Chapter 7.
Stereochemistry
Stereochemistry
• Some objects are not the same as their mirror
images (technically, they have no plane of
symmetry)
– A right-hand glove is different than a left-hand
glove
– The property is commonly called “handedness”
• Organic molecules (including many drugs) have
handedness that results from substitution
patterns on sp3 hybridized carbon
Enantiomers – Mirror Images
• Molecules exist as three-dimensional objects
• Some molecules are the same as their mirror image
• Some molecules are different than their mirror image
– These are stereoisomers called enantiomers
9.1 Enantiomers and the Tetrahedral
Carbon
• Enantiomers are molecules that are not the same as
their mirror image
• They are the “same” if the positions of the atoms can
coincide on a one-to-one basis (we test if they are
superimposable)
• This is illustrated by enantiomers of
bromochlorofluoromethane
Enantiomers of
bromochloro-
fluoromethane
9.2 The Reason for Handedness:
Chirality
• Molecules that are not superimposable with their mirror
images are chiral (have handedness)
• A plane of symmetry divides an entire molecule into
two pieces that are exact mirror images
• A molecule with a plane of symmetry is the same as its
mirror image and is said to be achiral (See Figure 9.4
for examples)
Chirality
• If an object has a plane of symmetry it is
necessarily the same as its mirror image
• The lack of a plane of symmetry is called
“handedness”, chirality
• Hands, gloves are prime examples of chiral
object
– They have a “left” and a “right” version
Plane of Symmetry
• The plane has the
same thing on both
sides for the flask
• There is no mirror
plane for a hand
Examples of Enantiomers
• Molecules that have one carbon with 4 (count-em 4)
different substituents have a nonsuperimposable mirror
image – enantiomer
Plane of symmetry in
chlorodifluoromethane
Chiral Carbons
• A point in a molecule where four different groups (or
atoms) are attached to carbon is called the chiral
carbon
• There are two nonsuperimposable ways that 4 different
different groups (or atoms) can be attached to one
carbon atom
– If two groups are the same, then there is only one
way
• A chiral molecule usually has at least one chiral carbon
Chirality Centers in Chiral Molecules
• Groups are considered “different” if there is anystructural
variation (if the groups could not be superimposed if
detached, they are different)
• In cyclic molecules, we compare by following in each
direction in a ring
Locate all chiral carbons if any):
O CH3
CH3CH2CHCH2CH3
OH
CH3
CH3CHCH2CH2CH3
OH
CH3
9.3 Optical Activity
• Light restricted to pass through a plane is plane-
polarized
• Plane-polarized light that passes through
solutions of achiral compounds remains in that
plane
• Solutions of chiral compounds rotate plane-
polarized light and the molecules are said to be
optically active
• Phenomenon discovered by Biot in the early 19 th
century
Optical Activity
• Light passes through a plane polarizer
• Plane polarized light is rotated in solutions of
optically active compounds
• Measured with polarimeter
• Rotation, in degrees, is []
• Clockwise rotation is called dextrorotatory
• Anti-clockwise is levorotatory
Measurement of Optical Rotation
• A polarimeter measures the rotation of plane-polarized
that has passed through a solution
• The source passes through a polarizer and then is
detected at a second polarizer
• The angle between the entrance and exit planes is the
optical rotation.
