Stereochemistry
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1 Stereochemistry
description
Stereochemistry. Handedness. Some things have a “handedness,” that is look at your right and left hand. They look alike, but are not the same. They are mirror images. - PowerPoint PPT Presentation
Transcript of Stereochemistry
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Stereochemistry
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Handedness Some things have a “handedness,”
that is look at your right and left hand. They look alike, but are not the same. They are mirror images.
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Nobel Prize - 2001
Their research deals with the fact that many molecules appear in two forms that are mirror images of each other, just like the left and right hands.
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The mirror imageof a chiral object isdifferent and will notsuperimpose on the original object.
Objects which are chiral have a sense of “handedness” and exist in two forms.
Chirality
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Mirror Image
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HCl
HCl Are these two
structures identical?
mirror
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HCl
HCl
Stereoisomers
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Stereoisomers
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Stereoisomers
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Stereoisomers
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Stereoisomers
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Stereoisomers
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enantiomersenantiomers
Stereoisomers that are nonidentical mirror images are called enantiomers.enantiomers.
Stereoisomers
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Visualize, visualize ….
C CBr
F
H
Cl
BrH
CCBr
F
H
Cl
BrH
CCH
Br
F
Cl
BrH
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Visualize, visualize …C C
Br
F
H
Cl
BrH CC
Br
F
H
Cl
BrH
Cl
HBr
F
H Br
Cl
BrH
F
Br H
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C
CH3
Br FH
C
CH3
F BrH
enantiomer
1..3..5…etc interchanges = enantiomer2..4..6...etc interchanges = original compound
ODD:EVEN:
Visualize, visualize …
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C C
CH3
Br FH CH3
H
FBr
C C C CCH3
Br F H CH3
Br
F H CH3
H
BrF
H
CH3 BrF
ENANTIOMER ENANTIOMERSAME
1 2
3
YOU CAN USEINTERCHANGES
Are these identical or are they enantiomers?
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Isomers Isomers: different compounds with the
same molecular formula Constitutional isomers: isomers with a
different connectivity Stereoisomers: isomers with the same
molecular formula, the same connectivity but a different orientation of their atoms in space that cannot be interconverted by rotation about a single bond
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Chirality Mirror image: the reflection of an object in a
mirror Objects that are not superposable on their
mirror images are said to be chiral, that is, they show handedness
Objects that are superposable on their mirror images are said to be achiral, that is, they do not show handedness. An achiral object has at least one element of symmetry
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Chirality A molecule
cannot be chiral if it has a plane of symmetry.
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Chirality A plane of symmetry is a plane that
cuts through an object in such a way that one half of the object is an exact mirror image of the other half.
A molecule that has a plane of symmetry must be identical to its mirror image and therefore must be nonchiral, or achiral.
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BrFH
Cl stereocenterThis is one type of ….
…. others are possible
A stereogenic carbon is tetrahedral and has four different groups attached.
Stereogenic Carbons
23ClClBr
F F
BrCl Cl
Elements of Symmetry Plane of symmetry: an imaginary
plane passing through an object dividing it such that one half is the mirror image of the other half
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ClCl
Br
H
H
Br
center of symmetry
Elements of Symmetry Center of symmetry: a point so
situated that identical components of the object are located equidistant on opposite sides and equidistant from the point along any axis passing through the point
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Two identical groups renders a tetrahedral carbon achiral.
