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3-3-11
StereoisomerismStereoisomerismand Chiralityand Chirality
3-3-22
Isomers
Nonidentical compounds having the same molecular formula
3-3-33
IsomersIsomers Isomers:Isomers: different compounds with the same
molecular formula Constitutional isomers:Constitutional isomers: isomers with a different
connectivity Stereoisomers:Stereoisomers: isomers with the same
connectivity but a different orientation of their atoms in space
3-3-44
Are the following pairs of compounds consitutional isomers or stereoisomers?
a)
b)
c)
constitutional
constitutional
stereoisomer
3-3-55
ChiralityChirality Chiral:Chiral: from the Greek, cheir, hand
• an object that is not superposable on its mirror image
Achiral:Achiral: an object that lacks chirality; one that lacks handedness• an achiral object has at least one element of symmetry• plane of symmetry:plane of symmetry: an imaginary plane passing
through an object dividing it so that one half is the mirror image of the other half
• center of symmetry:center of symmetry: a point so situated that identical components are located on opposite sides and equidistant from that point along the axis passing through it
3-3-66
Elements of SymmetryElements of Symmetry Symmetry in objectsSymmetry in objects
3-3-77
Elements of SymmetryElements of Symmetry Plane of symmetry (cont’d)
HO OH
mirrorplane
3-3-88
Chiral CenterChiral Center The most common (but not the only) cause of
chirality in organic molecules is a tetrahedral atom, most commonly carbon, bonded to four different groups
A carbon with four different groups bonded to it is called a chiral centerchiral center• all chiral centers are stereocenters, but not all
stereocenters are chiral centers (see Figure 3.5)
Enantiomers:Enantiomers: stereoisomers that are nonsuperposable mirror images• refers to the relationship between pairs of objects
3-3-99
A stereocenter (stereogenic center) is an atom at which the interchange of two groups produces a stereoisomer
3-3-1010
EnantiomersEnantiomers 2-Butanol
• has one chiral center• here are four different representations for one
enantiomer
• using (4) as a model, here are two different representations for the enantiomer of (4)
OH
CH3C CH2CH3
H
OH
CH3C CH2CH3
HH OH OH
(1) (2) (3) (4)
OH
(4)
OH OH
representations for theenantiomer of (4)
3-3-1111
3-3-1212
EnantiomersEnantiomers The enantiomers of lactic acid
• drawn in two different representations
C
C
HOCH3
H
OHO
C
C
OHCH3
H
O OH
OHOH
O
OHHO
O
3-3-1313
EnantiomersEnantiomers 2-Chlorobutane
CH3CHCH2CH3
Cl
ClH Cl H
3-3-1414
EnantiomersEnantiomers 3-Chlorocyclohexene
Cl Cl
3-3-1515
EnantiomersEnantiomers A nitrogen chiral center
N
CH2CH3H3C
N
CH3CH3CH2
A pair of enantiomers
++
3-3-1616
R,SR,S Convention Convention Priority rules
1. Each atom bonded to the chiral center is assigned a priority based on atomic number; the higher the atomic number, the higher the priority
2. If priority cannot be assigned per the atoms bonded to the chiral center, look to the next set of atoms; priority is assigned at the first point of difference
(53)(35)(17)(16)(8)(7)(6)(1)
Increasing priority
-H -CH3 -NH2 -OH -SH -Cl -Br -I
Increasing priority
(8)(7)(6)(1)-CH2-OH-CH2-NH2-CH2-CH3-CH2-H
3-3-1717
R,S ConventionR,S Convention
3. Atoms participating in a double or triple bond are considered to be bonded to an equivalent number of similar atoms by single bonds
-CH=CH2
O
-CH
C CH
O
H
C
C
O
C
-CH-CH2
C
C C HC
C
C
C
is treated as
is treated as
is treated as
3-3-1818
Naming Chiral CentersNaming Chiral Centers1. Locate the chiral center, identify its four substituents, and assign
priority from 1 (highest) to 4 (lowest) to each substituent
2. Orient the molecule so that the group of lowest priority (4) is directed away from you
3. Read the three groups projecting toward you in order from highest (1) to lowest priority (3)
4. If the groups are read clockwise, the configuration is RR; if they are read counterclockwise, the configuration is SS
(S)-2-Chlorobutane
ClH2 3
