5b_stereochemistry_post

Sec. 6 - Stereochemistry - 2 Forsey

1

ChiralityRecognition and Nomenclature

A molecule that cannot be superposed on its mirror image is said to be chiral.A molecule that can be superposed on its mirror image is said to be achiral.

H

BrCl

H

H

BrCl

H

In the above molecule bromochloromethane the mirror image is the same compound, thus the molecule is achiral. Also notice that a plane of symmetry or mirror plane can be located in the molecule.A plane of symmetry is defined as an imaginary plane that bisects a molecule in such a way that the two halves of the molecule are mirror images of each other. All molecules with a plane of symmetry are achiral.

H

Br

Cl

H

planeof

symmetry


2

achiral

C

Cl

CH3H3C

H

CH3CHClCH3

Another exampleplane of symmetry

Bromochlorofluoromethane is chiral because the mirror image is nonsuperposable, also a plane of symmetry can not be located within the molecule. Thus the two molecules are different.These two stereoisomers are called enantiomers which is simply a pair of stereoisomers that are nonposable mirror images.

Chiral Molecules

C

F

BrCl

HC

F

BrCl

H

2-chloropropane


3

Why is this important?

Another example

The molecules are different. They have the same physical properties such as boiling and melting points but may act totally different biologically.

CH3CHOHCH2CH3

2-butanol


4

CH3

H3C

H

CH3

CH3

H

N

O

ONH

H

OO

(S)-LimoneneLemon smell

(R)-LimoneneOrange smell

(S)- Thalidomideteratogen: causes birth

defects

(R)- Thalidomidesedative

N

O

ONH

H

O O

Thalidomide used to alleviate symptoms of morning sickness- The two isomers are interconverted (racemizes) in biological conditions (H+)

Synthesized in 1953Available in 46 countries until 1962

stereogenic carbons


5

Identification of chiral atoms

Mirror image

rotate

Mirror image

rotate

To have a chiral carbon it must be bonded to four different groups.

sp3 hybridized with four different groups attached. Thus –CH2- and -CH3 are not chiral carbons

CH2CH3

CH2CH2Br

C

BrH2CH2C

Br BrH2CH2C

CH2CH3

C

CH2CH2Br

Br

CH2CH3

CH3

C

BrH2CH2C

Br H3C

CH2CH3

C

CH2CH2Br

Br

CH3CH2CH2CH2 C

CH2CH3

CH3

CH2CH2CH3

CH3CH2CH2CH2 C

CH2CH3

CH3

CH2CH3


6

Nomenclature of Enantiomers: The (R-S) system Cahn-Ingold-Prelog Rules

C

CH3

HO H

CH2

CH3

C

CH3

H OH

CH2

CH3

2-butanol

Priority is first based on the atomic number of the atom that is directly attached to the stereo center. The group with the lowest atomic number is given the lowest priority and so on.

When a priority cannot be assigned on the basis of the atomic number of the atoms that are directly attached to the stereocenter, then the next set of atoms in the unassigned groups are examined. Assign priority at the first point of difference


7

C

CH3

HO H

CH2

CH3

1. Assign priority based on atomic number

a

C

C

HO H

C

CH3

H H

H

H H

Now rotate the structure so that the group with the lowest priority is directed away. Then trace a path from the highest priority to the lowest priority. If the path is clockwise, the enantiomer is designated (R) [Latin rectus meaning right]. If the path is counterclockwise, the enantiomer is designated (S) [Latin sinister meaning left].

C

CH3

HO H

CH2

CH3

CH3C OH

CH2

CH3

rotate so that the lowestpriority is at the back

c

a d

b


8

C

CH3

HO H

CH2

CH3

CH3C OH

CH2

CH3


a d

b

CHO CH3

CH2

CH3

C

CH3

H OH

CH2

CH3

ac

b

c

c


enantiomers

mirror images


9

C

C

C OH

C

CH3

H2C

H3C CH3

C

H

C

H

HH

If the groups attached to the chiral carbon contain double or triple bonds the priority assigned is as if both atoms were duplicated.

R

C Y

R

R

C YR

CY

Y

C YR

CY

C

C YR

C

CH3

HC OH

C

CH3

H2C

H3C CH3

C

HC OH

C

CH3

H2C

H3C CH3

C

CH3

C C(CH3)3

H

HC C

C

C C

H

C

C

C

C

C

H

C

C

C

HH

H HHH

HH

H

H HH

C

CH3

C C(CH3)3HC


10

Do the following molecules have an R or S configuration?

