Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI0809A3_STEREO.pdf · w3.ualg.pt\~abrigas...

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w3.ualg.pt\~abrigas QOI 0809 A3 1 Química Orgânica I 2008/09

Transcript of Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI0809A3_STEREO.pdf · w3.ualg.pt\~abrigas...

Page 1: Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI0809A3_STEREO.pdf · w3.ualg.pt\~abrigas QOI 0809 A3 8 Cis-Trans Isomerism • Because of restricted rotation about a C-C double

w3.ualg.pt\~abrigas QOI 0809 A3 1

Química Orgânica I

2008/09

Page 2: Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI0809A3_STEREO.pdf · w3.ualg.pt\~abrigas QOI 0809 A3 8 Cis-Trans Isomerism • Because of restricted rotation about a C-C double

w3.ualg.pt\~abrigas QOI 0809 A3 2

H

OO

O

O

H3CO

H3C

O

OHH

OO

N

H

CH3

O

O

HO

O

OH

H

CH3

CH3

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w3.ualg.pt\~abrigas QOI 0809 A3 3

Adaptado de:

• Jo Blackburn; 2006, Prentice Hall; Organic Chemistry, 6th Edition; L. G. Wade, Jr.

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w3.ualg.pt\~abrigas QOI 0809 A3 4

Kinds of Isomers

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w3.ualg.pt\~abrigas QOI 0809 A3 5

Conformational Isomers

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Conformational Vs Configurational Isomers

O

HOO

HO

OH

HOOC

OH

HOO

HO

OHCOOH

OH

HOOC

OH

OH

OH

OH

D-Glucuronic Acid

L-Iduronic Acid

L-Iduronic Acid

C5-epimerase

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Configurational Isomers: Cis-Trans diastereomers

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Cis-Trans Isomerism

• Because of restricted rotation about a C-C double bond, groups on adjacent carbons are either cis or trans to each other

cis-2-Butene mp -139°C, bp 4°C

trans-2-Butene mp -106°C, bp 1°C

C

H3 C

C

H

CH 3

C

HH

C

CH 3

HH3 C

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Z

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Sequence Rules: The E, Z Designation

• When the carbon double bond is tri– ortetra–substituted, how can we name the substituents?

C C

H

A

C

B

C C

C

A

D

B

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Configuration - E,Z

Z (zusammen) E (entgegen)

C

higherC

higher

lowerlower

C

lower higher

C

lowerhigher

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C C

H3C

H Cl

C C

CH3

H

H3C

C C

H3C

H Cl

C C

CH3

H

H3C

Configuration - E,Z

C C

H3C

H Cl

C C

CH3

H

H3C

(2E, 4E)-3-chloro-4methyl-2,4-hexadiene

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Alkene Stability

• Cis alkenes less stable than trans due to steric strain

• Relative stability gained through catalytic hydrogenation

Cis 24% Trans 76%

C CH

CH3

CH3

HC C

H

CH3 CH3

H

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Efecto de la isomería geométrica sobre las propiedades físicas

1,2-dicloroeteno

48-50trans

60-80cis

Punto Ebullición (°C)

Punto Fusión (°C)

Isómero

2- buteno

1-106trans

4-139cis

Punto Ebullición (°C)

Punto de Fusión (°C)

Isómero

Tema 4. Estereoquímica

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Quiralidade

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w3.ualg.pt\~abrigas QOI 0809 A3 16

Chirality

Any object that has a plane or point of symmetry is achiral (not chiral).

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Chirality

• “Handedness”: right glove doesn’t fit the left hand.

• Mirror-image object is different from the original object. =>

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Chirality in Molecules

• The cis isomer is achiral.

• The trans isomer is chiral.

• Enantiomers: nonsuperimposable mirror images, different

molecules.

=>

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Stereocenters

• Any atom at which the exchange of two groups

yields a stereoisomer.

• Examples:• Asymmetric carbons

• Double-bonded carbons in cis-trans isomers

=>

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Chiral Carbons

• Tetrahedral carbons with 4 different attached groups are chiral.

