Organic Chemistry

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Stereochemistry- Chapter 3
1. Stereoisomerism 2. Chirality 3. Naming
stereocenters - R/S configuration 4. Acyclic
Molecules with 2 or more stereocenters 5. Cyclic
Molecules with 2 or more stereocenters 6.
Properties of Stereocenters 7. Optical
activity 8. Separation of Enantiomers,
Resolution 9. Significance of Chirality in the
biological world
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Isomers - same molecular formula - different
compounds
constitutional isomers - different connectivity
stereoisomers - same connectivity - different
orientation in space (recall cis/trans)
3
Chirality handednessnot superposable on its
mirror image
symmetry superposable

• types
• plane imaginary plane through an object
• one half is the mirror image of the other

center identical parts on an axis equidistant
from a point
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Elements of Symmetry
Conformations of 2,3-butanediol
.
If symmetry is present, the substance is achiral.
meso or R,S (later)
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Elements of Symmetry

• Plane of symmetry

achiral
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Chiral Center

• common source of chirality - tetrahedral (sp3)
  carbon (atom) - bonded to 4 different groups

chiral center - carbon (atom) with 4 different
groups
Enantiomers stereoisomers nonsuperposable
mirror images
All chiral centers are stereocenters Not all
stereocenters are chiral centers
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Enantiomers

• 2-Butanol - 1 chiral center

different representations for this enantiomer
representation of mirror image or enantiomer
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Enantiomers

• 3-Chlorocyclohexene

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Enantiomers

• A nitrogen chiral center

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Enantiomers

• 2-Chlorobutane

How is handedness designated?
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Enantiomers

• Enantiomers of lactic acid

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R,S Convention - Priority rules
Each atom bonded to the chiral center assigned a
priority by atomic number higher atomic
number, higher the priority
Same atoms bonded to the chiral center look to
the next set of atoms priority assigned to 1st
point of difference
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R,S Convention

• double (triple) bond atoms viewed as bonded to an
  equivalent number of atoms by single bonds

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Naming Chiral Centers
1. Locate the chiral center, prioritize four
substituents 1 (highest) to 4 (lowest)
2. Orient molecule so that lowest priority (4)
group is directed away ( behind )
3. Read three groups toward you (in front) (1)
to (3) Clockwise R configuration
counterclockwise S
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Naming Chiral Centers

• ( )-3-Chlorocyclohexene

R
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Stereochemistry- Chapter 3
1. Stereoisomerism 2. Chirality 3. Naming
stereocenters - R/S configuration 4. Acyclic
Molecules with 2 or more stereocenters 5. Cyclic
Molecules with 2 or more stereocenters 6.
Properties of Stereocenters 7. Optical
activity 8. Separation of Enantiomers,
Resolution 9. Significance of Chirality in the
biological world
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Ibuprofen
S isomer particularly active, but R slowly
converted to S
S isomer
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Assign R or S to carvone
spearmint
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Enantiomers Diastereomers

• molecule with 1 chiral center
• 21 2 stereoisomers are possible

molecule with 2 chiral centers a max of 22 4
stereoisomers possible
molecule with n chiral centers 2n maximum
stereoisomers are possible
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2n
256 (ignore sugar)
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Enantiomers Diastereomers

• 2,3,4-trihydroxybutanal 2 chiral centers

22 4 stereoisomers possible exist
2 pairs of enantiomer
(Erythrose)
Diastereomers stereoisomers that are not mirror
images
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Enantiomers Diastereomers

• 2,3-Dihydroxybutanedioic acid (tartaric acid)
• 2n 4 possible

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Enantiomers Diastereomers

• 2-Methylcyclopentanol

cis-2-Methylcyclopentanol
trans-2-Methylcyclopentanol
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Enantiomers Diastereomers

• 1,2-cyclopentanediol

trans-1,2-cyclopentanediol (enantiomers)
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Enantiomers Diastereomers

• cis-3-methylcyclohexanol

flip axial-equatorial reverse
but still cis
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Enantiomers Diastereomers