F
BrClCl
ClClBr
F The plane of the paper is a plane of symmetry
Achiral
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Cl
ClBr
F F
BrCl Cl
plane ofsymmetry
side view edge view
Two Views of the Plane of Symmetry
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Symmetry Plane
CCOOH
HHCOOH
CCH3
HCOOH
OH
Symmetry plane No symmetry plane
achiral chiral
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CONSTITUTIONAL ISOMERS
Isomers with a differentorder of attachment ofthe atoms in their molecules
STEREOISOMERSIsomers with the same orderof attachment, but a differentconfiguration (3D arrangement)of groups on one or more of the atoms
ISOMERSDifferent compoundswith the same molecular formula
cis/trans ISOMERS
ENANTIOMERSStereoisomers whose molecules are non-superimposible mirrorimages of each other
DIASTEREOMERSStereoisomers whose molecules are not mirror images of each other
each isomer could
double bond or ring
both can apply
have stereoisomers
with a ring
TYPES OF ISOMERISMTYPES OF ISOMERISM(geometric)
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Enantiomers Enantiomers: stereoisomers that
are nonsuperposable mirror images; refers to the relationship between pairs of objects
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BrFH
Cl Cl
HBrF
H FBr
Cl
rotate
this moleculeis chiral
note that the fluorineand bromine have beeninterchanged in theenantiomer
do interchanges in class
Enantiomers
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Enantiomers Lactic acid
C
C
HOCH3
H
OHO
C
C
OHH3CH
O OH
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Enantiomers 1,2-propanediol
CH3CHCH2OHOH
C
OH
H
CH2OHH3C C
OH
H
HOH2C CH3
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Enantiomers 3-Chlorocyclohexene
Cl
H
Cl
H
Cl
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CH3CH2CH2CH2CH2 C CH2CH2CH2CH3
Br
H
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HO CH3
CH3
CH3
HH
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CH3O
O
carvone nootkatonespearment oil grapefruit oil
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CH3
O
HCH3CCH2
CH3
O
HCH3CCH2
(R)-carvonecaraway and dill seed oils
(S)-carvonespearmint oil
Carvone
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LimoneneCH3
HCH3CCH2
CH3
HCH3CCH2
(R)-limoneneodor of oranges
(S)-limoneneodor of lemons
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Chiral Drugs Most pharmaceutical drugs are
chiral thalidomide
NN
O
O O
O
H
HN
N
O
O O
O
HH
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Optically Active Refers to molecules that interact
with plane-polarized light
Jean Baptiste Biot French Physicist - 1815
He discovered that some natural substances (glucose, nicotine, sucrose) rotate the plane of plane-polarized light and that others did not.
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Optical Activity
incidentpolarizedlight
transmittedlight (rotated)
sample cell
angle ofrotation,
(usually quartz)
a solution of the substance to beexamined is placed inside the cell
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Plane Polarized Light Ordinary light: consists of waves vibrating
in all planes perpendicular to its direction of propagation
Plane polarized light: consists of waves vibrating only in one plane
Plane polarized light is an equal mixture of left and right-circularly polarized light. These two forms are nonsuperposable mirror images and, therefore, enantiomers.
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Plane-Polarized Light Beam
.
unpolarizedbeam
wavelength
= c
frequency ( n )
c = speed of light
polarized beam
Sine wavesare not alignedin the sameplane.
NOT PLANE-POLARIZED
ENDVIEWSIDE
VIEW
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Plane Polarized Light Because of its handedness, circularly
polarized light reacts one way with a stereocenter with R-handedness, and differently with its enantiomer
The net effect of the interaction of plane polarized light with a chiral compound is that the plane of polarization is rotated
Polarimeter: a device for measuring the extent of rotation of plane polarized light
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Optical Activity optical activity - ability of certain molecules
to rotate plane polarized light
detected using a polarimeter
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l(dam)
sample cell
Na vapor lamp
polarizer analyzer
Polarimeter
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Optical Activity Observed rotation: the number of
degrees, , through which a compound rotates the plane of polarized light
Dextrorotatory (+): rotation of the plane of polarized light to the right
Levorotatory (-): rotation of the plane of polarized light to the left
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Optical Activity Specific rotation:
Observed rotation of the plane of polarized light when a sample is placed in a tube 1.0 dam in length and at a concentration of 1g/mL.
= observed rotation
c = concentration ( g/mL )
l = length of cell ( dm )
D = yellow light from sodium lamp
T = temperature ( Celsius )
cl
TD
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Optical Activity For a pair of enantiomers, the
value of the specific rotation of each is the same, but opposite in sign
[]25D -13.52 +13.52D
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(R)-(-)-2-Butanol(S)-(+)-2-Butanol
C
OH
CH3CH3CH2H
C
HO
H3C CH2CH3H
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Discovery of EnantiomersLouis Pasteur Recrystallized
tartaric acid Two different kinds
of crystals that were mirror images.
Each type of crystal rotated light in opposite directions.
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Discovery of Enantiomers“There is no
doubt that in dextro tartaric acid there exists an assymetric arrangement having a nonsuperimposible image.”