H CH3

Cl

CH2

CH3

H3CH2C C

CH3

H

CH2Cl

Rotate around bond to get hydrogen to the back


11

Are the following pairs of molecules the same or enantiomers?

CF CH3

Cl

H

CH Cl

CH3

F

hydrogen at back already

OH

H3CH

CH2CH3

H

H3CH2C

H3COH

hydrogen at back already


12

Properties of Enantiomers: Optical Activity

Enantiomers have almost all identical physical properties (melting point, boiling point, density)

However enantiomers rotate the plane of plane-polarized light in equal but opposite directions

Plane polarized light

Oscillation of the electric field of ordinary light occurs in all possible planes perpendicular to the direction of propagation

If the light is passed through a polarizer only one plane emerges


13

The Polarimeter


14

Specific Rotation

An empty sample tube or one containing an achiral molecule will not rotate the plane-polarized light

An optically active substance (e.g. one pure enantiomer ) will rotate the plane-polarized light

The amount the analyzer needs to be turned to permit light through is called the observed rotation

If the analyzer is rotated clockwise the rotation is (+) and the molecule is dextrorotatory

If the analyzer is rotated counterclockwise the rotation is (-) and the molecule is levorotatory


15

The specific rotation of the two pure enantiomers of 2-butanol are equal but opposite

There is no straightforward correlation between the R,S designation of an enantiomer and the direction [(+) or (-)]in which it rotates plane polarized light

Racemic mixture

No net optical rotation

A 1:1 mixture of enantiomers

Often designated as (+)


16

Racemic Forms and Enantiomeric Excess

Often a mixture of enantiomers will be enriched in one enantiomerOne can measure the enantiomeric excess (ee)

Example : The optical rotation of a sample of 2-butanol is +6.76o. What is the enantiomeric excess?


17

The Synthesis of Chiral Molecules

Most chemical reactions which produce chiral molecules produce them in racemic form


18

Molecules with More than One Stereogenic Center

The maximum number of stereoisomers available will not exceed 2n, where n is equal to the number of tetrahedral stereogenic centers

C

C

CH3

CH2CH3

BrH

H Br

C

C

CH3

CH2CH3

HBr

Br H

C

C

CH3

CH2CH3

HBr

H Br

C

C

CH3

CH2CH3

BrH

Br H

1 2 3 4

1 and 2 are enantiomers, as is 3 and 4, but what are 1 and 3 or 1 and 4. They are stereoisomers because they have the same connectivity. These are called diastereomers.

enantiomers enantiomers

CH3CHCHCH2CH3

Br Br

2,3-Dibromopentane. Two chiral centers therefore4 stereoisomers

* *


19

Diastereomers

Diastereomers: stereoisomers which are not mirror images of each other

They have different physical properties and unlike enantiomers can be more readily separated or isolated from each other

C

C

CH3

CH2CH3

BrH

H Br

C

C

CH3

CH2CH3

HBr

H Br

C

C

CH3

CH2CH3

BrH

Br H

enantiomers enantiomers

C

C

CH3

CH2CH3

HBr

Br H

C

C

CH3

CH2CH3

BrH

H Br

C

C

CH3

CH2CH3

BrH

Br H

Connectivity is the sameand the

orientation in space is different ∴stereoisomers but they are not mirror images

Diastereomers


20

C

C

CH3

CH2CH3

BrH

H Br

C

C

CH3

CH2CH3

HBr

Br HC

C

CH3

CH2CH3

HBr

H Br

C

C

CH3

CH2CH3

BrH

Br H

Nomenclature1

2

3

4 5

-2,3-dibromopentane-2,3-dibromopentane

-2,3-dibromopentane

-2,3-dibromopentane


21

Fisher Projections

Each intersection of the horizontal and vertical lines represents a chiral carbon. Each horizontal line represents a bond coming toward the viewer.Each vertical line represents bonds going back away from the viewer.

