Stereoisomers | Organic Chemistry 1

Stereoisomerism concept is studied in this chapter: chirality of chemical compounds, absolute configuration of a stereocenter, types of stereoisomers (enantiomers, diastereomers, meso compound), optical activity of stereoisomers, racemic mixture and enantiomeric excess

Chirality

Asymmetric atom (or stereocenter or chirality center): 

An atom connected to 4 different substituents. They are sometimes marked with a star. For n stereogenic centers, the maximum of different stereoisomers is 2n
 

The central C is connected to 4 different substituents:
it is an asymmetric carbon

 

The central C is connected to only 3 different substituents (2 methyl groups):
it is not an asymmetric carbon

 


Chiral molecule:

A molecule that is not superimposable upon its mirror image. Molecules with only 1 stereocenter are always chiral. Molecules with more than 1 stereocenter are chiral if they do not contain a plane of symmetry. If they do not have a stereocenter or if they have a plane of symmetry, they are said to be achiral
 

2 stereocenters + no plane of symmetry:
the molecule is chiral

 

2 stereocenters but plane of symmetry:
the molecule is achiral

Absolute Configuration R / S

R / S label system:

A nomenclature system to distinguish asymmetric centers
 

How to assign R or configuration:

  1. Identify the 4 atoms attached to the chirality center and prioritize them by atomic number
    - if 2 atoms are identical, make a list of substituents, and look for the first point of difference
    - a multiple bond equals the same number of single bonds

  2. Orient the molecule with the lowest priority group backwards (dashed line)

  3. Identify the direction of rotation of the 1-2-3 sequence: clockwise is R, counterclockwise is S

 

Enantiomers vs. Diastereomers

Enantiomers: 

Stereoisomers that are nonsuperimposable mirror images of each other. 2 enantiomers have their stereocenters opposite in configuration. 2 enantiomers of a given compound have identical physical properties (melting point, solubility, density ...) except for the direction of rotation of polarized light
 

Diastereomers: 

Stereoisomers that are not mirror images of each other. At least one stereocenter of 2 diastereomers has the same configuration and one is opposite. 2 diastereomers have different physical properties

 

nonsuperimposable mirror images
opposite configuration for all C*
⇒ enantiomers


 

not mirror images
opposite configuration for 1 C*
same configuration for 1 C*
⇒ diastereomers

Optical Activity

Optical activity:

A compound is said to be optically active when the plane of linearly polarized light is rotated as it passes through a solution of that compound. Chiral molecules are optically active

 

Specific rotation [α]D:

The angle of rotation of the plane of polarization of a ray of monochromatic light passing through a solution of a substance

[α]D = αl x c 

[α]D: specific rotation (usually given as °)
α: observed rotation (in °)
l: length of sample tube (in dm)
c: concentration (in g.mL-1)

 

Dextrorotatory vs. levorotatory:

[α]D ≠ 0°: molecules in solution are optically active
[α]D > 0°: the plane-polarized light is rotated clockwise and the compound is called dextrorotatory. The rotation is labeled (+) or d 
[α]D < 0°: the plane-polarized light is rotated counterclockwise and the compound is called levorotatory. The roation is labeled (-) or 


There is no relationship between a R or S compound and a d or l compound

2 enantiomers rotate polarized light with the same extent but in the opposite direction: their [α]D have the same absolute value but of opposite sign. [α]D of 2 diastereomers have a different absolute value and an identical or opposite sign

Meso Compounds

Meso compound:

An achiral compound ([α]D = 0°) with 2 or more stereocenters. A meso compound generally has a plane of symmetry and is superimposable on the compound having opposite configurations at all stereocenters

 

(1R,3S)-cyclohexane-1,3-diol is a meso compound:

1. It has a plane of symmetry

2. It is superimposable on the compound having opposite configurations at all stereocenters (after a rotation of 180°):

Racemic Mixture and Enantiomeric Excess

Racemic mixture or racemate:

The 50/50 mixture of 2 enantiomers of a given compound. A racemic mixture is optically inactive: [α]D = 0°. A sample of a single enantiomer is said to be enantiomerically pure
 

Enantiomeric excess (ee) or optical purity:

The measure of the amount of an enantiomer present in excess relative to the the racemic mixture

ee = % of one enantiomer - % of the other enantiomer = observed [α]D of the mixture[α]D of the pure enantiomer x 100