W6 Chiral Synthesis Flashcards
Chirality
What is the definition of chirality?
- Non-superimposable mirror images
Discerning Chiral Tetrahedral
Molecules
- For simple tetrahedral molecules, the two non-superimposable mirror
images are designated R (Latin rectus, right) and S (Latin sinister, left). - Priorities are assigned according to atomic number:
: < H < C < N < O < F < Cl < Br < I - The molecule is viewed along the axis from the chiral centre to the lowest priority element
- If the remaining priorities define a right/clockwise circle, the structure is R, and S if the relationship is left/counterclockwise
Chiral centre:
What do the hash and triangle bonds mean?
Hash= Away from you
Triangle= Towards you
Physical Properties of Enantiomers
All physical properties are the same for enantiomers (bp, mp, solubility etc.)
Except: How groups bonded to the chiral centre are arranged in space
This is where plane-polarized light comes in
Polarimetry:
What does it measure?
- Polarimetry measures the observed specific rotation
- A pure sample of one enantiomer, a racemic mixture, and a mixture of enantiomers
in unequal amounts will all have different observed specific rotation values
For Example:
-A pure sample of (S)-(+)-2-bromobutane has an observed specific rotation of +23.1
-A racemic mixture has an observed specific rotation of 0
-If the observed specific rotation is positive but less than +23.1, the sample is a mixture of the enantiomers but contains more S enantiomers than R
Calculation
% ee = observed alpha / alpha of pure enantiomer x 100
Furthermore, the amount of each enantiomer present in the mixture can be calculated using the formula above
Separation of Enantiomers:
Can Fractional distillation and Crystallisation be used?
NO to both
Fractional distillation?- same boiling point
Crystallisation?- same solubility
Introducing Louis Pasteur (for info)
The first to succeed at separating a pair of enantiomers (1848)
* Noticed that his crystals of sodium ammonium tartrate were not identical
* Right-handed and Left-handed crystals observed
* Separated the crystals using tweezers and then dissolved into solution
* The solution of the RH crystals rotated plane-polarised light clockwise and the LH
crystals rotated the light counter-clockwise
* Tartaric acid is obtained from grapes – racemus is Latin for “a bunch of grapes”
* Separation of enantiomers is called resolution of a racemic mixture
Separating Enantiomers via
Chromatography
What are the steps? (5)
- Dissolve mixture in a solvent
- Pass solution through a packed column
- Use chiral material to absorb
compound - Two enantiomers have different affinities for chiral material
- One enantiomer emerges before the other
Why bother separating drugs?
Receptors are chiral
e.g. thalidomide and ketamine and propranolol, fluoxetine, ibuprofen, heroin
Theophylline, a methylxanthine, is a useful bronchodilator. Methylxanthines are also known to be active in the central nervous system (CNS) and gastrointestinal system (GIS). Which of the following should be considered when tailoring drug activity?
a. Electronegativity
b. Steric Effects
c. Hydrophobicity
d. A and C Only
e. A, B and C should all be considered
E
Which of the following drug modifications is most likely to increase the hydrophilicity of the molecule
a. Addition of Methylene groups
b. Addition of a Hydroxy group
c. Cleavage of a Carboxylic acid group
d. Addition of a Methyl group
e. None of the above
B
Which of the following properties differ among a pair of enantiomers?
a. Boiling Point
b. How atoms are arranged in space
c. Solubility
d. Melting Point
e. None of the above
B
=pair of molecules that exist in two forms that are mirror images of one another but cannot be superimposed one upon the other