C

CH

O

OHH

CH2OH

glyceraldehyde

CH

O

OHH

CH2OH

Fisher projection

C

CH

O

OHH

C

CH2OH

OHH

Fisher projection

erythrose

CH

O

OHH

CH2OH

OHH

CH

O

OHH

OHH

CH2OH

HO H

1

2

3

4

5

Which carbons are chiral?


22

As stated in the above slides there are 2n optical isomers, where n is the number of chiral carbons. But what about tartaric acid?

mp = 168° mp = 168°

o 12 20D

CO2H

OHH

CO2H

OHH

R

S

CO2H

HO H

CO2H

HO H S

R

enantiomers

CO2H

HO H

CO2H

H OHR

R

CO2H

H OH

CO2H

HO H

Are these two mirror images enantiomers?

CO2H

OHH

CO2H

OHH

What do you call a compound that has chiral carbons but its mirror image is exactly the same molecule. You call that molecule a meso compound

mp = 200°

Thus there are only3 stereoisomers not 4

same

o 12 20D

0 20D


23

How many stereoisomers does 2,3,4-trihydroxy-pentanedioic acid have?

HO2CCHCHCHCO2H

OH

OH

OH

CO2H

OHH

OHH

OHH

CO2H CO2H

HO H

HO H

HO H

CO2H CO2H

OHH

HHO

OHH

CO2H CO2H

HO H

H OH

HO H

CO2H

CO2H

HO H

H OH

H OH

CO2H

CO2H

H OH

HO H

HO H

CO2H

2n possible isomers = 8

1 2 3 4

657 8

CO2H

H OH

H OH

HO H

CO2HCO2H

OHH

HHO

HHO

CO2H

1 and 2 are the same

Meso compound or achiral and optically inactive

3 and 4 are the same

Meso compound

5 and 6 are non-superposable mirror images

Therefore enantiomers

7 and 8 are the same as 5 and 6


24

CO2H

OHH

OHH

OHH

CO2H CO2H

HO H

H OH

HO H

CO2H

CO2H

HO H

H OH

H OH

CO2H

CO2H

H OH

HO H

HO H

CO2H

CO2H

H OH

H OH

HO H

CO2HCO2H

OHH

HHO

HHO

CO2H

How many stereoisomers does 2,3,4-trijydroxy-pentanedioic acid have?4 and not 8 stereoisomers because of the meso compounds and

both ends of the molecule have the same substituents

Meso compounds contain 2 or more chiral carbons atoms (stereogenic carbons) but have at least one conformation that is achiral, usually by virtue of a plane of symmetry. Remember you can only get a meso compound when the “top” and “bottom” halves have the same substituents.

Plane of symmetry

meso meso

1 2 3 4 65

(±) enantiomers

Pairs of enantiomers have identical physical and chemical properties except for interactions with other chiral molecules and with polarized light.

Diastereomers however are chemically and physically different. They have different melting points and different solubilities and often undergo chemical reactions in a different fashion.

(±) enantiomers but the same as 3 and 4


25

Diastereomers have the same connectivity (stereoisomers) but have a different spatial arrangement and are therefore different compounds.

Structural isomers have the same molecular formula but the connectivity is different and therefore not stereoisomers

Diastereomers and alkenes

C C

Cl

Br

F

I

C C

Cl

Br

I

F

C C

Cl

F

Br

I

C C

Cl

F

I

Br

Diastereomers

Structural isomers

same connectivity same orientations same connectivity different orientations

differentconnectivity


26

Cycloalkanes and stereochemistry

How many isomers are there for the following cycloalkanes?

C3H5X – only one

C3H4X2 – 4 isomers – what are they?

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

enantiomers

C4H7X – only one


27

C4H6X2 – 6 isomers – what are they?

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

enantiomers

flip

sameplane of symmetryno plane of symmetry

plane of symmetry

Notice how the meso compounds have a plane of symmetry


28

Cyclohexane

Neither the cis not trans isomers is optically active

1,4-dimethylcyclohexane

What is the isomeric relationship between the cis and trans structures ?

