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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.
Bromochlorofluoromethane is Chiral
Br
It cannot be superimposed point for point on its mirror image.
Bromochlorofluoromethane is Chiral
Br Br
H F
Cl
H F
Cl
Cl F
Bromochlorofluoromethane is Chiral
Another Look
Br
Br
H F
Cl
H Cl
Enantiomers
nonsuperimposable mirror images are called enantiomers constitutional isomers and
Isomers
stereoisomers
enantiomers
are enantiomers with respect to each other
diastereomers
Chlorodifluoromethane is Achiral
Chlorodifluoromethane is Achiral
The two structures are mirror images, but are not enantiomers, because they can be superimposed on each other.
w x C z
CH2CH3
a chiral alkane
Interactive Question
Which one of the following is achiral? A) 2-chloropentane B) 3-chloropentane C) 1,2-dichloropentane D) 1,3-dichloropentane
OH
CHCH3
C CH3
CH2
But, a molecule with two or more chirality centers may be chiral or it may not (Sections 7.10-7.14).
A Plane of Symmetry
Symmetry tests for achiral structures
Any molecule with a plane of symmetry or 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.
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
A plane of symmetry bisects a molecule into two mirror image halves. 1-Bromo-1-chloro-2-fluoroethene has a plane of symmetry.
A Center of Symmetry
A point in the center of the molecule 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.
Interactive Question
Which one of the following compounds is chiral? A) 1-methylcyclohexanol B) cis-2-methylcyclohexanol C) trans-4-methylcyclohexanol D) cyclohexanol
Optical Activity
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.
Light
Light
Polarized Light
ordinary (nonpolarized) light consists of many beams vibrating in different planes plane-polarized light consists of only those beams that vibrate in the same plane
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
Polarization of Light
Nicol prism
Specific Rotation
observed rotation () depends on the number of molecules encountered and is proportional to: path length (l), and concentration (c) therefore, define specific rotation [] as:
Racemic Mixtures
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
[] =
100 cl
Optical Purity
an optically pure substance consists exclusively of a single enantiomer enantiomeric excess = % one enantiomer % other enantiomer % optical purity = enantiomeric excess
Interactive Question
Which of the molecules below is optically active?
Configuration
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
Relative Configuration
Pd CH3CHCH OH [] + 33.2 CH2 CH3CHCH2CH3 OH [] + 13.5
Two Possibilities
H OH
Pd, H2
OH
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.
HO
Pd, H2
HO
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
H OH
Pd, H2
Absolute Configurations
OH
OH
Pd, H2
OH
[] = +13.5
[] = +33.2
HO
Pd, H2
HO
HO
Nor can we tell which structure corresponds to (+)-2-butanol, and which one to ()-2-butanol.
Pd, H2
HO
[] = -13.5
[] = -33.2
Relative Configuration
HBr CH3CH2CHCH2OH CH3 [] -5.8 CH3CH2CHCH2Br CH3 [] + 4.0
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.
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.
Example
R-Configuration at Chiral
Interactive Question
Which one of the following groups has the highest ranking when precedence is assigned according to the Cahn-IngoldPrelog rules? A) -CH=CH2 B) -CH=O C) -CH2CH2Br D) -CH2F
Center
Lowest priority group is pointed away and direction of higher 3 is clockwise, or right turn
S-Configuration at Chiral
Center
Enantiomers of 2-Butanol
H CH3CH2 C H3C (S)-2-Butanol OH HO C CH3 (R)-2-Butanol H CH2CH3
Lowest priority group is pointed away and direction of higher 3 is counterclockwise, or left turn
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?
Interactive Question
What is the absolute configuration of the molecule shown?
Fischer Projections
Purpose of Fischer projections is to show configuration at a chirality center without the necessity of drawing wedges and dashes or using models.
Arrange the molecule so that horizontal bonds at chirality center point toward you and vertical bonds point away from you.
Br
Cl
Br
Cl
F
Projection of molecule on page is a cross. When represented this way it is understood that horizontal bonds project outward, vertical bonds are back.
F Projection of molecule on page is a cross. When represented this way it is understood that horizontal bonds project outward, vertical bonds are back.
