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Chapter 5Stereochemistry

Assignment for March 13th Class.

1. What is the difference between cellulose and starch?

2. Number of stereoisomers in compounds with molecular formular C8H18?

There are 18 structural isomers!4 of them have mirror images (enantiomers)1 has three stereoisomers ( enantiomers and diastereomers).

There are 11 stereoisomers!!

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Stereochemistry

• constitutional (structural) isomers and stereoisomers.Constitutional/structural isomers have different connectivity : different IUPAC names, different physical and chemical properties.

Stereoisomers have the same connectivity but different oriention in space : identical IUPAC names (except for a prefix like cis or trans).

• Configuration : A particular three-dimensional arrangement.

Stereoisomers differ in configuration.

The Two Major Classes of Isomers

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Stereochemistry

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• Importance of the stereochemistryExample

Starch

Cellulose

: glucose polymer, a food source to provide energy for growth. It is a major component of human diet: when cereals (barley, rice, wheat etc) and vegetables (potato, sweet potato, etc) are eaten, enzymes break down the starch molecules to glucose

: glucose polymer, gives rigidity to tree trunks, plant stems and leaves and it is resistant to hydrolysis by chemical or biological agents. It is indigestible to humans.

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Stereochemistry

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Stereochemistry

• Although everything has a mirror image, mirror images may or may not be superimposable.

• Some molecules are like hands. Left and right hands are mirror images, but they are not identical, or superimposable.

Chiral and Achiral Molecules

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Stereochemistry

• A molecule or object that is superimposable on its mirror image is said to be achiral.

• Two socks from a pair are mirror

images that are superimposable. A sock and its mirror image are identical.

Achiral Molecules

• Chiral : hand in Greek

So, we say right-handed /left-handed molecules

But which one is which?

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Stereochemistry

• Chirality check

Chiral and Achiral Molecules

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Stereochemistry

Chiral and Achiral Molecules

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Stereochemistry

• A and B are stereoisomers—specifically, they are enantiomers.• A carbon atom with four different groups is a tetrahedral stereogenic

center (chiral center).

Chiral and Achiral Molecules

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Stereochemistry

• With one stereogenic center, a molecule will always be chiral.• With two or more stereogenic centers, a molecule may or may not

be chiral.• In general, a molecule with no stereogenic centers will not be

chiral. There are exceptions to this.• Achiral molecules usually contain a plane of symmetry but chiral

molecules do not. • A plane of symmetry : a mirror plane that cuts the molecule in half,

so that one half of the molecule is a reflection of the other half.

Chiral and Achiral Molecules

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Stereochemistry

• locate a stereogenic center: examine each tetrahedral carbon atom in a molecule, and look at the four groups—not the four atoms—bonded to it.

• Always omit from consideration all C atoms that cannot be tetrahedral stereogenic centers. These include

CH2 and CH3 groups

Any sp or sp2 hybridized C

Stereogenic Centers

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Stereochemistry

• Larger organic molecules can have two, three or even hundreds of stereogenic centers.

Stereogenic Centers

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Stereochemistry

• To draw both enantiomers

Stereogenic Centers

CH3

OHCH3CH2

H

CH3

HCH3CH2

OH

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Stereochemistry

Stereogenic Centers

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StereochemistryStereogenic Centers in Cyclic Compounds

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StereochemistryStereogenic Centers

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StereochemistryImportance of Stereogenic Centers

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Stereochemistry

• Enantiomers are distinguished by adding the prefix R or S to the IUPAC name of the enantiomer.

• This is called the Cahn-Ingold-Prelog system.• How to designate enantiomers as R or S: priorities must be assigned to each group bonded to the stereogenic center, in

order of decreasing atomic number. The atom of highest atomic number gets the highest priority (1).

Labeling Stereogenic Centers with R or S

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Stereochemistry

• If two atoms on a stereogenic center are the same

assign priority based on the atomic number of the atoms bonded to these atoms. One atom of higher atomic number determines the higher priority.

