Stereochemistry:

E-Z Nomenclature & R-S Nomenclature

 Isomers

• Compounds that have the same molecular formula but are not identical are called isomers.
• Isomers fall into two main classes: constitutional isomers and stereoisomers.

• Constitutional isomers differ in the way their atoms are connected. For example, ethanol and
dimethyl ether are constitutional isomers because they have the same molecular formula C2H6O, but
the atoms in each compound are connected differently.
• Stereoisomers (also called configurational isomers) differ in the way their atoms are arranged in
space.
• Stereoisomers are different compounds that do not readily interconvert. Therefore, they can be
separated.
• There are two kinds of stereoisomers: cis–trans isomers and isomers that contain chirality
centers.
 Cis–Trans Isomers
• Cis–trans isomers (also called geometric isomers) result from restricted rotation. Restricted
rotation can be caused either by a double bond or by a cyclic structure.
 The E,Z-System of Nomenclature
• As long as each of the carbons of an alkene is bonded to only one substituent, we can use
the terms cis and trans to designate the structure of the alkene.
• If the hydrogens are on the same side of the double bond, it is the cis isomer; if they are
on opposite sides of the double bond, it is the trans isomer.

• But how would we designate the isomers of a compound such as 1-bromo-2-chloropropene?

 The E,Z-System of Nomenclature
• For a compound such as 1-bromo-2-chloropropene, the cis–trans system of nomenclature cannot be
used because there are four different substituents on the two vinylic carbons.
• The E,Z-system of nomenclature was devised for these kinds of situations.
• To name an isomer by the E,Z-system, we first determine the relative priorities of the two groups
bonded to one of the carbons and then the relative priorities of the two groups bonded to the other
carbon.

• If the high-priority groups are on the same side of the double bond, the isomer has the Z
configuration (Z is for zusammen, German for “together”).
• If the high-priority groups are on opposite sides of the double bond, the isomer has the E
configuration (E is for entgegen, German for “opposite”).
 The E,Z-System of Nomenclature
The relative priorities of the two groups bonded to an sp2 carbon are determined using the following
rules:

• Rule 1. The relative priorities of the two groups depend on the atomic numbers of the atoms that are
bonded directly to the sp2 carbon. The greater the atomic number, the higher is the priority.
For example, in the following compounds, one of the sp2 carbons is bonded to a Br and to an H:

The greater the atomic number of the atom bonded to an sp2 carbon, the higher is the priority of the
substituent.
 The E,Z-System of Nomenclature
• Rule 2. If the two substituents bonded to an sp2 carbon start with the same atom(there is a tie), you
must move outward from the point of attachment and consider the atomic numbers of the atoms that
are attached to the “tied” atoms. In the following compounds, one of the carbons is bonded both to a Cl
and to the C of a CH2Cl group:

If the atoms attached to sp2 carbons are the same, the atoms attached to the “tied” atoms are
compared; the one with the greatest atomic number belongs to the group with the higher priority.
 The E,Z-System of Nomenclature
• Rule 3. If an atom is doubly bonded to another atom, the priority system treatsit as if it were singly
bonded to two of those atoms. If an atom is triply bonded toanother atom, the priority system treats it
as if it were singly bonded to three ofthose atoms.

• If an atom is doubly bonded to another atom, treat it as if it were singly bonded to two of
those atoms.
• If an atom is triply bonded to another atom, treat it as if it were singly bonded to three of
those atoms.
• Cancel atoms that are identical in the two groups; use the remaining atoms to determine
the group with the higher priority.
The E,Z-System of Nomenclature
 The E,Z-System of Nomenclature
• Rule 4. In the case of isotopes (atoms with the same atomic number, but different mass numbers),
the mass number is used to determine the relative priorities.
In the following structures, for example, one of the carbons is bonded to a deuterium (D) and a
hydrogen (H):

• If atoms have the same atomic number, but different mass numbers, the one with the greater
mass number has the higher priority.
 Chirality
• A chiral object has a non superimposable mirror image. In other words, its mirror image is not the
same as itself.
• The feature that most often is the cause of chirality in a molecule is an asymmetric carbon.
• An asymmetric carbon is a carbon atom that is bonded to four different groups. The asymmetric
carbon in each of the following compounds is indicated by an asterisk.

