Isomers (Chirality) Flashcards
Define Isomers
Different compounds with the same molecular formula
Define Constitutional Isomers / Structural Isomers
Isomers whose atoms have a different connectivity.
Define Stereosiomers / optical / configurational
Isomers with the same molecular formula and same connectivity of atoms but different arrangement of atoms in space.
2 branches of Stereosiomerism:
Enantiomers (mirror images)
Diastereomers (not mirror images)
Geometric Isomerism
‘cis’ and ‘trans’
cis = same side (Z) trans = opposite (E)
Optically inactive..
chiral
Racemic mixture
1:1 mixture of enantiomers, racemate
Geometric Isomerism
How do we assign priority group?
CIP rule
Based on highest atomic number = priority
Chiral means..
Assymetrical and mirror image are not superimposable.
In a chiral molecule, how do we differentiate them?
S or R rotation
S= anticlockwise R = clockwise
How do we assign S or R rotation?
Assign priority groups using CIP - number 1-4
and see the direction of priority groups
What should always be assigned priority group number 4?
Hydrogen - lowest priority.
What if Hydrogen is not on number 4?
Assign chirality then reverse
e.g. if its S with H at the front, answer becomes R.
What if Hydrogen is on a plane bond?
Rotate before assigning.
Do R and S enantiomers have the same physical and chemical properties? Why?
Yes because they have the same arrangement.
How do R and S enantiomers differ? (2)
Based on
rotation of plane polarised light
interaction with other chiral molecules
Is a racemic mixture optically active or inactive?
Inactive - equal amounts.
How to calculate light passing through a polarising filter? (equation)
a (Degrees) = measured rotation / C x L
c = conc g/ml
L = path length
What is enantiomeric excess?
When one enantiomer is present in higher concentration than the other.
Equation for enantiomeric excess
What if its in moles/grams?
observes rotation / rotation of pure. X 100
R - S / R+ S X100
Significance of Enantiomers in drugs
Ibuprofen
Whats it for?
Whats the significance here?
S enantiomer is responsible for the anti-inflammatory properties.
R = not harmful and there is an enzyme that converts R to S.
Significance of Enantiomers in drugs
Fluoxetine
Whats it for?
Whats the significance here?
Depression
S = pharmacological activity
Significance of Enantiomers in drugs
Warfarin
Whats it for?
Whats the significance here?
Reduce blood clots
S = more active than R
Significance of Enantiomers in drugs
Thalidomide
Whats it for?
Whats the significance here?
Was for morning sickness but caused babies to be born without limbs.
Only one enantiomer had this effect.
Describe Enantiomers
A single chiral centre, can either be R or S.
Optically Active
Describe Diastereisomers
Multiple chiral centres.
Can be RR SR etc
and can use 2 n to find out all the possibilities.
where n is the number of chiral centres
Describe Meso-compounds
Can have multiple chiral centres but are symmetrical (unlike the rest)
Optically INACTIVE.
Can Enantiomers be separated?
No because of their identical properties but they can be converted to diastereoisomers with different physical properties.
What is a classic method of ‘separating’ Enantiomers?
Resolution
Through the preparation of appropriate diastereoisomeric derivates.
Can Diastereisomers be separated?
Yes because they have different physical properties and reactivity - melting point, boiling points, solubilities etc.
Give an example of how we can separate Diastereoisomers: (3)
Use a solvent in which one diastereoisomer is very soluble in and the other is less.
Both will dissolve, less soluble one crystallises out and is filtered
other is evaporated
Define Resolution
The separation of enantiomers from either racemic mixture or enantiomerically enriched mixture.
Via converting into diastereoisomers.
Describe Chiral Chromatography
Racemic solution is passed over a chiral stationary phase giving rapid and reversible diastereotopic interaction.
Classic Resolution
involving Salts
R- acid + S-acid enantiomers
converted into R,S salt and S,S salt diastereoisomers
Crystalise and separate into —–
R, S salt and S,S salt
Reacidify using HCL.
S-baseH+ and S-baseH+
becomes
R-acid and S-acid
separated
Resolution by Esterification
Form covalent bond between chiral carboxylic acid and alcohol = diastereoisomers.
Separate them by crystallisation and then recover the separate enantiomers by ester hydrolysis.
How many stereoisomer can Meso compounds have?
3 stereoisomers
assuming 2 identical chiral carbon atoms with no other stereo centres
2 examples of pharmacological effects of chirality:
one may have strong binding to target, other may not
one may be active with no adverse effects, other may be toxic
2 examples of biochemical effects of chirality:
if a chiral reactant is used, do the isomers form the same products or does each form a different product?
Are some stereoisomers formed more than others?
Stereoselective reaction
Preferential formation of one stereoisomer over another
No prevention of formation but one predominates
Stereospecific reaction
Each stereoisomeric reactant produces a different stereoisomeric product or a different set of products.
Stereoselectivity reaction can… (2)
- can show no stereoselectivity, results in racemisation
- can show by inverting stereochemistry, conserving it to preferentially reacting to form particular ones,
Stereochemical outcomes are important in: (3)
metabolism of drugs
drug action at receptors
toxicity through undesirable activity of stereoisomers
What is a concerted reaction?
Bond making and breaking happens in the same step. (SN2)
Stereochemistry is either …… or …… in concerted reactions
inverted or conserved
What is a non-concerted reaction?
Bond breaking and making occurs in different steps. (SN1)
Intermediates allow changes to stereochemistry.
Do non-concerted reactions have stereoselectivity?
no stereoselectivity
In non concerted reactions, from where can the planar intermediate be attacked?
can attack planar intermediate from above or below the plane equally easily.
Forms planar intermediate carbocation. Also planar radicals.
What is syn addition?
Two substituents added to the same side of the double bond
similar to cis
What is anti addition?
Two substituents added to opposite sides of the double bonds
similar to trans
Enzymes can react with pharmaceuticals to…
destroy stereochemistry or to form chiral products with alternative activities which is why its important a drug is administered to the right place.
