what are the forces in a molecular structure? bond angle strain: when a bond angle, a-b-c, diverges...
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What are the forces in a molecular structure?
Bond angle strain: when a bond angle, A-B-C, diverges from the ideal (180, 120, 109)
Torsional strain: Strain between groups on adjacent atoms.
A-B-C-D. Worst when eclipsed; best when staggered.
Rotation about C2 – C3 in butane
H
CH3
H
H
CH3
H
Anti conformation Methyls 180 deg, lower energy
120 deg.
Gauche conformation, Methyls closer, 60 deg, more repulsion, higher energy
H3C
H
H
H
CH3
H
Gauche!!
View from here yields view below.
View from here yields view below.
Anti!!
Energy Profile for Rotation in Butane
Three valleys (staggered forms) 120 apart; Three hills (eclipsed) 120 apart.
Problem: Rotational profile of 2-methylbutane about C2-C3.
Me
H
Me
H
Me
H
First, staggered structures.
Me
H
Me
Me
H
H
Me
H
Me
H
H
Me
Rotate the front Me group.
Relative energies….
18060 300
Now, eclipsed….
Me
H
Me
H
Me
H
This was the high energy staggered structure,180 deg. Shown for reference only.
Me
H
Me
H
HMe
Me
H
Me
H
MeH
120 240180
Me
H
Me
Me
HH
Me
H
Me
Me
HH
0 360 = 0
Now relative energies…..
Now put on diagram…
Me
H
Me
H
MeHMe
H
Me
H
HMe
Me
H
Me
Me
HH Me
H
Me
Me
HH
Me
H
Me
H
Me
H
Me
H
Me
Me
H
H
Me
H
Me
H
H
Me
0 180 36060 120 240 300
staggered
eclipsed
Conformations of cycloalkanes: cyclopropane
Planar ring (three points define a plane); sp3 hybrization: 109o.
Hydrogens eclipsing. Torsional angle strain.
Bond angle strain. Should be 109 but angle is 60o.
Cyclopropane exhibits unusual reactivity for an alkane.
Conformation of cyclobutane
Planar: eclipsing, torsional strain and bond angles of 90o
Folded, bent: less torsional strain but increased bond angle strain
Fold on diagonal
Cyclohexane
planar: bond angle 120, eclipsed.
Chair conformation
Boat conformation
Ideal solution: Everything staggered and all angles tetrahedral.
Axial and EquatorialAxial Up/Equatorial
Down: (A/E)
Equatorial Up/Axial Down: (E/A)
E/A
E/A
E/A
A/E
A/E
A/E
Substituents: Axial vs Equatorial
Substituent, R G Preference for Equatorial
K at 25 deg
-CH3, methyl 7.28 kJ/mol 18.9
-CH2CH3, ethyl 7.3 19.
-CH(CH3)2, iso propyl 9.0 38.
-C(CH3)3, tert butyl 21.0 4.8 x 103
R
R
equatorialsubstituent
axial substituent
REach repulsion is still about 3.6 kJ. Note that the gauche interaction in butane is about 3.8.
Substituent InteractionsRH
H
1,3 diaxial repulsions
Destabilizes axial substituent. Each repulsion is about 7.28/2 kJ = 3.6 kJ
Alternative description:
gauche interactions
Newman Projection of methylcyclohexane
CH3
H
H
H
ring
ring
Axial methyl group Equatorial methyl group
H
CH3
H
H
ring
ring
gauche anti
0.0 kJ equatorial
7.3 kJ (axial)7.3 kJ (axial)
0.0 kJ equatorial
Disubstituted cyclohexanes1,2 dimethylcyclohexane
3.6 kJ (gauche)
H
CH3
CH3
Hring
ringH3C
H
H
CH3
ring
ring
7.3 + 3.6 = 10.9 kJ 7.3 + 3.6 = 10.9 kJ
interactions
3.6 kJ (gauche)
CH3
H3C
CH3
CH3
7.3 kJ (axial)0.0 kJ equatorial
0.0 kJ
equato
rial
7.3 kJ (axial)
diequatorial diaxial
H
CH3
H
CH3ring
ringH3C
H
CH3
H
ring
ring
3.6 kJ (gauche)
0.0 kJ + 3.6 kJ = 3.6 kJ 14.6 kJ + 0.0 kJ = 14.6 kJ
Translate ring planar structure into 3D
E/A
E/A
E/A
C(CH3)3
A/E
A/E
A/E
C(CH3)3Energy accounting
No axial substituents
One 1,2 gauche interaction between methyl groups, 3.6 kJ/mol
Total: 3.6 kJ
Assume the tert-butyl group is equatorial.
