7 Stereochem

8/8/2019 7 Stereochem

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Stereochemistry

&Chiral Molecules


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Stereochemistry

stereochemistry is the three-dimensional structure of a

molecule.

As a consequence of stereochemistry, apparently minor

differences in 3-D structure can result in vastly different

properties. We can observe this by considering starch and

cellulose, which are both composed of the same repeating

unit.


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Stereochemistry of Carbohydrates


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isomers are different compounds with the samemolecular formula.

The two major classes of isomers are constitutional

isomers and stereoisomers.

Constitutional isomers have different IUPAC names,

the same or different functional groups, different

physical properties and different chemical properties.

Stereoisomers differ only in the way the atoms areoriented in space. They have identical IUPAC names

(except for a prefix like cis ortrans and E or Z). They

always have the same functional group.

Two Major Classes of Isomers


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Configurational Isomers

Configurational isomers have a particular three-

dimensional arrangement of atoms called a

configuration.

Configuration is the spatial array of atoms that

distinguishes stereoisomers.

Configurational isomers are stereoisomers that

differ in configuration.


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Constitutional Isomers vs Stereoisomers


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

Some molecules are like hands. Left and right hands are

mirror images, but they are not identical, or

superimposable.

Chirality or Handedness


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Other molecules are like

socks. Two socks from a pair

are mirror images that are

superimposable. A sock and

its mirror image are identical.

A molecule or object that is

superimposable on its mirror

image is said to be achiral.

Achiral Objects and Molecules


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Do these molecules conatain a Plane of Symmetry (Mirror Plane)?

Achiral Molecules


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The molecule labeled A and its mirror image labeled B

are not superimposable. No matter how you rotate A and

B, all the atoms never align. Thus, CHBrClF is a chiral

molecule, and A and B are different compounds.

A and B are stereoisomersspecifically, they are

enantiomers. A carbon atom with four different groups is a tetrahedral

stereogenic center.

Chiral Molecules


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In general, a molecule with no stereogenic centers willnot be chiral. There are exceptions to this that will be

considered in Chapter 17.

With one stereogenic center, a molecule will always be

chiral.

With two or more stereogenic centers, a molecule may or

may not be chiral, e.g. Meso compound (contains a plane

of symmetry or a mirror plane)

Achiral molecules contain a plane of symmetry but chiral

molecules do not. A plane of symmetry is a mirror plane that cuts the

molecule in half, so that one half of the molecule is a

reflection of the other half.

Chiral vs Achiral


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Plane of Symmetry

or

Mirror Plane


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Chiral vs Achiral


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To locate a stereogenic center, examine the four

groupsnot the four atomsbonded to each tetrahedralcarbon atom in a molecule.

Omit from consideration all C atoms that cannot be

tetrahedral stereogenic centers. These include

Methylene and methyl units, i. e. CH2 and CH3 groups

respectively.

Any sp orsp2 hybridized Carbons, e.g. triple bonds,

and double bonds in alkenes (C=C) and carbonyls

(C=O).

Stereogenic Centers


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Larger organic molecules can have two, three or even

hundreds of stereogenic centers.

Number of Stereogenic Centers in a Molecule


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Enantiomers


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One of a pair of molecular species that

are mirror images of each other and

not superposable.

They are mirror-image stereoisomers.

Enantiomers


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To draw both enantiomers of a chiral compound such as2-butanol, use the typical convention for depicting a

tetrahedron: place two bonds in the plane, one in front of

the plane on a wedge, and one behind the plane on a

dash. Then, to form the first enantiomer, arbitrarily place

the four groupsH, OH, CH3 and CH2CH3on any bondto the stereogenic center. Then draw the mirror image.

Drawing Enantiomers


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Pairs ofEnantiomers


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Stereogenic centers may also occur at carbon atoms

that are part of a ring.

To find stereogenic centers on ring carbons, always

draw the rings as flat polygons, and look for tetrahedral

carbons that are bonded to four different groups.

Stereogenic Centers in a cyclic Alkane


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In 3-methylcyclohexene, the CH3 and H substituents thatare above and below the plane of the ring are drawn with

wedges and dashes as usual.