S1
3-3-1919
Naming Chiral CentersNaming Chiral Centers
• (R)-3-Chlorocyclohexene
• (R)-Mevalonic acid
Cl
H2
3
R
1
23
41
HO OH
OHO CH3
23
1
R
3-3-2020
Enantiomers & DiastereomersEnantiomers & Diastereomers For a molecule with 1 chiral center, 21 = 2
stereoisomers are possible For a molecule with 2 chiral centers, a maximum
of 22 = 4 stereoisomers are possible For a molecule with n chiral centers, a maximum
of 2n stereoisomers are possible
3-3-2121
Enantiomers & DiastereomersEnantiomers & Diastereomers 2,3,4-Trihydroxybutanal
• two chiral centers• 22 = 4 stereoisomers exist; two pairs of enantiomers
Diastereomers:Diastereomers:• stereoisomers that are not mirror images• refers to the relationship among two or more objects
C
C
H OH
CHO
OH
CH2OH
H
C
C
HHO
CHO
HO
CH2OH
H
C
C
H OH
CHO
H
CH2OH
HO
C
C
HHO
CHO
H
CH2OH
OH
A pair of enantiomers(Erythreose)
A pair of enantiomers(Threose)
3-3-2222
Enantiomers & DiastereomersEnantiomers & Diastereomers 2,3-Dihydroxybutanedioic acid (tartaric acid)
• two chiral centers; 2n = 4, but only three stereoisomers exist
Meso compound:Meso compound: an achiral compound possessing two or more chiral centers that also has chiral isomers
C
C
H OH
COOH
OH
COOH
H
C
C
HHO
COOH
HO
COOH
H
C
C
H OH
COOH
H
COOH
HO
C
C
HHO
COOH
H
COOH
OH
A pair of enantiomersA meso compound(plane of symmetry)
3-3-2323
Fischer ProjectionsFischer Projections
Flat representation of a 3-D molecule. A chiral carbon is at the intersection of horizontal
and vertical lines. Horizontal lines are forward, out-of-plane. Vertical lines are behind the plane.
3-3-2424
Fischer Projections (Continued)
3-3-2525
Fischer RulesFischer Rules
Carbon chain is on the vertical line. Highest oxidized carbon is at top. Rotation of 180 in plane doesn’t change
molecule. Do not rotate 90!
3-3-2626
180180°° Rotation Rotation
A rotation of 180° is allowed because it will not change the configuration.
3-3-2727
9090°° Rotation Rotation
A 90° rotation will change the orientation of the horizontal and vertical groups.
Do not rotate a Fischer projection 90°.
3-3-2828
Fischer Mirror ImagesFischer Mirror Images
Fisher projections are easy to draw and make it easier to find enantiomers and internal mirror planes when the molecule has 2 or more chiral centers.
CH3
H Cl
Cl H
CH3
3-3-2929
Fischer (Fischer (RR) and () and (SS))
Lowest priority (usually H) comes forward, so assignment rules are backwards!
Clockwise 1-2-3 is (S) and counterclockwise 1-2-3 is (R).
Example:
(S)
(S)
CH3
H Cl
Cl H
CH3
3-3-3030
DiastereomersDiastereomers
Molecules with two or more chiral carbons. Stereoisomers that are not mirror images.
3-3-3131
Enantiomers & DiastereomersEnantiomers & Diastereomers 2-Methylcyclopentanol
H H
CH3 OH
H H
HO H3C
H OH
CH3 H
HO H
H H3C
cis-2-Methylcyclopentanol (a pair of enantiomers)
trans-2-Methylcyclopentanol (a pair of enantiomers)
diastereomers
3-3-3232
Enantiomers & DiastereomersEnantiomers & Diastereomers 1,2-Cyclopentanediol
H H
OH HO
H H
OH HO
H HO
OH H
OH H
H HO
cis-1,2-Cyclopentanediol (a meso compound)
trans-1,2-Cyclopentanediol (a pair of enantiomers)
diastereomers
3-3-3333
Enantiomers & DiastereomersEnantiomers & Diastereomers cis-3-Methylcyclohexanol
OHH3C HO CH3
3-3-3434
Enantiomers & DiastereomersEnantiomers & Diastereomers trans-3-Methylcyclohexanol
OH
H3C
HO
CH3
3-3-3535
IsomersIsomers
Compounds with thesame molecular formula
ConformationalIsomers
rotation aboutsingle bonds
with chiral centers
Stereoisomers
MesoCompounds
Enantiomers
ConstitutionalIsomers
Cis,Trans (E,Z) Isomers(can be calleddiastereomers)
Conformations
rotation restricted
differentconnectivity
Diastereomers
stereoisomersbut no chiral centers
Enantiomers
one chiral centerm ore than
one chiral center
chiralachiral
not mirror images
mirror images
Atropisomers
sameconnectivity
3-3-3636
Properties of StereoisomersProperties of Stereoisomers
Enantiomers have identical physical and chemical properties in achiral environments
Diastereomers are different compounds and have different physical and chemical properties• meso tartaric acid, for example, has different physical
