re-draw the structure,
so that the H is facing away, but that takes time. This is the time to apply the switch
rule. If the H is facing the wrong way, then simply reverse the rule. Counting from high
priority to low priority, 1,2,3 and reversing the rule, it is R.
OK, what about double and triple bonds? How are these handled? In this case, we add what
are called phantom atoms. So, carbon double bonded to oxygen is counted like this Carbon
bonded to two oxygens is higher priority than carbon bonded to only one oxygen. Therefore,
this one is S. A carbon-carbon double bond is counted as
if each carbon is bonded to a phantom carbon. A carbon bonded to 2 carbons is higher priority
than a carbon bonded to one carbon. Therefore, this has S stereochemistry.
Triple bonds work the same way. A nitrile is counted as if the carbon is bonded to three
nitrogen atoms making it higher priority than a carbon bonded to only one nitrogen. 1,2,3
clockwise, so the stereochemistry is R. Here's a structure with an asymmetric carbon
and a carbon-carbon double bond. Based on the rules we have learned, it is designated
R. Easy enough. The orientation of the double bond gives us two possible geometrical isomers,
and the CIP rules are used to describe these also.
If the two highest priority groups are on opposite sides of the double bond, it is designated
E (from the German entgegen, meaning "opposite"). If the two groups of highest priority are
on the same side of the double bond, then it is assigned Z (from the German zusammen,
meaning "together. Let's look at a couple more examples of E and Z pairs. Highest priority
on the same side, it's Z. Opposite side, E . Highest priority on the same side, it's
Z. Opposite side, E. OK, what about this bad boy? This is an opiate
called morphine isolated from poppies. First, you want to draw the implied hydrogens. There
are five asymmetric carbons in this structure, and you can assign R or S to all five using
the rules you have learned. Most of these hydrogens are sticking out toward you. So,
you'll definitely want to apply the switch rule rather than drawing the whole molecule
again. Starting with this carbon atom, the highest priority substituent is going to the
oxygen. Looking at the other substituents, the carbon bonded to an oxygen is higher priority
than the one bonded to a carbon. So, it's 1,2,3. Applying the switch rule makes it R
stereochemistry. You can do the rest. Check yourself. You should get the following R and
S assignments. We hope this video has provided a foundation
in your understanding of the CIP rules for R and S assignments and E / Z geometrical
isomers. If you want to see more ScienceSketch videos, please click the subscribe button.