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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
Stereochemistry
Handedness
Stereochemistry of organic molecules can be understood, if we understand the meaning of handedness the fundamental reason for this is that our hands are not identical, rather they are mirror images
Chirality
The mirror image of a chiral object is different and will not superimpose on the original object.
Objects which are chiral have a sense of handedness and exist in two forms.
Mirror Image
Achiral Molecules
Do these molecules contain a Plane of Symmetry (Mirror Plane)?
Chiral Molecules
The molecule labeled A and its mirror image labeled B are not superimposable. No matter how you rotate A and B, all the atoms never align. Thus, CHBrClF is a chiral molecule, and A and B are different compounds. A and B are stereoisomersspecifically, they are enantiomers. A carbon atom with four different groups is a tetrahedral stereogenic center.
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Elements of Symmetry
Symmetry in objects
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F Br Cl
F Cl Br
F Cl Br
edge view
Cl
side view
Cl
Plane of Symmetry
Symmetry plane COOH H C H COOH achiral No symmetry plane CH3 H C OH COOH chiral
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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
Br Cl Cl H Br ce nter of symmetry H
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Chiral Center
The most common (but not the only) cause of chirality in organic molecules is a tetrahedral atom, most commonly carbon, bonded to four different groups
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Cl H
stereocenter
F Br
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Stereogenic Centers
To locate a stereogenic center, examine the four groupsnot the four atomsbonded to each tetrahedral carbon atom in a molecule. Omit from consideration all C atoms that cannot be tetrahedral stereogenic centers. These include Methylene and methyl units, i. e. CH2 and CH3 groups respectively. Any sp or sp2 hybridized Carbons, e.g. triple bonds, and double bonds in alkenes (C=C) and carbonyls (C=O).
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Enantiomers
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Enantiomers
One of a pair of molecular species that are mirror images of each other and not superposable. They are mirror-image stereoisomers.
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Drawing Enantiomers
To draw both enantiomers of a chiral compound such as 2-butanol, use the typical convention for depicting a tetrahedron: place two bonds in the plane, one in front of the plane on a wedge, and one behind the plane on a dash. Then, to form the first enantiomer, arbitrarily place the four groupsH, OH, CH3 and CH2CH3on any bond to the stereogenic center. Then draw the mirror image.
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Pairs of Enantiomers
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Enantiomers
Cl H
this molecule is chiral
Cl F Br
rotate
F Br
Cl H Br F
H
note that the fluorine and bromine have been interchanged in the enantiomer
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Enantiomers
Lactic acid
HO C C HO H CH3 H H3 C O O C C OH OH
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Enantiomers
3-Chlorocyclohexene
Cl Cl
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Enantiomers
OH
1,2-propanediol
OH H3 C C H CH2 OH HOH2 C C H
CH 3 CHCH 2 OH
OH CH3
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Enantiomers
A nitrogen chiral center
+
H3 C
N CH2 CH3
A pair of enantiomers
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Two Stereocenters
Cl Br H3C H H CH3 H3C H Br Cl H H3C H CH3 Br Cl H CH3
d i a s t e r o m e r s
entaiomers
Cl Br H3C H H CH3
entaiomers
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CH2 OH
CH2 OH
CH2 OH
CH2 OH
Diastereomers:
stereoisomers that are not mirror images refers to the relationship among two or more objects
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COOH
COOH
COOH
COOH
A pair of enantiomers
Meso compound: an achiral compound possessing two or more chiral centers that also has chiral isomers
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diastereomers
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diastereomers
OH
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Meso compounds
Meso compounds are achiral by virtue of a symmetry plane, but contain a stereogenic center.
plane of symmmetry
mirror
Cl Cl H CH3
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Meso compounds
Meso compound: achiral despite the presence of stereogenic centers
Not optically active Superposable on its mirror image Has a plane of symmetry
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Because one stereoisomer of 2,3-dibromobutane is superimposable on its mirror image, there are only three stereoisomers, not four.
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OH CH3
* C CH2 CH CH CH3 *
RR RS SR SS
* *
CH3
OH CH3
CH
23 = 8 stereoisomers
CONFIGURATION
ABSOLUTE CONFIGURATION ( R / S )
CONFIGURATION
The three dimensional arrangement of the groups attached to an atom
clockwise
2 C
counter clockwise
3
view with substituent of lowest priority in back
(rectus)
(sinister)
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R or S Enantiomers
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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
1 H 6 CH3 7 NH2 8 OH 16 SH 17 Cl 35 Br 53 I
Increasing Priority
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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.