and chemical properties from its enantiomers (see Table 3.1)
3-3-3737
Plane-Polarized LightPlane-Polarized Light Ordinary light:Ordinary light: light vibrating in all planes
perpendicular to its direction of propagation Plane-polarized light:Plane-polarized light: light vibrating only in
parallel planes Optically active:Optically active: refers to a compound that
rotates the plane of plane-polarized light
3-3-3838
Plane-Polarized LightPlane-Polarized Light
• plane-polarized light is the vector sum of left and right circularly polarized light
• circularly polarized light reacts one way with an R chiral center, and the opposite way with its enantiomer
• the result of interaction of plane-polarized light with a chiral compound is rotation of the plane of polarization
3-3-3939
Plane-Polarized LightPlane-Polarized Light Polarimeter:Polarimeter: a device for measuring the extent of
rotation of plane-polarized light
3-3-4040
Optical ActivityOptical Activity
• observed rotation:observed rotation: the number of degrees, , through which a compound rotates the plane of polarized light
• dextrorotatory (+):dextrorotatory (+): refers to a compound that rotates the plane of polarized light to the right
• levorotatory (-):levorotatory (-): refers to a compound that rotates of the plane of polarized light to the left
• specific rotation:specific rotation: observed rotation when a pure sample is placed in a tube 1.0 dm in length and concentration in g/mL (density); for a solution, concentration is expressed in g/ 100 mL
DD
H3CC
OHH
COOH
CH3
C
HOH
COOH
[]21 = -2.6°= +2.6°21
[]
(R)-(-)-Lactatic acid(S)-(+)-Lactic acid
3-3-4141
Optical PurityOptical Purity Optical purity:Optical purity: a way of describing the
composition of a mixture of enantiomers
Enantiomeric excess:Enantiomeric excess: the difference between the percentage of two enantiomers in a mixture
• optical purity is numerically equal to enantiomeric excess, but is experimentally determined
x 100[]samplePercent optical purity =
[]pure enantiomer
x 100[R] + [S][R] - [S]
Enantiomeric excess (ee) = = %R - %S
3-3-4242
Enantiomeric ExcessEnantiomeric Excess
Example:Example: a commercial synthesis of naproxen, a nonsteroidal anti-inflammatory drug (NSAID), gives the S enantiomer in 97% ee
Calculate the percentages of the R and S enantiomers in this mixture
H3CO
COOH
CH3
(S)-Naproxen
3-3-4343
ResolutionResolution Racemic mixture:Racemic mixture: an equimolar mixture of two
enantiomers• because a racemic mixture contains equal numbers of
dextrorotatory and levorotatory molecules, its specific rotation is zero
Resolution:Resolution: the separation of a racemic mixture into its enantiomers
3-3-4444
ResolutionResolution One means of resolution is to convert the pair of
enantiomers into two diastereomers • diastereomers are different compounds and have
different physical properties
A common reaction for chemical resolution is salt formation
• after separation of the diastereomers, the enantiomerically pure acids are recovered
RCOOH B RCOO-
HB+
(R,R)-Salt + (S,R)-Salt)(R)-Base(R,S)-Carboxylicacid
+ :
3-3-4545
ResolutionResolution
• racemic acids can be resolved using commercially available chiral bases such as 1-phenylethanamine
• racemic bases can be resolved using chiral acids such as
NH2 NH2
(S)-1-Phenylethanamine (R)-1-Phenylethanamine
H3C CH3COOHHOOCCH3
OHHO
O
OOH
OHOH
HO
O
O
OH(2R,3R)-(+)-Tartaric acid (S)-(-)-Malic acid (1S,3R)-(+)-Camphoric acid
3-3-4646
Amino AcidsAmino Acids
• the 20 most common amino acids have a central carbon, called an -carbon, bonded to an NH2 group and a COOH group
• in 19 of the 20, the -carbon is a chiral center • 18 of the 19 -carbons have the R configuration, one
has the S configuration• in the D,L system, all have the L configuration• at neutral pH, an amino acid exists as an internal salt• in this structural formula, the symbol RR = a side chain
O-
OH3N
R
side chain
Ionized or zwitterionform of an amino acid