Specific Rotation
• To have a basis for comparison, define specific
rotation, []D for an optically active compound
• []D = observed rotation/(pathlength x concentration)
= /(l x C) = degrees/(dm x g/mL)
9.4 Pasteur’s Discovery of Enantiomers (1849)
• Louis Pasteur discovered that sodium ammonium salts
of tartaric acid crystallize into right handed and left
handed forms
• The optical rotations of equal concentrations of these
forms have opposite optical rotations
• The solutions contain mirror image isomers, called
enantiomers and they crystallized in distinctly different
shapes – such an event is rare
Relative 3-Dimensional Structure
• is the mirror image of L-
erythrose
• This does not apply in
general The original
method was a correlation
system, classifying
related molecules into
“families” focused on
carbohydrates
– Correlate to D- and L-
glyceraldehyde
– D-erythrose
9.5 Sequence Rules for Specification of
Configuration
• A general method applies to the configuration at each
chiral carbon (instead of to the the whole molecule)
• The configuration is specified by the relative positions of
all the groups with respect to each other at the chiral
carbon
• The groups are ranked in an established priority
sequence and compared
• The relationship of the groups in priority order in space
determines the label applied to the configuration,
according to a rule
Cahn-Ingold-Prelog Priority Rules
Sequence Rules (IUPAC)
• Assign each group priority according to the Cahn-
Ingold-Prelog scheme With the lowest priority group
pointing away, look at remaining 3 groups in a plane
• Clockwise is designated R (from Latin for “right”)
• Counterclockwise is designated S (from Latin word
for “left”)
R-Configuration at Chirality Center
• Lowest priority group is pointed away and direction of
higher 3 is clockwise, or right turn
Examples of Applying Sequence Rules
• If lowest priority is back, clockwise is R and
counterclockwise is S
– R = Rectus
– S = Sinister
9.6 Diastereomers
• Molecules with more than
one chiral carbon have
mirror image
stereoisomers that are
enantiomers
2R,3R 2S,3S
• In addition they can have
stereoisomeric forms that
are not mirror images,
called diastereomers
2R,3S 2S,3R
Stereoisomers of 2,3-Dichloropentane
CH3CHCHCH2CH3
Cl Cl
CH3 CH3 CH3 CH3
H C Cl Cl C H Cl C H H C Cl
H C Cl Cl C H H C Cl Cl C H
CH2CH3 CH2CH3 CH2CH3 CH2CH3
Enantiomers Enantiomers
Diastereomers
9.7 Meso Compounds
• Tartaric acid has two chiral carbons and two diastereomeric forms
• One form is chiral and the other is achiral, but both have two chiral
carbons
• An achiral compound with chiral carbons is called a meso compound –
it has a plane of symmetry
• The two structures on the right in the figure are identical so the
compound (2R, 3S) is achiral
Stereoisomers of 2,3-Dichlorobutane
CH3CHCHCH3
Cl Cl
CH3 CH3 CH3 CH3
H C Cl
_________
Cl C H
_________
Cl C H H C Cl
H C Cl Cl C H H C Cl Cl C H
CH3 CH3 CH3 CH3
Meso Compound Enantiomers
Fisher Projections
CHO CHO
H C OH H OH
HO C H HO H
H C OH
= H OH
H C OH H OH
CH2OH CH2OH
Vertical – Bonds are going away from you
Horizontal – Bond are coming toward you
Fischer projection formulas of the
enantiomers
of bromochlorofluoromethane
CH3CHCHCH3
Cl Cl
CH3 CH3 CH3 CH3
H C Cl Cl C H Cl C H H C Cl
H C Cl Cl C H H C Cl Cl C H
CH3 CH3 CH3 CH3
CH3 CH3 CH3 CH3
H Cl Cl H Cl H H Cl
H Cl Cl H H Cl Cl H
CH3 CH3 CH3 CH3
Cholesterol has eight chiral carbons
9.9 Physical Properties of
Stereoisomers
• Enantiomeric molecules differ in the direction in which
they rotate plane polarized but their other common
physical properties are the same
• Daistereomers have a complete set of different common
physical properties
9.11 A Brief Review of Isomerism
• The flowchart summarizes the types of isomers we have
seen
Constitutional Isomers
• Different order of connections gives different carbon
backbone and/or different functional groups
Stereoisomers
• Same connections, different spatial arrangement of atoms
– Enantiomers (nonsuperimposable mirror images)
– Diastereomers (all other stereoisomers)
• Includes cis, trans and configurational
9.15 Chirality at Atoms Other Than
Carbon
• Trivalent nitrogen is tetrahedral
• Does not form a chiral nitrogen since it rapidly flips
• Also applies to phosphorus but it flips more slowly
9.16 Chirality in Nature
• Stereoisomers are readily distinguished by chiral receptors
in nature
• Properties of drugs depend on stereochemistry
• Think of biological recognition as equivalent to 3-point
interaction
