StereochemistryThe arrangement of atoms in space

By: Dr. Manal F. Abou Taleb

Organic Chemistry, 5th EditionL. G. Wade, Jr. chapter 5

Isomerism

• 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.

Cahn-Ingold-Prelog Rules• Assign a priority number to each group

attached to the chiral carbon.• Atom with highest atomic number assigned

the highest priority #1.• In case of ties, look at the next atoms along

the chain.• Double and triple bonds are treated like

bonds to duplicate atoms. =>

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Geometric Isomers

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cis-trans isomers

Geometric isomers:

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IC C

Cl

F

Brcis or trans?

E and Z Based on Priority:

Cahn- Ingold-Prelongo:

1. Atomic Number2. Atomic weight3. Atomic number of the next atom

----------------

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5311

2 17

9 2

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Higher priority at the opposite side of pi bond (E) Higher priority at the same side of pi bond (Z)

(E) ? ethene(E)-1-bromo-2-chloro-2-fluoro-1-iodoethene

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cis or trans?

E and Z Based on Priority:

CH3

C2H5

C

H

CH

----------------

1

12

11

2 12

12

2

11(E) ? pentyne

(E)-3-ethyl-2-pentene-4-yne

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• Stereoisomers can be either enantiomers or diasteriomers

• A) Enanatiomers are stereoisomers whose molecules are nonsuperimposable mirror images of each other (different molecules).

cis-1,2-dichlorocyclopentane trans -1,2-dichlorocyclopentane

H

ClH

Cl

H

ClH

Cl

H

ClCl

H

H

ClCl

H

These two structures are enantiomers.

Nonsuperimposable mirror images are called enantiomers, they occur in pairs.

Enantiomers

• B) Diastereomers (Geometric) are stereoisomers whose molecules are not mirror images of each other.

Enanatiomers “Optical isomer”Same carbonSame connection Are mirror imageNonsuperimposableAll configurations are opposite

Diastereomers Same carbonSame connection Are Not mirror imageNonsuperimposableNot All configurations are opposite

Chirality• “Handedness”: right glove doesn’t fit the left hand.• Mirror-image object is different from the original

object. =>

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Molecule may be chiral or achiral

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StereoisomerismsChiral: An object that cannot be superposed on its mirror imageمتطابق

Chiral Carbon atomChiral Carbon atomChiral centerChiral center

Chiral molecules does Not contain a plane of symmatry

Chiral Carbons• Tetrahedral carbons with 4 different attached groups

are chiral.

• A tetrahedral carbon atom with four different groups attached to it is an asymmetric carbon.

• Its mirror image will be a different compound (enantiomerenantiomer). =>

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BrCl

H

F

Bromochlorofluoromethane is chiral

It is not superimposable point for point on its mirror image.

Note the four different attachments on C.

BrCl

H

F

Bromochlorofluoromethane is chiral

H

ClBr

F

To demonstrate nonsuperimposability, rotate this model 180° around a vertical axis.

BrCl

H

F

Bromochlorofluoromethane is chiral

H

ClBr

F

The structure on the right has been rotated.

• Example: 2-butanol I and II are mirror images of each other (figures a and b) I and II are not superposable and so are enantiomers (figure c)2-butanol is chiral molecule

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Chlorodifluoromethaneis achiral

Chlorodifluoromethaneis achiral

The two structures at the top are mirror images, but because they can be superimposed on each other they are identical and are not enantiomers.

Mirror Planes of Symmetry

If two groups are the same, carbon is achiralachiral. (animation)

A molecule with an internal mirror plane cannot be chiral.*

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Notes ! If there is no plane of symmetry, molecule may be chiral or achiral. See if mirror image can be superimposed. =>

Chiral molecules does Not contain a plane of symmatry σ

Symmetry tests for achiral structures Any molecule with a plane of symmetryor a centerof symmetry must be achiral.

Achiral center: a C atom is attached by 2 or more same groups. ---------------------------------------------------------------------Chiral Non-superimposable with its mirror imageasymmetric carbon4 different attached groupsEnanatiomers

achiralSuperimposablewith its mirror imageplane of symmetry2 or more same attach groups.not enantiomers

CH3CCH2CH3

CH3

H

CH3CCH2CH3

Cl

HCH3CH2CCH2CH2CH3

CH3

H

2-methylbutane

2-chlorobutane 3-methylhexane

achirall

chirall chirall

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Clasiffy each of the following pairs as chiral or achiral.

a)

CH3

ClCH3

Br

CH3

ClH3C

Br

b)

CH3

ClBr

H

CH3

ClBr

H

F

H Br

F

HBr

c)

achiral

chiral

chiral

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Label the stereogenic centers in each molecule and decide if it is chiral.

a) CH3CH2CH(Cl)CH2CH3

H Clachiral

b) CH3CH(OH)CH=CH2

H OH

chiral

c) (CH3)2CHCH2CH2CH(CH3)CH2CH3H CH3

chiral

A plane of symmetry bisects a molecule into two mirror image halves. Chlorodifluoromethane

has a plane of symmetry.

Plane of symmetry

A plane of symmetry bisects a molecule into two mirror image halves.

1-Bromo-1-chloro-2-fluoroethene has a planeof symmetry.

Plane of symmetry

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These mirror images are not the same, even after rotation!These are two distinct 3-methylhexane

enantiomersenantiomers

•(a) 2-Propanol and its mirror image, (b) When either one is rotated, the two structures are superposable and so do not represent enantiomers. They represent two molecules of the same compound. 2- Propanol does not have a stereocenter.

On the molecular level, most biologically important molecules are chiral. The biological activity of chiral molecules is specifically associated with a specific enantiomer. This specificity results from reaction between a chiral molecule and a chiral receptor that only accomodates one enantiomer. This enantioselectivity is a key factor in drug design.

The Importance of Chirality in Biological Systems

How is each pair of the following structures is related:(i) The Same (ii) Geometric isomers(iii) Structural isomers (iv) Not related at all

(a) (b) (c) (d)

Which one of the following compounds can exist as a pair of geometric isomers?

Cl Cl

Cl

Cl

(i) (ii) (iii) (iv)

Cl

Which compound of the following cannot exhibit cis / trans isomerism (i) 1,4-Dibromocyclohexane (ii) 1,2-Dibromocyclohexane (iii) 1,1-Dibromocyclohexane (iv)1,3-Dibromocyclohexane

Which of the following molecules is trans-1, 2-dimethylcyclohexane?

(i) (ii) (iii) (iv)

Absolute ConformationAssign (R) or (S)

• Working in 3D, rotate molecule so that lowest priority group is in back.

• Draw an arrow from highest to lowest priority group.

• Clockwise = (R), Counterclockwise = (S) =>

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• Since enantiomers are two different compounds, they need to be distinguished by name. This is done by adding the prefix R or S to the IUPAC name of the enantiomer.

• Naming enantiomers with the prefixes R or S is called the Cahn-Ingold-Prelog system.

• 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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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.

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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:

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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 of singly bonded atoms. For example, the C of a C=O is considered to be bonded to two O atoms.

Other common multiple bonds are drawn below:

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Figure 5.6Examples of assigningpriorities to stereogenic centers

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Labeling Stereogenic Centers with R or S

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Figure 5.7Examples: Orienting the lowestpriority group in back

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Label each compound as R or S.

a)Cl

H3C BrH

2

3 1

2

3 1

S

b) CH2Br

OHH3C

ClH2C

rotateCH2Br

CH2ClHO

H3C

2

1 3

2

1 3

R