Transcript Document

Biological Chemistry
First Year Organic Chemistry
Lecture Nine : Stereochemistry
Convener : Dr. Fawaz Aldabbagh
Isomers are different compounds that have the same molecular formula
Constitutional isomers are isomers that differ because their
atoms are connected in a different order
C2H10
Butane
Isobutane
Stereoisomers differ only in the arrangement of
their atoms in space
Geometric Isomers
Cl
H
Cl
H
C2H2Cl2
Cl
H
cis-1,2-Dichloroethene
H
Cl
trans-1,2-Dichloroethene
Enantiomers are stereoisomers whose molecules are
nonsuperimposable mirror images of one another
Objects that are superimposable on their
mirror images are said to be achiral
Involves a tetrahedral sp3 atom
H
CH3
C
CH2
CH3
OH
Chiral Centre
2-Butanol
CH3
H
C OH
Interchanging any two groups at a chiral
CH2
CH2
different groups converts one enantiomer
CH3
CH3
into another
CH3
HO
H
C
centre (stereocentre) that bears four
One structure can be superimposed on another
CH3
H C OH
CH3
CH3
HO C H
CH3
If any of the
attached groups onto
the tetrahedral atom
are the same, the
centre is achiral.
2-Propanol
The ultimate way to test for
molecular chirality is to construct
models of the molecule and its
mirror image and then determine
whether they are superimposable
Screwdriver is achiral
Socks are achiral
Golf club is chiral
Gloves are chiral
A molecule will not be chiral if it possess a
centre or plane of Symmetry
Properties of Enantiomers
Enantiomers have identical melting points and boiling points
Enantiomers have identical solubilities in solvents
Enantiomers have identical spectra and refractive index
Enantiomers interact, and react with achiral molecules in the
same manner
Enantiomers interact and react with other
chiral molecules at different rates
Enantiomers rotate plane-polarised light by
equal amounts but in opposite directions
Chiral molecules are
optically active
Plane-polarised light
Oscillation of electrical field of ordinary light
occurs in all possible directions
Polarimeter is a devise used to measure the effect of planepolarised light on an optically active compound
Nomenclature of Enantiomers (R-S) System
Enantiomers have opposite configuration at the chiral or stereocentre
Priority
1. Highest atomic number first; 2. If the first atom attached to
the chiral centre has the same mass, then next set of atoms in
the unassigned groups are examined; 3. We now rotate the
formula (or model) so that the group with lowest priority is
away from us; 4. Unsaturated substituents have greater
priority than saturated substituents
The Absolute
Configuration
c
CH3
HO
H
a C d
b
CH2
CH3
c
CH3
H
d C OH
a
b
CH2
CH3
H
Clockwise
R-2-butanol
H
anticlockwise
S-2-butanol
Assign (R) or (S)
H2 C
H CH3
Cl
C
C
H2C
H H
OH
C
C
C(CH3)3
CH2CH3
Which structures represent enantiomers or two
molecules of the same compound in different
orientations?
H
Br
H
F
C
Br
Cl
C
and
Cl
F
CH3
H
Cl
C
Cl
Br
Br
and
C
H
CH3
No Correlation between the direction of rotation of plane
polarised light and the absolute configuration of a molecule
Clockwise Rotation (+) – dextrorotatory
Anti-Clockwise Rotation (-) – levorotatory
Same Configuration
CH3
H2 C
C H
HO
CH2CH3
(R)-(+)-2-Methyl-1-butanol
CH3
H2 C
C H
Cl
CH2CH3
(R)-(-)-1-Chloro-2-methylbutanol
An equimolar mixture of two enantiomers is called a Racemic Mixture
It is Optically Inactive
O
O
H
S-(+)-Carvone
Principle component of
Caraway seed oil and
responsible for the
characteristic odour
H
R-(-)-Carvone
Principle component
of Spearmint oil and
responsible for the
characteristic odour
Receptor Sites in the Nose are Chiral
Biochemical effects arise when
molecules interact with
biomolecules such as enzymes
or receptors. These are
constructed of chiral building
blocks called amino acids.
Therefore, the biomolecule only
accepts molecules of a certain
configuration or shape.
Only the S- is pharamacologically active
COOH
H3 C
H
Ibuprofen - anti-inflammatory drug
COOH
H3 C
Ph
H
COOH
H3 C
H
R-
H
O
*
N
O
CH3
CH3
O
N
*
O
H
Ph
S-
Thus, only one enantiomer will fit into
the receptor or enzyme active site
thalidomide
S – induces a teratogenic response
R – induces a hypnotic or seductive response
Draw the R- and S- forms of thaildomide
Nobel Prize 2001
Professor William Knowles
Professor Ryoji Noyori
Professor K. Barry Sharpless
For synthesis of optically active compounds – asymmetric synthesis
SN2
H3C
HO
H C Br
C6H13
R-(-)-2-Bromooctane
CH3
CH3
HO C Br
H
C6H13
HO
H
C6H13
S-(+)-2-Octanol
Transition State
Inversion of Stereochemistry