• If there’s only one chiral carbon in a molecule, its mirror image will be a different compound (enantiomer).

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 21

Mirror Trick

Whenever two structures can be positioned

around a symmetry plane if they aren’t

identical they’re enantiomers.

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w3.ualg.pt\~abrigas QOI 0809 A3 22

Mirror Planes of Symmetry

• If two groups are the same, carbon is achiral.

• A molecule with an internal mirror plane cannot be chiral.

Caution! If there is

no plane of

symmetry, molecule

may be chiral or

achiral.

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w3.ualg.pt\~abrigas QOI 0809 A3 23

Chirality in Molecules

• The cis isomer is achiral.

• The trans isomer is chiral.

• Enantiomers: nonsuperimposable mirror images, different molecules.

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 24

Stereocenters

• Any atom at which the exchange of two groups

yields a stereoisomer.

• Examples:

• Asymmetric carbons

• Double-bonded carbons in cis-trans isomers

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 25

(R), (S) Nomenclature

• Different molecules (enantiomers) must have different names.

• Usually only one enantiomer will be biologically active.

• Configuration around the

chiral carbon is specified

with (R) and (S).

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 26

Naming Enantiomers: The R,S System of Nomenclature

1. Rank groups by atomic number of the atom bonded to the chirality center. Use the same system that was used for the E and Z isomers of alkenes

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w3.ualg.pt\~abrigas QOI 0809 A3 27

2. Orient molecule so that group (or atom) of lowest priority is directed into plane.

3. Draw a curve from group of highest priority through the group of second priority to group of third priority

Naming Enantiomers: The R,S

System of Nomenclature

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w3.ualg.pt\~abrigas QOI 0809 A3 28

Naming Enantiomers: The R,S System of Nomenclature

• R (Latin rectus) = right turn• S (Latin sinister) = left turn

1

2 3

4

(S)-2-bromobutane

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� If for any reason you ever wish a group were in a different position simply swap it with another group.

� Swap simply reverses the chirality.

R for switched compound implies S for

actual compound

Swap Trick

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If the low priority group in figure points up rather than down simply draw circular arrow and reverse chirality.

Low Priority Group Up Trick

R for reversed chirality implies S for actual chirality

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w3.ualg.pt\~abrigas QOI 0809 A3 31

� If low priority group on vertical line (into plane) draw normal rotating arrow.

� If low priority group on horizontal line draw rotating arrow and reverse the R or S result.

� Rule of thumb: If group 4 is Vertical, Very true. If group 4

is Horizontal, Horribly wrong.

(R)-2-bromobutane

Fischer Tricks

(S)-2-bromobutane

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� 90º rotation reverses all chiralities.

� 180ºrotation maintains all chiralities.

Fischer Tricks

1

2 3

4 5

6 7

8 1

23

45

67

8

180°

everything winds up in opposite pos'n

Page 33: Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI0809A3_STEREO.pdf · w3.ualg.pt\~abrigas QOI 0809 A3 8 Cis-Trans Isomerism • Because of restricted rotation about a C-C double

w3.ualg.pt\~abrigas QOI 0809 A3 33

� Similar C’s are never more than 2 swaps diff.

� If 1 swap won’t line up groups C’s are same!

Multi-Carbon Fischer Trick

H

F

FCl

ClH

Cl

F

HF

HCl

top carbons have same config

bottom carbons have opposite config's (swap H and Cl)

Page 34: Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI0809A3_STEREO.pdf · w3.ualg.pt\~abrigas QOI 0809 A3 8 Cis-Trans Isomerism • Because of restricted rotation about a C-C double

w3.ualg.pt\~abrigas QOI 0809 A3 34

� For front C swap low priority group to back C

� If swap was necessary curved arrow now gives reversed chirality; otherwise correct

Newman Projections

H

F

Cl H

F

Cl 1 2

3

4

swap 3 and 4

H

F

Cl H

F

Cl 1 2

3

4

Configuration is R

Page 35: Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI0809A3_STEREO.pdf · w3.ualg.pt\~abrigas QOI 0809 A3 8 Cis-Trans Isomerism • Because of restricted rotation about a C-C double

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Two or More Chiral Carbons

• Enantiomer? Diastereomer? Meso? Assign

(R) or (S) to each chiral carbon.

