isomeria geometrica

Química Orgânica I
2008/09
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O
H3C
O
O
O
H3C
O
OH
H
CH3
N
O
CH3
H
OH
HO
O
H
H
O
O
O
CH3
O
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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
OH
OH
HOOC
O
HOOC
HO
HO
O
OH
OH
OH
D-Glucuronic Acid
OH
L-Iduronic Acid
C5-epimerase
O
HO
HO
OH
COOH OH
L-Iduronic Acid
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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
H
H
C
H3 C
C
CH 3
C
CH 3
cis-2-Butene
mp -139°C, bp 4°C
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H
H3 C
C
H
trans-2-Butene
mp -106°C, bp 1°C
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Z
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Sequence Rules: The E, Z
Designation
• When the carbon double bond is tri– or
tetra–substituted, how can we name the
substituents?
H
C
C
A
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C
C
D
C
B
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A
C
B
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Configuration - E,Z
higher higher
higher
C
lower
C
C
lower
Z (zusammen)
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lower
lower
C
higher
E (entgegen)
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Configuration - E,Z
(2E, 4E)-3-chloro-4methyl-2,4-hexadiene
H
Cl
C
C
H3C
H
C
H3C
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C
CH3
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Alkene Stability
• Cis alkenes less stable than trans due to
steric strain
• Relative stability gained through catalytic
hydrogenation
H
H
H
C C
C C
CH3
CH3
CH3
H
Trans 76%
Cis 24%
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CH3
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Tema 4. Estereoquímica
Efecto de la isomería geométrica sobre las propiedades físicas
1,2-dicloroeteno
Isómer
o
Punto Fusión
(°C)
Punto Ebullición
(°C)
cis
-80
60
trans
-50
48
2- buteno
Isómer
o
Punto de Fusión
(°C)
Punto Ebullición
(°C)
cis
-139
4
trans
-106
1
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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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Naming Enantiomers: The R,S
System of Nomenclature
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
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•
•
Naming Enantiomers: The
R,S System of Nomenclature
R (Latin rectus) = right turn
S (Latin sinister) = left turn
1
4
2
3
(S)-2-bromobutane
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Swap Trick
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
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Low Priority Group Up Trick
If the low priority group in figure points up rather
than down simply draw circular arrow and reverse
chirality.
R for reversed chirality implies S for actual chirality
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Fischer Tricks
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.
(S)-2-bromobutane
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(R)-2-bromobutane
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Fischer Tricks
90º rotation
reverses all
chiralities.
180º
rotation
maintains
all
chiralities.
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1
8
2
3
4
5
6
7
180 °
7
6
5
4
3
2
8
1
everything winds up in opposite pos'n
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Multi-Carbon Fischer Trick
Similar C’s are never more than 2 swaps diff.
If 1 swap won’t line up groups C’s are same!
top carbons have same config
H
Cl
Cl
F
F
H
H
Cl
Cl
H
F
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F
bottom carbons have opposite config's
(swap H and Cl)
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Newman Projections
For front C swap low priority group to back C
If swap was necessary curved arrow now gives
reversed chirality; otherwise correct
H4
Cl
H3
Cl
H
3
4
F2
1 Cl
H
F2
1 Cl
F
F
swap 3 and 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
S
CH3
CH3
CH3
H
Br
Br
H
Br
H
Br
H
H
Br
Br
H
CH3
R,R isomer
R
CH3
CH3
S,S isomer
=
H
Br
H
Br
CH3
CH3
R
S
meso isomer is R,S = S,R
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Meso Compounds
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Topology of Stereoisomers With
Two Chiral Centers
Two Pairs of Identical Substituents
E
R,R
S,S
E
R,R
S,S
erythro/threo
erythro/threo
D
D
Three Pairs of Identical Substituents
D
D
D
D
D
D
D
D
R,S
threo/erythro
E
D
S,R
threo/erythro
D
= diasteriomers
E
= enantiomers
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D
R,S
meso
I
D
E
I
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S,R
meso
= diasteriomers
= enantiomers
= identical (meso)
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R,S System for isomers with more
than one Chirality Center
H3C
Br
H
H
HO
CH3
CH3
H
OH
H
Br
CH3
(2S,3R)-3-bromo-2-butanol
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Relative and Absolute
Configurations
• (–) amphetamine is known to have the Rconfiguration
• Therefore the (+) form has S configuration
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Enantiotopic, Diastereotopic, and
Homotopic Hydrogens
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Enantiotopic, Diastereotopic, and
Homotopic Hydrogens
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Enantiotopic, Diastereotopic, and
Homotopic Hydrogens
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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 chiral
molecules
– 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 chiral
conformers, 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
H
Br
H
Br
Br
H
Br
Nonsuperimposable mirror images,
but equal energy and interconvertible.
H H
Br Br
Use planar
approximation.
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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-Rosanoff
Convention
• 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
*
CHO
OH
H
CH2OH
D-(+)-glyceraldehyde
HO
H
COOH
H 2N
*
H
CH 2 CH 2 COOH
L -(+)-glutamic
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=>
acid
OH
H
OH
H *
OH
CH2OH
D-(+)-glucose
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aminoácidos
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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
H
O
O
N
O
*
N
O
Talidomida
H
H3C
*C
OH
HO2C
N
H
OCH3
(R)-naproxeno
antiartrítico
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O
*
H
(S)-propanolol
antihipertensivo
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O
O
H
N
N
H
O
O
O
H
N
N
H
O
H3C
O
N
O
O
O
N
mild sedative
H2N
H
O
O
OH
HO
thyroid hormone
H
NH2
antihypercholesterolemic
H OH
CH3
β-Blocker
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CH3
I
I
I
OH
H
CH2
H3C
odor/taste
of lemon
H2C
H
CH3
odor/taste
of orange
Limonene
CH3
CH3
CH3
N
H
narcotic
O
Thyroxin
O
CH3
O
CH3
I
O
I
N
Barbituate
Derivatives
I
HO
O
convulsive
Thalidomide
I
O
N
O
Extreme teratogen
(causes birth defects)
I
H
H
CH3
H3C
N
H
O
CH2
H2C
O
HO H
contraceptive
Propanolol
O
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H
H3C
spearmint
H
CH3
caraway
Carvone
63
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
major product
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Br
no measurable
quantity formed
64
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
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base
(1Z)-3,3-dimethylcyclohexene
no E (trans) isomer is formed
65
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
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(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
H
Pt
C
C
H
C
C
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 Example
H
H3C
CH3
CH (CH 3 )2
1. BH3/THF
2. H2O2, HO−
syn addition
trans methyls
−
H2B H
opposite side
put markers (methyls) in vertical pos'ns
OH
+
?
H3 C − H
CH (CH3 )2
+
CH3
CH3
CH3
HO
H
H
OH
(CH3 )2 CH
H
H
CH(CH3 )2
CH3
CH3
produces ERYTHRO isomers!!!
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Stereochemistry of Addition
Pro-Fischer Analysis
H
H3C
CH3
addition reaction
CH (CH3 )2
down
H
H
up
CH3
up
CH (CH3 )2
up
CH3
CH(CH3 )2
CH3
CH3
syn addition
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?
anti addition
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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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