• Notice that the only carbons that can be asymmetric carbons are sp3 hybridized carbons; sp2 and sp
hybridized carbons cannot be asymmetric carbons because they cannot have four groups attached to
them.
• An asymmetric carbon is also known as a chirality center.
 Isomers with One Asymmetric Carbon
A compound with one asymmetric carbon, such as 2-bromobutane, can exist as two different stereoisomers.
The two isomers are analogous to a left and a right hand. Imagine a mirror between the two isomers;
notice how they are mirror images of each other. The two stereoisomers are non-superimposable mirror
images—they are different molecules.

Non-superimposable mirror-image molecules are called enantiomers (from the Greek enantion, which
means “opposite”). The two stereoisomers of 2-bromobutane are enantiomers.
 Naming Enantiomers: The R,S-System of Nomenclature
• We need a system of nomenclature that indicates the configuration(arrangement) of the atoms or
groups about the asymmetric carbon.
• Chemists use the letters R and S to indicate the configuration about an asymmetric carbon.
• For any pair of enantiomers with one asymmetric carbon, one will have the R configuration and the
other will have the S configuration.
• The R,S-system was devised by Cahn, Ingold, and Prelog.

First, let’s look at how we can determine the configuration of a compound drawn as a perspective formula. As an
example, we will determine which of the enantiomers of 2-bromobutane has the R configuration and which has
the S configuration.
1. Rank the groups (or atoms) that are bonded to the asymmetric carbon in order of priority. In the
following pair of enantiomers, bromine has the highest priority (1), the ethyl group has the second
highest priority (2), the methyl group is next (3), and hydrogen has the lowest priority (4). (priorities
are assigned using the same rules as in E-Z nomenclature)

2. If the group (or atom) with the lowest priority is bonded by a hatched wedge, draw an arrow from
the group (or atom) with the highest priority (1) to the group (or atom) with the second highest
priority (2). If the arrow points clockwise, the compound has the R configuration, and if it
points counterclockwise, the compound has the S configuration.
3. If the group with the lowest priority (4) is NOT bonded by a hatched wedge, then switch two
groups so group 4 is bonded by a hatched wedge. Then proceed as in step #2 (previous slide): Draw an
arrow from the group (or atom) with the highest priority (1) to the group (or atom) with the second
highest priority (2). Because you have switched two groups, you are now determining the configuration
of the enantiomer of the original molecule. So if the arrow points clockwise, the enantiomer (with the
switched groups) has the R configuration, which means the original molecule has the S configuration. In
contrast, if the arrow points counterclockwise, the enantiomer (with the switched groups) has the S
configuration, which means the original molecule has the R configuration.
4. In drawing the arrow from group 1 to group 2, you can draw past the group with the lowest priority (4), but
never draw past the group with the next lowest priority (3).
Now let’s see how to determine the configuration of a compound drawn as a Fischer projection.

1. Rank the groups (or atoms) that are bonded to the asymmetric carbon in order of priority.

2. Draw an arrow from the group (or atom) with the highest priority (1) to the group(or atom) with the
next highest priority (2). If the arrow points clockwise, the enantiomer has the R configuration; if it
points counterclockwise, the enantiomer has the S configuration, provided that the group with the
lowest priority (4) is on a vertical bond.

3. If the group (or atom) with the lowest priority is on a horizontal bond, the answer we get from the
direction of the arrow will be the opposite of the correct answer. For example, if the arrow points
clockwise, suggesting that the asymmetric carbon has the R configuration, it actually has the S
configuration; if the arrow points counterclockwise, suggesting that the asymmetric carbon has the
S configuration, it actually has the R configuration. In the following example, the group with the
lowest priority is on a horizontal bond, so clockwise signifies the S configuration, not the R
configuration.
4. In drawing the arrow from group 1 to group 2, you can draw past the group (or atom) with
the lowest priority (4), but never draw past the group (or atom) with the next lowest priority
(3).
 Isomers with More than One Asymmetric Carbon
• Many organic compounds have more than one asymmetric carbon. The more asymmetric carbons a
compound has, the more stereoisomers are possible for the compound.
• A compound can have a maximum of 2n stereoisomers (provided it doesn’t have any other
stereocenters),where n equals the number of asymmetric carbons.
• For example, 3-chloro-2-butanol has two asymmetric carbons. Therefore, it can have as many as four (2n =
4)stereoisomers.

