hougland che275 chapter7 slides
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Organic ChemistryTRANSCRIPT
Organic Chemistry
CHE 275
Chapter 7Stereochemistry
• A molecule is chiral if its two mirror image
forms are not superimposable upon one another.
• A molecule is achiral if its two mirror image
forms are superimposable.
Chirality
It cannot be superimposed point for point on its mirror image.
Bromochlorofluoromethaneis Chiral
Br
ClH
FTo show nonsuperimposability, rotate this model 180°around a vertical axis.
Bromochlorofluoromethaneis Chiral
Br
ClH
F
Br
ClH
F
Bromochlorofluoromethaneis Chiral
Br
ClH
F
Br
Cl
H F
AnotherLook
are enantiomers with respect to each other
and
nonsuperimposable mirror images are called enantiomers
EnantiomersIsomers
stereoisomersconstitutionalisomers
diastereomersenantiomers
Chlorodifluoromethaneis Achiral
The two structures are mirror images, but are not enantiomers, because they can be superimposed on each other.
Chlorodifluoromethaneis Achiral
a carbon atom with fourdifferent groups attached to it
also called:chiral centerasymmetric centerstereocenterstereogenic center
w
x y
z
C
The Chirality Center
A molecule with a single chirality center is chiral.
Bromochlorofluoromethane is an example.
Cl F
Br
H
C
Chirality and Chirality Centers
A molecule with a single chirality center is chiral.
2-Butanol is another example.
CH3
OH
H
C CH2CH3
Chirality and Chirality Centers
CH3
C
CH2CH3
CH2CH2CH2CH3CH3CH2CH2
a chiral alkane
One Chirality Center
Interactive Question
Which one of the following is achiral?
A) 2-chloropentane
B) 3-chloropentane
C) 1,2-dichloropentane
D) 1,3-dichloropentane
Linalool, a naturally occurring chiral alcohol
OH
One Chirality Center
1,2-Epoxypropane: a chirality centercan be part of a ring
O
H2C CHCH3
attached to the chirality center are:
—H
—CH3
—OCH2
—CH2O
One Chirality Center
Limonene: a chirality center can be part of a ring
CH3
H C
CH3
CH2
attached to thechirality center are:
—H
—CH2CH2
—CH2CH=
—C=
One Chirality Center
Chiral as a result of isotopic substitution
CH3CD
T
H
One Chirality CenterA molecule with a single
chirality center must be chiral.
But, a molecule with two or more chirality centers may be chiral
or it may not (Sections 7.10-7.14).
Symmetry tests for achiral structures
Any molecule with a plane of symmetryor a center of symmetry must be achiral.
A plane of symmetry bisects a molecule into two
mirror image halves. Chlorodifluoromethane
has a plane of symmetry.
A Plane of Symmetry
Plane of Symmetry
• The plane has the same thing on both sides for the flask
• There is no mirror plane for a hand
• We can apply this same analysis to molecules
A plane of symmetry bisects a molecule into two
mirror image halves.
1-Bromo-1-chloro-2-fluoroethene has a plane
of symmetry.
A Plane of Symmetry
A point in the center of themolecule is a center of symmetry if a line drawn from it to any element, when extended an equal distance in the opposite direction, encounters an identical element.
A Center of Symmetry Interactive Question
Which one of the following compounds is chiral?
A) 1-methylcyclohexanol
B) cis-2-methylcyclohexanol
C) trans-4-methylcyclohexanol
D) cyclohexanol
A substance is optically active if it rotates
the plane of polarized light.
In order for a substance to exhibit optical
activity, it must be chiral and one enantiomer
must be present in excess of the other.
Optical Activity
• has wave properties
• periodic increase and decrease in amplitude of wave
Light
• optical activity is usually measured using light having a wavelength of 589 nm
• this is the wavelength of the yellow light from a sodium lamp and is called the D line of sodium
Lightordinary (nonpolarized) light consists of many beams vibrating in different planes
plane-polarized light consists of only those beams that vibrate in the same plane
Polarized Light
Polarization of Light
Nicol prism
Rotation of Plane-Polarized Light
observed rotation () depends on the number
of molecules encountered and is proportional to:
path length (l), and concentration (c)
therefore, define specific rotation [] as:
100
cl
concentration = g/100 mLlength in decimeters
[] =
Specific Rotation
a mixture containing equal quantities
of enantiomers is called a racemic mixture
a racemic mixture is optically inactive
( = 0)
a sample that is optically inactive can be
either an achiral substance or a racemic
mixture
Racemic Mixtures
an optically pure substance consists exclusively
of a single enantiomer
enantiomeric excess =
% one enantiomer – % other enantiomer
% optical purity = enantiomeric excess
Optical Purity
Which of the molecules below is optically active?