1 CH2 H 6 CH2 CH3 7 CH2 NH2 8 CH2 OH
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
C -CH=CH2 O -CH is treated as is treated as C -CH-CH2 O C C H C CH is treated as C C C C H C C O
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Priorities
1. -OH
2. -COOH 3. -CH3 4. -H
HO H C COOH
HOOC
OH
Bromochlorofluoroiodomethane
1 1
I
4
I
4
F Cl
C Br
3
F Br
2
C Cl
3
R
Enantiomers
S
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1,3-dimethylcyclohexane
The trans and cis compounds each have two stereogenic centers The cis compound has a plane of symmetry and is meso The trans compound exists as a pair of enantiomers
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Properties of Stereoisomers
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Properties of Stereoisomers
Enantiomers have identical physical and chemical properties in achiral environments 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 (see Table 3.1)
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Plane-Polarized Light
Ordinary light: light vibrating in all planes perpendicular to its direction of propagation Plane-polarized light: light vibrating only in parallel planes Optically active: refers to a compound that rotates the plane of plane-polarized light
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Plane-Polarized Light
plane-polarized light is the vector sum of left and right circularly polarized light circularly polarized light reacts one way with an R chiral center, and the opposite way with its enantiomer the result of interaction of plane-polarized light with a chiral compound is rotation of the plane of polarization
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Plane-Polarized Light
Polarimeter: a device for measuring the extent of rotation of plane-polarized light
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Optical Activity
observed rotation: the number of degrees, , through which a compound rotates the plane of polarized light dextrorotatory (+): refers to a compound that rotates the plane of polarized light to the right levorotatory (-): refers to a compound that rotates of the plane of polarized light to the left specific rotation: observed rotation when a pure sample is placed in a tube 1.0 dm in length and concentration in g/mL (density); for a solution, concentration is expressed in g/ 100 mL
COOH H H3 C OH (S)-(+)-Lactic acid [] D = +2.6
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Optical Purity
Optical purity: a way of describing the composition of a mixture of enantiomers
Percent optical purity =
x 100
Enantiomeric excess: the difference between the percentage of two enantiomers in a mixture
[R] - [S] x 100 = %R - %S Enantiomeric excess (ee) = [R] + [S]
Resolution
Racemic mixture: an equimolar mixture of two enantiomers
because a racemic mixture contains equal numbers of dextrorotatory and levorotatory molecules, its specific rotation is zero
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Racemates
An equal amount of two enantiomers is called a racemate or a racemic mixture. A racemic mixture is optically inactive. Because two enantiomers rotate plane-polarized light to an equal extent but in opposite directions, the rotations cancel, and no rotation is observed.
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Specific Rotation
Specific rotation is a standardized physical constant for the amount that a chiral compound rotates planepolarized light. Specific rotation is denoted by the symbol [] and defined using a specific sample tube length (l, in dm), concentration (c in g/mL), temperature (25 0C) and wavelength (589 nm).
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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.
COO Na H C OH HO C H COO Na
-
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OH OH HOOC H H
meso COOH
Tartaric Acid
OH OH OH OH H HOOC COOH H H COOH enantiomers
HOOC H
(+)-tartaric acid
(-)-tartaric acid
OH OH HOOC H H OH OH
meso COOH
ALSO FOUND
(as a minor component)
OH OH
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Diastereoisomer
Stereoisomers that are not mirror images of each other. Different configuration at some locations.
