Ch 5 - Stereoisomerism Flashcards
3 phases of drug testing
- phase I(20-100 people)
- phase II(a few hundred people)
- phase III(a few thousand people)
- all after animal testing
stereoisomers
compounds that differ from each other only in the three dimensional spatial arrangement of their atoms but NOT in the connectivity of their atoms
isomer
compounds that are constructed from the same atoms(same molecular formulas) but still differ from each other
cis stereoisomer exhibits groups on
the same side of a double bond
the trans stereoisomer exhibits groups on
opposite sides of the double bond
pie bonds are formed from the overlap of
two p orbitals
when two identical groups are connected to the same position there
cannot be cis-trans isomerism(either way its flipped it’s the exact same)
superimposable
an object and its mirror image are the exact same
- pair of sunglasses
nonsuperimposable
an object and its mirror image are NOT the exact same
- a pair of sunglasses missing one lens - a left and right hand are mirror images of each other BUT they will not fit in the same glove
chiral objects
objects which are mirror images but are not superimposable
- right and left hands
achiral objects
mirror images which are superimposable
- pair of sunglasses
the most common source of molecular chirality is the presence of a carbon atom bearing four different groups
- they are different compounds even though all the parts are the same
- stereoisomers because the only difference is the spatial arrangement
chirality center
a tetrahedral carbon bearing four different groups
- other common names: chiral center, stereocenter, ctereogenic center, and asymmetric center
sp2 hybrids can not be chirality centers
only 3 groups
enantiomer
when a compound is chiral it will have one nonsuperimposable mirror image call the enantiomer
- the compound and its mirror image are a pair of enantiomers - each compound is said to be the enantiomer of the other
in most cases it is easiest to draw an enantiomer by placing the mirror
behind the molecule
3 ways to draw an enantiomer
- mirror behind the molecule
- mirror next to the molecule
- mirror below the molecule
mirror behind the molecule
- the skeleton of the molecule is drawn the exact same except all dashed become wedges and all wedges become dashes
mirror next to the molecule
draw the mirror image, all dashes remain dashes and all wedges remain wedges
mirror under the molecule
- draw the mirror image, all dashes stay dashes and all wedges stay wedges
there are 3 ways to mirror a molecule but they still only produce
one enantiomer(produce the same one just at different angle of view)
bicyclic compounds will need to be drawn with the mirror next to the molecule or below it
no wedges and dashes for a mirror to be placed behind
Cahn-Ingold-Prelog System
system of nomenclature for identifying each enantiomer individually
5 steps for nomenclature for identifying each enantiomer individually
- identify the four atoms directly attached to the chirality center
- assign a priority to each atom based on its atomic number. The highest atomic number receives priority 1 and the lowest atomic number(often a Hydrogen atom) receives priority 4
- if two atoms have the same atomic number, more away from the chirality center looking for the first point of difference. When constructing lists to compare remember that a double bond is treated as two separate single bonds
- rotate the molecule so that the fourth priority is on a dash(going behind the plane of the page)
- determine whether the sequence is 1-2-3 follows a clockwise(R) order or a counterclockwise(S)
enantiomers exhibit identical physical properties
same melting and boiling points etc
enantiomers do exhibit different behavior when exposed to
plane-polarized light
light is an electric and
magnetic perpendicular set of planar waves
polarization
the orientation of the electric field(shown in red) for a light wave
plane-polarized light
light passing through a polarizing filter allows only photons of a particular polarization to pass through the filter
optically active
certain organic compounds rotate the plane of plane polarized light
optically inactive
organic compounds which cannot rotate the plane polarized light
polarimeter
device which measures the rotation of plane polarized light caused by optically active compounds
optical activity is a direct consequence of chirality
chiral compounds are optically active while achiral compounds are not
Enantiomers(nonsuperimposable mirror images) will
rotate the plane polarized light in equal amounts but in opposite directions
observed rotation(symbolized by alpha)
when a solution of a chiral compound is placed in a polarimeter the observed rotation will be dependent on the number of molecules that the light encounters as it travels through the solution
if the concentration of the solution is doubles then
the observed rotation will double
if the pathlength is doubled then
the observed rotation is doubled
specific rotation
the observed rotation under standard conditions
- concentration = 1g/mL - pathlength = 1dm
Specific rotation =
[alpha(symbolized observed rotation] = (alpha)/(c)(l)
- [alpha] = specific rotation - alpha = the observed rotation - c = concentration(g/mL) - l = pathlength(1dm = 10cm) - allows the calculation of nonstandard conditions
the specific rotation of a compound is a physical constant much like
melting and boiling points
specific rotation is temperature and wavelength but these factors can not be incorporated into the equation
- these two factors are reported as follow:
- [alpha]^T wavelength(upsidedown Y)
- T = Celsius
- Y is the wavelength of the light used
