Transcript Alice and Lewis Carroll

OPTICAL ISOMERISM
OPTICAL ISOMERISM DEALS WITH CHIRALITY
The word chiral derives from the Greek word ceir (cheir), meaning hand.
Our hands are chiral - the right hand is a mirror image of the left as are most of life's molecules such as (R)-alanine and (S)-alanine,
which are mirror images of each other.
NOT ALL OBJECTS EXHIBIT CHIRALITY, BUT MOST OBJECTS** HAVE MIRROR
IMAGES.
EXCEPTIONS ARE: VAMPIRES,THE DEVIL, FALLEN MEN
FAUST
GOUNOD
HOFFMAN (TALES OF HOFFMAN) HAD HIS REFLECTION
STOLEN BY ANTONIO WHO GAVE IT TO DAPERTULU (A
SORCEROR).
Alone in his study, the aged Dr. Faust despairs that his lifelong search for
a solution to the riddle of life has been in vain. Twice he raises a goblet of
poison to his lips but falters when the songs of young men and women
outside his window re-awaken the unfulfilled passions and desires of his
youth. Cursing life and human passion, the envious philosopher calls on
Satan for help. The Devil appears, and Faust tells him of his longing for
youth and pleasure; Méphistophélès replies that these desires can be
realized if he will forfeit his soul. Faust hesitates until the Devil conjures
up a vision of a lovely maiden, Marguerite. A magic potion transforms
Faust into a handsome youth, and he leaves with Méphistophélès in search
of Marguerite (Duet: "A moi les plaisirs").
SO HOW ONE DISTINGUISHED MOLECULES THAT EXHIBIT CHIRALITY
AND MOLECULES THAT LACK CHIRALITY (CALLED ACHIRAL
MOLECULES)?
MIRROR IMAGES OF CHIRAL MOLECULES ARE NON-SUPER
POSABLE (THAT IS THEY ARE DIFFERENT)
MIRROR IMAGES OF A CHIRAL MOLECULES ARE SUPER
POSABLE (THAT IS THEY ARE THE SAME)
CHIRAL OBJECTS: FEET, SCREWS, GOLF CLUBS,
STUDENTS ARM CHAIRS, ENGLISH AND AMERICAN CARS
ACHIRAL OBJECTS: SPOONS, KNIVES, FORKS
Alice and Lewis Carroll
Mathematic Don at Christ Church,
Oxford University
Real name was Charles Dodgson
Amateur Photographer
Alice’s father was Dean of Christ Church, Oxford
WHAT DO CHIRAL MOLECULES LACK THAT ACHIRAL HAVE?
CHIRAL MOLECULES LACK SYMMETRY
A CHIRAL MOLECULES POSSESS SYMMETRY
A symmetry element is a plane, a line or a point in or through an object,
about which a rotation or reflection leaves the object in an orientation
indistinguishable from the original.
CONSIDER 1,2-DIMETHYLCYCLOPENTANE
Me
Me
Me
Me
each has a plane of
symmetry
SAME, thus achiral
Me
Me
Me
Me
different mirror images
ASYMMETRIC CARBON ATOM (CHIRALITY CENTER) OR (STEREOCENTER)
MOLECULE THAT HAS ONE OF THE ABOVE WILL BE CHIRAL
THAT IS, LACKS SYMMETRY
REQUIREMENT: 4 DIFFERENT GROUPS
A
A
A
D
D
C
B
B
C
D
A
B
C
B
D
C
NOTE: EXCHANGE ANY TWO GROUPS TO GO FROM ENANTIOMER
TO THE OTHER ENANIOMER!!
EXAMPLES
O
Me
H
CHO
NH2
OH
H3C
H
OH
H
CH2OH
O
Cl
OMe
O
O
Me
Me
(R), (S) Nomenclature
• Different molecules (enantiomers) must
have different names.
•Usually only one enantiomer will be biologically
O
•Configuration around the
chiral carbon is specified
with (R) and (S).
C
OH
C H
H3C
NH2
natural alanine
=>
Cahn-Ingold-Prelog Rules Overview
Assign priorities to each group
View molecule with the lowest
priority away from the viewer
Arrow is drawn from the atom with
1st priority through the atom with 2nd
priority to the atom with 3rd priority.
If arrow points
clockwise - R(rectus)
If arrow points counterclockwise - S (sinister)
Assigning priorities-CASE 1
CASE 1 - four different atoms attached to chiral atom
• Assign a priority number to each atom attached to the
chiral carbon.
•Atom with highest atomic number assigned
the highest priorities #1.
In case of isotopes, high(er)est priority given to
the isotope with high(er)est mass number.
3-D Examples Assigning Priorities
Cl 2
Cl
2
PERSPECTIVE
3
F
H
4
Br 1
Br
1
2
Cl
Cl
Br 1
1 Br
4
3
WEDGE
Cl
Br
H
F
4 H
Cl
F
3
2
3 F
H
H
4
F
F
Br
H
FISHER
PRIORITY ASSIGNMENT EXAMPLES
CASE 2 - In case of ties among 1st atom, go to 2nd
atoms, then to 3rd etc until the tie is broken.