Problem: Which has a higher heat of combustion per mole, A or B?
t-Bu t-Bu
A B
E/A
E/AE/A
E/A
E/A E/A
A/E A/E
3.6 3.6 3.67.3
7.3
7.2 18.2
More repulsion, higher heat of combustion by 11.0 kJ/mol
Trans and Cis Decalin
Trans decalin
Locked, no ring flipping Cis decalin, can ring flip
decahydronaphthalenedecalinbicyclo [4.4.0] decane
Build trans decalin starting from cyclohexane, one linkage up, one down
Now build cis decalin, both same side.
Trans sites used on the left ringTrans sites used on the right ring Cis sites used on left ring.
Cis sites used on right ring.
Trans fusions determine geometry
H
H
H3C
HO
What is the geometry of the OH and CH3?
Trans fusions, rings must use equatorial position for fusion. Rings are locked.
The H’s must both be axial
Work out axial / equatorial for the OH and CH3.
A/EA/E
A/E
E/A
E/A E/A
OH is equatorial and CH3 is axial
Isomerism
• Constitutional Isomers: Same atoms but linked (bonded) together differently. Spatial orientation not important.
3-methylpentanehexanecyclohexane
Are these constitutional isomers of hexane?No, different molecular formulae!!Are these constitutional isomers of cis but-2-ene?
Not this one! It is 2-butene. Cis / trans does not matter.
Stereoisomerism• Stereoisomers: Same molecular formulae,
same connectivity; same constitutional isomer. Different spatial orientation of the bonds.
Are these stereoisomers of cis but-2-ene?
How does the connectivity differ between these two?
Enantiomers and Diastereomers
Two kinds of Stereoisomers– Enantiomers: stereoisomers which are mirror
objects of each other. Enantiomers are different objects, not superimposable.
– Diastereomers: stereoisomers which are not mirror objects of each other.
If a molecule has one or more tetrahedral carbons having four different substituents then enantiomers will occur. If there are two or more such carbons then diastereomers may also occur.
Isomers, contain same atoms, same formula
Constitutional isomers, different connectivities, bonding.
Stereoisomers, same connectivity, different three dimensional orientation of bonds
Enantiomers, mirror objects Diastereomers, not mirror objects
Summary of Isomerism Concepts
Mirror Objects – Carbon with 4 different substituents. We expect enantiomers (mirror objects).
Reflect!
These are mirror objects. Are they the same thing just viewed differently ?? Can we superimpose them?
We can superimpose two atoms. but not all four atoms.
The mirror plane still relates the two structures. Notice that we can characterize or name the molecules by putting the blue in the back, drawing a circle from purple, to red, to green. Clockwise on the right and counterclockwise on the left. Arbitrarily call them R and S.
RS
Arrange both structures with the light blue atoms towards the rear….
Notice how the reflection is done, straight through the mirror!
Recap: Tetrahedral Carbon with four Different Substituents. Enantiomers
Simple Rotation, Same
Simple Rotation, Same
Mirror objects. Different, not superimposable.
Enantiomers
But the reflection might have been done differently. Position the mirror differently….
Reflection can giveany of the following…
Can you locate the mirror which would transform the original molecule into each mirror object?In the course of each reflection,
two substitutents are swapped. The other two remain unchanged.