Enantiomers of 3-methylcyclohexene


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Enantiomers of Biomolecules

Manybiologically

active

molecules

contain

stereogeniccenters on

ring carbons.


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Polycyclic Ethers

How many stereogenic centers are in this

polycyclic ether structure?

O

O

O

O

HO

OHH

HH

Me

HH

H

H

H

H

O

H

O


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R/S Isomers


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Since enantiomers are two different compounds, theyneed to be distinguished by name. This is done by

adding the prefix RorS to the IUPAC name of the

enantiomer.

Naming enantiomers with the prefixes RorS is called

the Cahn-Ingold-Prelog system.

To designate enantiomers as RorS, 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 RorS


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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 priority

determines the higher priority.

Priority Rules for Naming Enantiomers (R or S)


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If two isotopes are bonded to the stereogenic center,assign priorities in order of decreasing mass number.

Thus, in comparing the three isotopes of hydrogen, the

order of priorities is:

Priority of Isotopes on a Stereogenic Center


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To assign a priority to an atom that is part of a multiple bond,

treat a multiply bonded atom as an equivalent number ofsingly bonded atoms. For example, the C of a C=O is

considered to be bonded to two O atoms.

Priority Rules for Multiple Bonds in (R or S) Labeling

Other common multiple bonds are drawn below:


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Examples Assigning Priorities


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Cahn-Ingold-Prelog System for

Naming Enantiomers R or S


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RorSEnantiomers


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R-enantiomer (ClockwiseRotation)

S-enantiomer (CounterclockwiseRotation)


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Manipulation of Chiral Molecules


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Switching any two groups on a molecule with a

single stereogenic center, converts the

molecule into its enantiomer.


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Enantiomers have identical physical properties, exceptfor how they interact with plane-polarized light.

Plane-polarized (polarized) light is light that has an

electric vector that oscillates in a single plane. Plane-

polarized light arises from passing ordinary light

through a polarizer.

A polarimeteris an instrument that allows polarized light

to travel through a sample tube containing an organic

compound. It permits the measurement of the degree to

which an organic compound rotates plane-polarizedlight.

Physical Properties of Stereoisomers


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With achiral compounds, the light that exits the sampletube remains unchanged. A compound that does not

change the plane of polarized light is said to be optically

inactive.

Polarimeter


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With chiral compounds, the plane of the polarized light is

rotated through an angle E. The angle E is measured indegrees (0), and is called the observed rotation. A

compound that rotates polarized light is said to be optically

active.

Optically Active Compounds


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The rotation of polarized light can be clockwise or

anticlockwise.

If the rotation is clockwise (to the right of the noon

position), the compound is called dextrorotatory. The

rotation is labeled dor (+).

If the rotation is counterclockwise, (to the left of noon),the compound is called levorotatory. The rotation is

labeled lor (-).

Two enantiomers rotate plane-polarized light to an equal

extent but in opposite directions. Thus, if enantiomer A

rotates polarized light +50, the same concentration of

enantiomer B rotates it 50.

No relationship exists between Rand Sprefixes and the

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

Rotation of Polarized Light


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An equal amount of two enantiomers is called a

racemate or a racemic mixture. A racemic mixture is

optically inactive. Because two enantiomers rotate

plane-polarized light to an equal extent but in opposite

directions, the rotations cancel, and no rotation is

observed.

Racemates


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Specific rotation is a standardized physical constant forthe amount that a chiral compound rotates plane-

polarized light. Specific rotation is denoted by the

symbol [E] and defined using a specific sample tube

length (l, in dm), concentration (cin g/mL), temperature

(25 0C) and wavelength (589 nm).

Specific Rotation


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Enantiomeric excess (optical purity) is a measurement of

how much one enantiomer is present in excess of theracemic mixture. It is denoted by the symbol ee.

Optical Purity

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

Calculating ee - If a mixture contains 75% of oneenantiomer and 25% of the other, the enantiomeric

excess is 75% - 25% = 50% ee.

50% ee means that there is a 50% excess of one

enantiomer over the racemic mixture.

The enantiomeric excess can also be calculated if the

specific rotation [E] of a mixture and the specific rotation

[E] of a pure enantiomer are known.