• Enantiomers have opposite configurations at

each corresponding chiral carbon.

• Diastereomers have some matching, some

opposite configurations.

• Meso compounds have internal mirror plane.

• Maximum number is 2n, where n = the

number of chiral carbons.

=>

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Compounds with More Than One Chirality Center

Two Pairs of Similar Groups

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w3.ualg.pt\~abrigas QOI 0809 A3 37

Compounds with More Than One Chirality Center

Three Pairs of Similar Groups

CH3

CH3

BrH

HBr

CH3

CH3

HBr

BrH

CH3

CH3

HBr

HBr

CH3

CH3

BrH

BrH

R,R isomer S,S isomer

S

R S

R

=

meso isomer is R,S = S,R

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Meso Compounds

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Topology of Stereoisomers With Two Chiral Centers

R,R S,S

erythro/threo erythro/threo

R,S S,R

threo/erythro threo/erythro

DD DD

D

D

E

E

D

E

= diasteriomers

= enantiomers

Two Pairs of Identical Substituents

R,R S,S

R,S S,R

meso meso

DD DD

D

D

E

I

D

E

= diasteriomers

= enantiomers

Three Pairs of Identical Substituents

I = identical (meso)

Page 40: Química Orgânica I - w3.ualg.ptw3.ualg.pt/~abrigas/QOI0809A3_STEREO.pdf · w3.ualg.pt\~abrigas QOI 0809 A3 8 Cis-Trans Isomerism • Because of restricted rotation about a C-C double

w3.ualg.pt\~abrigas QOI 0809 A3 40

R,S System for isomers with more

than one Chirality Center

(2S,3R)-3-bromo-2-butanol

CH3

CH3

OHH

BrH

H3C

CH3HO

H

H

Br

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Relative and Absolute Configurations

• (–) amphetamine is known to have the R-configuration

• Therefore the (+) form has S configuration

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Enantiotopic, Diastereotopic, and

Homotopic Hydrogens

http://www-personal.une.edu.au/~sglover/NMR/sld060.htm

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Enantiotopic, Diastereotopic, and

Homotopic Hydrogens

http://www-personal.une.edu.au/~sglover/NMR/sld060.htm

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Enantiotopic, Diastereotopic, and

Homotopic Hydrogens

http://www-personal.une.edu.au/~sglover/NMR/sld060.htm

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Enantiotopic, Diastereotopic, and Homotopic Hydrogens

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w3.ualg.pt\~abrigas QOI 0809 A3 46

Enantiotopic, Diastereotopic, and Homotopic Hydrogens

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Properties of Enantiomers

• Same boiling point, melting point, density

• Same refractive index

• Different direction of rotation in polarimeter

• Different interaction with other chiralmolecules – Enzymes

– Taste buds, scent

=>

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Plane-Polarized Light

• Polarizing filter –calcite crystals or plastic sheet.

• When two filters are used, the amount of light transmitted depends on the angle of the

axes.

=>

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Polarimetry

• Use monochromatic light, usually sodium D

• Movable polarizing filter to measure angle

• Clockwise = dextrorotatory = d or (+)

• Counterclockwise = levorotatory = l or (-)

• Not related to (R) and (S)

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 50

Specific Rotation

Observed rotation depends on the length of the cell and concentration, as well as the strength of optical activity, temperature, and wavelength of light.

[α] = α (observed)

c • l

c is concentration in g/mL

l is length of path in decimeters.

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 51

Tema 4. Estereoquímica

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w3.ualg.pt\~abrigas QOI 0809 A3 52

Chirality of Conformers

• If equilibrium exists between two chiralconformers, molecule is not chiral.

