Kamis, 14 Juni 2012

Stereochemistry



Stereochemistry
chemistry in three dimensions
includes both structure and reactivity effects
Enantiomers
mirror-image stereoisomers
like left and right hands
(see page 172 in your text)
observed when a carbon atom has four different groups attached to it
CHXYZ or CX1X2X3X4
Enantiomer Examples






Chirality
property of having "handedness"
(different from its mirror image)
a molecule with any element of symmetry (e.g., a mirror plane) must be achiral
Stereogenic Centers
chiral centers or stereocenters
a molecule with a stereogenic center (e.g., CX1X2X3X4) will be chiral
a stereogenic center cannot be:
sp- or sp2-hybridized (must be sp3)
an atom with 2 identical substituents (e.g., any -CH2- group)
Identifying Chiral Molecules
achiral
chiral

Properties of Enantiomers
enantiomers have identical physical and chemical properties,
EXCEPT they
interact with another chiral molecule differently
(like trying on left- or right-handed gloves - left and right hands react differently)
rotate the plane of plane-polarized light by equal amounts but in opposite directions
Optical Activity
chiral compounds rotate the plane of plane-polarized light
rotation measured in degrees
clockwise (dextrorotatory or +) or
counterclockwise (levorotatory or -)
polarimeter - instrument for measuring optical activity
Specific Rotation
standard amount of optical rotation by 1 g/mL of compound
in a standard 1 decimeter (10 cm) cell
[a] = a / l C
where [a] is specific rotation
a = observed rotation in degrees
l = path length in dm
C = concentration in g/mL
Absolute Configuration
nomenclature method for designating the specific arrangement of groups about a stereogenic center
differentiates between enantiomers
uses the same sequence rules for establishing priority of groups as was used for E and Z
R and S Designations
assign priorities 1-4 (or a-d) to the four different groups on the stereogenic center
align the lowest priority group (4 or d) behind the stereogenic carbon
if the direction of a-b-c is clockwise, it is R
if a-b-c is counterclockwise, it is S
Right- and Left-Hand Views
textbook analogy - steering wheel
alternative analogy - your hands
assign priorities to your fingers in order of height
a = middle finger, b = pointer finger, c = thumb, d = wrist
R - this works for your right hand
S - this works for your left hand
Drawing 3-D Structures
practice with models
dotted-line & wedge
Fischer projections
Fischer Projections
a method for depicting stereochemistry at a series of chiral centers
arrange the chiral center so that:
    • horizontal groups are forward
    • vertical groups are oriented backward
Note that there are numerous ways to show a given chiral center
12 different Fischer projections represent (R)
12 different Fischer projections represent (S)
Multiple Stereogenic Centers
compounds with more than 2 stereocenters have more than 2 stereoisomers
e.g., 2-bromo-3-chlorobutane
(2R,3R) and (2S,3S) are enantiomers
(2R,3S) and (2S,3R) are enantiomers
in general, n stereocenters give 2^n stereoisomers
Diastereomers
stereoisomers that are not enantiomers
e.g., (2R,3R) and (2R,3S)
(not mirror images, but not the same either)
diastereomers may have different chemical and physical properties
Meso Compounds
compounds with stereogenic centers but which are not chiral
e.g., (2R,3S)-2,3-dibromobutane
(same as its mirror image)
Identifying Meso Compounds
mirror plane of symmetry
one stereocenter is the mirror image of the other
cis-1,2-disubstituted cycloalkanes are meso if the two substituents are identical
Cyclohexane Derivatives
chair interconversions affect conformation, but not configuration
trans-1,2-dichlorocyclohexane is (R,R) or (S,S)
cis-1,2-dichlorocyclohexane is (R,S)
one chair has the R stereocenter with axial Cl and S with equatorial
the other chair has R equatorial and S axial
the two chair forms are enantiomers but not isolatable
Configurations and Conformations of Disubstituted Cyclohexanes
substitution
cis
trans
1,2-X2
eq,ax <==> ax,eq
(R,S)
interconverting enantiomers
eq,eq <==> ax,ax
(R,R) & (S,S)
isolable enantiomers
two conformations each
 1,2-XY
 eq,ax <==> ax,eq
isolable enantiomers
two conformations each
 eq,eq <==> ax,ax
isolable enantiomers
two conformations each
1,3-X2
eq,eq <==> ax,ax
(R,S) - meso compound
two conformations
eq,ax <==> ax,eq
isolable enantiomers
two conformations each
 1,3-XY
 eq,eq <==> ax,ax
isolable enantiomers
two conformations each
 eq,ax <==> ax,eq
isolable enantiomers
two conformations each
 1,4-X2
no stereocenters
 eq,ax <==> ax,eq
equivalent conformations
 eq,eq <==> ax,ax
two conformations
1,4-XY
no stereocenters
eq,ax <==> ax,eq
two conformations
eq,eq <==> ax,ax
two conformations
Racemic Mixtures
an equal mix of both enantiomers (also called a racemate)
a common form in the laboratory (but not in nature)
optical resolution - separating enantiomers from a mix (typically difficult)
Optical Purity / Enantiomeric Excess
unequal mixtures of enantiomers may occur
optical purity - compare actual rotation with what a pure enantiomer would give (in %)
enantiomeric excess - % excess of one pure enantiomer over the other
% optical purity = % enantiomeric excess
example - consider a mix of 75% (R) + 25% (S)
    • optical rotation would be 50% (50% inactive racemic + 50% R)
    • enantiomeric excess is also 50% (75% - 25%)
Optical Resolution
for acids or bases - formation of diastereomeric salts from a naturally ocurring acid or base
enzymatic resolution - preferential binding or reaction of just one enantiomer
Isomerism - Summary
isomers - same molecular formula (same collection of atoms used)
constitutional isomers -differ in the connections between atoms
different carbon skeletons
different functional groups
different locations of a functional group
Stereoisomers - Summary
stereoisomers - same connections but in different 3D arrangement
enantiomers - mirror-image stereoisomers
diastereomers - non-mirror-image stereoisomers:
cis-trans diastereomers
other diastereomers




