Stereoisomerism

Subtle Changes Create Fragrant Differences

CH3 CH2

CH3

H

CH2 CH3

CH3

H

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Chirality and Enantiomers Gloves v. Socks Chiral

Exhibits handedness Non-superimposable images in mirror test

Achiral Does not exhibit handedness Identical or superimposable images in

mirror test

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Enantiomers A pair of molecules related as

nonsuperimposable mirror images Look at 2-chloropropane

Chiral? Superimposable mirror images?

Now, look at 2-chlorobutane Superimposable mirror images? Chiral?

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Stereogenic Centers C atom with 4 different groups attached

to it Marked with an asterisk (*) Indicates existence of enantiomers Lacks plane of symmetry

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Configurations and R-S Convention Arrangement of groups around

stereogenic center Enantniomers…opposite configurations Need for identifying each enantiomer

Cahn-Ingold-Prelog (CIP) system…otherwise known as the R-S system

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R-S Convention Four groups attached to stereogenic

center are placed in priority order (abcd)

Stereogenic center is then observed from the view point opposite the lowest priority group, d If remaining groups form clockwise array,

then it’s R If counterclockwise, then it’s S

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R-S Convention—Assigning Priority of Groups Rule 1

Atoms directly attached to stereogenic C are ranking according to At#...>At# = higher priority

H always has lowest priority If H is a group, then you’ll look down the

C-H bond to view the molecule, otherwise look down the C-lowest priority bond

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R-S Convention—Assigning Priority of Groups Rule 2

Used if Rule 1 does not allow you to reach a decision…two groups are identical

Work outward from the stereogenic center until a decision is reached

Ethyl has higher priority than methyl Saturated cyclic cpds follow same rules

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R-S Convention—Assigning Priority of Groups Rule 3

Required to handle unsaturated bonds and aromatic rings

Multiple bonds are treated as if the atoms involved bonded singly to each other

vinyl group, CH=CH2

CH CH2

C C

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E-Z Convention of Cis-Trans Isomers Eliminates ambiguity Prioritize each group attached to

double-bonded C, and do same for other C in double bond

E (entgegen)—if both higher priority groups on opposite side of double bond

Z (zusammen)—if high priority groups are on same side of double bond

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Polarized Light

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Polarized Light and Optical Activity

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Polarized Light and Optical Activity = observed rotation depends on

Molecular structure Concentration Length of sample tube Wavelength of light Temperature

Dextrorotatory (+) Levorotatory ()

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Calculating Specific Rotation…

= observed rotation l = length of tube in dm c = concentration of soln in g/mL t = temperature of soln…usually RT (298K) = wavelength of light (typically 589.3

nm, that of sodium vapor’s D-line )

[] = t

l x c

[] t

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What Makes a Molecule Optical Active Achiral molecules cancel polarity…

1 molecule rotates light in one direction, while mirror image molecule rotates light in opposite direction…cancelling activity

Chiral molecule solns consisting of a single type of enantiomer (R or S, but not both) are optically active…a 1:1 mixture of R&S enantiomers are known as racemic mixtures and are optically inactive

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Properties of Enantiomers

Baseball Ball Bat Glove

Identical achiral properties (mp, bp, D) Different chiral properties

Direction of rotation of plane –polarized light

NOT degrees of rotation

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Lactic Acid Enantiomers

(R)-()-lactic acid

3.33 (H2O)

mp = 53°C

[] 25°C

D

(S)-(+)-lactic acid

+3.33 (H2O)

mp = 53°C

[] 25°C

D

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Enantiomers in Biology

Neither R nor S dictates () or (+) Direction can determine rxn that will

occur Lactic acid dehydrogenase reacts with

(+)-lactic acid to make pyruvic acid, but not with ()-lactic acid

()-adrenalin, cardiac stimulant; (+)-adrenalin is ineffective

One could be toxic, the other harmless

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Fischer Projections Replaces dashed and solid wedges to 2-

dimensions Stereogenic C is intersection of horizontal

and vertical Horizontal represent groups connected to

stereogenic C above (toward you) plane of page

Vertical represent groups connected to stereogenic C below (away from you) plane of page

If lowest priority group is not on vertical arm, rotate three of four groups to make it so

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Fischer Projections

CO2H

CH3

OHH

(R)-lactic acid

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Compounds with More Than One Stereogenic Center

Biochemistry, carbohydrate chemistry Consider 2-bromo-3-chlorobutane

2 stereogenic centers Each center could be R or S Four isomers: (2R,3R), (2S,3S), (2R,3S),