CCCOO-Na+
COO-Na+
HHO H
OH
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H COOHH
OHOHHOOC
HOOC HH COOHOHOH
H HCOOH
OHOHHOOC
meso
enantiomers
(as a minor component)ALSO FOUND
more about thiscompound later
H COOHH
OHOHHOOC
HOOC HH COOHOHOH
H HCOOH
OHOHHOOC
meso
enantiomers(+)-tartaric acid (-)-tartaric acid
[]D = 0
meso -tartaric acid
Tartaric Acid
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R,S Convention Priority rules (Cahn, Ingold, Prelog)
Each atom bonded to the stereocenter is assigned a priority, based on atomic number. The higher the atomic number, the higher the priority
Increasing Priority
H CH3 NH2 OH SH Cl Br I1 6 7 8 16 17 35 53
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R,S Convention If priority cannot be assigned on the
basis of the atoms bonded to the stereocenter, look to the next set of atoms. Priority is assigned at the first point of difference.
CH2 H CH2 CH3 CH2 NH2 CH2 OH1 6 7 8
Increasing Priority
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R,S Convention Atoms participating in a double or
triple bond are considered to be bonded to an equivalent number of similar atoms by single bonds
CH
O CH
OOC
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Naming Enantiomers1. Locate the stereocenter2. Assign a priority to each
substituent from 1 (highest) to 4 (lowest)
3. Orient the molecule so that the group of lowest priority (4) is directed away from you
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Naming Enantiomers4. Read the three groups projecting
toward you in order from highest (1) to lowest priority (3)
5. If reading is clockwise, configuration is R (from the Latin rectus). If it is counterclockwise, configuration is S (from the Latin sinister).
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2clockwise counterclockwise
(rectus) (sinister)
view with substituentof lowestpriority inback
1 2
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C C
1
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R S
R, S Convention
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I
CBrCl
F
I
CClBr
F
1
2
3
4
RR SS
1
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4
Enantiomers
Bromochlorofluoroiodomethane
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Priorities1. -OH2. -COOH3. -CH3
4. -H (R)-(-)-lactic acid
C
HHO COOH
CH3
C
H
CH3
HOOC OH
(S)-(+)-lactic acid
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You try it!1. Br2. COOH3. CH3
4. H
CH3Br
H
COOHH
H3C
Br
COOH
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Diastereoisomer Enantiomers: opposite
configurations at all stereogenic centers.
Diastereomers: Stereoisomers that are not mirror images of each other. Different configuration at some locations.
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Diastereoisomer Stereoisomers
that are not mirror images of each other. Different configuration at some locations.
COOHCC
H
HCH3
NH2
OH
COOHCC
H
H OHCH3
H2N
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Two Stereocenters
diasteromers
entaiomers
entaiomers
Br Cl
H3CH
HCH3
Cl Br
HH3C
CH3H
Cl Br
HH3C
HCH3
Br Cl
HH3C
HCH3
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Diastereomers Threonine: 2 pairs
of enantiomers
COOHCC
H
H OHCH3
H2N
COOHCC
H
HCH3
NH2
OH
2R, 3S 2S, 3R
2R, 3R 2S, 3S
COOHCC
H
HHOH3C
NH2
COOHCC
H
HH3C
H2N
HO
2R,3R 2S,3S 2R,3S & 2S,3R2S,3S 2R,3R 2R,3S & 2S,3R2R,3S 2S,3R 2R,3R & 2S,3S2S,3R 2R,3S 2R,3R & 2S,3S
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Enantiomers & Diastereomers For a molecule with 1 stereocenter, 2
stereoisomers are possible For a molecule with 2 stereocenters,
a maximum of 4 stereoisomers are possible
For a molecule with n stereocenters, a maximum of 2n stereoisomers are possible
2n-1 pairs of enantiomers
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Enantiomers & Diastereomers For tartaric acid, the three possible
stereoisomers are one meso compound and a pair of enantiomers.
Meso compound: an achiral compound possessing two or more stereocenters.