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
HN H H2N CO2H
Alanine
Phenylalanine
Serine
Tryptophan
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
Chirality in Nature
Penicillin V
(( S )S ) -Ibuprofen Ibuprofin
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
When drugs are made and sold only one enantiomer is marketed This is because the other enantiomer sometimes has toxic properties An exception is Ibuprofen, which is sold as a racemate Only one enantiomer is active, but it racemizes in the body anyway
Odor
CH3 O O CH3
H3C
CH2
H3C
CH2
In the appropriately substituted biphenyls, rotation around the bond joining the rings is slowed and the enantiomers can be isolated:
A X
Substituted 1,1-binaphthyl derivatives exhibit atropisomerism due to hindered rotation about the single bond that connects the two naphthalene rings.
P(C6H5)2 B Y P(C6H5)2
Conformational isomers that are stable, isolable compounds are called atropisomers.
Example
O CH3COOH H3C H C O Chiral, but racemic CH2
Example
R Br2, H2O CH3CH CH2 CH3CHCH2Br OH Achiral Chiral, but racemic
50%
Example
Example
HBr CH3CHCH2CH3 Br Chiral, but racemic
Biochemical Reactions
Reactions in living systems are catalyzed by enzymes, which are enantiomerically homogeneous. 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." HO2C C H C H
Example
H H2O fumarase CO2H HO2CCH2 (S)-()-Malic acid Single enantiomer HO2C C OH
2,3-Hydroxybutanoic Acid
O
3 2
CH3CHCHCOH How many stereoisomers when a particular molecule contains two chirality centers? HO OH
What are all the possible R and S combinations of the two chirality centers in this molecule?
Carbon-2 R Carbon-3 R
R S
S R
S S
2,3-Hydroxybutanoic Acid
O
3 2
2,3-Hydroxybutanoic Acid
O
3 2
Carbon-2 R Carbon-3 R
R S
S R
S S
Carbon-2 R Carbon-3 R
R S
S R
S S
2,3-Hydroxybutanoic Acid
HO
CO2H
[] = -9.5
[] = +9.5
CO2H
R
H H OH CH3 CO2H enantiomers HO H
S
OH H
O
3 2
S
CH3 CO2H
R
H H enantiomers H H
S
OH OH
Carbon-2 R Carbon-3 R
R S
S R
S S
HO
S
CH3 [] = +17.8 [] = -17.8
R
CH3
2,3-Dihydroxybutanoic Acid
O
3 2
Isomers
CH3CHCHCOH HO OH But not all relationships are enantiomeric Stereoisomers that are not enantiomers are diastereomers Carbon-2 R Carbon-3 R R S S R S S
constitutional isomers
stereoisomers
enantiomers
diastereomers
CO2H
[] = -9.5
[] = +9.5
CO2H
R
HO H H OH CH3 diastereomers CO2H enantiomers HO H
S
OH H
Fischer Projections
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
S
CH3 CO2H
CO2H
R
HO HO H H enantiomers H H
S
OH OH
CH3
S
CH3 [] = +17.8 [] = -17.8
R
CH3
Fischer Projections
transform molecule to eclipsed conformation in order to construct Fischer projection
Fischer Projections
CO2H H H CH3 OH OH
Erythro
when carbon chain is vertical, same (or analogous) substituents on same side of Fischer projection CO2H HO HO CH3 CO2H H H +9.5
Threo
when carbon chain is vertical, same (or analogous) substituents on opposite sides of Fischer projection
CO2H H OH
cis-1-Bromo-1-chlorocyclopropane
trans-1-Bromo-1-chlorocyclopropane
3 Stereoisomers of 2,3Butanediol
CH3CHCHCH3 HO OH Consider a molecule with two equivalently substituted chirality centers such as 2,3butanediol.