Consider straight chain groups
Me < Et<n-propyl etc
Consider effect of branching
Et< isopropyl < tert-butyl
Consider effect of hetero atom
Tert-butyl < CH2OMe
Groups possessing multiple bonds
C=C
CC
C-C
Carbon doubly bonded
to carbon is likened unto
a carbon bonded to two
carbons
Assign Priorities
O 2 OH
C
Cl
3 C
4
H
H3C
1NH2
H
natural alanine
3
H
C
H C
1
O
CH2
*C 4
CH(CH )
CH2OH
2
expands to
3 2
4
H3
*
2
Cl
1
C C
H C CH2
O
*C
CH(CH3)2
C
CH2OH
H
O
C
=>
Assign (R) or (S)
• Working in 3D, rotate molecule so that lowest
priority group is in back.
• Draw an arrow from highest to lowest priority
group.
• Clockwise = (R), Counterclockwise = (S)
=>
Examples
Fischer Projections
• Flat drawing that represents a 3D molecule
• A chiral carbon is at the intersection of horizontal and
vertical lines.
• Horizontal lines are forward, out-of-plane.
• Vertical lines are behind the plane.
Fischer Rules
• Carbon chain is on the vertical line.
• Highest oxidized carbon at top.
• Rotation of 180 in plane doesn’t change
molecule.
• Do not rotate 90!
• Do not turn over out of plane! =>
Fischer Mirror Images
• Easy to draw, easy to find enantiomers, easy
to find internal mirror planes.
• Examples:
CH3
CH3
CH3
H
Cl
Cl
H
H
Cl
Cl
H
H
Cl
H
Cl
CH3
CH3
CH3
=>
Fischer (R) and (S)
• Lowest priority (usually H) comes forward, so assignment
rules are backwards!
• Clockwise 1-2-3 is (S) and counterclockwise 1-2-3 is (R).
• Example:
(S)
CH3
(S)
H
Cl
Cl
H
CH3
=>
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
=>
Optical Activity
• Rotation of plane-polarized light
• Enantiomers rotate light in opposite directions, but
same number of degrees.
=>
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)
=>
Biological Discrimination
=>
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!
=>
Racemic Products
If optically inactive reagents combine to form
a chiral molecule, a racemic mixture of
enantiomers is formed.
=>
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.
=>
Mobile Conformers
H
H
H H
Br
H
Br
Br
H
Br
Nonsuperimposable mirror images,
but equal energy and interconvertible.
Br Br
Use planar
approximation.
=>
Nonmobile Conformers
If the conformer is sterically hindered, it may
exist as enantiomers.
=>
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.
=>
Fischer Projections
• Flat drawing that represents a 3D molecule
• A chiral carbon is at the intersection of horizontal and
vertical lines.
• Horizontal lines are forward, out-of-plane.
• Vertical lines are behind the plane.
Fischer Rules
• Carbon chain is on the vertical line.
• Highest oxidized carbon at top.
• Rotation of 180 in plane doesn’t change
molecule.
• Do not rotate 90!
• Do not turn over out of plane! =>
Fischer Mirror Images
• Easy to draw, easy to find enantiomers, easy
to find internal mirror planes.
• Examples:
CH3
CH3
CH3
H
Cl
Cl
H
H
Cl
Cl
H
H
Cl
H
Cl
CH3
CH3
CH3
=>
Fischer (R) and (S)
• Lowest priority (usually H) comes forward, so assignment
rules are backwards!
• Clockwise 1-2-3 is (S) and counterclockwise 1-2-3 is (R).
• Example:
(S)
CH3
(S)
H
Cl
Cl
H
CH3
=>
Diastereomers
• Stereoisomers that are not mirror images.
• Geometric isomers (cis-trans)
• Molecules with 2 or more chiral carbons.
=>
Alkenes
Cis-trans isomers are not mirror images, so
these are diastereomers.
H
H
CH3
C C
C C
H3C
H
CH3
cis-2-butene
H3C
H
trans-2-butene
=>
Ring Compounds
• Cis-trans isomers possible.
• May also have enantiomers.
• Example: trans-1,3-dimethylcylohexane
CH3
CH3
H
H
H
CH3
H
CH3
=>
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.
=>
Examples
COOH
COOH
H
HO
HO
OH
H
H
H
OH
COOH
COOH
(2S,3S)-tartaric acid
(2R,3R)-tartaric acid
COOH
H
OH
H
OH
COOH
(2R,3S)-tartaric acid
=>
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.
=>
D and L Assignments
CHO
H
*
CHO
OH
H
CH2OH
D-(+)-glyceraldehyde
HO
H
COOH
H2N
*
H
=>
CH2CH2COOH
L-(+)-glutamic
acid
OH
H
OH
H *
OH
CH2OH
D-(+)-glucose
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.
=>
Resolution of Enantiomers
React a racemic mixture with a chiral compound to form
diastereomers, which can be separated.
=>
Chromatographic
Resolution of Enantiomers
=>
End of Chapter 5