• Judge chirality by looking at the most symmetrical conformer.

• Cyclohexane can be considered to be planar, on average.

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 53

Mobile Conformers

H

Br

H

Br

H

Br

H

Br

Nonsuperimposable mirror images,but equal energy and interconvertible. BrBr

H H

Use planarapproximation.

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 54

Nonmobile Conformers

If the conformer is sterically hindered, it may exist as enantiomers.

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 55

Allenes

• Chiral compounds with no chiral carbon

• Contains sp hybridized carbon with adjacent double bonds: -C=C=C-

• End carbons must have different groups.

Allene is achiral. =>

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w3.ualg.pt\~abrigas QOI 0809 A3 56

Fischer-RosanoffConvention

• Before 1951, only relative configurations could be

known.

• Sugars and amino acids with same relative

configuration as (+)-glyceraldehyde were assigned

D and same as (-)-glyceraldehyde were assigned

L.

• With X-ray crystallography, now know absolute

configurations: D is (R) and L is (S).

• No relationship to dextro- or levorotatory. =>

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w3.ualg.pt\~abrigas QOI 0809 A3 57

D and L Assignments

CHO

H OH

CH2OH

D-(+)-glyceraldehyde

*

CHO

H OH

HO H

H OH

H OH

CH2OH

D-(+)-glucose

*

COOH

H2N H

CH2CH2COOH

L-(+)-glutamic acid

*=>

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w3.ualg.pt\~abrigas QOI 0809 A3 58

aminoácidos

http://www.med.unibs.it/~marchesi/stereoch.html

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w3.ualg.pt\~abrigas QOI 0809 A3 59

The CORN Law

• Imagine looking along the Hydrogen - alpha Carbon bond of an amino acid

• CORN is an acronym for -COOH; the -R group;

and -NH2

• Starting at the carboxylic acid group, if you move

your eyes clockwise and see the mentioned -

COOH group then the -R group then the -NH2

group: CORN.

• L- form

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w3.ualg.pt\~abrigas QOI 0809 A3 60

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w3.ualg.pt\~abrigas QOI 0809 A3 61

Properties of Diastereomers

• Diastereomers have different physical properties: m.p., b.p.

• They can be separated easily.

• Enantiomers differ only in reaction with other chiral molecules and the direction in which polarized light is rotated.

• Enantiomers are difficult to separate.=>

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w3.ualg.pt\~abrigas QOI 0809 A3 62

Estereoquímica das reacções

N

O

H O

N

O

O

*

Talidomida

OCH3

CH3C

H

HO2C

*

(R)-naproxenoantiartrítico

O

H

OH

NH

*

(S)-propanololantihipertensivo

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w3.ualg.pt\~abrigas QOI 0809 A3 63

N

O

O

N

O

H

O

H

N

O

O

N

O

H

O

H

Thalidomide

Extreme teratogen(causes birth defects)

mild sedative

N N

O

OO

H3C H NN

O

O O

CH3H

convulsive narcotic

Barbituate Derivatives

O O

OHH2N

H

I

I

IHO

I

OO

HONH2

H

I

I

I OH

I

Thyroxin

thyroid hormone antihyper-cholesterolemic

CH3

H CH2

H3C

CH3

HH2C

CH3

CH3

H CH2

H3C

CH3

HH2C

CH3

O O

O NH

CH3

CH3

H OH

ONH

CH3

H3C

HHO

odor/taste of lemon

odor/tasteof orange

Limonene

Carvone

spearmint caraway

Propanolol

β-Blocker contraceptive

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w3.ualg.pt\~abrigas QOI 0809 A3 64

Regioselective, Stereoselective,

and Stereospecific Reactions

A regioselective reaction is one in which multiple constitutional isomers possible, but more of some formed than others.