(2S,3R)

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Compounds with More Than One Stereogenic Center

(2R,3R) (2S,3S) (2R,3S) (2S,3R)

-2-bromo-3-chlorobutane suffix for allRemember to rotate 3 of 4 groups to get lowest

priority on vertical axis

Br

C

C

CH3

CH3

H

H

Cl

H

C

C

CH3

CH3

Cl

Br

H

Br

C

C

CH3

CH3

Cl

H

H

H

C

C

CH3

CH3

H

Br

Cl

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Compounds with More Than One Stereogenic Center

(2R,3R) & (2S,3S) enantiomers (2R,3S) & (2S,3R) also enantiomers of

each other So, how are (2R,3R) & (2R,3S) related to

each other

Br

C

C

CH3

CH3

H

H

Cl

Br

C

C

CH3

CH3

Cl

H

H

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Diastereomers

(2R,3R) & (2R,3S) are stereoisomers, but not enantiomers

Diastereomers—stereoisomers that are not mirror images of each other May differ in all properties, including

achiral properties…mp, bp, D, rotation, degrees of rotation…could be everything

2 different cpds

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Calculating Number of Stereoisomers

As number of stereogenic centers (n) increases, so does number of stereoisomers

Every time a stereogenic center is added, R and S configurations are possible Rule: 2n = number of stereoisomers What is the maximum number of

enantiomers equation?

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Meso Compouds

Occur when diastereomers are achiral and therefore identical isomers

Optically inactive due to achirality Consider 2,3-dichlorobutane

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Meso Compounds

enantiomers, chiral identical, achiral, meso

Cl

C

C

CH3

CH3

H

H

Cl

H

C

C

CH3

CH3

Cl

Cl

H

Cl

C

C

CH3

CH3

Cl

H

H

H

C

C

CH3

CH3

H

Cl

Cl

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Meso Compouds

Plane of symmetry Represent a single cpd Same 4 groups attached Superimposable mirror images Identical Achiral Cl

C

C

CH3

CH3

Cl

H

H

H

C

C

CH3

CH3

H

Cl

Cl

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A Research Project on Meso Cpds and Racemic Mixtures

Conduct independent research on Louis Pasteur’s work with tartaric acid.

Learn all that you can about his work Be prepared to discuss such work on

examination

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Combinations of Stereoisomers Consider cis-2-butene and trans-2-

butene, also known as Z-2-butene and E-2-butene

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Combinations of Stereoisomers Consider staggered and eclipsed ethane

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Combinations of Stereoisomers Consider (R)-lactic acid and (S)-lactic

acid

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Combinations of Stereoisomers Consider meso-tartaric acid and (R,R)-

tartaric acid

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Stereochemistry and Rxns

Achiral reactants chiral product (both enantiomers are formed at equal rates and in equal concentrations—racemic mixture)

Chiral and achiral reactants new stereogenic center (diastereomers, different rates, different concentrations)

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Achiral Reactants Chiral Product Write the rxn of 1-butene with HBr…

remember Markovnikov’s Rule

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Achiral Reactants Chiral Product

CH3CH2CH=CH2 + H+ CH3CH2CHCH3

CH3CH2CHCH3

2-butyl cation

+ Br -

Br

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Achiral Reactants Chiral Product

Br C

H CH3CH2 CH3

CH3CH2—C

CH3

CH3CH2

CBr

(S)-2-bromobutane

H

HCH3

Br -

(R)-2-bromobutane

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Achiral Reactant + Chiral Reactant Write the rxn of 3-chloro-1-butene with

HBr.

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CH3CHCH=CH2 + HBr

Cl

+

Achiral Reactant + Chiral Reactant

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Cl

CH

C

CH2

CH3

H Cl

C

C

CH3

CH3

H

H

Br

Cl

C

C

CH3

CH3

Br

H

H

HBrR R R

SR +

(R)-3-chloro-1-butene (2R,3R)-2-bromo-3-chlorobutane (2S,3R)-2-bromo-3-chlorobutane

The Cl group remains R; the new stereogenic center can be either R or S.

Resolving Racemic Mixtures Separation of racemic mixture’s

enantiomers is resolution Convert to diastereomers

By letting enantiomers react w/chiral reagent Pasteur was 1st to resolve racemic mixture

Convert separate diastereomers back to enantiomers

Same concept as specificity in biological rxns—enzymes usually chiral reagent

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