1.    What are we talking about?
The bottom line of this whole chapter is learning the difference between isomers.  There are two types of isomers, constitutional and stereoisomers.  Constitutional isomers are two compounds that have the same atoms present, but differ in their connectivity. 
ie:  

These compounds contain the same number of atoms, but the oxygen has been moved to form an ether instead of an alcohol.  Therefore, these compounds are constitutional isomers.
Stereoisomers also have the same atoms present, however the connectivity is the same.  This means the same number of hydrogens will be attached to each carbon and the same number of carbons will be attached to each carbon.  Picture this:

Now, these structures both appear to be the same, but careful observation will reveal that the amine groups attached are in the cis conformation on the left and the trans conformation on the right.  Therefore, the same atoms are present, but just in a different spatial arrangement. 
Not to beat this idea into your head, but here is another example of a stereoisomer, but this time we will use a hydrocarbon chain.

Notice that the chain on the left is in the cis conformation at the double bond and the chain on the right is trans.  This makes them stereoisomers.



2.    I understand that chiral compounds are mirror images of each other that are not superposable, but how do I tell they are superposable?
The easiest way to tell if the mirror image is superimposable or not and superposable is to find the stereochemistry at the stereocenter. This entails you to find the stereocenter first and then label the groups attached to it in order of their priority. This means the atom with the highest atomic number will be labeled A and the next highest B. The next step is to rotate the molecule so the D group is facing away from you.
ie.

If the groups go from A to C clockwise, it is in the R configuration. If the groups are arranged counterclockwise, it is in the S configuration.
Practice a few
A                                                           B                                      C

 A has two stereocenters.  The top stereocenter is an R configuration and the bottom stereocenter is an S configuration.  For B the stereocenter is an S.  C does not have to be considered because there are two of the same groups attached, and is not chiral.
If the two compounds you are looking at are mirror images of each other, but the configuration at the stereocenter differs, they are not superposable.  Therefore they are chiral compounds.  If they are superposable, then they are achiral.    


3.    How do I tell the difference between an Enantiomer and Diastereomer?
The easiest way to tell apart an enantiomer and a diastereomer is to look at whether or not the compounds are mirror images of each other. The best way to learn this is through practice. Here are a few examples, see if you can determine whether or not the compounds are enantiomers, the same, or diastereomers.
Hint: first determine if the compounds are mirror images of each other, and then find the individual stereochemistry around each chiral carbon.  Remember the hand rule or the clockwise/counterclockwise arrangement discussed in the previous section.