A) 1 only
B) 1 and 3
C) 1 and 2
D) 1, 2 and 3
Interactive Question
Relative configuration compares the arrangement of atoms in space of one compound with those of another.
Absolute configuration is the precise arrangement of atoms in space.
Configuration
Relative configuration compares the arrangement of atoms in space of one compound with those of another.
until the 1950s, all configurations were relative
Absolute configuration is the precise arrangement of atoms in space.
we can now determine the absolute configuration of almost any compound
Configuration
No bonds are made or broken at the chirality center
in this experiment. Therefore, when (+)-3-buten-2-ol
and (+)-2-butanol have the same sign of rotation, the
arrangement of atoms in space is analogous. The two
have the same relative configuration.
CH3CHCH2CH3
OH
Pd
[] + 33.2° [] + 13.5°
CH3CHCH
OH
CH2
Relative Configuration
But in the absence of additional information, we can't tell which structure corresponds to(+)-3-buten-2-ol, and which one to (–)-3-buten-2-ol.
Two Possibilities
OHH
HHO
Pd, H2 OHH
Pd, H2 HHO
Nor can we tell which structure corresponds to(+)-2-butanol, and which one to (–)-2-butanol.
Two Possibilities
OHH
HHO
Pd, H2 OHH
Pd, H2 HHO
Absolute Configurations
OHH
HHO
Pd, H2 OHH
Pd, H2 HHO
[] = +13.5°
[] = -13.5° [] = -33.2°
[] = +33.2°
Not all compounds that have the same relative
configuration have the same sign of rotation. No bonds
are made or broken at the chirality center in the
reaction shown, so the relative positions of the atoms
are the same. Yet the sign of rotation changes.
CH3CH2CHCH2Br
CH3
HBr
[] -5.8° [] + 4.0°
CH3CH2CHCH2OH
CH3
Relative Configuration
1. need rules for ranking substituents at chirality center in order of decreasing precedence
2. need convention for orienting molecule so that order of appearance of substituents can be compared with rank
The system that is used was devised by R. S. Cahn, Sir Christopher Ingold, and V. Prelog.
Two requirements for a systemfor specifying absolute configuration
1. Rank the substituents at the chirality
center according to same rules used in
E-Z notation.
2. Orient the molecule so that lowest-ranked
substituent points away from you.
Cahn-Ingold-Prelog Rules(Table 7.1)
Order of decreasing rank:4 > 3 > 2 > 1
Example
1. Rank the substituents at the chirality center according to same rules used in E-Z notation.
2. Orient the molecule so that lowest-ranked substituent points away from you.
3. If the order of decreasing precedence traces a clockwise path, the absolute configuration is R. If the path is counterclockwise, the configuration is S.
The CIP Rules
Order of decreasing rank:4 3 2
clockwiseR
counterclockwiseS
Example
Interactive Question
Which one of the following groups has the highest ranking when precedence is assigned according to the Cahn-Ingold-Prelog rules?
A) -CH=CH2
B) -CH=O
C) -CH2CH2Br
D) -CH2F
R-Configuration at ChiralCenter
• Lowest priority group is pointed away and
direction of higher 3 is clockwise, or right turn
S-Configuration at ChiralCenter
• Lowest priority group is pointed away and
direction of higher 3 is counterclockwise, or left turn
C OH
H3C
HCH3CH2
CHO
CH3
HCH2CH3
(S)-2-Butanol (R)-2-Butanol
Enantiomers of 2-Butanol
Interactive Question
Determine the absolute configuration of the molecule shown.
A) (S)
B) (R)
C) not optically active
Very important! Two different compounds with the same sign of rotation need not
have the same configuration.