specific rotations for enantiomers are equal in magnitude but
opposite in direction
dextrorotatory(d)
a compound exhibiting a positive rotation(+)
levorotatory(l)
a compound exhibiting a negative rotation(-)
a chirality center can be R/S indefinitely but the optical activity can
change from +/- as other factors change
optically pure(enantiomerically pure)
a solution containing a single enantiomer
racemic mixture
solution containing equal amounts of both enantiomers
- will be optically inactive - the net rotation will be zero(cancels out) - the individual compounds are active the net effect is not
a solution containing both enantiomers in unequal amounts will be optically active
enantiomeric excess(ee) – the difference between the % of enantiomer in solution(70%-30% = 40% excess - %ee = ((absolute value alpha)/(alpha of pure enantiomer))(100%)
enantiomeric excess(ee)
the difference between the % of enantiomer in solution(70%-30% = 40% excess
- %ee = ((absolute value alpha)/(alpha of pure enantiomer))(100%)
enantiomers are stereoisomers that are
mirror images of one another
diastereomers are stereoisomers that are not
mirror images of one another
cis-trans are diastereomers
they are not mirror images of each other
enantiomers have the same physical properties while diastereomers have
different physical properties
maximum number of stereoisomers =
2^n
any compound with a single chirality center must be
chiral
with two chirality centers
- trans isomer is chiral
- cis isomer is not chiral
two types of symmetry
- rotational
- reflectional
trans isomer exhibit rotational symmetry
think an axis of a spinning top which can spin
axis of symmetry
the imaginary stick which a molecule can be rotated around for rotational symmetry
reflectional symmetry splits a molecule in half with each half being
the same as the other half
plane of symmetry
split a molecule in half and see if reflected which creates reflectional symmetry
chirality is only dependent on the presence or absence of
reflectional symmetry
any compound that possesses a plane of symmetry in any conformation will be achiral
the absence of a plane of symmetry DOES NOT necessarily mean the compound is chiral
plane of symmetry is only one type of reflectional symmetry
the presence of any kind of reflectional symmetry renders the compound achiral
inversion
reflection about a point(rather than a plane)
- still reflection symmetry - renders compound achiral
the presence or absence of rotational symmetry is
irrelevant to chirality
a compound that has a plane of symmetry will be
achiral
a compound that lacks a plane of symmetry will most likely be chiral
there are rare exceptions, which can mostly be ignored
meso compounds
a compound that exhibits reflectional symmetry will be achiral even though it has chirality centers
meso compounds is a family of stereoisomers containing fewer than 2^n stereoisomers
if a structure has 2 chirality centers we expect 2^2 = 4 however if one is meso there would be a total of 3(a pair of enantiomers + the 3rd with reflectional symmetry which makes 3 instead of 4)
fischer projections
for compounds with multiple chirality centers these drawings are quick
- the horizontal lines are considered to be coming out of the page - the vertical lines are considered to be going behind the page
fischer projections are primarily used for
analyzing sugars
fischer projections are helpful in comparing the relationship between stereoisomers
- if a componds 2 images have mirrored groups then its an enantiomer
- all chirality centers have opposite configurations
if a compound has 2 groups trans in one and 2 groups cis in the other then
it’s a diastereomer
butane can adopt two staggered conformations with gauche interactions
- nonsuperimposable and therefore enantiomeric
- however butane is not chiral compound and optically inactive
- the two conformations are constantly interconverting via single bond rotation
a chirality center cannot invert configuration via single bond rotations
(R)-2-Butanol cannot be converted into (S)-2-Butanol via a conformational change
if a plane of symmetry is apparent then the compound is
not optically active
enantiomers have the same
physical properties
resolution
the separation of enantiomers
Resolution
Crystallization
- Pasteur allowed tartrate salts to crystalize in 1847 and noticed the enantiomers created a mix of two shaped crystals
- he sorted them by hand with a pair of tweezers
- then dissolved each pile in water and placed the solutions in a polarimeter
- discovered the specific rotations were equal in amount but opposite in sign
- concluded the molecules must be nonsuperimposable mirror images of each other
- most racemic mixtures are not easily resolved via crystallization
Resolution
Chiral Resolving Agents
when a racemic mixture is treated with a single enantiomer of another compound, the resulting reaction produces a pair of distereomers(as opposed to enantiomers)
- diastereomers have different physical properties and can then be separated by conventional means(like crystallization)
Resolution
Chiral Resolving Agents
resolving agent
often acids which can split an enantiomer into its diastereomers
Resolution
Chiral Column Chromatography
- column chromatography – compounds which are enantiomers are separated from each other based on a different way they interact with the medium(the absorbent) the which they are passed
- a traditional column they travel at the same rate because their properties are the same
- if a chiral absorbent is used the enantiomers interact with the absorbent differently, causing them to travel through the column at different rates
- thus separating the enantiomer