HBr

Br Br

+

major product no measurable quantity formed

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w3.ualg.pt\~abrigas QOI 0809 A3 65

Regioselective, Stereoselective,

and Stereospecific Reactions

A stereoselective reaction can produce multiple stereoisomers theoretically, but more of some produced than others.

Br Br

+

(2R)-2-bromo-1,1-dimethylcyclohexane

+(2S)-2-bromo-1,1-dimethylcyclohexane

base

(1Z)-3,3-dimethylcyclohexene

no E (trans) isomer is formed

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w3.ualg.pt\~abrigas QOI 0809 A3 66

Regioselective, Stereoselective,

and Stereospecific Reactions

• A stereospecific reaction produces different stereoisomer products from different stereoisomer reactants.

Br2 (2R,3R)-2,3-dibromobutane

+(2S,3S)-2,3-dibromobutane

(no meso isomer formed)

Br2 (2R,3S)-2,3-dibromobutane

meso isomer

(no R,R or S,S isomers formed)

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w3.ualg.pt\~abrigas QOI 0809 A3 67

Syn Addition

• When the two substituents add to the same side

C C C C

HHPt

� Addition of H2 is a syn addition

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w3.ualg.pt\~abrigas QOI 0809 A3 68

Anti Addition

When the two substituents add to opposite sides

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w3.ualg.pt\~abrigas QOI 0809 A3 69

Stereochemistry of Addition

CIS-SYN-ERYTHRO RULE

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w3.ualg.pt\~abrigas QOI 0809 A3 70

Stereochemistry of Addition

Cis-Syn-Erythro ExampleCH

3

CH(CH3)2

H

CH3

1. BH3/THF?

2. H2O2, HO−

CH3

CH(CH3)2

HCH3

+ −−−−BH

2H

+

−−−−

OH

CH3

CH3

HOH

H(CH3)2CH

CH3

CH3

OHH

CH(CH3)2

H

trans methyls syn addition opposite side

put markers (methyls) in vertical pos'ns

produces ERYTHRO isomers!!!

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w3.ualg.pt\~abrigas QOI 0809 A3 71

Stereochemistry of Addition

Pro-Fischer Analysis

CH3

H

CH(CH3)2

CH3

CH3

H

CH(CH3)2

CH3

down

up

up up

syn addition anti addition

CH3

CH(CH3)2

H

CH3

addition reaction?

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w3.ualg.pt\~abrigas QOI 0809 A3 72

Biological Discrimination

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 73

Racemic Mixtures

• Equal quantities of d- and l-enantiomers.

• Notation: (d,l) or (±)

• No optical activity.

• The mixture may have different b.p. and m.p. from the enantiomers!

=>

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Racemic Products

If optically inactive reagents combine to form a chiral molecule, a racemic mixture of enantiomers is formed.

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 75

Optical Purity

• Also called enantiomeric excess.

• Amount of pure enantiomer in excess of the racemic mixture.

• If o.p. = 50%, then the observed rotation will be only 50% of the rotation of the pure enantiomer.

• Mixture composition would be 75-25. =>

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Resolution of Enantiomers

React a racemic mixture with a chiral compound to

form diastereomers, which can be separated.

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 77

Chromatographic Resolution of Enantiomers

=>

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w3.ualg.pt\~abrigas QOI 0809 A3 78

LINKS

• http://mooni.fccj.org/~ethall/stereo/stereo.htm• http://www.chem.uic.edu/web1/OCOL-II/WIN/STEREO.HTM• http://www.colby.edu/chemistry/OChem/STEREOCHEM/• http://infohost.nmt.edu/~chem/heagy/Lectures/lec13.pdf• http://www.colby.edu/chemistry/OChem/demoindex.html#table• http://www.chem.qmul.ac.uk/iupac/stereo/• http://www.chemhelper.com/stereochemistrytest.html• http://tigger.uic.edu/~kbruzik/text/chapter2.htm• http://www.dq.fct.unl.pt/qof/stereo1.html• http://www.stereochemistry-buergenstock.ch/