Chapter 5- Chirality
Chirality
• A chiral object is an object that possesses the
property of handedness
• A chiral object, such as each of our hands, is
one that cannot be placed on its mirror
image so that all parts coincide
• Another words, a chiral object is not
superposable on its mirror image
• Ex.
Isomer Review
• Isomers are different compounds that have
the same molecular formula
• Constitutional Isomers have the same
molecular formula but different connectivity
• Stereoisomers are not constitutional isomers
• Stereoisomers have the same connectivity but
different arrangement of atoms in space
Isomer Review
• We have seen some forms of stereoisomers:
– Cis/Trans isomers in alkenes
– Cis/Trans forms of substituted cyclic molecules
• Stereoisomers can be subdivided into two
general categories: enantiomers and
diastereomers
New Definitions
• Enantiomers- are stereoisomers whose
molecules are nonsuperposable mirror images
of each other
• Diastereomers- are stereoisomers whose
molecules are not mirror images of each other
– Cis/tran isomers are one type of diastereomer
Chirality
• Enantiomers occur only with compounds
whose molecules are chiral
• Chiral Molecule- is defined as one that is not
superposable on its mirror image
• Alkene stereoisomers are not chiral
Chirality
• Examples of Chiral Molecules
• A chiral molecule and its mirror image are
called a pair of enantiomers.
• Molecules that are superposable on their
mirror image are achiral.
Example of a Chiral Molecule
• Consider 2-butanol
• Until now, we have presented the formula as
one compound
• But there are actually two different molecules
of 2-butanol
• They are enantiomers!
When to expect enantiomers
• How do we know when to expect the
possibility of enantiomers?
• One way, but not the only way, is to recognize
that a pair of enantiomers is always possible
for molecules that contain one tetrahedral
atom with four different groups attached to it
• For 2-butanol, it is C2
Stereogenic Carbon
• In enantiomers, exchanging any two groups at
the chiral carbon converts one enantiomer
into the other.
• Stereogenic Carbon- a carbon atom bearing
groups of such nature that an interchange of
any two groups will produce a stereoisomer.
• Enantiomers do not interconvert since this
would require breaking covalent bonds.
Achiral Compounds
• If all the tetrahedral atoms in a molecule have
two or more groups attached that are the
same, the molecule does not have a
stereogenic carbon
• The molecule is superposable on its mirror
image and is achiral.
• Read section 5.5, page 199, about the
Biological importance of Chirality
Testing for Chirality
• The ultimate way to test for molecular
chirality is to construct models of the
molecule and its mirror image and then
determine whether they are superposable.
• If they are superposable, the molecule is
achiral.
• If they are not superposable, then the
molecule is chiral.
Other Aids
• There are other aids to help recognize chiral
molecules
1) The presence of a single tetrahedral stereogenic
carbon. (If there is more than one, it may or may not
be chiral!)
2) Planes of symmetry- if a molecule posses a plane of
symmetry, it will not be chiral
Plane of Symmetry
• Plane of Symmetry- an imaginary plane that
bisects a molecule in such a way that the two
halves of the molecule are mirror images of each
other.
• The plane may pass through atoms, between
atoms, or both.
• Ex.
• All molecules with a plane of symmetry are
achiral.
Nomenclature of Enantiomers:
The R/S System
• Uses the Cahn-Ingold-Prelog system
• Rules:
1) Assign each group attached to the stereogenic
center a priority.
Priority is assigned based on the atomic number of
the atom directly connected to the stereogenic
center. In case of isotopes, the greater atomic mass
has higher priority
Nomenclature of Enantiomers:
The R/S System
2) When priority cannot be assigned based on
the atom directly attached, move to the next set
of atoms until a point of difference is found.
3) Rotate the molecule so that the group with
the lowest priority is pointing away from you.
Then trace a path from 1 to 2 to 3.
Nomenclature of Enantiomers:
The R/S System
• If the path is clockwise, the enantiomer is
designated (R)
• If the path is counter clockwise, the
enantiomer is designated (S)
4) Groups containing double or triple bonds are
assigned priorities as if both atoms were
duplicated or triplicated.
Enantiomer or Same Molecule?
• Deciding whether molecules are enantiomers
or the same molecule can be challenging!
• There are sever options available for this task:
1) Build model and check for superposability
2) Rotate molecules on paper
3) Exchange groups (remember, exchanging two
groups changes configuration)
4) Name the molecule
Properties of Enantiomers
• Enantiomers are not like constitutional
isomers
• Enantiomers have many of the same chemical
and physical properties, such as MP, BP,
solubility, density, etc
• Enantiomers only show different behavior
when the interact with other chiral substance.
Properties of Enantiomers
• The easiest observable difference in
enantiomers is their behavior towards planepolarized light.
• When a beam of plane-polarized light passes
through an enantiomer, the plane of
polarization rotates
• Each enantiomer rotates the beam an equal
amount, but in opposite directions
Interaction with Plane-Polarized Light
• Because of these interactions, separate
enantiomers are said to be optically active
compounds.
• These interactions are measured with a
polarimeter
Plane-Polarized Light
• Normal light exist with 2 perpendicular oscillating
fields, an electric field and a magnetic field
• We are only concerned with the electric field
• If we looked down a normal beam of light, we
would see many different electric fields in every
possible plane
• If the light beam passes through a polarizer, the
light that emerges would only be in one plane.
• That is called plane-polarized light.
Polarimeter
• Clockwise rotation
(+) dextrorotatory
• Counterclockwise
(-) levorotatory
• This designations have nothing to do with
R/S configurations!