• The four stereoisomers of 3-chloro-2-butanol consist of two pairs of enantiomers.

• Stereoisomers 1 and 2 are non-superimposable mirror images. They, therefore, are enantiomers.
• Stereoisomers 3 and 4 are also enantiomers.
• Stereoisomers 1 and 3 are not identical, and they are not mirror images. Such stereoisomers are called diastereomers.
• Numbers 1 and 4, 2 and 3, and 2 and 4 are also diastereomers.
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 Isomers with More than One Asymmetric Carbon
• Enantiomers have identical physical properties (except for the way they interact with polarized light)
and identical chemical properties—they react at the same rate with a given achiral reagent.
• Diastereomers have different physical properties (different melting points, different boiling points, different
solubilities, different specific rotations, and so on) and different chemical properties—they react with the
same achiral reagent at different rates.
• Cis-Trans isomers are also considered to be diastereomers because they are stereoisomers that are not
enantiomers.

• When Fischer projections are drawn for stereoisomers with two adjacent asymmetric carbons (such as
those for 3-chloro-2-butanol), the enantiomers with similar groups on the same side of the carbon
chain are called the erythro enantiomers. Those with similar groups on opposite sides are called the
threo enantiomers.
• Therefore, 1 and 2 are the erythro enantiomers of 3-chloro-2-butanol (the hydrogens are on the same
side), whereas 3 and 4 are the threo enantiomers.
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 Meso Compounds
• In the examples we have just seen, each compound with two asymmetric carbons has four stereoisomers.
However, some compounds with two asymmetric carbons have only three stereoisomers.
• An example of a compound with two asymmetric carbons that has only three stereoisomers is 2,3-dibromobutane.

The “missing” isomer is the mirror image of 1 because 1 and its mirror image are the same molecule. This can be
seen more clearly if you look either at the perspective formulas drawn in their eclipsed conformations or at the
Fischer projections.

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 Meso Compounds

• Stereoisomer 1 is called a meso compound. Even though a meso compound has asymmetric carbons, it is
an achiral molecule because it is superimposable on its mirror image.
• Mesos is the Greek word for “middle.”
• A meso compound can be recognized by the fact that it has two or more asymmetric carbons and a plane
of symmetry.
• A plane of symmetry cuts the molecule in half, and one-half is the mirror image of the other half.
• Stereoisomer 1 has a plane of symmetry, which means that it does not have a nonsuperimposable mirror
image—it does not have an enantiomer.

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 The R,S-System of Nomenclature for Isomers with More
than One Asymmetric Carbon
If a compound has more than one asymmetric carbon, the steps used to determine whether an asymmetric
carbon has the R or the S configuration must be applied to each of the asymmetric carbons individually. As an
example, let’s name one of the stereoisomers of 3-bromo-2-butanol.

First, we will determine the configuration at C-2. The OH group has the highest priority, the C-3 carbon (the C attached
to Br, C, H) has the next highest priority, CH3 is next, and H has the lowest priority. Because the group with the lowest
priority is bonded by a hatched wedge, we can immediately draw an arrow from the group with the highest priority to
the group with the next highest priority. Because that arrow points counterclockwise, the configuration at C-2 is S.

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 The R,S-System of Nomenclature for Isomers with More
than One Asymmetric Carbon
Now we need to determine the configuration at C-3. Because the group with the lowest priority (H) is not bonded
by a hatched wedge, we must put it there by temporarily switching two groups.

The arrow going from the highest priority group (Br) to the next highest priority group (the C attached to O, C, H)
points counterclockwise, suggesting it has the S configuration. However, because we switched two groups before we
drew the arrow, C-3 has the opposite configuration—it has the R configuration.

Thus, the isomer is named (2S,3R)-3-bromo-2-butanol.

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