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


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DiastereomersRelative Configuration


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For a molecule with n stereogenic centers, the maximumnumber of stereoisomers is 2n. Let us consider the stepwise

procedure for finding all the possible stereoisomers of 2,3-

dibromopentane.

Chiral Molecules with more than one

Stereocenter


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Diastereomers & Enantiomers

2,3-dibromopentane


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Let us now consider the stereoisomers of 2,3-dibromobutane.

Since this molecule has two stereogenic centers, the maximumnumber ofstereoisomers is 4.

Enantiomers of 2,3-dibromobutane

To find all the stereoisomers of 2,3-dibromobutane, arbitrarily

add the H, Br, and CH3 groups to the stereogenic centers,

forming one stereoisomer A, and then draw its mirror image, B.


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To find the other two stereoisomers if they exist, switch the

position of two groups on one stereogenic center of one

enantiomer only. In this case, switching the positions of H and Br

on one stereogenic center of A forms C, which is different from

both A and B.

Meso Compounds


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A meso compound is an achiral compound that containstetrahedral stereogenic centers. All meso compounds

contain a plane of symmetry.

Compound C has two stereogenic centers but it contains

a plane of symmetry, and is achiral; C is a meso

compound.

Meso Compounds


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The Three Stereoisomers of

2,3-dibromobutane

Because one stereoisomer of 2,3-dibromobutane is

superimposable on its mirror image, there are only three

stereoisomers, not four.


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When a compound has more than one stereogenic

center, the Rand Sconfiguration must be assigned to

each of them.

Rand SAssignments in Compounds with Two or More

Stereogenic Centers.

One stereoisomer of 2,3-dibromopentaneThe complete name is (2S,3R)-2,3-dibromopentane


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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


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Fischer projection formulas.


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Cis/Trans Isomers

Stereoisomers of Disubstituted

Cycloalkanes


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Cis/Trans 1,2-dimethylcyclopentanes

There are two different 1,2-dimethylcyclopentanesone having

two CH3 groups on the same side of the ring and one havingthem on opposite sides of the ring.

A and B are stereoisomers.


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Cis/trans Isomers

Stereoisomers are isomers that differ only in the way theatoms are oriented in space.

The prefixes cis and trans are used to distinguish these

isomers.

The cis isomerhas two groups on the same side of thering.

The trans isomerhas two groups on opposite sides of the

ring.


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Naming Rules for Disubstituted Cycloalkanes

Each of the cis and trans isomers of a disubstituted

cyclohexane, such as 1,4-dimethylcyclohexane, has twopossible chair conformations.

Cis and trans isomers are named by adding the prefixes cis

and trans to the name of the cycloalkane. Thus, the cis isomer

would be named cis-1,2-dimethylcyclopentane, and the trans

isomer would be named trans-1,2-dimethylcyclopentane.

All disubstituted cycloalkanes with two groups bonded to

different atoms have cis and trans isomers.


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Consider 1,3-dibromocyclopentane. Since it has two

stereogenic centers, it has a maximum of four stereoisomers.

Cis/Trans 1,3-disubstituted Cycloalkanes

Recall that a disubstituted cycloalkane can have two

substituents on the same side of the ring (cis isomer, A) or on

opposite sides of the ring (trans isomer, B). These

compounds are stereoisomers but not mirror images.


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To draw the other two stereoisomers if they exist, draw mirror

images of each compound and determine whether the

compound and its mirror image are superimposable.

cis-1,3-dibromocyclopentane

The cis isomer is superimposable on its mirror image, making

the images identical. Thus, A is an achiral meso compound.


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The trans isomer is not superimposable on its mirror image,

labeled C, making B and C different compounds. B and C areenantiomers.

trans-1,3-dibromocyclopentane

Because one stereoisomer of 1,3-dibromocyclopentane is

superimposable on its mirror image, there are only three

stereoisomers, not four.


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Skip problems 30, 31, 32, 61, 62 d,c


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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 ofEnantiomers


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Chemical Properties ofEnantiomers


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Actually because of

priority rules a few are R,

but they all have thisconfiguration.


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Proteins


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