• trans-3-methylcyclohexanol

flip axial-equatorial reverse
but still trans
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Isomers
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Properties of Stereoisomers

• Enantiomers identical physical and chemical
  properties in achiral environments

m. pt. 174o 174o pK1 2.98 2.98
Diastereomers different compounds different
physical and chemical properties
m. pt. 146o 174o pK1 3.23 2.98
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Plane-Polarized Light
optical activity

• Light vibrating in all planes ? to direction of
  propagation
• Plane-polarized light light vibrating only in
  parallel planes

Plane-polarized light the vector sum of left and
right circularly polarized light
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Optically Activity Enantiomers (chiral) interact
with circularly polarized light

• rotating the plane one way with R center
• and opposite way with S

result rotation of plane-polarized light
clockwise () or counterclockwise (-)
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Plane-Polarized Light (polarimeter)
Change in the polarized plane?
achiral sample
no change in the plane
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Plane-Polarized Light (polarimeter)
Change in the polarized plane?
?
CHIRAL
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Stereochemistry- Chapter 3
1. Stereoisomerism 2. Chirality 3. Naming
stereocenters - R/S configuration 4. Acyclic
Molecules with 2 or more stereocenters 5. Cyclic
Molecules with 2 or more stereocenters 6.
Properties of Stereocenters 7. Optical
activity 8. Separation of Enantiomers,
Resolution 9. Significance of Chirality in the
biological world
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Optical Activity

• observed rotation ?, degrees a compound rotates
  polarized light - dextrorotatory () right
• - levorotatory (-) left

( )-()-lactic acid ( )-(-)-lactic acid
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R-enantiomer is (-) R or S above?
a deg (cm2g-1 )
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Optical Activity

• Racemic mixture equal amounts of () and (-)
  enantiomers - rotation is 0o

For a 50/50 mixture of S and R, ? ?
0o
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Its not pure possibly some R present! If some
R, what percent?
23.1o gt 9.2o lt 0o
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40 excess 40S
(60S/R mixture)
40 excess 40S (30S 30R)
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Optical Purity composition of a mixture of
enantiomers

• enantiomeric excess (ee) difference between the
  percent of 2 enantiomers in a mixture

ee optical purity
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e.g. 6g of ()-2-butanol plus 4g of
(-)-2-butanol, ee ?
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?obs (.20)(13.5) 2.7o
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Enantiomeric Excess

• Example A commercial synthesis of naproxen
  (Aleve) gives the S enantiomer in 97 ee.
• What are the percentages of the R S in this
  mixture?

100 sample
97S (3S and R)
97S (1.5S1.5R)
98.5S 1.5R
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Resolution - separation of enantiomers

• One strategy convert enantiomeric pair into 2
  diastereomers

diastereomers - different compounds different
physical properties
Common - reaction forming salt
separate diastereomers remove B leaves pure
enantiomers
4
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Resolution

• racemic acids - resolved w/ available chiral
  bases, e.g. (S)- and (R)-1-phenylethanamine

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Resolution by acid-base reactions
Pure-Sb
racemic mix
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Resolution

• Examples of enantiomerically pure bases

H
H
H
H
H
H
N
HO
N
H
HO
H
CH3O
N
N
()-Cinchonine
(-)-Quinine
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228
D
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-165
D
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?D -127o HCCl3 from Strycnos seeds (S
nux-vomica)
brucine
Strychnine no methoxy groups
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enantiomeric mixture
Resolution
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enantiomeric mixture
pure enantiomer
Resolution
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50/50 mix
R-Enzyme
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gt69ee
A 50/50 enantiomeric mixture of esters
forms R-acid and recover S-ester.
R-Enzyme
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• Enzymes as resolving agents

racemic mix ethyl ester of (S)- and (R)-naproxin
(R)-ester - no effect (S)-now
acid different functional gp.
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Proteins

• proteins are long chains of amino acids
  covalently bonded by amide bonds formed between
  the carboxyl group of one amino acid and the
  amino group of another amino acid

Chapter 5