Transcript Chapter 1 Chemical Bonding and Chemical Structure

Chapter 15
Principles of Stereochemistry
***Bring Your Model Kits to Class!***
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• Stereoisomers: compounds that have the same connectivity,
but a different arrangement of atoms in space
• Enantiomers: molecules that are non-superimposable (noncongruent) mirror images
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Enantiomers
Carvone
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Problem
• Draw the missing enantiomer:
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• Enantiomers are said to be “chiral”
– They possess the property of “chirality”
– Greek: “hand” or “handedness”
– No plane of symmetry
• If a molecule is superimposable on its mirror image it is said
to be “achiral”
– Has a plane of symmetry
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Chiral Carbons
• Many chiral molecules contain one or more asymmetric
carbons
– Called “Chiral Carbons”
– Attached to four different groups
– Denoted by an asterisk
– Source of stereoisomerism
• Interchange of groups = other stereoisomer
• Stereocenters
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Problems
• Identify, with an asterisk, the chiral carbons in the following molecules:
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How do we differentiate between these two
enantiomers? What do we call them?
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Nomenclature of Enantiomers
1) Identify your chiral carbon
2) Prioritize your substituents on the chiral carbon according to
the Cahn-Ingold-Prelog priority rules
• Highest priority = 1, Lowest Priority = 4
• Priority assignment rules:
a) Higher atomic # = higher priority
b) Higher isotopic mass = higher priority
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c) If the first atoms connected to the chiral carbon are the
same, continue moving outward until the first point of
difference
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d) Multiple-bonded atoms are equivalent to the same number
of single bonded atoms
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3)
Point the lowest priority substituent away from you and look at the 3
remaining groups in a plane
4) Count  1, 2, 3
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If you go CW = R
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(rectus, Latin “proper”)
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If you go CCW = S
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(sinister, Latin “left”)
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5) Name your enantiomers by placing an “(R)-” or an “(S)-” in
front of the molecule’s IUPAC name
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Problems
1) Identify whether the following molecules are R or S.
2) Identify and name the following molecules:
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• For pharmaceuticals, slight differences in 3D spatial
arrangement can make the difference between targeted
treatment and undesired side effects. WHY?
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Physical Properties of Enantiomers
• Enantiomers share identical physical properties
– m.p., b.p., nD, density, heats of formation etc.
• Example: Lactic Acid
– m.p. = 53°C
– b.p. = 122°C
Lactic Acid
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• Enantiomers rotate a plane of polarized light in equal, but
opposite directions
– Called “Optical Activity”
– Use Polarimeter
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Optical Activity
• If the sample rotates the plane of polarized light CW
→ dextrorotatory (+)
– Latin: Dexter = Right
• If the sample rotates the plane of polarized light CCW
→ levorotatory (-)
– Latin = Laevus = Left
• If one enantiomer is +, the other will be –
(+)-lactic acid
(–)-lactic acid
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• The sign of optical rotation is unrelated to R and S
configuration of a compound
(S)-(+)-lactic acid
(R)-(–)-lactic acid
• Optical rotation (a) is a quantitative measure
of optical activity





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[a] = a/cl
[a] = specific rotation
a = Observed rotation (degrees)
c = concentration (g/mL)
l = path length (dm)
Often, temp and wavelength indicated
(R)-(+)-glyceraldehyde
[α]20 = +13.5° mL g-1 dm-1
(S)-(-)-glyceraldehyde
[α]20 = -13.5° mL g-1 dm-1
Racemic Mixtures
• Racemic mixture/Racemate: a mixture
containing equal amounts of two enantiomers
– typically have different physical properties from
that of the pure enantiomers
– Example: Lactic Acid
• m.p. (R or S) = 53°C
• m.p. (R and S)= 17°C
– Indicating racemic mixture:
• Racemic Lactic Acid
• (±)-Lactic Acid
– Optical rotation = 0
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Celexa vs. Lexapro
R-(−)-citalopram
• Celexa = racemic mixture
• Lexapro = enantiopure S
– escitalopram
S-(+)-citalopram
Fischer Projections
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Convenient 2D representation of 3D carbohydrate molecules
Carbon chain written vertically
All bonds depicted horizontally and vertically
Chiral carbons are represented by crossing lines
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• Vertical bonds go back
• Horizontal bonds come forward
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Fischer Projections – More Complex
• Based on an eclipsed molecular conformation
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• An interchange of any two of the groups bound to an
asymmetric carbon changes the configuration of that carbon
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Problems
1) Draw the enantiomer for the
following molecule. Then, draw it
as a molecular representation
with dashes and wedges. Which
is R? Which is S?
2) How many chirality centers does
the following molecule possess?
Draw L-Glucose.
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Isomer Identification Flowchart
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• 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
Diastereomers and Enantiomers
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• Fischer Projections can also be used to quickly assess
stereoisomeric relationships
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Problem
• Which of the following molecules are enantiomers?
Which are diastereomers?
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