Transcript Topic 20.6 Organic Chemistry Stereoisomerism

20.6 Stereoisomerism
Assessment Statements
 20.6.1 Describe Stereoisomers as compounds with the same
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structural formula but with different arrangements of atoms in
space.
20.6.2 Describe and explain geometrical isomerism in non-cyclic
alkanes.
20.6.3 Describe and explain geometrical isomerism in C3 and c4
cycloalkanes
20.6.4 Explain the difference in the physical and chemical
properties of geometrical isomers.
20.6.5 Describe and explain optical isomers in simple organic
molecules.
20.6.6 Outline the use of a polarimeter in distinguishing between
optical isomers.
20.6.7 Compare the physical and chemical properties of
enantiomers.
Terms
 Isomer
 Stereoisomer
 Chiral
 Racemic
 Geometric Isomer
 Symmetrical
 Optical Isomer
Assessemt Statements
 20.6.1 Describe stereoisomers as compounds with
the same structural formula but with different
arrangements of atoms in space.
Isomers
 Structural isomers as compounds with the same
molecular formula but with different
arrangements of atoms.
 May or may not have different properties ( boiling
point, melting point etc) depending on the type of
isomerism present
Types of Isomerism
Structural Isomers
 Have the same molecular formula but different
structural formula.
Structural Isomers
1. Pentane and 2-methylbutane are both C5H12.
2.
CH2 CH CH2 CH3
1-butene
CH3
CH2 C
CH3
2-methylpropene
CH3 CH CH CH3
CH2 CH2
CH2 CH2
cyclobutane
2-butene
CH2
CH2 CH
CH3
methylcyclopropane
3. C4H10 has 2 isomers (2-methylpropane, butane).
C4H8 has more isomers because the position of
the double bond affects the name and because
ring structures can be drawn.
Stereoisomerism
Stereoisomerism are isomers with same Molecular
Formula + Structural Formula but different in
spatial arrangement (different 3 Dimensional
shapes)
Cl
Cl
C
H
Cl
C
H
C
H
H
C
Cl
 Two types of stereoisomers
Geometric
Stereoisomers
Optical
Stereoisomers
Cl
Cl
C
C
H
H
Cl
H
C
H
C
Cl
Assessment Statements
 20.6.2 Describe and explain geometrical
isomerism in non-cyclic alkanes.
Geometric Isomers
 Geometric Isomerism occurs when the
ARRANGEMENT OF BONDS PREVENTS FREE
ROTATION AROUND THE AXIS through the
molecule.
 The restricted rotation occurs in alkenes for
example.
 In a single Bond (sp3), there is free rotation of
the head to head overlap of σ (sigma) bonds
When a double bond (sp2) is
present, the side to side
overlap of the П (pi) bonds
from the p orbitals must
remain in the same plane.
Therefore cis and trans are
stable isomers.
Geometric Isomers
Cl
Cl
Cl
Cl
cis-1,2-dichlorocyclopentane trans-1,2-dichlorocyclopentane
Cl
Cl
C
H
Cl
H
C
C
H
H
C
Cl
cis-1,2-dichloroethene trans-1,2-dichloroethene
Geometric Isomers
4. cis = same side, trans = opposite sides
5. 1,2-dichloroethene requires cis or trans.
1,2-dichloroethane does not require cis or trans
because they would both represent the same
molecule (to move chlorine from the same side
to opposite sides only requires that the C – C
single bond be rotated).
6.
cis-1,2-dimethylcyclopentane
CH3
CH3
CH3
CH3
trans-1,2-dimethylcyclopentane
CH3
7.
8.
9.
1,1-dimethylcyclopentane
CH3
A molecule is relatively inflexible when a multiple
(double or triple) bond is present or if a ring
structure (including benzene) exists.
a) not isomers (they don’t have the same chemical
formula: C5H12 vs. C5H10)
b) structural isomers (same as question #1)
c) geometric isomers
d) not isomers (both diagrams represent the exact
same molecule)
Assessment Statements
 20.6.3 Describe and explain geometrical
isomerism in C3 and c4 cycloalkanes
Cyclic Alkanes
 Cyclic alkanes are restricted in the rotation of
single bonds.
 Once again there are cis and trans structures.
Assessment Statements
 20.6.4 Explain the difference in the physical and
chemical properties of geometrical isomers.
