Chapter 6. Isomers and Stereochemistry

Home , Diastereomer, Meso compound, Racemic mixture, Stereocenter

Learning objectives:

1. Differentiate chiral and achiral molecules. 2. Recognize and draw structural isomers (constitutional isomers), stereoisomers including enantiomers and diastereomers, racemic mixture, and meso compounds. 3. Identify the stereocenters in a molecule and assign the configuration as R or S. 4. Know the relationship between enantiomers and their specific rotations.

Sections to be covered (in the order of delivery):

6.1 Stereoisomers 6.2 Chiral Molecules 6.3 Enantiomers and Diastereomers 6.4 Properties of Chiral Molecules

6.1 Stereoisomers

Important Terminologies: achiral, chiral, plane of symmetry, mirror image and superimposable

A. Classification of Isomers

1 Examples:

B. Cis-trans (E/Z) Isomers are Diastereomers of Restricted C-C Bond Rotation

CH3 CH3 CH3

CH3 CH3 CH3 I II III

H CH3 H CH3

H3C H H CH3

IV V

2 C. A chiral object has a nonsuperimposable mirror image

D. Drawing Mirror Image (Enantiomers)

Examples:

H CH3CH2

E. Self-assessment Questions

 Can you identify stereoisomer and same molecule using mirror image?  Can you draw the mirror image of a given compound?  Can you describe the definition of structural isomer, conformer (conformational isomer), stereoisomer, enantiomer and diastereomer?

4 6.2 Chiral Molecules

Chiral molecules: molecules without plane of symmetry! Enantiomers: chiral molecules that are mirror image to each other Diastereomers: chiral molecules that are not mirror image to each other

A. Criteria of Being Chiral Molecule

Know stereocenter (chiral center, chiral atom)

(i) Universal definition

 Not superimposable with its mirror image.

 No plane of symmetry.

(ii) Simplified criteria but may have exception

 The presence of stereocenter (chiral center, chiral atom): four different substituents for an sp3 hybridized atom.

Chiral molecules may have no stereocenter. Having sterocenters may not be chiral.

(iii) Stereocenter and chiral center (chiral atom)

B. Find Plane of Symmetry

C. Stereocenters (chiral atoms)

For molecules that are hard to find plane of symmetry, find stereocenter (atom). sp3 hybridized C and N

S and P

Examples:

D. Identify Chiral Molecules Using Stereocenter

(i) Molecules with odd number of stereocenters:

(ii) Molecules with even number of stereocenters:

Look for plane of symmetry or assign R and S

E. Assign R and S for Stereocenters

Know racemic mixture and meso compounds

8 (i) Useful for molecules that have multiple stereocenters

(ii) How to Assign R and S for Stereocenters?

1. Prioritize (atomic number) four substituents (groups) attached to a stereocenter. 2. Place the less prioritized one (4) away from you and then rotate from 1-2-3.

Examples:

10 F. Self-assessment Questions

 Can you identify stereoisomer(s)?  Can you explain the relationship among stereocenter, chiral molecule, enantiomer and diastereomer?  Can you assign R and S of stereocenter (atom)?  Can you explain what are racemic mixture and meso compound?

6.3 Enantiomers and Diastereomers

Know the difference between enantiomers and diastereomers

 Mirror image to each other: enantiomers

 Not mirror image to each other: diastereomers (commonly have multiple stereocenters)

 Both enentiomers and diastereomers are stereoisomers

Example:

Threonine

A. Assign R and S for identification:

Enantiomers:

Diastereomers:

B. Racemic Mixtures: a pair of enantiomers in 1/1 ratio

Optical property is canceled intermolecularly.

12 C. Meso Compounds (the presence of plane of symmetry)

Meso compounds have asymmetric centers but are optically inactive Optical property is canceled intramolecularly.

O OH OH

C OH HO2C HO C CO2H HO O HO

(i) Assign R and S for identification and check the presence of plane of symmetry:

D. More examples Racemic Mixture and Meso Compounds

(i) OH

HO2C CH3 HO

13 (ii)

CH CH3 CH3 CH3 CH3 3

OH OH OH OH CH3 V I II III IV

(iii) OH OH CH3 H3C OH OH

CH3 CH3 IV I II III

CH3

14 E. Molecules with Three or More Stereocenters

OH OH

Menthol

Number of possible stereoisomers: 2n, n = number of stereocenters

H H

H H HO HO

F. Self-assessment Questions

 Can you identify a pair of enantiomers and diastereomers?  Can you explain racemic mixture and meso compound?  Can you calculate the possible stereoisomers for molecules with three or more stereocenters?

15 6.4 Properties of Chiral Molecules

Important Terminologies: plane-polarized light, optically active, optical activity.

A. Plane-Polarized Light

B. A Polarimeter

Light source

Light filter with grid 2

Sample tube with chiral compound 3

Rotatable filter with grid 4

Specific rotation: the observed rotation of an optically active substance at a concentration of 1 g/100 mL in a sample tube 10 cm long; for a pure liquid, concentration is in g/mL (density)

C. Chiral compounds with clockwise rotation is designated as (+).Chiral compounds with counterclockwise rotation is designated as (-).

(+) and (-) have no correlation with R and S assignment.

16 D. Racemic Mixture and Meso Compounds Are Optically Inactive

E. Properties of stereoisomers

Enantiomers: same chemical properties (reactivity), same physical properties (ex. boiling point, melting point, density and pKa) except for the specific rotation (a pair of Enantiomers has the exact opposite direction in rotation).

Diastereomers: different chemical and physical properties.

(i) Separation of Enantiomers: Resolution

Removal of optically pure [R] reagent [R] [R,R*] [R] [R] [R] Addition of [S,R*] [R] [R] [S] optically pure [R,R*] [R,R*] [S] reagent [R*] [R] [R] [S,R*] separation of [S] [S] [R,R*] [S,R*] [R*] diastereomers [S] [R] [R,R*] [R] Removal of [S] [S,R*] optically pure [S,R*] [R,R*] reagent [S] [S] a racemic mixture [S,R*] a pair of enantiomers a mixture of diastereomers [S] ([R] and [S]) ([R,R*] and [S,R*]) [S] [S] [R*]

17 (ii) The Significance of Chirality in the Biological World

H3C H H3C H

HO2C HO2C

OCH3 (S)-Ibuprofen (S)-Naproxen

F. Stereoselectivity: Selection Between Stereoisomers

(i) reactions for alkenes

18 (ii) The stereochemistry of enzyme-catalyzed reactions

- - CO2 H CO2 C HO C H fumarase + H2O C H C H

-O C 2 H - CO2 fumurate malate

G. Self-assessment Questions

 Do you know the relationship of chemical and physical properties between a pair of enantiomers and diastereomers?  Can you explain why racemic mixture and meso compound are optically inactive?  Can you explain the process of separating a pair of enantiomers (resolution)?  Can you identify a stereoselective reaction?