Verify this statement by doing Problem 7.9 on page 289. All four compounds have positive rotations. What are their configurations according to the Cahn-Ingold-Prelog rules?
HH3C
H
H
R
—CH2C=C > —CH2CH2 > —CH3 > —H
Chirality Center in a RingInteractive Question
What is the absolute configuration of the molecule shown?
A) (R)
B) (S)
C) not optically active
Purpose of Fischer projections is to show configuration at a chirality center without the necessity of drawing wedges and dashes or using models.
Fischer Projections
Arrange the molecule so that horizontal bonds at chirality center point toward you and vertical bonds point away from you.
Rules for Fischer Projections
Br Cl
F
H
Projection of molecule on page is a cross. When represented this way it is understood that horizontal bonds project outward, vertical bonds are back.
Br Cl
F
H
Rules for Fischer Projections
Br Cl
F
H
Rules for Fischer Projections
Projection of molecule on page is a cross. When represented this way it is understood that horizontal bonds project outward, vertical bonds are back.
Same:melting point, boiling point, density, etc
Different: properties that depend on shape of molecule (biological-physiological properties) can bedifferent
Physical Properties of Enantiomers
Why is Chirality Important?
• Chirality is important because of the structure of all of the proteins in your body• Consider the above structure of myoglobin, a muscle protein found in sea mammals
Proteins Are Made Up of Amino Acids
Amino Acids Are Chiral
• All proteins are made up of the same 20 amino acids
• 19 of the 20 amino acids are chiral
• This means that all biological interactions are by definition
chiral
• Enantiomers of the same molecule may have completely
different biological properties
H2N CO2H
CH3H
Alanine
H2N CO2H
H
Phenylalanine
H2N CO2H
H
Serine
HO
H2N CO2H
H
Tryptophan
HN
Chirality in Nature
• Stereoisomers are readily distinguished by chiral proteins(receptors) in nature
• Properties of drugs depend on stereochemistry
• Think of biological recognition as equivalent to 3-point
interaction
Many Drugs Are Chiral
• When drugs are made and sold only one enantiomer ismarketed
• This is because the other enantiomer sometimes hastoxic properties
• An exception is Ibuprofen, which is sold as a racemate• Only one enantiomer is active, but it racemizes in the body anyway
N
S CH3
CH3
CO2H
HHN
O
H
OO
Penicillin V
CH3
CO2HH
(S) - Ibuprofin(S)- Ibuprofen
O O
CH3 CH3
H3C H3CCH2 CH2
(–)-Carvonespearmint oil
(+)-Carvonecaraway seed oil
Odor The Chirality Axis
A diverse group of molecules are chiral but do not contain a chirality center. Some of these contain a chirality axis-an axis about which groups are arranged so that the spatial arrangement is not superimposable on its mirror image.
Examples include substituted biphenyls and allenes:
A
BY
X
In the appropriately substituted biphenyls, rotation around the bond joining the rings is slowed and the enantiomers can be isolated:
A
BY
X
Conformational isomers that are stable, isolable compounds are called atropisomers.
P(C6H5)2
P(C6H5)2
Substituted 1,1’-binaphthyl derivatives exhibit atropisomerism due to hindered rotation about the single bond that connects the two naphthalene rings.
Example: (S)-(-)-BINAP
(discussed further next semester)
If all of the components of the starting state (reactants, catalysts, solvents, etc.) are achiral, any chiral product will be formed as a racemic mixture.
"Optically inactive starting materials can't give optically active products."
Remember: In order for a substance to be optically active, it must be chiral and one enantiomer must be present in greater amounts than the other.
Chiral Reaction Products
CH3CH CH2
CH3COOH
O
H3C
O
CH2C
H
Chiral, but racemicAchiral
Example
50%
50%
Epoxidation from this direction gives S epoxide
Epoxidation from this direction gives R epoxide
R
S
CH3CH CH2
Chiral, but racemic
Br2, H2O
CH3CHCH2Br
OH
Achiral
Example
CH3CH2CH CH3
HBrCH3CHCH2CH3
Br
Example
Chiral, but racemicAchiral
Mirror Image Transition States• Transition states are mirror images and product is racemic
Many Reactions Convert Chiral Reactants to Chiral Products
However, if the reactant is racemic, the product will also be racemic.