2R,3R chiral
2S,3S chiral
2R,3S achiral
3 Stereoisomers of 2,3Butanediol
CH3 HO H CH3 2R,3R chiral H OH H HO CH3 2S,3S chiral CH3 OH H H H CH3 2R,3S achiral CH3 OH OH
3 Stereoisomers of 2,3Butanediol
2R,3R chiral
2S,3S chiral
3 Stereoisomers of 2,3Butanediol
CH3 HO H CH3 2R,3R chiral H OH H HO CH3 2S,3S chiral CH3 OH H these two are enantiomers
3 Stereoisomers of 2,3Butanediol
2R,3S achiral
3 Stereoisomers of 2,3Butanediol
therefore, this structure and its mirror image are the same
3 Stereoisomers of 2,3Butanediol
CH3 HO HO therefore, this structure and its mirror image H are the same H H CH3 H it is called a meso form a meso form is an achiral molecule that has chirality centers CH3 2R,3S achiral CH3 OH OH
it is called a meso form a meso form is an achiral molecule that has chirality centers
2R,3S achiral
3 Stereoisomers of 2,3Butanediol
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 2,3Butanediol
CH3 HO HO CH3 H H A line drawn the center of the Fischer projection of a meso form bisects it into two mirrorimage halves. CH3 H H CH3 2R,3S achiral OH OH
2R,3S achiral
Interactive Question
Determine the relationship between the compounds shown below.
Cyclic Compounds
meso chiral
S
A) identical B) enantiomers C) diastereomers D) meso
There are three stereoisomers of 1,2-dichlorocyclopropane; the achiral (meso) cis isomer and two enantiomers of the trans isomer.
Example
O HOCH2CHCHCHCHCH
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 meso forms are possible
OH OH OH
4 chirality centers 16 stereoisomers
OH
E H
S OH
HO H
R HO H
Z H
S OH
Interactive Question
(+)-Glucose has the Fischer projection shown. How many compounds are diastereomers of (+)-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)
50%
Epoxidation of trans-2Butene
R RCO3H R S + S
Epoxidation of cis-2-Butene
R
S RCO3H R
50%
50%
Stereospecific Reaction
of two stereoisomers of a particular starting material, each one gives different stereoisomeric forms of the product related to mechanism: terms such as syn addition and anti addition refer to stereospecificity
cis-2-butene
bromination .
anti
2R,3R + 2S,3S
trans-2-butene bromination
anti
meso
Stereospecific reaction
cis-2-butene
epoxidation
syn syn
trans-2-butene epoxidation
Stereoselective Reaction
a single starting material can give two or more stereoisomeric products, but gives one of them in greater amounts than any other
Interactive Question
Which compound gives only a single stereoisomer of 1,3-dimethylcyclopentane on catalytic hydrogenation?
H CH3 CH2 H2 Pt
Resolution of Enantiomers
enantiomers separation of a racemic mixture into its two enantiomeric forms C(+) C(-)
Strategy
C(+) P(+) C(+)P(+) C(-)P(+) C(+)P(+) C(-)P(+) C(-) P(+)
2P(+)
diastereomers
Resolution of Enantiomers
Resolution of Enantiomers
Use of a chiral amine leads to diastereotopic salts Diastereomers have different physical properties and can then be separated
Stereoregular Polymers
Atactic Polypropylene
Isotactic Polypropylene
Syndiotactic Polypropylene
stereoregular polymer; all methyl groups on same side of main chain useful properties prepared by coordination polymerization under Ziegler-Natta conditions
stereoregular polymer; methyl groups alternate side-to-side on main chain useful properties prepared by coordination polymerization under Ziegler-Natta conditions
silicon, like carbon, forms four bonds in its stable compounds and many chiral silicon compounds have been resolved
pyramidal geometry at nitrogen can produce a chiral structure, but enantiomers equilibrate too rapidly to be resolved
Phosphorus
b a P c : slow : P c b a a
Sulfur in Sulfoxides
b slow +S O_ : : S+ O_ b a
pyramidal geometry at phosphorus can produce a chiral structure; pyramidal inversion slower than for amines and compounds of the type shown have been resolved
pyramidal geometry at sulfur can produce a chiral structure; pyramidal inversion is slow and compounds of the type shown have been resolved
Summary: Chapter 7
Summary: Chapter 7 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 7.9 Molecular Chirality: Enantiomers The Chirality Center Symmetry in Achiral Structures Optical Activity Absolute and Relative Configuration Cahn-Ingold-Prelog Notation Fischer Projections Properties of Enantiomers The Chirality Axis 7.10 7.11 7.12 7.13 7.14 7.15 7.16 7.17
Summary: Chapter 7
Summary: Chapter 7 Reactions that Create a Chirality Center Chiral Molecules with 2 Chirality Centers Achiral Molecules with 2 Chirality Centers Molecules with Multiple Chirality Centers Diastereomers Resolution of Enantiomers Stereoregular Polymers Chirality Centers other than Carbon