Labeling Stereogenic Centers with R or S

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Stereochemistry

• Among isotopes: assign priorities in order of decreasing mass number.

Labeling Stereogenic Centers with R or S

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Stereochemistry

• Assigning a priority to an atom that is part of a multiple bond:treat a multiply bonded atom as an equivalent number of singly bonded

atoms.

Labeling Stereogenic Centers with R or S

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Stereochemistry

Labeling Stereogenic Centers with R or S

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Stereochemistry

Labeling Stereogenic Centers with R or S

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Stereochemistry

Labeling Stereogenic Centers with R or S

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Stereochemistry

Labeling Stereogenic Centers with R or S

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StereochemistryLabeling Stereogenic Centers with R or S

Figure 5.7Examples: Orienting the lowest

priority group in back

Stereochemistry

Labeling Stereogenic Centers with R or S

Stereochemistry

Labeling Stereogenic Centers with R or S

more examples

HOOC CH3

H OH

Lactic acid

HOOC CH2

H OH

MethoxyLactic acid

OCH3

O

O

O

HO

H3C

H

H

CH3

H OH

O

O O

H

S

CH2

H OH

O

O O

H

OCH3

S

Stereochemistry

Labeling Stereogenic Centers with R or S

more examples

O

O

O

HO

H3C

H

H

R

S

O

CH2HO

H

H2C C

OC

O

CH2O

H

H2C C

OC

H3C

Stereochemistry

Labeling Stereogenic Centers with R or S

more examples

H3C H

H H

HF

H

IH

H F

H

Cl

HH

Br

H

BrCl Br

H

H

H

H

1 1

2

2

2

2

3

3

3

3

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3 3

3

3

3

3

H3C H

H H

HF

H

IH

H F

H

Cl

HH

Br

H

BrCl Br

H

H

H

H

Stereochemistry

• For a molecule with n stereogenic centers, the maximum number of stereoisomers is 2n.

• possible stereoisomers of 2,3-dibromopentane.

Diastereomers

Diastereomers are stereoisomers that are not mirror images of each other.

Stereochemistry

• stereoisomers of 2,3-dibromobutane. • the maximum number of stereoisomers is 4.

Meso Compounds

Stereochemistry

• Compound C contains a plane of symmetry, and is achiral.

• Meso compounds generally contain a plane of symmetry so that they possess two identical halves.

Meso Compounds

• or center of symmetryBrCl

Br Cl

Stereochemistry

Meso Compounds

Stereochemistry

• When a compound has more than one stereogenic center, R and S configurations must be assigned to each of them.

One stereoisomer of 2,3-dibromopentane

The complete name is (2S,3R)-2,3-dibromopentane

Stereochemistry

C C

CH3 CH2CH3

Br BrH H

A

CH3CH2

C C

CH3

Br BrH H

B

C C

CH3 CH2CH3

BrH

HBr

C

CH3CH2

C C

CH3

BrH

HBr

D

C C

CH3 CH2CH3

BrH

HBr

C

CH3CH2

C C

CH3

BrH

HBr

D

(S) (R)(S) (S) (S)(R)(R)

Enantiomers

Diastereoisomers

C C

CH3 CH2CH3

Br BrH H

(S) (R)

(R)

Identical

Stereochemistry

• 1,3-dibromocyclopentane.

Disubstituted Cycloalkanes

Stereochemistry

Summary—Types of isomers

Stereochemistry

Determining the relationship between two nonidentical molecules

Stereochemistry

• enantiomers have identical chemical and physical properties except in their interaction with chiral substances and plane-polarized light.

• Plane-polarized (polarized) light : light that has an electric vector that oscillates in a single plane. Plane-polarized light arises from passing ordinary light through a polarizer.

• A polarimeter : measures of the degree to which an organic compound rotates plane-polarized light.