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Symmetry Plane 2R, 3S and 2S, 3R
are identical Molecule has a
plane of symmetry perpendicular to C-C and is therefore achira
COOHCC
H
HO HCOOH
OH
2R, 3S 2S, 3R
2R, 3R 2S, 3S
COOHCC
H
OHHCOOH
OHCOOHCC
H
HO HCOOH
HO
COOHCC
H
OHCOOH
HO
H
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Symmetry Plane 2R, 3S and 2S, 3R
are identical Molecule has a
plane of symmetry perpendicular to C-C and is therefore achira
One meso compound and a pair of enantiomers
COOHCC
H
HO HCOOH
OH
2R, 3S 2S, 3R
2R, 3R 2S, 3S
COOHCC
H
OHHCOOH
OHCOOHCC
H
HO HCOOH
HO
COOHCC
H
OHCOOH
HO
H
Mirror image is identical
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H CH3CH3 H
Cl Br
CH3 HH CH3
Br Cl
H HCH3 CH3
Br Cl
CH3CHCHCH3
Cl Br
H HCH3 CH3
Cl Br
enantiomers 1
enantiomers 2
diastereomers
S R RS
S S R R
mirror
2-Bromo-3-chlorobutane
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H HCH3 CH3
Cl Cl
CH3CHCHCH3
Cl Cl
H HCH3 CH3
Cl Cl
CH3 HH CH3
Cl Cl
H CH3
CH3 H
Cl Clmeso
enantiomers
diastereomers
S R
S S R R
mirror image is identical
2,3-Dichlorobutane
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Meso Meso compounds are achiral by virtue
of a symmetry plane, but contain a stereogenic center.
Cl Cl
HH3C
HCH3
Cl Cl
HH3C
HCH3
plane of symmmetry mirror
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Racemic Mixture Racemic mixture (d,l;): an
equimolar mixture (50:50) of two enantiomers because a racemic mixture contains
equal numbers of dextrorotatory and levorotatory molecules, its specific activity is zero.
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Properties of Stereoisomers Enantiomers have identical physical
(except for ) and chemical properties.
Diastereomers are different compounds and have different physical and chemical properties
Meso-tartaric acid, for example, has different physical and chemical properties from its enantiomers
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Tartaric Acid(-) - tartaric acid
[]D = -12.0o
mp 168 - 170o
solubility of 1 g 0.75 mL H2O
1.7 mL methanol 250 mL ether
insoluble CHCl3 d = 1.758 g/mL
(+) - tartaric acid[]D = +12.0o
mp 168 - 170o
solubility of 1 g 0.75 mL H2O
1.7 mL methanol 250 mL ether
insoluble CHCl3 d = 1.758 g/mL
meso - tartaric acid[]D = 0o solubility of 1 gmp 140o 0.94 mL H2Od = 1.666 g/mL insoluble CHCl3
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H OH
CH3
CH2CH3Fischer Projections Fischer projection: a two-
dimensional representation showing the configuration of a stereocenter horizontal lines represent bonds
projecting forward vertical lines represent bonds
projecting to the rear the only atom in the plane of the paper
is the stereocenter
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Fischer Projections
(R)-lactic acid
C
COOH
HOH CH3
COOH
CH3
H OH
How?
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Fischer Projections
C
COOH
HOH CH3
COOH
CH3
H OH
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Fischer Projections
COOH
CH3
H OH
COOH
CH3
H OH
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Fischer Projections1. Orient the stereocenter so that bonds
projecting away from you are vertical and bonds projecting toward you are horizontal
2. Flatten it to two dimensions
(S)-2-Butanol (3-D formula)
(1) (2)
(S)-2-Butanol (Fischer projection)
CH3CH2H
CH3
OH
C
CH3
CH2CH3
OHH HC OH
CH3
CH2CH3
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Assigning R,S Configuration Lowest priority group goes to the
top. View rest of projection. A curved arrow from highest to
lowest priority groups. Clockwise - R (rectus) Counterclockwise - S (sinister)
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Assigning R,S Configuration
1
2
3
4
H
OHH3C COOH
s-lactic acid
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Rules of Motion Can rotate 180°, but not 90°
because 90° disobeys the Fischer projection. Same groups go in and out of plane
CH3HO H
COOH
CH3
COOHHO H
180COOH
H OH
CH3
COOH
CH3
H OH= =
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Rules of Motion Can rotate 180°, but not 90°
because 90° disobeys the Fischer projection. Different groups go in and out of
plane This generates an enantiomeric
structureH
H3C COOH
OH
H
OHH3C COOH
90COOH
H OH
CH3
COOH
CH3
H OH= =
(R)-lactic acid (S)-lactic acid
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Rules of Motion One group can be held steady and
the others rotated.