Remember: "Optically inactive starting materials can't give optically active products."
Chiral, but racemic
HBrCH3CHCH2CH3
OH
CH3CHCH2CH3
Br
Chiral, but racemic
Example
Reactions in living systems are catalyzed by enzymes, which are enantiomericallyhomogeneous.
The enzyme (catalyst) is part of the reacting system
Such reactions don't violate the generalization that
"Optically inactive starting materials can't give optically active products."
Biochemical Reactions
fumarase
H2O
C C
HO2C H
CO2HH
C OH
HHO2C
HO2CCH2
Fumaric acid (S)-(–)-Malic acid
Achiral Single enantiomer
Example
How many stereoisomers when a particular molecule contains two chirality centers?
Molecules with Two Chirality Centers
What are all the possible R and S combinations of the two chirality centers in this molecule?
O
CH3CHCHCOH
HO OH
23
Carbon-2 R R S SCarbon-3 R S R S
2,3-Hydroxybutanoic Acid
4 Combinations = 4 Stereoisomers
O
CH3CHCHCOH
HO OH
23
Carbon-2 R R S SCarbon-3 R S R S
2,3-Hydroxybutanoic Acid
4 Combinations = 4 Stereoisomers
What is the relationship between these stereoisomers?
O
CH3CHCHCOH
HO OH
23
Carbon-2 R R S SCarbon-3 R S R S
2,3-Hydroxybutanoic Acid
O
CH3CHCHCOH
HO OH
23
Carbon-2 R R S SCarbon-3 R S R S
enantiomers: 2R,3R and 2S,3S2R,3S and 2S,3R
2,3-Hydroxybutanoic AcidHO
CO2H
CH3
H
OHHR
R
CO2H
CH3
H
HHO
OH
S
S
CO2H
H
CH3
HO
HHO
R
S
CO2H
CH3
H OH
OHHR
S
enantiomers
enantiomers
[] = -9.5° [] = +9.5°
[] = -17.8°[] = +17.8°
O
CH3CHCHCOH
HO OH
23
Carbon-2 R R S SCarbon-3 R S R S
But not all relationships are enantiomeric
Stereoisomers that are not enantiomers are diastereomers
2,3-Dihydroxybutanoic Acid Isomers
stereoisomersconstitutionalisomers
diastereomersenantiomers
HO
CO2H
CH3
H
OHHR
R
CO2H
CH3
H
HHO
OH
S
S
CO2H
H
CH3
HO
HHO
R
S
CO2H
CH3
H OH
OHHR
S
[] = -9.5° [] = +9.5°
[] = -17.8°[] = +17.8°
enantiomers
enantiomers
diastereomers
CO2H
CH3
recall for Fischer projection: horizontal bonds point toward you; vertical bonds point away
staggered conformation does not have correct orientation of bonds for Fischer projection
Fischer Projections
transform molecule to eclipsed conformation in order to construct Fischer projection
Fischer Projections
CO2H
CH3
OH
OH
H
H
Fischer Projections
stereochemical prefixes used to specify relative configuration in molecules with two chirality centers
easiest to apply using Fischer projections
orientation: vertical carbon chain
Erythro and Threowhen carbon chain is vertical, same (or analogous) substituents on same side of Fischer projection
CO2H
CH3
OH
OH
H
H
–9.5° +9.5°
CO2H
CH3
H
H
HO
HO
Erythro
when carbon chain is vertical, same (or analogous) substituents on opposite sides of Fischer projection
+17.8° –17.8°
OH
CO2H
CH3
H
H
HO
CO2H
CH3
OHH
HHO
Threo
nonsuperimposable mirror images; enantiomers
trans-1-Bromo-1-chlorocyclopropane
Two Chirality Centers in a Ring
SSRR
nonsuperimposable mirror images; enantiomers
cis-1-Bromo-1-chlorocyclopropane
Two Chirality Centers in a Ring
S R S R
stereoisomers that are not enantiomers; diastereomers
cis-1-Bromo-1-chloro-cyclopropane
trans-1-Bromo-1-chloro-cyclopropane
Two Chirality Centers in a Ring
RSSS
It is possible for a molecule to have chirality centers yet be achiral.
