Molekul Kiral Proyeksi Fiesher Dan Konfigurasi R Dan S 31 Januari 2010

Stereoisomerism and Chirality

Constitutional Isomers Functional Group Isomers Positional Isomers Geometric Isomers

Stereoisomers Enantiomers Diastereomers Meso Compounds

Conformational Isomers Eclipsed, gauche, staggered, syn-clinal, anti-clinal forms Chair, boat

Isomers

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.

Enantiomer/Diastereomer/Identik?

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!

Urutan Prioritas : 1. Ungu, 2. Merah, 3. Hijau, 4. Biru

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.


Four different substituents.

Different, not superimposble, enantiomers.

Is a chiral carbon needed? No!


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

Assigning Priorities 2

Start with first atom attached to chiral carbon

C vs. F

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.

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”.

Soal latihan

Jelaskan bahwa dari molekul abcd dapat digambarkan dengan banyak proyeksi Fiesher tetapi sebenarnya hanya merupakan sepasang enantiomer.

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


H Br

CH3

Cl H


S

S

CH3

Br H

CH3

H Cl

R

R


CH3

Br H

CH3

Cl H

R

S

CH3

H Br

CH3

H Cl

S

R


Enantiomers

Enantiomers


H Br

CH3

Cl H


S

S

CH3

Br H

CH3

H Cl

R

R


CH3

Br H

CH3

Cl H

R

S

CH3

H Br

CH3

H Cl

S

R


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 Compounds

CH3

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.

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.

Mengapa Mempelajari Konfigurasi R dan S

S-(+)-Ketamine R-(-)-Ketamine

2-4 times more potent than R-(-)-ketamine in anaesthesia

Causes spontaneous motor activity and post-emergent distress

Cl

NHCH3

O

Cl

NHCH3

O

Chirality in the Biological World

A schematic diagram of an enzyme surface capable of binding with (R)-glyceraldehyde but not with (S)-glyceraldehyde.

All three substituents match up with sites on the enzyme.

If two are matched up then the third will fai!

Sumber

academic.brooklyn.cuny.edu/.../chem%2051%20Lecture%20Slides/Lecture%2004.ppt

31 Januari 2010 jam 22.10 (Alkane filetype:ppt)

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Molekul Kiral Proyeksi Fiesher Dan Konfigurasi R Dan S 31 Januari 2010