What is common to each of these reflection operations?
All three of these structures are the same, just made by different mirrors. The structures are superimposable. What rotations of the whole molecules are needed to superimpose the structures?
Again. all three objects on the right are the mirror object of the structure above. They are different views of the enantiomer.
A swap of two substituents is seen to be equivalent to a reflection at the carbon atom.
Now Superimposable mirror objects: Tetrahedral Carbon with at least two identical
substituents.
Reflection can interchange the two red substituents. Clearly interchanging the two reds leads to the same structure, superimposable! Remember it does not make any difference where the mirror is held for the reflection.
This molecule does not have an enantiomer; the mirror object is superimposable on the original, the same object.
SummaryA reflection on a tetrahedral carbon with four different substituents produces a different, non-superimposable structure, the enantiomer. A different three dimensional arrangement of the bonds is produced, a different configuration.
Such a carbon is called chiral. The carbon is a chiral center, a stereogenic center.
The swapping two of the substituents on the chiral carbon is equivalent to a reflection.
If a tetrahedral carbon has two or more substituents which are the same then reflection produces the same structure, the same configuration. Such a carbon is called achiral.
There is only one mirror object produced by reflection, no matter where the mirror is located. It is either the same as the original structure (superimposable) or it is different (non-superimposable), the enantiomer.
Multiple reflectionsOne reflection (swap of substituents) on a chiral carbon produce the enantiomer.
Two reflections (swaps) yields the original back again.
Even number (0, 2, 4…) of reflections (swaps) on a chiral carbon yields the original structure. An odd number (1, 3, 5…) yields the enantiomer.
One swap
HO Br Br OH
Br
OH
Second swap
EnantiomersEnantiomers
Same molecule.
Repeating….
Reflection (in this plane) yields.
Three different substitutents.
Same, not enantiomers.
Reflection (in this plane) yields.
Four different substituents.
Different, not superimposble, enantiomers.
Is a chiral carbon needed? No!
Reflection (in this plane) yields.
Different, not superimposable, enantiomers.
The (distorted) tetrahedral array of the substitutents (huh??) suffices to allow for enantiomers.
C
Recall allene:
Naming of configurations.
A priority is assigned to each substituent on the chiral carbon
Rotate the structure so that the lowest priority towards the rear.
Draw an arc from the highest, to the next lower, to the next lower.
If arc is clockwise it is R configuration. If arc is counterclockwise it is S.
S R
O
N
H
H
H
H
O
C
H
F
F
F
F
When the first atom is the same…Examine what is bonded to it.
Start with first atom attached to chiral carbon. No decision!!
Examine atoms bonded to first atom
O vs O
N vs C
Example: assigning Priorities
Br
H
Substituents
C C C
H
H
H
H
H
H
H
H BrC
H
H
H
Assign on the basis of the atomic number of the first atom in the substituent.
Highest,1Lowest, 4
If the atoms being compared are the same examine the sets bonded to the atoms being compared.
2 3
S configuration
C has priority over H!!
More… If the first atom is the same and the second shell is the same then proceed to the atoms attached to the
highest priority of the second shell.
N
H
Cl
FH
H
N
H
F
ClH
H
H
H
Examine the first atom, directly attached to the chiral atom.
Examine the atoms bonded to the first atom (the second shell) .
N vs N
C vs C
H vs H
Examine atoms bonded to highest priority of second shell, N
Cl vs F Cl wins!
Unsaturation
So far have not worried about double or triple bonds.
Double and triple bonds are expanded as shown below.
H
H
H
Expanded into
H
H
H
C
C
C N becomesC N
N
N
C
C
Let’s investigate what happens if low priority is positioned closer to us than chiral carbon…
ClH
CH3
C2H5
(S)-2-chlorobutane
HCl
CH3
C2H5
(R)-2-chlorobutane
Now let’s swap any two substituents. We know that this produces the enantiomer, R. Swap the H and the Cl.
