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Chapter 3
Chapter 3
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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 connectivity but a different orientation of their atoms in space
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Chirality
Chiral:
Elements of Symmetry
Symmetry
in objects
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Elements of Symmetry
Plane
of symmetry (contd)
mirror plane
HO
OH
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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 A carbon with four different groups bonded to it is called a chiral center
all chiral centers are stereocenters, but not all stereocenters are chiral centers (see Figure 3.5)
Enantiomers:
Enantiomers
2-Butanol
has one chiral center here are four different representations for one enantiomer
OH C H H3 C CH2 CH 3 (1) H H3 C C CH 2 CH3 (2) OH H OH (3) OH
(4)
using (4) as a model, here are two different representations for the enantiomer of (4)
OH (4) OH OH
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Enantiomers
The
O OH OH HO
O OH
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Enantiomers
2-Chlorobutane
Cl CH3 CHCH2 CH3
H Cl Cl H
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Enantiomers
3-Chlorocyclohexene
Cl
Cl
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Enantiomers
A
A pair of enantiomers
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R,S Convention
Priority
rules
1. Each atom bonded to the chiral center is assigned a priority based on atomic number; the higher the atomic number, the higher the priority
(1) (6) (7) (8) (16) (17) (35) (53)
-H
-CH 3
-N H 2
- OH
- SH
- Cl
- Br
-I
Increasing priority
2. If priority cannot be assigned per the atoms bonded to the chiral center, look to the next set of atoms; priority is assigned at the first point of difference
(1) (6) (7) (8)
- CH 2 -H
- CH 2 -CH 3
- CH 2 -NH2
- CH 2 -OH
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R,S Convention
3. 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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H Cl
(S)-2-Chlorobutane
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(R)-Mevalonic acid
1
1 4 HO CH3 O HO 3 2 OH
3
R 2
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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 3-19 has chiral isomers
diastereomers
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OH HO
OH HO
diastereomers
OH
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H3 C
OH HO
CH3
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H3 C OH HO
CH3
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Isomers
Compoun ds w ith the same molecu lar formula same conn ectivity Stereoisomers s tereoisomers bu t no ch iral centers Cis,Trans (E,Z ) Isomers (can b e called diastereomers) d ifferen t conn ectivity Constitu tion al Isomers rotation ab ou t sin gle b on ds Con formations rotation restricted Conformation al Isomers Atropisomers m ore than on e chiral cen ter ach iral Meso Comp ou nds ch iral mirror images En antiomers one ch iral center
D iastereomers
En antiomers
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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:
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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
21
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Optical Purity
Optical
x 100
Enantiomeric
Enantiomeric Excess
Example: a commercial synthesis of naproxen, a nonsteroidal anti-inflammatory drug (NSAID), gives the S enantiomer in 97% ee
CH3 COOH H3 CO (S)-N ap roxen
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Resolution
Racemic
Resolution:
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Resolution
One
after separation of the diastereomers, the enantiomerically pure acids are recovered
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Resolution
racemic acids can be resolved using commercially available chiral bases such as 1-phenylethanamine
NH2 NH2
(R)-1-Phenylethan amin e
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Resolution
Enzymes
as resolving agents
O OEt CH3 EtO H3 C OCH3 Ethyl ester of (R )-nap roxen (n ot affected b y th e esterase) O
H3 CO Ethyl ester of (S)-nap roxen 1. esterase NaOH, H2 O 2 . HCl, H2 O O OH CH3 H3 CO (S)-N ap roxen
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Amino Acids
the 20 most common amino acids have a central carbon, called an -carbon, bonded to an NH2 group and a COOH group in 19 of the 20, the -carbon is a chiral center 18 of the 19 -carbons have the R configuration, one has the S configuration in the D,L system, all have the L configuration at neutral pH, an amino acid exists as an internal salt in this structural formula, the symbol R = a side chain
sid e chain O H3 N O-
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Proteins
proteins are long chains of amino acids covalently bonded by amide bonds formed between the carboxyl group of one amino acid and the amino group of another amino acid
R H3 N O H N R O N H R H N n O O R
-
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for inorganic salts and a few lowmolecular-weight organic substances, the molecules of living systems are chiral Although these molecules can exist as a number of stereoisomers, generally only one is produced and used in a given biological system Its a chiral world!
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the substrate fits into a binding site on the enzyme surface a left-handed molecule will only fit into a left-handed binding site and a right-handed molecule will only fit into a righthanded binding site enantiomers have different physiological properties because of the handedness of their interactions with other chiral molecules in living systems
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End Chapter 3
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