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Organic Chemistry

Course Number: PCH 1120-217

Lecture # 7

Sunday September 22, 2013

Structural Isomerism-Stereoisomerism with One and Two Chiral Carbons

Prof. Oludotun A. Phillips

Room # 2-81, 2nd Floor Pharmacy Building

Email: dphillips@hsc.edu.kw

Tel: 24986070

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Learning ObjectivesAt the end of the class students should be able to:

describe structural and stereo-isomerism.

identify chiral carbon / stereocenter and achiral carbon.

draw structures of stereoisomers.

identify enantiomers and diastereomers.

distinguish between diastereomers and meso compounds.

describe optical activity in stereoisomers.

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Relationship Among Isomers

Geometric isomersRigidity in a molecule leads to isomerism

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Structural (Constitutional) Isomers

Constitutional isomers: compounds with the same molecular formula but different connectivity (order of attachment) of their atoms.

There are two constitutional isomers with molecular formula C4H10.

CH3CH2CH2CH3 CH3CHCH3

CH3

Butane(bp -0.5°C)

2-Methylpropane(bp -11.6°C)

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Structural (Constitutional) Isomers The potential for constitutional isomerism is

enormous:

4,111,846,763

4,347

75

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Constitutional Isomers

MolecularFormula

CH4

C5H12

C10H22

C15H32

C30H62

36,797,588C25H52

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Assignment

Submit to me during the next class:-

Questions:

1. How many constitutional isomers would you expect for each of the molecular formulas: C5H12, C6H14, C2H6O and C4H10O?

2. Draw all the possible constitutional isomers for the molecular formulas above.

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Stereoisomerism Stereoisomers: compounds with the same

molecular formula and same connectivity (order of attachment) of their atoms, but different 3D

(3-dimensional) orientations of their atoms in space.

Stereoisomerism relates to the three dimensional structure of the molecule in space.

Stereochemistry is the study of the orientation of molecules in space, relating how the atoms are arranged in space relative to each other.

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Stereoisomerism Three aspects of Stereochemistry:

1. Chirality of molecules: with right- or left-handed arrangement of the atoms around a carbon atom.

Chiral (from the Greek: cheir; hand) molecules are compds that are non-superimposable on their mirror images are stereoisomers; e.g Enantiomers

2. Geometric isomers: relates to how rigidity in the molecule can lead to isomerism.

3. Conformation of molecules: relates to how the change in the shapes of molecules can lead to isomerism.

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Stereoisomers with One Chiral Carbon Atom

A carbon with four different bonded groups is referred to as a Chiral Carbon (a Stereocenter, Chiral center; Stereocenter, Stereogenic center):

I C Cl

F

Br

H3C C CH2CH3

CH2CH2CH3

CH2CH2CH2CH3

Chiral Carbons(Stereocenter)

all four groups are different

H3CH2C C CH3

F

H

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Stereoisomers with One Chiral Carbon Atom

On the other hand, a carbon with all the four or two of the groups the same is referred to as an Achiral carbon:

H C H

H

H

achiral Carbons

all the four groups are the same

H3C C CH3

CH3

CH3

H3CH2C C CH2CH3

CH2CH3

CH2CH3

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Stereoisomers with One Chiral Carbon Atom

A Chiral carbon can exist in either of two 3D structural arrangements, because of the tetrahedral geometry.

The Two 3D representations are non-superimposable, mirror-image configurations referred to as Enantiomers.

Configuration refers to the orientation of the groups around the chiral carbon (stereocenter).

For example the two structural representation of Lactic acid, shown in next slide are in 3D, tetrahedral geometry of the chiral carbon:…

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Stereoisomers with One Chiral Carbon Atom

The two structural forms

are referred to as a pair

of Enantiomers.

Structure (i) is different from Structure (ii), they are both non-superimposable mirror images.

Each structural form exists independently: e.g. isomer (i): L(+)-lactic acid - is produced in muscles of the

body during exercise and responsible for the soreness.

while isomer (ii): D(+)-lactic acid is found in sour milk.

CO2H

C

HH3C

OH

CO2H

C

HCH3

HO

Lactic Acid: mirror images, both structures are different

Structure (i) Structure (ii)

(S) (R)

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Stereoisomers with One Chiral Carbon Atom Enantiomers of

2-butanol shown below:

To confirm that the mirror image of 2-butanol is not

superimposable on the original; rotate the mirror image by 180o

OH

CH3C CH2CH3

H

HO

CCH3

HCH3CH2

Original molecule Mirror image

Original molecule

OH

CH3C CH2CH3

H

OH

CCH3

HCH3CH2

OH

CH3C H

CH2CH3

Mirror image The mirror imagerotated by 180°

180°

rotate themirror imageby 180° about

the C-OH bond

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Stereoisomers with One Chiral Carbon Atom now try to fit one molecule (original on mirror image rotated

180o) on top of the other so that all groups and bonds match or align exactly:

The original and mirror images are non-superimposable…. they are different molecules with identical physical properties They are enantiomers (non-superimposable mirror images)

OH

CH3C CH2CH3

H

OH

CH3C H

CH2CH3

The original molecule

The mirror imageturned by 180°

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Stereoisomers with One Chiral Carbon Atom

Enantiomers:

are non-superimposable on their mirror images

are chiral molecules, having a center of chirality (the carbon with all the four different groups attached is the center of Chirality) – i.e. show handedness

contain stereogenic center, stereocentre, chiral center or asymmetric carbon atom.

do not have a plane of symmetry

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Stereoisomers with One Chiral Carbon Atom

The Physical properties of Enantiomers, such as melting point, boiling point, and refractive index are identical.