Properties of Isomers
 In general, geometrical isomers,
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Trans have higher melting points
Cis has higher boiling points
There must be stronger intermolecular forces between cis isomers than trans.
Since they have the same composition , Van der Waals must be the same.
But the direction of the constituents can affect polarity greatly.
Melting Point and Boiling Point
 Why does trans have a higher melting point?
 To become a solid, the molecules have to pack
together into a lattice structure. Trans has a
better shape for this.
 Why does cis have a higher boiling point?
 The polarity of the cis isomer allows it to have
dipole/dipole interactions.
Assessment Statements
 20.6.5 Describe and explain optical isomers in
simple organic molecules.
 Key Terms: Symmetry, optical, Enantiomers,
Racemic, Chiral, Optically Active
Symmetry
 The quality of being made up of exactly similar
parts facing each other or around an axis.
Optical Isomerism
(Organic)
• Chiral, asymmetrical carbon
• 4 different gps attached to carbon
central
• Non superimposable
• Mirror image ( right, left handed )
• Enantiomers
• Identical chemical/physical
properties
• 2 enantiomers rotate plane of
polarised light to diff directions
Terms
 Chiral molecules  no axis or plane of symmetry (the most
common are tetrahedral molecules
 Enantiomers  pair of non superimposable isomers +
mirror image + diff 3D
 Isomers  compounds with same MF + SF but differ
in spatial arrangement
 Racemic  equal (50/50)% mixture of both
enantiomers S and R ( optically inactive ), no net
rotation of plane-polarized light, rotations cancel out.
Vocabulary
 Stereoisomers have chiral centers.
 Carbon atoms can be
 chiral or achiral
 Asymmetric or symmetric
 If two molecules are stereoisomers, they are also
called enantiomers
 Chiral molecules are optically active
 Enantiomers are optical isomers
Optical Isomers
 Appear to have same structure in 2D
 In 3D have different structures
 Are non-superimposable mirror images of each other
 With modeling kit build a model: carbon atom with
four different colors attached (use same size bonds!)
 Look at your model in a mirror, build what you see in
the mirror.
 Are the two superimposable?
How to draw 3D: Dash-Wedge Formula
 Draw two straight lines
about 110  from each
other
 Bond angle is 109.5
 These represent the
bonds in the plane of the
page
 Draw dashed line for the
bond that extends
behind the plane of the
page
 Draw wedge for bond
that extends in front of
the plane of the page
H
Cl
OH
CH3
Drawing Enantiomers
 Draw the molecule you built, using the dash-wedge
formula and colored pens
 Use a mirror to see the enantiomer
 Sketch the mirror image, using the dash-wedge
formula
 Draw the two stereoisomers of 1-chloro-1-bromoethane.
 There is no convention for which atom is attached
to a wedge.
Chiral
Centers
 Carbon attached to 4 different substituent
groups
 Even if two substituent groups start with C, they
could still be different
H
H
H3CH2C
OH
CH3
HO
CH2CH3
H3 C
 C=O, never chiral (C only attached to 3
things)
 CH3, CH2 groups, never chiral because they
are symmetric:
Optical Activity
Your left hand is the
mirror image of your right.
The two hands are "nonsuperimposable mirror
images". Molecules that are
"non-superimposable mirror
images" are optically
active. We say the
molecules are "chiral". We
say the pair of molecules is
an "enantiomeric pair".
Optical Activity
 Stereoisomers are said to be optically active if
the rotate plane polarized light
 Each type of enantiomer rotates light the same
amount, but in different directions.
 Amount and direction of rotation must be
experimentally determined using a polarimeter
Optical isomers can rotate the plane of polarisation
of plane-polarised light:
•one enantiomer rotates the polarised light
clockwise (to the right) and is the (+) enantiomer;
•the other rotates the polarised light anticlockwise
(to the left) and is called the (–) enantiomer.
A mixture containing equal concentrations of the (+)
and (–) enantiomers is not optically active (it will not
rotate the plane of polarisation). It is called a
racemic mixture or racemate.
Task
 Use the molecular modeling kit to build
structures on worksheet.
 HL need to understand how the structures are
arranged for geometric, structural and optical
isomers.
 SL use the worksheet to practice
understanding naming structures by building
them,
Assessment Statements
 20.6.6 Outline the use of a polarimeter in
distinguishing between optical isomers.
