MEDCHEM.02

Stereoisomers

• Stereoisomers:

  • Differ by the 3-D arrangement of atoms in space.

  • Bold wedge = towards viewer.

  • Dashed wedge = away from viewer.

  • Example: 2-Chloro-2-hydroxyacetic acid; tetrahedral carbon significantly affects interactions with chiral molecules.

Enantiomers

• Definition:

  • Non-superimposable mirror images are called enantiomers.

  • Enantiomers exhibit identical physical properties (e.g., melting point, boiling point, density).

Optical Activity of Chiral Molecules

• Chirality and Optical Activity:

  • Chiral molecules rotate polarized light:

    • Clockwise = Dextrorotatory = (+)

    • Anti-clockwise = Laevorotatory = (-)

  • Enantiomers rotate light in opposite directions, but by the same number of degrees.

Example - Lactic Acid

• Lactic Acid Enantiomers:

  • Different enantiomers rotate plane-polarized light oppositely.

  • Configuration: (R) or (S) designation.

  • Note: (R)/(S) classification does not determine direction of light rotation (+)/(-).

  • Example data:

    • (+)-lactic acid: melting point = 53°C, [α]25 = +3.33 (H2O)

    • (-)-lactic acid: melting point = 53°C, [α]25 = -3.33 (H2O)

Specific Rotation

• Factors Affecting Observed Rotation:

  • Specific rotation depends on:

    • Length of the cell

    • Concentration

    • Temperature and wavelength of light

  • Formula: [α] = α (observed rotation) / (concentration × path-length).

  • Common wavelength for measurement: 589 nm (sodium D line).

  • Specific rotation noted as [α]D, with "D" indicating the sodium D line.

Specific Rotation Calculations

• Example Calculations:

  • Given:

    • 1.00 g sample in 20 ml ethanol. 5.00 ml from this solution shows 1.25° clockwise rotation.

  • Calculate [α]D:

    • Using the formula, observe initial calculations.

  • Additional case: 1.20 g sample of coniline with [α]D = -16 in 7.5 ml of chloroform.

Assigning (R) and (S) Enantiomers

• Determining Configuration:

  • Definition of absolute configuration in chiral molecules.

  • Cahn-Ingold-Prelog rules for assigning (R) and (S).

Cahn-Ingold-Prelog Rules - Step 1 & 2

• Steps for Configuration Assignment:

  1. Locate the chiral carbon.

  2. Assign priorities (1-4) based on atomic numbers.

Cahn-Ingold-Prelog Rules - Step 3

• Handling Identical Atoms:

  • If two or more identical atoms are present, prioritize based on further bonded atoms.

Cahn-Ingold-Prelog Rules - Step 4

• Prioritizing Multiple Bonds:

  • Triple bonds > Double bonds > Single bonds for determining priority.

Prioritizing Multiple Bonds

• Explanation on Priorities:

  • Example: A double bond (C=O) takes precedence over a single bond (C-O).

Assigning Configuration to Chiral Molecule

• Assignment Procedure:

  1. Rotate molecule to position the lowest priority group at the back.

  2. Assess arrow direction for priority sequence:

     • Clockwise = (R) configuration.

     • Anti-clockwise = (S) configuration.

Orientation of Groups

• Visualizing Configuration:

  • Lowest priority group at the back leads to configuration identification based on the direction of priority arrangement (clockwise/anticlockwise).

Visualizing Group Arrangement

• Configuration Identification in Visuals:

  • Depicts R and S configurations clearly based on orientation.

How to Orientate Enantiomer for Assignment

• Orientation Steps:

  • Proper orientation is crucial for identifying absolute configuration accurately.

Assigning Absolute Configuration – Example

• Applying the Assignment Steps in Practice:

  • Walk through additional examples to reinforce assignment practices.

Double-Switch Trick

• Stereochemistry Assignment Tips:

  • Manipulate structures to position the lowest priority correctly.

  • Double-switch maintains stereochemistry while modifying arrangement.

More Examples for Practice

• Engagement Exercises:

  • Provide additional examples to reinforce learning.

Fischer Projections

• Representation Technique:

  • 3D molecule represented flat; distinguishes chiral centers through lines representing spatial orientation.

Manipulation Techniques for Fischer Projections

• Allowed Manipulation:

  • 180° rotation only; illegal to rotate by 90°.

Further Manipulation Techniques for Fischer Projections

• Rotational Flexibility:

  • Holding one group steady allows related groups to be repositioned appropriately.

Assigning R and S Configuration to Fischer Projections

• Step-by-Step Procedure:

  1. Assign priorities based on Cahn-Ingold-Prelog rules.

  2. Manipulate Fischer projection to place the lowest priority group appropriately.

  3. Determine R/S based on clockwise versus counterclockwise assignments.