H
COOHHO CH3same as
CH3
COOHH OH
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Rules of Motion To determine if two Fischer
projections represent the same enantiomer carry out allowed motions. C2H5
CH3
HO HOH
C2H5
H CH3
H
OHH3C C2H5
A B C
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Rules of Motion By performing two allowed
movements on B, we are able to generate projection A. Therefore, they are identical.
HCH3
HOCH2CH3
CH2CH3
HHOCH3
HOH
CH3
CH2CH3CH3
B A
CH3CH2
C2H5
CH3
HO HOH
C2H5
H CH3
H
OHH3C C2H5
A B C
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Rules of Motion Perform one of the two allowed
motions to place the group with lowest priority at the top of the Fischer projection.
180H
CH3
OHCH2CH3
C not A
CH3HOH
CH2CH3
CH2CH3
HH3COH
OH90
C2H5
CH3
HO HOH
C2H5
H CH3
H
OHH3C C2H5
A B C
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Priorities1. NH2
2. COOH3. CH3
4. H
S - stereochemistry
CH3
HHOOC NH2
H
CH3
HOOC NH2
CH3
H2N H
HOOC
CH3
H2N H
HOOC
CH3
HOOC NH2
HCH3
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Stereochemistry of Reactions
CH3CH2CH CH2ether
CH3CH2CHCH3
Br
achiral chiral
H Br
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Addition of HBr
Br-
Br-
CCH3CH2
Br
HCH3
CCH3CH2
Br
HCH3
CH3CH2 CCH3
H
CH3CH2CH CH2etherH Br
CH3CH2 CCH3
H
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Addition of Br2 Cis
Racemic mixture Achiral bromonium ion
C CH H
CH3 CH3Br
Br
C CH H
CH3 CH3
Br2C C
H H
CH3 CH3
Br
Br-
aC C
H H
CH3 CH3Br
Br
ab
ba
b
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Addition of Br2
Trans
Symmetry plane, therefore meso Models are superimposible
C CBr
Br
H
H3C
CH3
H
ba
C CBr
H
H3C
CH3
HBr
a
Br-
C CH
CH3
Br
H
CH3Br2C C
H
CH3 H
CH3
b
a b
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Addition of Br2
C CBr
Br
H
H3C
CH3
H
C CBr
H
H3C
CH3
HBr
C CBr
H3C
H
CH3
H
Br
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Addition of HBr to a Chiral Alkene
CH3 H HBrC CH3
CH3 H HBr-
CH3
CH3 H Br H
CH3
CH3 H BrH
2S,4R 2R,4R
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Addition of HBr to a Chiral Alkene Chiral intermediate is not attacked
equally from top and bottom because of steric reasons. Therefore, a mixture of product is formed in unequal amounts.
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Chirality in Substituted Cyclohexanes Symmetry plane No stereogenic centers 1,4-disubstituted Only cis & trans diastereomers
CH3
CH3
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1,3-disubstituted Cis Symmetry plane Meso compound
CH3
CH3
CH3
CH3
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1,3-disubstituted Trans No symmetry plane Therefore enantiomers
CH3
CH3
CH3
CH3
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1,2-disubstituted Trans Enantiomers
CH3
CH3
CH3
CH3
102
1,2-disubstituted Cis Meso
CH3
CH3
CH3
CH3
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Br Cl BrCl
Cl
Br Br
Cl
enantiomers
enantiomersdiastereomers
cis
trans
1-Bromo-2-chlorocyclohexane
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ClBr BrCl
Cl
Br Br
Cl
enantiomers
enantiomers
cis
trans
diastereomers
R S SR
R R S S
1-Bromo-2-chlorocyclopropane
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BrBr BrBr
Br
Br Br
Br
mirror image identical
meso
enantiomers
diastereomers
cis
trans
1,2-Dibromocyclopropane
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(S)-ibuprofen
CH
CH3
COOH