Arc going in wrong direction because the low priority substituent is closer to us than the chiral center!!!!!!
We are looking at the molecule from the wrong side.
INVERT NAMING if LOW PRIORITY IS CLOSER THAN CHIRAL CENTER:
Clockwise is S
Counterclockwise is R
H towards the rear where it belongs…
Physical Properties of Enantiomers
Enantiomers: different compounds but have same
Melting Point
Boiling Point
DensityEnantiomers rotate plane polarized light in opposite directions.
OPTICALLY ACTIVE!!
The enantiomers rotate plane polarized light the same amount but in opposite directions. One clockwise; the other counterclockwise.
How to know if a compound is optically (in)active. Symmetry elements.
The symmetry of an object is described in terms of symmetry elements. The use of a symmetry element may only interchange identical atoms.
Proper Rotation. Rotation about an axis. Think of a propeller.
Inversion Point. An equidistant line through the center of the molecule.
Reflection plane (mirror plane).
Improper Rotation. Rotation followed by reflection in plane perpendicular to axis.
If a molecule has a reflection plane, inversion point, or improper rotation axis: inactive
The presence of any of these symmetry elements except for proper rotation rules out enantiomers.
Allene, let’s find the symmetry elements in it.
Reflection Plane
Reflection Plane
Proper Rotational Axis, 180 deg
Two Proper Rotational Axes, 180 deg.
We recognize this molecule as being achiral because of the reflection planes or because of the improper rotational axis. Usually they go together. Can you, however, design a molecule having an improper axis but not reflection planes.
Improper Rotational Axis, 90 and 270 deg
Polarimeter
))(,(
)(][
ionconcentratdmlength
rotationobservedrotationspecific
Concentration: pure liquid in g/mL; solution in g per 100 mL of solvent
beforeafter
Optical Activity
• Optically Active compounds rotate plane polarized light. Chiral compounds (compounds not superimposable on their mirror objects) are expected to be optically active.
• Optically Inactive compounds do not rotate plane polarized light. Achiral compounds are optically inactive.
Problems…
If the specific rotation of pure R 2-bromobutane is 48 degrees what is the specific rotation of the pure S enantiomer?
The pure S enantiomer has a specific rotation of -48 degrees.
Equal but opposite!!
Mixtures of Enantiomers• These are high school mixture problems.• If you know the specific rotation of the pure enantiomers
and the composition of a mixture then the specific rotation of the mixture may be predicted. And conversely the specific rotation of the mixture may be used to calculate the composition of the mixture.
Specific rotation of mixture = (fraction which is R)(specific rotation of R)
+ (fraction which is S)(specific rotation of S)
Example
• Mixture of 30% R and 70% S enantiomer.• The pure R enantiomer has a specific
rotation of -40 degrees.• What is the specific rotation of the
mixture?
.16.)40)(70.0(.)40)(30.0(][ mixture
Contribution from R
Contribution from S
• Using the specific rotation to obtain the composition of the mixture.
• For the same two enantiomers ([of R = -40) , suppose the specific rotation of a mixture is 8. degrees what is the composition?
Specific rotation of mixture = (fraction which is R)( specific rotation of R)
+ (fraction which is S)( specific rotation of S)
8. -40.
40.+ (1. – fraction which is R)
Fraction which is R = 40%; fraction which is S is 60%.
Racemic Mixtures, Racemates
• The racemic mixture (racemate) is a 50:50 mixture of the two enantiomers.
• The specific rotation is zero.
• The racemic mixture may have different physical properties (m.p., b.p., etc.) than the enantiomers.
Optical Purity, Enantiomeric Excess
Consider a mixture which is 80% R (and 20% S). Assume the specific rotation of the pure R enantiomer is 50 degrees.
R R R R R
R R R S S
As before
Specific rotation of mix = 0.80 x 50. + .20 x (-50.)