Diastereomers


29


Two stereogenic carbons therefore the possibility of 4 stereoisomers, but there is only three because one structure is a meso compound.

enantiomers

CH3H3C H3C CH3


30


Two stereogenic carbons therefore the possibility of 4 stereoisomers, but there is only three because one structure is a conformation stereoisomer.

trans-1,2-dimethylcyclohexane

enantiomers

ax ax

eq eq

cis-1,2-dimethylcyclohexane

The cis mirror images are not identical and are enantiomers but one molecule readily interconverts to the other by a ring flip and at room temperature so

rapidly that the two forms are indistinguishable. Structures c and d

are conformational stereoisomers.

both conformations have one axial and equatorial methyl group and are

of equal energy


31

Not all stereogenic centers are carbon atoms

Reactions and stereogenic centers. Very important later.

If a reaction takes place in a way so that no bonds to the stereogenic carbon are broken, the is said to proceed with retention of configuration

chiral carbonretention of configuration note: optical activity may

change direction


32

Retention of configuration will not always maintain its (R) or (S) designation.

chiral carbonretention of configuration

Reaction at stereogenic center

Something to look forward

too


33

Chiral compounds with no chiral atoms.

Allenes

What is the hybridization of each carbon?C C C

R1

R2

R3

R4

sp2 sp2sp

enantiomers


34hexahelicene

phenanthrene

Helicenes

The helicenes, first synthesized in 1956 by Newmann, are a fascinating class of chrial molecules. Helicenes are benzologs of phenanthrene in which a regular cylindrical helix is formed through an all-ortho annelation of the aromatic rings. Their structure is a consequence of the repulsive steric interaction between terminal aromatic rings. Helicenes have large optical rotation for example hexahelicene has an enormous optical rotation:

These spirals are unusual molecules because there are "right-" and "left-" handed forms. Helicenes are "chiral" because they have right and left isomers. The two forms can be differentiated by imagining that the spiral is the inclined plane of a screw. If you rotate a screw clockwise and it advances, it is right-handed. If you rotate it counterclockwise and it advances, it is left-handed. The conversion between right- and left-handed forms is called racemization

o 3700 20D


35

Review and Additional Examples

Structural isomers: Different compounds with the same molecular formula or Constitutional isomers but with different order of attachment.

Stereoisomers: Different compounds which have the same structure, differing only in the arrangement of the atoms in space.

Geometric isomers: Stereoisomers that differ by groups being on the same side or on opposite sides of a site of rigidity in a molecule.

Chiral: Any object that cannot be superposed on its mirror image.

Achiral: Any object that can be superposed on its mirror image.

Enantiomers: A pair of stereoisomers that are nonsuperposable mirror images.

Diastereomers: Any pair of stereoisomers that are not enantiomers.

Meso form: A stereoisomer that contains chiral carbons but can be superposed on its mirror image


36

Methodology for the Determination of Chirality

How many chiral centers

One

Chiral

Zero

Is there a mirror plane?

Yes

Yes

Yes

No

No No

NoAchiral

Are they non-identical mirror

images?

Chiral

Two or more

Is there a mirror plane?

Achiral(meso)

Are they non-identical mirror

images?

Yes

Chiral


37

Methodology for the Classification of Stereoisomers

Two structures with same molecular formulas

same connectivity

are they superimposable? Constitutional isomers

Stereoisomers

are they mirror images of each

other?

structures are the same compounds

Enantiomers Diastereomers

Yes No

Yes No

Yes No


38

Identify the following as diastereomers, enantiomers, or meso compounds.

CH2N H

CH2OH

CO2H

CH NH2

CH2OH

CO2H

C CH3C

H

CH3

HC C

H3C

H

H

CH3

C

O

H

OHH

OHH

CH2OH

C

O

H

OHH

HHO

CH2OH

Is the connectivity the same?

Are they mirror images of each other?




39


CHO

OHH

OHH

OHH

CH2OH

CHO

HO H

HO H

HO H

CH2OH

CH2OH

OHH

OHH

OHH

CH2OH

CH2OH

HO H

HO H

HO H

CH2OH

CHO

HHO

OHH

OHH

CH2OH

CHO

OHH

HHO

HHO

CH2OH



Can one image be superposed on the other?








40

CO2H

OHH

HHO

HHO

CO2H

CO2H

OHH

OHH

OHH

CO2H

CO2H

HHO

OHH

OHH

CO2H

1 2 3


Enantiomers

Diastereomers

Meso compound


41

5b_stereochemistry_post

Documents

h br br

plane of h symmetry

biological conditions

c br bromochlorofluoromethane

mirror plane

lowest priority

ch2ch3 forsey

imaginary plane