Achiral Molecules withTwo Chirality Centers
CH3CHCHCH3
HO OH
32
Consider a molecule with two equivalently substituted chirality centers such as 2,3-butanediol.
2R,3R 2S,3S
chiral chiral
2R,3S
achiral
3 Stereoisomers of 2,3-Butanediol
2R,3R 2S,3S 2R,3S
chiral chiral achiral
CH3
CH3
OHH
HHOH OH
CH3
CH3
HHO H
CH3
CH3
OH
OHH
3 Stereoisomers of 2,3-Butanediol
2R,3R 2S,3S
chiral chiral
these two areenantiomers
3 Stereoisomers of 2,3-Butanediol
2R,3R 2S,3S
chiral chiral
CH3
CH3
OHH
HHOH OH
CH3
CH3
HHO
3 Stereoisomers of 2,3-Butanediol
these two areenantiomers
2R,3S
the third structure is superimposable on itsmirror image
3 Stereoisomers of 2,3-Butanediol
achiral
2R,3S
achiral
therefore, this structure and its mirror imageare the same
it is called a meso form
a meso form is an achiral molecule that has chirality centers
3 Stereoisomers of 2,3-Butanediol
2R,3S
achiral
H
CH3
CH3
OH
OHHHHO
CH3
CH3
HHO
3 Stereoisomers of 2,3-Butanediol
therefore, this structure and its mirror imageare the same
it is called a meso form
a meso form is an achiral molecule that has chirality centers
2R,3S
achiral
meso forms have a plane of symmetry and/or a center of symmetry
plane of symmetry is most common case
top half of molecule is mirror image of bottom half
3 Stereoisomers of 2,3-Butanediol
2R,3S
achiral
H
CH3
CH3
OH
OHHHHO
CH3
CH3
HHO
A line drawnthe center ofthe Fischer projection of ameso formbisects it intotwo mirror-image halves.
3 Stereoisomers of 2,3-Butanediol
Interactive QuestionDetermine the relationship between the
compounds shown below.
A) identicalB) enantiomersC) diastereomersD) meso
chiralmeso
There are three stereoisomers of 1,2-dichloro-cyclopropane; the achiral (meso) cis isomer and two enantiomers of the trans isomer.
Cyclic Compounds
RS R R
Maximum number of stereoisomers = 2n
where n = number of structural units capable of stereochemical variation
structural units include chirality centers and cis and/or trans double bonds
number is reduced to less than 2n if mesoforms are possible
Multiple Chirality Centers
4 chirality centers
16 stereoisomers
O
HOCH2CH—CH—CH—CHCH
OH OH OH OH
Example
Interactive Question
How many chirality centers are in the molecule shown at the right?
A) 1
B) 2
C) 3
D) 4HO OH
H
H
HO
H3C
H
HCH2CH2CO2H
CH3
H
CH3
11 chirality centers
211 = 2048 stereoisomers
one is "natural" cholic acid
a second is the enantiomer of natural cholic acid
2046 are diastereomers of cholic acid
Cholic Acid (Figure 7.11)
Maximum number of stereoisomers = 2n
where n = number of structural units capable of stereochemical variation
structural units include chirality centers and cis and/or trans double bonds
number is reduced to less than 2n if mesoforms are possible
Multiple Chirality Centers
3-Penten-2-ol
HO H
E R
H OH
E S
HHO
Z R
H OH
SZ
How Many Stereoisomers?
Interactive Question
(+)-Glucose has the Fischer projection shown. How many compounds are diastereomersof (+)-glucose?
A) 8
B) 14
C) 15
D) 16
In order to know understand stereochemistry of product, you need to know two things:
(1) stereochemistry of alkene (cis or trans; Z or E)(2) stereochemistry of mechanism (syn or anti)
C C + E—Y C CE Y
Reactions That ProduceDiastereomers
R
S
Anti addition to trans-2-butene gives meso diastereomer.
Bromine Addition to trans-2-Butene
Br2
meso
anti addition to trans-2-butene gives meso diastereomer
Bromine Addition to trans-2-Butene
R
S R
S
R
S
Anti addition to cis-2-butene gives racemic mixture of chiral diastereomers.