Enantiomers differ in only one physical property, the direction in which they rotate Plane-Polarized light.

Hence, Enantiomers are Optically active molecules.

Racemic mixture or Racemate: a mixture of equal (1:1) parts of enantiomers.

Racemic mixtures are Optically Inactive.

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Plane of Polarization of Plane Polarized Light Ordinary light waves - oscillate in all E-vector planes

perpendicular to its direction of propagation.

Plane-Polarized Light waves – oscillate in a single E-vector plane to its direction of propagation.

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Schematic diagram of a polarimeterMeasurement of Optical Activity – Polarimeter:

Polarimeter: instrument for measuring the rotation of plane-polarized light by a chiral compound.

Optically active: indicates that a compound rotates plane-polarized light.

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Rotation of Plane Polarized LightOptical Activity:

Dextrorotatory: clockwise rotation of plane-polarized light

Levorotatory: counterclockwise rotation of plane-polarized light

Specific rotation (): the observed rotation of an optically active substance at a concentration of 1g/100mL in a sample tube 10cm long; for a pure liquid, concentration is in g/mL (density):

Specific rotation ()= ________observed rotation “degrees”__________

length of sample tube “dm” X conc of sample “g/cm3”

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Stereoisomers with One Chiral Carbon Atom

Enantiomerism: is the presence of a carbon with four different groups bonded to it.

A compound having one chiral carbon with four different attached groups will exist in two non-superimposable mirror-image forms.

However, If a compound and its mirror image are superimposable, they are identical and there is no possibility of enantiomerism.

Such molecules are referred to as Achiral (without chirality):

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Isomers without Chiral Carbon Atom

A carbon having the two or more identical groups around it is referred to as Achiral carbon:

E.g. Propanoic acid:

Here two groups on the center carbon are similar, therefore both compounds are identical.

CO2H

C

HH

CH3

Propanoic acid: Both structures are identical

Structure (i) Structure (ii)

CO2H

C

HH

H3C

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Stereoisomers with Two Chiral Carbon Atoms

1. Molecules with Two Dissimilar Chiral Carbon Atoms – will give Enantiomers and Diastereomers:

e.g. 2,3,4-Trihydroxybutanal have two stereocenters.

Maximum possible number of stereoisomers = 2n; (n= number of chiral carbons)

22 = 4 stereoisomers are possible

HOCH2-CH-CH-CHOHOH

O* *

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Stereoisomers with Two Chiral Carbon Atoms1. Molecules with Two Dissimilar Chiral Carbon Atoms:

Enatiomers and Diastereomers:

Four Stereoisomers of 2,3,4-Trihydroxybutanal are possible:

Structures AC, AD, BC and BD are Diastereomers.

C

C

H OH

CHO

OH

CH2OH

H

C

C

HHO

CHO

HO

CH2OH

H H

CH2OH

HO

C

C

H OH

CHO

C

C

HHO

CHO

H

CH2OH

OH

A pair of enantiomers(Erythrose)

A pair of enantiomers(Threose)

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Stereoisomers with Two Dissimilar Chiral Carbon Atoms

Diastereomers are stereoisomers having more than one chiral carbon atom, but they are not mirror images.

Diastereomers differ in physical properties such as:

melting points, boiling points, densities refractive indices, and if they are chiral, specific rotations can differ.

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Stereoisomers with Two Chiral Carbon Atoms

2. Molecules with Two Similar Chiral Carbon Atoms - gives Enatiomers, Diastereomers and Meso Compounds:

Meso compound: an achiral compound having two or more stereocenters that is superimposable on its mirror image.

e.g. as may be found in

tartaric acid

Have two stereocenters; hence the expected number of stereoisomers 2n = 22 = 4; but only three stereoisomers truly exist

CC

OH

COOH

OH

H

HOOC

H

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Stereoisomers with Two Similar Chiral Carbon Atoms

Meso compounds (E and F) are achiral compounds therefore they are optically inactive molecules (they are the same molecule).

Compounds (G and H) are Enantiomers. While compounds (E and G), and (E and H) are Diastereomers.

E. F. G. H.

C

C

H OH

COOH

OH

COOH

H

C

C

HHO

COOH

HO

COOH

H

C

C

H OH

COOH

H

COOH

HO

C

C

HHO

COOH

H

COOH

OH

A pair of enantiomersA meso compound(plane of symmetry)

Has a Plane of Symmetry!!

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Rotation of Plane Polarized Light

Optical Activity: Like melting point and boiling point, Specific

rotation is a physical property of a compound e.g.

DD

H3CC

OHH

COOH

CH3

C

HOH

COOH

[]21 = -2.6°= +2.6°21

[]

(R)-(-)-Lactatic acid(S)-(+)-Lactic acid

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Questions - Stereoisomerism

Submit to me during the next class:-

How many stereoisomers are possible for the carbohydrate molecule 2-Deoxyribose shown below?

Draw all the possible stereoisomers of 2-Deoxyribose shown above, and identify the enantiomers and diastereomers.

CH2

OH

HC

OH

HC

OH

CH2 C H

O

2-Deoxyribose [A carbohydrate that is a structural component of the genetic material Deoxyribonucleic acid (DNA)]