Physical Properties of Stereoisomers

Stereochemistry

• achiral compounds : optically inactive --- the light that exits the sample tube remains unchanged.

Physical Properties of Stereoisomers—Optical Activity

Stereochemistry

• chiral compounds: optically active --- rotates the plane of the polarized light through an angle .

• The angle is measured in degrees (°), and is called the observed rotation.

Physical Properties of Stereoisomers—Optical Activity

Stereochemistry

• If the rotation is clockwise – dextrorotatory -- d or (+).• If the rotation is counterclockwise – levorotatory -- l or

(-).• Two enantiomers rotate plane-polarized light to an equal

extent but in opposite directions. • Thus, if enantiomer A rotates polarized light +5°, the

same concentration of enantiomer B rotates it –5°.• No relationship exists between R and S prefixes and the

d (+) and l (-) designations that indicate optical rotation.

Physical Properties of Stereoisomers—Optical Activity

Stereochemistry

• racemic mixture (racemate) : mixture of an equal amount of two enantiomers.

• A racemic mixture is optically inactive -- the rotations cancel, and no rotation is observed.

Physical Properties of Stereoisomers—Racemic Mixtures

Stereochemistry

• Specific rotation : a standardized optical rotation

denoted by the symbol []

defined using a specific sample tube length (l, in dm),

concentration (c in g/mL),

temperature (250C) ,

wavelength (589 nm).

Physical Properties of Stereoisomers

• optical rotation : concentration, length of the path, temperature dependent

• optical rotation v.s. specific rotation – ratio of two enantiomers, purity of one

• Since enantiomers have identical physical properties, they cannot be separated by common physical techniques like distillation.

• Diastereomers and constitutional isomers have different physical properties, and therefore can be separated by common physical techniques.

Physical Properties of Stereoisomers

Stereochemistry

Fig. 9-13, p. 308

Stereochemistry• Separation of enantiomers• Recognition of enationmers differently

• Two enantiomers have exactly the same chemical properties except for their reaction with chiral non-racemic reagents.

• Many drugs are chiral and often must react with a chiral receptor or chiral enzyme to be effective. One enantiomer of a drug may effectively treat a disease whereas its mirror image may be ineffective or toxic.

Chemical Properties of Enantiomers

Stereochemistry

Stereochemistry

• Enantiomeric excess (optical purity) : a measurement of how much one enantiomer is present in excess of the racemic mixture. It is denoted by the symbol ee.

• cf. enantiomeric ratio

Physical Properties of Stereoisomers—Optical Purity

ee = % of one enantiomer - % of the other enantiomer.

• Example—If a mixture contains 75% of one enantiomer and 25% of the other,

the enantiomeric excess is 75% - 25% = 50%. Thus, there is a 50% excess of one enantiomer over the racemic

mixture.• The enantiomeric excess can also be calculated if the specific rotation []

of a mixture and the specific rotation [] of a pure enantiomer are known.

ee = ([] mixture/[] pure enantiomer) x 100.

Stereochemistry

• Enantiomeric excess (optical purity) : a measurement of how much one enantiomer is present in excess of the racemic mixture. It is denoted by the symbol ee.

• cf. enantiomeric ratio

Physical Properties of Stereoisomers—Optical Purity

Enantiomers and the Sense of Smell• Because enantiomers interact with chiral smell receptors, some enantiomers

have different odors.

Stereochemistry

Research suggests that the odor of a particular molecule is determined more by its shape than by the presence of a particular functional group.

ClCl

Cl Cl

Cl Cl Camphorelide ordor

5.31, 5.36, 5.37, 5.43, 5.47, 5.49, 5.51, 5.58, 5.60, 5.62,

5.64

Homework

Preview of Chapter 6

Understanding organic reactions

Kind of organic reactions- substitution, elimination, addition reaction

Bond breaking and bond making -Radicals, carbocations, carbanions thermodynamics and kinetics of organic reactions