= 30.
Now, recall that a racemic mixture is 50% R and 50% S. Mixture is 60% R and 40% racemic.
Specific rotation of mix = 0.60 x 50. + .40 x (0.)
= 30.
The optical purity (or enantiomeric excess) is 60%.
Look from
this point of
view.
Fischer Projection
HCl
CH3
C2H5
(R)-2-chlorobutane
H,low priority substituent, is closer so CCW is R.
Reposition to
Standard Fischer projection orientation:
vertical bonds recede
horizontal bonds come forward
Standard short notation:Cl H
CH3
C2H5
Cl H
CH3
C2H5
R and S designations may be assigned in Fischer Projection diagrams. Frequently there is an H horizontal making R CCW and S CW.
Cl to Ethyl to Methyl
Manipulating Fischer Projections
Cl H
CH3
C2H5
Even number of swaps yields same structure; odd number yields enantiomer.
1 swap
H Cl
CH3
C2H5
or C2H5 H
CH3
Cl
Cl CH3
H
C2H5
or Etc.
All of these represent the same structure, the enantiomer (different views)!!
R
S
Manipulating Fischer Projections
Cl H
CH3
C2H5
Even number of swaps yields same structure; odd number yields enantiomer.
2 swaps
H CH3
Cl
C2H5
or C2H5 H
Cl
CH3
H Cl
C2H5
CH3
or Etc.
All of these represent the same structure, the original (different views)!!
R
R
H3C H
Cl
C2H5
Rotation of Entire Fischer Diagrams
CH3
H Br
C2H5
Rotate diagram by 180 deg
CH3
HBr
C2H5
Same Structure simply rotated: H & Br still forward; CH3 & C2H5 in back.
CH3
H
Br
C2H5
Rotation by 90 (or 270) degrees.
Enantiomers. Non superimposable structures! Not only has rotation taken place but reflection as well (back to front). For example, the H is now towards the rear and ethyl is brought forward.
This simple rotation is an example of “proper rotation”.
This combination of a simple rotation and reflection is called an “improper rotation”.
Multiple Chiral CentersCH3
H Br
CH3
Cl H
(2S,3S) 2-bromo-3-chlorobutane
S
S
CH3
Br H
CH3
H Cl
R
R
(2R,3R) 2-bromo-3-chlorobutane
Do a single swap on each chiral center to get the enantiomeric molecule.
Each S configuration has changed to R.
CH3
Br H
CH3
Cl H
Now do a single swap on only one chiral center to get a diastereomeric molecule (stereoisomers but not mirror objects).
R
S
CH3
H Br
CH3
H Cl
S
R
(2R,3S) 2-bromo-3-chlorobutane (2S,3R) 2-bromo-3-chlorobutane
Multiple Chiral CentersCH3
H Br
CH3
Cl H
(2S,3S) 2-bromo-3-chlorobutane
S
S
CH3
Br H
CH3
H Cl
R
R
(2R,3R) 2-bromo-3-chlorobutane
CH3
Br H
CH3
Cl H
R
S
CH3
H Br
CH3
H Cl
S
R
(2R,3S) 2-bromo-3-chlorobutane (2S,3R) 2-bromo-3-chlorobutane
Enantiomers
Enantiomers
Multiple Chiral CentersCH3
H Br
CH3
Cl H
(2S,3S) 2-bromo-3-chlorobutane
S
S
CH3
Br H
CH3
H Cl
R
R
(2R,3R) 2-bromo-3-chlorobutane
CH3
Br H
CH3
Cl H
R
S
CH3
H Br
CH3
H Cl
S
R
(2R,3S) 2-bromo-3-chlorobutane (2S,3R) 2-bromo-3-chlorobutane
Diastereomers
Diastereomers
Diastereomers
Everyday example: shaking hands. Right and Left hands are “mirror objects”
R --- R is enantiomer of L --- L
and have equivalent “fit” to each other.