COOH NH2 H C H C OH CH3 COOH H 2N C H H C OH CH3
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Diastereomers
Threonine: 2 pairs of enantiomers
2R,3R 2S,3S 2R,3S 2S,3R 2S,3S 2R,3R 2S,3R 2R,3S 2R,3S & 2S,3R 2R,3S & 2S,3R 2R,3R & 2S,3S 2R,3R & 2S,3S
COOH NH2 H C H C CH3 OH COOH H H 2N C HO H H 3C 2S, 3S COOH H 2N C H H C OH CH3 C
2S, 3R
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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
COOH H C OH C HO H COOH 2R, 3R H COOH H HO C C OH COOH 2S, 3S
COOH H C OH H C OH COOH
2R, 3S
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
COOH H C OH C HO H COOH 2R, 3R H COOH H HO C C OH COOH 2S, 3S
COOH H C OH H C OH COOH
2R, 3S
CH3CHCHCH3
2-Bromo-3-chlorobutane
Cl Br
S R
mirror
Cl Br
Br Cl
S R
CH3
diastereomers
H Cl Br
CH3
CH3
H Br Cl
CH3
enantiomers 1 S S
CH3
H CH3
enantiomers 2
H CH3
CH3
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CH3CHCHCH3
2,3-Dichlorobutane
Cl Cl
S R
Cl Cl
Cl Cl CH3
meso mirror image CH3 is identical CH3
CH3
diastereomers
H Cl Cl
Cl Cl
R R
CH3
H CH3
enantiomers
H CH3
CH3
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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
Fischer Projections
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CH 3 H OH CH 2 CH 3
Fischer 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
COOH
COOH
OH H C H CH3 OH CH3
How?
(R)-lactic acid
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Fischer Projections
COOH C H H OH CH3
COOH OH CH3
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Fischer Projections
COOH H CH3 OH H
COOH OH CH3
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Fischer Projections
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
1.
OH H CH 3 CH 2 C CH 3 CH 2 CH 3 CH 2 CH 3 (S)-2-Butanol (Fischer projection)
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CH 3 (1) H C OH (2) H
CH 3 OH
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H
2 3
H 3C OH 1
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
COOH H OH CH3
CH3 H COOH =
CH3 HO H COOH
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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 structure
COOH H OH CH3 COOH =H OH CH3 90 H 3C OH (S)-lactic acid
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H COOH = H 3C
H COOH OH
(R)-lactic acid
Rules of Motion
One group can be held steady and the others rotated.
COOH H OH CH3 same as HO H COOH CH3
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Rules of Motion
To determine if two Fischer projections represent the same enantiomer carry out allowed motions.
H H 3C OH A C2H 5 HO C2H 5 H CH3 B H OH CH3 C 2H5 C
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H H 3C OH C2H 5 HO
C2H 5 H CH3 B H
OH CH3 C 2H5 C
Rules of Motion
A
By performing two allowed movements on B, we are able to generate projection A. Therefore, they are identical.
CH2CH3 HO H CH3 B CH3 HO H CH2CH3 CH3 CH3CH2 CH3 HO A
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H CH2CH3
H H 3C OH C2H 5 HO
C2H 5 H CH3 B H
OH CH3 C 2H5 C
Rules of Motion
A
Perform one of the two allowed motions to place the group with lowest priority at the top of the Fischer projection.
CH2CH3 H OH OH 90 CH3
H OH
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CH2CH
Priorities
1. NH2
2. COOH 3. CH3 4. H
H HOOC NH 2 CH 3 S - stereochemistry HOOC H NH 2 CH 3
HOOC CH3 H2N H CH3 HOOC H NH2 CH3
1-Bromo-2-chlorocyclohexane
Br Cl Cl Br
cis
diastereomers
Br Cl
enantiomers
Br Cl
trans
enantiomers
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1-Bromo-2-chlorocyclopropane
Br R
S
Cl
Cl R
Br
cis
diastereomers Br
enantiomers R R S S
Br
trans
Cl Cl
enantiomers
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1,2-Dibromocyclopropane
mirror image identical
Br
Br
Br
Br
cis
meso
diastereomers
Br Br Br
Br
trans
enantiomers
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Properties
Biological effects
Example Pasteurs plant mold metabolized (+)-tartaric acid but not (-)-tartaric acid
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Thalidomide
Marketed in 50 countries 1956-1962 Sedative for hysterical pregnant women Antiemetic to combat morning sickness Caused thousands of birth defects
N N O O H
Sold as racemic mixture: 1:1 mixture of enantiomers R enantiomer = antiemetic (not teratogenic) S enantiomer = teratogenic (not antiemetic) Single-enantiomer drug not useful: quickly racemizes in body
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enantiomers
OH H2N O
Most amino acids are chiral, so protein cavity is also chiral Metaphor: Stereoisomer = left hand or right hand Protein hole = left glove or right glove Left hand fits left glove but not right glove Left hand triggers left protein but not right protein (R)-carvone triggers spearmint smell receptor but not caraway smell receptor
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