Bromine Addition to cis-2-Butene
Br2
50% 50%anti addition to cis-2-butene gives racemic mixture of chiral diastereomers
+
Bromine Addition to cis-2-Butene
R
R S
S
RCO3H
syn addition to trans-2-butene gives a racemic mixture of chiral diastereomers
50% 50%
Epoxidation of trans-2-Butene
R
R
+
S
S
syn addition to cis-2-butene gives the mesodiastereomer
RCO3H
meso
Epoxidation of cis-2-Butene
R
S R
S
of two stereoisomers of a particular starting material, each one gives differentstereoisomeric forms of the product
related to mechanism: terms such assyn addition and anti addition refer tostereospecificity
Stereospecific Reaction .
trans-2-butene
cis-2-butene
trans-2-butene
cis-2-butene bromination anti 2R,3R + 2S,3S
bromination
epoxidation
epoxidation
anti
syn
syn
meso
meso
2R,3R + 2S,3S
Stereospecific reaction
a single starting material can give two or more
stereoisomeric products, but gives one of them
in greater amounts than any other
+
CH3
H
CH3
H
68% 32%
CH3
CH2
H
CH3
H
CH3
H
H2
Pt
Stereoselective ReactionInteractive Question
Which compound gives only a single stereoisomer of 1,3-dimethylcyclopentane on catalytic hydrogenation?
A) B)
C) D) both A and B
separation of a racemic mixture into its two enantiomeric forms
Resolution of Enantiomers enantiomers
C(+) C(-)
2P(+)
C(+)P(+) C(-)P(+)
diastereomers
C(+)P(+)
C(-)P(+)
P(+)
P(+)
C(+)
C(-)
Strategy
Resolution of Enantiomers
• Amine salts are often used for resolution of carboxylic acids
Resolution of Enantiomers
• Use of a chiral amine leads to diastereotopic salts• Diastereomers have different physical properties and can thenbe separated
atactic
isotactic
syndiotactic
Stereoregular Polymers
• random stereochemistry of methyl groups attached to main chain (stereorandom)
• properties not very useful for fibers etc.
• formed by free-radical polymerization
Atactic Polypropylene
• stereoregular polymer; all methyl groups onsame side of main chain
• useful properties
• prepared by coordination polymerization under Ziegler-Natta conditions
Isotactic Polypropylene
• stereoregular polymer; methyl groups alternate side-to-side on main chain
• useful properties
• prepared by coordination polymerization under Ziegler-Natta conditions
Syndiotactic Polypropylene
silicon, like carbon, forms four bonds in its stable compounds and many chiral silicon compounds have been resolved
Si Sid d
ab
c
ab
c
Chirality Centers on Other Atoms: Silicon
pyramidal geometry at nitrogen can produce a chiral structure, but enantiomers equilibrate too rapidly to be resolved
N N: :
ab
c
ab
c
very fast
Nitrogen Chirality Centers
pyramidal geometry at phosphorus can produce a chiral structure; pyramidal inversion slower than for amines and compounds of the type shown have been resolved
P P: :
ab
c
ab
c
slow
Phosphorus
pyramidal geometry at sulfur can produce a chiral structure; pyramidal inversion is slow and compounds of the type shown have been resolved
S S: :
ab
O_
ab
O_
slow
+ +
Sulfur in Sulfoxides
Summary: Chapter 7Summary: Chapter 7
7.1 Molecular Chirality: Enantiomers
7.2 The Chirality Center
7.3 Symmetry in Achiral Structures
7.4 Optical Activity
7.5 Absolute and Relative Configuration
7.6 Cahn-Ingold-Prelog Notation
7.7 Fischer Projections
7.8 Properties of Enantiomers
7.9 The Chirality Axis
Summary: Chapter 7Summary: Chapter 7
7.10 Reactions that Create a Chirality Center
7.11 Chiral Molecules with 2 Chirality Centers
7.12 Achiral Molecules with 2 Chirality Centers
7.13 Molecules with Multiple Chirality Centers
7.14 Diastereomers
7.15 Resolution of Enantiomers
7.16 Stereoregular Polymers
7.17 Chirality Centers other than Carbon