R --- L and L --- R are enantiomeric, have equivalent “fit”, but “fit” differently than R --- R or L – L.
Diastereomers
• Require the presence of two or more chiral centers.
• Have different physical and chemical properties.
• May be separated by physical and chemical techniques.
Meso CompoundsCH3
H Cl
CH3
Cl H
S
S
CH3
Cl H
CH3
H Cl
R
R
CH3
Cl H
CH3
Cl H
R
S
CH3
H Cl
CH3
H Cl
S
R
Must have same set of substituents on corresponding chiral carbons.
As we had before here are the four structures produced by
systematically varying the configuration at each chiral carbon.
Meso CompoundsCH3
H Cl
CH3
Cl H
S
S
CH3
Cl H
CH3
H Cl
R
R
CH3
Cl H
CH3
Cl H
R
S
CH3
H Cl
CH3
H Cl
S
RMirror images! But superimposable via a 180 degree rotation. Same compound.
Enantiomers
Mirror images, not superimposable.
Diastereomers.
Meso
What are the stereochemical relationships?
Meso Compounds: Characteristics
CH3
Cl H
CH3
Cl H
R
S
Meso
Can be superimposed on mirror object, optically inactive.
CH3
H Cl
CH3
H Cl R
Has at least two chiral carbons. Corresponding carbons are of opposite configuration.
S
Can demonstrate mirror plane of symmetry
Molecule is achiral. Optically inactive. Specific rotation is zero.
Can be superimposed by 180 deg rotation.
Meso Compounds: Recognizing
CH3
Cl H
CH3
Cl H
R
S
Meso
Cl
H CH3
CH3
Cl H
R
S
What of this structure? It has chiral carbons. Is it optically active? Is it meso instead?
Assign configurations.
Looks meso. But no mirror plane.
Rearrange by doing even number of swaps on upper carbon.
H
Cl CH3
CH3
Cl H
CH3
Cl H
CH3
Cl H
Now have mirror plane.
Original structure was meso compound. In checking to see if meso you must attempt to establish the plane of symmetry.
Cl
H CH3
CH3
Cl H
Cycloalkanes
Based on these planar ring diagrams we observe reflection plane and expect optical inactivity….
But the actual molecule is not planar!! Examine cyclohexane.
Look for reflection planes!
This plane of symmetry (and two similar ones) are still present. Achiral. Optically inactive. The planar diagrams predicted correctly.
There are other reflection planes as well. Do you see them?
Horizontal reflection plane.
Vertical reflection plane.
Substituted cyclohexanes
(1S,2R)-1,2-dimethylcyclohexane
cisThe planar diagram predicts achiral and optically inactive. But again we know the structure is not planar.
This is a chiral structure and would be expected to be optically active!!
But recall the chair interconversion….
Earlier we showed that the two structures have the same energy. Rapid interconversion. 50:50 mixture. Racemic mixture. Optically Inactive. Planar structure predicted correctly
Mirror objects!!
More…
trans 1,2 dimethylcyclohexane
(1R,2R)-1,2-dimethylcyclohexane
No mirror planes. Predicted to be chiral, optically active.
(1S,2S)-1,2-dimethylcyclohexane
Ring Flips??????
Each structure is chiral. Not mirror images! Not the same! Present in different amounts. Optically active!
Other isomers for you… 1,3 cis and trans, 1,4 cis and trans.
R,R R,R
trans
Enantiomer.
Resolution of mixture into separate enantiomers.
Mixtures of enantiomers are difficult to separate because the enantiomers have the same boiling point, etc. The technique is to convert the pair of enantiomers into a pair of diastereomers and to utilize the different physical characteristics of diastereomers.
Formation of diastereomeric salts. Racemic mixture of anions allowed to form salts with pure cation enantiomer.
Racemic mixture reacted with chiral enzyme. One enantiomer is selectively reacted.
Racemic mixture is put through column packed with chiral material. One enantiomer passes through more quickly.