Chapter 05 stereochemistry at tetrahedral centers

1. 5. Stereochemistry at
Tetrahedral Centers
Dr. Wong Yau Hsiung CHEM 221

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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

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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

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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, which is imaginary)
 This is illustrated by enantiomers of lactic acid

5. optical isomers of the
amino acid alanine

6. What is a non-superimposable mirror image?
OPTICAL ISOMERISMOPTICAL ISOMERISM

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Examples of Enantiomers
 Molecules that have one carbon with 4 different
substituents have a nonsuperimposable mirror image
– enantiomer
 Build molecular models to see this

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Mirror-image Forms of Lactic
Acid
 When H and
OH substituents match
up, COOH and CH3
don’t
 when COOH and CH3
coincide, H and OH
don’t

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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

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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

12. The Meaning of
Symmetry Plane

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Plane of Symmetry
 The plane has the same
thing on both sides for
the flask
 There is no mirror plane
for a hand

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Chirality Centers
 A point in a molecule where four different groups (or
atoms) are attached to carbon is called a chirality center
 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 chirality center

15. Worked Example
 Which of the following molecules are chiral?
 Identify the chirality center in each
 a)
 b)

16. Worked Example
 Solution:
 All –CH3 and –CX3 carbons are not chirality
centers
 All –CH2– and –CX2– carbons are not chirality
centers
 All aromatic ring carbons are not chirality
centers
 a)

17. Worked Example
 b)

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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

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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 [α]
 Clockwise rotation is called dextrorotatory
 Anti-clockwise is levorotatory

20. • If the light appears to have turned to the right turned to the left
clockwise anti-clockwise
DEXTROROTATORY LAEVOROTATORY
d or + form l or - form
•Racemate = a 50-50 mixture of the two enantiomers (dl) or (±) is a racemic mixture.
•The opposite optical effects of each isomer cancel each other out

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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.

22. Measurement of Optical Rotation

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Specific Rotation
 To have a basis for comparison, define specific
rotation, [α]D for an optically active compound
 [α]D = observed rotation/(pathlength x concentration)
= α/(l x C) = degrees/(dm x g/mL)
 Specific rotation is that observed for 1 g/mL in
solution in cell with a 10 cm path using light from
sodium metal vapor (589 nanometers)

24. Worked Example
 A 1.50 g sample of coniine was dissolved in
10.0 mL of ethanol and placed in a sample
cell with a 5.00 cm pathlength
 The observed rotation at the sodium D line
was 1.21°
 Calculate [α]D for coniine
 Solution:
 Given: l =5.00 cm = 0.500 dm; α = 1.21°;
C = 1.50g /10ml =0.150 g/mL

25. Worked Example
 Using the formula
D
α
[α] =
×cl
D[α] = +16.1°
D
+1.21°
[α] =
0.500dm×0.150g / ml

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Specific Rotation and Molecules
 Characteristic property of a compound that is
optically active – the compound must be chiral
 The specific rotation of the enantiomer is equal in
magnitude but opposite in sign

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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

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Relative 3-Dimensionl Structure
 The original method
was a correlation
system, classifying
related molecules into
“families” focused on
carbohydrates
 Correlate to D- and
L-glyceraldehyde
 D-erythrose is the
mirror image of L-
erythrose
 This does not apply in
general

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9.5 Sequence Rules for Specification
of Configuration
 A general method applies to the configuration at each
chirality center (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
chirality center
 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 known as Cahn–
Ingold–Prelog rules

30. Sequence Rules for Specifying
Configuration
 Rule 1
 Look at the four atoms directly attached to the
chirality center, and rank them according to
atomic number
 Atom with highest atomic number has highest
ranking, and atom with lowest atomic number
has lowest ranking

31. Sequence Rules for Specifying
Configuration
 Rule 2
 If a decision cannot be reached by ranking the
first atoms in the substituent, look at the
second, third, or fourth atoms until the
difference is found

32. Sequence Rules for Specifying
Configuration
 Rule 3
 Multiple-bonded atoms are equivalent to the
same number of single-bonded atoms

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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”)

34. Assigning Configuration to a Chirality
Center

35. Worked Example
 Rank the following sets of substituents:
 a) –H, –OH, –CH2CH3, –CH2CH2OH
 b) –SH, –CH2SCH3, –CH3, –SSCH3
 Solution:
 Using the sequence rules:
 a) –OH, –CH2CH2OH, –CH2CH3, –H
 b) –SSCH3, –SH, –CH2SCH3, –CH3
Highest Lowest
Highest Lowest

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R-Configuration at Chirality
Center
 Lowest priority group is pointed away and direction of
higher 3 is clockwise, or right turn

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Examples of Applying Sequence
Rules
 If lowest priority is back,
clockwise is R and
counterclockwise is S
 R = Rectus
 S = Sinister

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9.6 Diastereomers
 Molecules with more
than one chirality center
have mirror image
stereoisomers that are
enantiomers
 In addition they can
have stereoisomeric
forms that are not mirror
images, called
diastereomers
2R,3S 2S,3R
2R,3R 2S,3S

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9.7 Meso Compounds
 Tartaric acid has two chirality centers and two diastereomeric
forms
 One form is chiral and the other is achiral, but both have two
chirality centers
 An achiral compound with chirality centers 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

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9.8 Molecules with More Than
Two Chirality Centers
 Molecules can have very many chirality centers
 Each point has two possible permanent
arrangements (R or S), generating two possible
stereoisomers
 So the number of possible stereoisomers with n
chirality centers is 2n
Cholesterol has eight chirality centers

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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

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9.10 Racemic Mixtures and Their
Resolution
 A 50:50 mixture of two chiral compounds that are
mirror images does not rotate light – called a
racemic mixture (named for “racemic acid” that was
the double salt of (+) and (-) tartaric acid
 The pure compounds need to be separated ot
resolved from the mixture (called a racemate)
 To separate components of a racemate (reversibly)
we make a derivative of each with a chiral substance
that is free of its enantiomer (resolving agent)
 This gives diastereomers that are separated by their
differing solubility
 The resolving agent is then removed

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9.11 A Brief Review of Isomerism
 The flowchart summarizes the types of isomers we
have seen

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Constitutional Isomers
 Different order of connections gives different carbon
backbone and/or different functional groups

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Stereoisomers
 Same connections, different spatial arrangement of atoms
 Enantiomers (nonsuperimposable mirror images)
 Diastereomers (all other stereoisomers)
 Includes cis, trans and configurational

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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