Specific Rotation
• The number of degrees the plane rotates depends
on the number of chiral molecules it passes through
• In order to place measured rotations on a standard
basis, we calculate a quantity called specific
rotation, [α]
α
α =
𝑐 ×𝑙
α =specific rotation
α=observed rotation
c= concentration (g/mL) l= length of smaple (dm)
Specific Rotation
• When reported, you will see a superscript and
subscript on the right side of the [α].
• Superscript is the temperature
• Subscript indicates the type of light used.
Racemic Forms
• Consider 2-butanol
• We saw earlier there are two forms:
– A R form and a S form
• Each time plane polarized light passes through
the R form, the plane rotates a little to the left
• If the sample contains some S form, the plane
will shift back to the right as it passes them.
Racemic Forms
• If there are equal amounts of R and S, then
there will be no net rotation of the plane
• This equal mixture of two enantiomers is
called a Racemic mixture
• A racemic mixture is often labeled with a ±
in front.
Enantiomeric Excess
• A sample of an optically active compound that
consists of a single enantiomer is said to be
enantiomerically pure, or to have an
enantiomeric excess(ee) of 100%
• %𝑒𝑒 =
• %𝑒𝑒 =
𝑚𝑜𝑙𝑠 𝑒𝑛𝑎𝑛 𝐴 −𝑚𝑜𝑙𝑠 𝑒𝑛𝑎𝑛 𝐵
𝑚𝑜𝑙𝑠 𝑒𝑛𝑎𝑛 𝐵+𝑚𝑜𝑙𝑠 𝑒𝑛𝑎𝑛 𝐵
𝑜𝑏𝑠𝑒𝑟𝑣𝑒𝑑 [𝛼]
x 100%
𝑝𝑢𝑟𝑒 [𝛼]
x 100%
Example problem
• A sample of 2-butanol showed a [α]=+6.76.
What is the actual composition?
Synthesis of Chiral Molecules
• Reactions using Achiral reactants can often
lead to chiral products
• In the absence from of any chiral influence
from a catalyst, reagent, or solvent, the out
come will always be a racemic mixture
• Ex.
• Reasonings:
Stereoselective Reactions
• Stereoselective Reactions- are reactions that
lead to a preponderance of one stereoisomer
over other stereoisomers that could be
formed.
• If the reaction produces one enantiomer over
the other, it is said to be enantioselective.
• If the reaction leads to predominately one
diastereomer over others that are possible,
the reaction is said to be diastereoselective.
Stereoselective Reactions
• For a reaction to either be enantioselective or
diastereoselective, a chiral reagent, catalyst,
or sovent must assert an influence on the
reaction.
• In nature, special proteins called enzymes are
used to chirally influence reactions.
• Ex.
Kinetic Resolution
• The previous example of hydrolysis of an ester
is an example of Kinetic Resolution
• Kinetic Resolution- he rate of a reaction with
one enantiomer is different than with the
other, leading to a preponderance of one
product stereoisomer.
Molecules with more than one
Stereocenter
• Ex. 2,3-dibromopentane
• 2n rule- the total number of stereoisomers will
not exceed 2n where n= the number of
tetrahedral stereogenic centers
• Note: the rule states, “will not exceed”; not
that there will be that many!
Writing the Structures
• Begin by writing a 3D formula for one
stereoisomer, then draw its mirror image.
• Use the eclipsed conformation so that it is
easier to identify planes of symmetry
• Keep the longest C chain on the vertical axis so
the structures are directly comparable
• Label the pairs of enantiomers and
diastereomers.
Diastereomers
• Remember, Diastereomers are stereoisomers
that are not mirror images.
• They also have different physical properties
such as MP, BP, solubility, and so on.
Back to multiple stereocenters
• A structure with 2 stereogenic centers does
not always have 4 stereoisomes.
• Sometimes there is only 3.
• This happens because some molecules are
achiral even though they contain stereogenic
centers.
• Ex 2,3-dibromobutane
Meso Compound
• Meso Compound- An optically inactive
compound whose molecules are achiral even
though they contain stereogenic centers.
Practice Problems
• Practice problems 5.20, 5.21, and 5.22 on
pages 220 and 221 are very good practice
problems!
Nomenclature
• For naming, we do the same thing with
molecules that have multiple centers as we
did with molecules that just had one.
• Just take assign a configuration to each center
one at a time.
Fisher Projections
• These are basically a shorthand for what we have
been drawing.
• Bond orientations are implied so you have to make
sure you follow the rules:
– The carbon backbone is the vertical line
– Vertical lines are going back, while horizontal lines are
coming out
– Stereogenic Carbons are implied where lines cross
– Can NOT flip the projections over, only allowed to rotate
them
Stereoisomer of Cyclic Compounds
• 1,2-dimethylcyclopentane
– 2 enantiomers, 1 meso
• 1,4-dimethylcyclohexane
– No stereogenic centers!
– Can exists as cis/trans which are diastereomers,
but both are achiral and optically inactive
• 1,3-dimethylcyclohexane
– 2 enantiomers, 1 meso
Stereoisomer of Cyclic Compounds
• 1,2-dimethylcyclohexanes
– Trans has a pair of enantiomers
– Cis is a special case, the enantiomers are actually
conformational stereoisomers! Can be
interconverted by ring flip
Read section 5.15, page 227
• Relating configuration through reactions in
which no bonds to the chirality center are
broken
Resolution
• Resolution- the process of separating
enantiomers from one another.
• We have already seen Kinetic Resolution
• Pasteur’s way
• Resolution via Diastereomers
• Resolution visa interaction with another chiral
media.