D
If you are having problems determining the configuration at each stereocenter, I suggest building a model. 
A is a pair of diastereomers, because the configuration is S, S in the first compound and R,S in the second compound.
B is a tricky one.  They are both in the trans configuration and there is a plane of symmetry.  Also, notice there is no carbon with four different groups.  Therefore, they are not enantiomers and there is no stereochemistry. 
C does not have a carbon with four different groups, so it does not have a stereocenter either. 
D is a pair of enatiomers. Notice they are mirror images of each other.


4.    There is an R and there is an S, but I don’t know what to do with them.  Help!
If you have read the past few sections you know what the S and R designations are.    They tell what type of stereochemistry is found at the stereocenter.  Finding the stereochemistry at the stereocenters can help determine whether two compounds are enantiomers or diastereomers.  Also, R and S versions of the same compound will have different optical activity values. 


5.    Quick Review of optical activity
Optical activity is the only physical property that differs from one enantiomer to the next.  Optical activity is measured when plane polarized light is passed through a compound.  When the light passes through the compound, it is bent either with positive rotation (dextrorotary) or with negative rotation (levorotary).  There is no correlation between positive or negative rotation with the S or R configuration.  S can be either dextrorotary or levorotary and the R enantiomer will be the opposite of the S.  The value given to optical activity is specific rotation.  The equation to figure out specific rotation can be found page 203 in your textbook. 
 


6.    Okay, I’m getting this stereocenter thing, but somebody had to go and screw everything up and stick two stereocenters together.
When dealing with two or more stereocenters on the same compound, there are a lot of possibilities.  The first possibility is that the compounds are enantiomers of each other, the second that they are diastereomers, and finally that they can be meso compounds.  Diastereomers occur when the compounds have the same chemical formula, but are not mirror images of each other.
ie. 
 
Now look at these same atoms arranged differently to form an enatiomer.  These compounds are mirror images of each other.  However, they do have different stereochemistries, which makes them enantiomers.
 
You should also look at these next compounds and discover what makes them different from the above.


These compounds appear to be enatiomers, because they are mirror images of each other. They really are not. The middle two compounds are the meso compound, since they are the same. The outside two compounds are enatiomers of each other. Therefore, a meso compound is observed with stereoisomers where you would expect four different possible structures (two pairs of enantiomers), but there are only three stereoisomers.
 


7.    Fischer Projections doesn’t mean a weekend out on the lake.  How do I interpret them?
Fischer projections are a quick way to show three dimensions without the hassle of having to draw 3-D.  They are very effective for those of us who lack artistic skills.  When you look at the diagram the horizontal lines represent atoms that are coming out at you.  The vertical lines mean they are going away from you.  Fischer projections can be rotated 180 degrees and still be the same compound.  However, if you flip it vertically or horizontally, it becomes the enantiomer. 

This Fischer projection has been flipped horizontally.  These two are enatiomers of each other.  The first projection has an S, R configuration.  The second projection has an R, S configuration.  
Now lets look at a vertically flipped diagram.

These compounds are enatiomers of each other.  
Finally, notice what happens when the diagrams are rotated 180 degrees in the plane of the paper.
 
The configuration at each stereocenter remains the same.
 


8.    Cyclic Compounds
 
If you are anything like me, it is very hard for you to determine the stereochemistry in cyclic compounds the best way is just practice.   Hopefully, this area will help.  Do your best to determine the stereochemistry.
 
Analysis:

5 komentar:

  1. enantiomers have identical physical and chemical properties but not in diastereoisomers. Is there any specific explanation of that ??

    BalasHapus
  2. I want to ask, as i know Enantiomers is
    mirror-image stereoisomers
    like left and right hands, does they both has similarity chemical properties? while they have different isomer

    BalasHapus
  3. I want to ask, as i know Enantiomers is
    mirror-image stereoisomers
    like left and right hands, does they both has similarity chemical properties? while they have different isomer

    BalasHapus
  4. why enantiomers observed when a carbon atom has four different groups attached to it?

    BalasHapus
  5. thanks for you information utud

    BalasHapus