Polarimeter
Optical Isomers have
• Same MF, SF but differ in spatial arrangement.
• Same physical/chemical properties
• Differentiated using polarimeter, optically active enantiomers,
rotate plane of polarised light in diff direction
Video: Polarimeter
picture from
http://www.creation-science-prophecy.com/amino/
 The 2-amino acids (in your data booklet) are used
to synthesise proteins.
 Of the 20 amino acids (10 essential/10 non
essential) all but glycine are chiral
 Which means they all have enatiomers.
Assessment Statements
 20.6.7 Compare the physical and chemical
properties of enantiomers.
Mirror Image of Ibuprofen (pain killer drug)
has no side effect
• (S) enantiomer, effective as reducing fever and pain relief
• (R) enantiomer has no side effect!
• Most drugs in racemic mixture equal (R) and (S)
• Cheaper to synthesise racemic mix than pure enantiomer
• Single enantiomer appears to be more effective than racemic mix
• Clinical trial is essential to ensure no harmful side effect
sourcehttp://www.chemconnections.org/organic/chem226/Labs/opt-rotation/ibupro-resolution-09.html
Optical isomers (Thalidomide) tragedy due to Mirror Image
• Thalidomide exist as optical isomers
• Enantiomers (R) and (S)
• (R) effective against insomnia
and morning sickness
• S teratogenic, birth and limb defect
In nature, our body synthesises enzyme which have active site for
only one enantiomer
• Drug company, synthesise drug
with R and S ( racemic mix)
• (R) is effective but (S) has
side effect
• Enzyme recognises only one
enantiomer due to active site
Mirror image of thalidomide caused limb deformation
• (S) enantiomer causes limb defects and severe shortening of
the arms /legs.
• (R) enantiomer is effective drug
• Body will convert (R) to (S) by racemisation process,
producing a racemic mixture (R)/(S)
source:http://dermatology.cdlib.org/93/reviews/thalidomide/hsu.htm
source:http://chemwiki.ucdavis.edu/index.php?title=Special:Userlogin&returntomypage=y
IB Keywords
Enantiomers - pair of non superimposable isomers + mirror image + diff 3D
Isomers - compounds with same MF + SF but diff spatial arrangement
Racemic - equal (50/50)% mixture of both enantiomers S and R ( optically
inactive ), no net rotation of plane-polarized light, rotations cancel out.
History of Thalidomide
1954 - Thalidomide for insomnia and morning sickness.
1961 - Withdrawn, teratogenicity, birth defects result if drug is
taken during pregnancy.
1990 - FDA approved for erythema nodosum
leprosum, leprosy (skin disease)
1998 - FDA approved for multiple myeloma,
(cancer of plasma cells in the blood)
Sources and pictures from FDA/other contributors
http://www.cancer.gov/cancertopics/druginfo/lenalidomide
http://bloodjournal.hematologylibrary.org/content/108/10/3233/F1.expansion.html
http://animalculescience.blogspot.com/
• 2004 - Lenalidomide derived from Thalido able to strengthen immune cells
and effective against blood cancers
• 2011 - Thalidomide + Lenalidomide inhibit formation of new blood vessels
( anti-angiogenic) of tumor cells, Tumors unable to grow/spread due to lack
of nutrition. Researchers testing thalidomide in trials for other
HIV and Crohn’s disease.
Thalidomide making a come back after named as the greatest disaster in
medical history
Scientists discovered How Thalidomide caused Malformed Limbs
March 2010 - Published in Science by Takumi Ito.
Click HERE for info/source
• Defect Limb due to Thalidomide
• (S) enantiomers binds /inactivates the
protein cereblon, which is important in limb
formation. Inactivation, leads to
a teratogenic effect on LIMB DEFORMITIES
Published in Science .....
• Hiroshi Handa /Takumi Ito - Developed
tiny beads with Thalidomide attached.
• Thalidomide beads mix with cells
extract
• Protein Cereblon was bounded on beads
• ack of Protein Cereblon during embryo
development, causes limb deformities
Click HERE for info/source
http://www.rsc.org/chemistryworld/news/2010/march/11031001.asp
http://news.bbc.co.uk/2/hi/science/nature/8562998.stm
http://news.sciencemag.org/sciencenow/2010/03/-thalidomide-ranks-as-one.html