w3.ualg.pt\~abrigas QOI 0809 A3 1
Química Orgânica I
2008/09
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H
OO
O
O
H3CO
H3C
O
OHH
OO
N
H
CH3
O
O
HO
O
OH
H
CH3
CH3
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Adaptado de:
• Jo Blackburn; 2006, Prentice Hall; Organic Chemistry, 6th Edition; L. G. Wade, Jr.
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Kinds of Isomers
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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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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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Mirror Trick
Whenever two structures can be positioned
around a symmetry plane if they aren’t
identical they’re enantiomers.
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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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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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(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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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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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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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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� 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
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� 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)
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� 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
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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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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)
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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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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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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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Tema 4. Estereoquímica
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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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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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Nonmobile Conformers
If the conformer is sterically hindered, it may exist as enantiomers.
=>
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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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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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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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aminoácidos
http://www.med.unibs.it/~marchesi/stereoch.html
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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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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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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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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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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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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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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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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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Anti Addition
When the two substituents add to opposite sides
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Stereochemistry of Addition
CIS-SYN-ERYTHRO RULE
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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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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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Biological Discrimination
=>
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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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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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Chromatographic Resolution of Enantiomers
=>
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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/
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