Summary Slide

Stereochemistry For those students using “Fundamentals of

Organic Chem.” this presentation refers to Chapter 6.

Stereochemistry

The Origins of Stereochemistry

Stereochemistry is the branch of chemistry concerned with the three dimensional nature of molecules. This branch of chemistry originated as an offshoot of the research of the French physicist Jean Baptiste Biot (1774-1862). Biot was investigating the nature of "plane - polarized light" when he accidentally discovered optical activity. This discovery eventually led to the development of stereochemistry.

 

Plane Polarized Light A beam of ordinary (unpolarized) light consists of waves that oscillate

equally in all directions perpendicular to the line which defines the path of the light ray.

Certain materials affect ordinary light in a special way. Polarized films interact with all the oscillating waves of ordinary light and filter out all planes of oscillation except one. The light which emerges from a Polaroid film consists of waves oscillating in one plane only and hence is referred to as "plane polarized light".  

Manipulation of Light Using Polaroid Films

In order to see an object, you need light. Polarized films only transmit light vibrating in one plane and filter out

the rest. If two polarized films are set up in front of one another and one is rotated 90 degrees to the other, then the first will transmit light vibrating in a plane that is absorbed by the second and hence no light is transmitted and the object cannot be seen. If one of the two Polaroid films is rotated 90 degrees then the object can be seen again with maximum brightness

top

top

polaroid films

no light reaches eyeall is black

top top

polaroid films

light reaches eye

Optical Activity

In 1815, Biot discovered that when a beam of plane polarized light is passed through solutions of certain organic molecules, such as sugar or camphor, the plane of polarization is rotated. We call molecules that exhibit this property optically active.

A. The amount of rotation can be measured with an instrument known as polarimeter. In a polarimeter, plane polarized light is passed through a tube containing a solution of some optically active molecules and rotation occurs. The extent of rotation is determined by rotating a second polarized film until the light passes through it. The observed rotation is symbolized by the Greek letter In addition to determining the extent of rotation, the direction is also given.

The Direction of Rotation in a Polarimeter Some optically active molecules rotate plane

polarized light to the left (counter clockwise) and are said to be levoratatory.

Others rotate polarized light to the right (clockwise), and are said to be dextrorotatory

By convention rotation to the left is given a (-) minus sign, and rotation to the right is given a (+) positive sign

A Simple Polarimeter

Measures extent of rotation of plane polarized light

Operator lines up polarizing analyzer and measures angle between incoming and outgoing light

The Amount of Rotation

The amount of rotation obtained from a polarimeter is dependent upon the number of optically active molecules the beam encounters and the nature of the light source. Consequently, the amount of rotation is dependent upon:

length of sample tube concentration of optically active molecules in

solution the wavelength of the light used   Because optical rotation is dependent upon these

three variables,we must choose standard conditions so that comparisons can be made.

Specific Rotation

To have a basis for comparison, define specific rotation, []D for an optically active compound

[]D = observed rotation .

Path length l (dm) X concentration (g/ml) Specific rotation is that observed for 1 g/mL in

solution in cell with a 10 cm path using light from sodium metal vapor (589 nanometers)

Louis Pasteur and Optical Isomers

. While recrystallizing sodium ammonium tartrate, Louis Pasteur noticed two differently shaped types of crystals. Separating the two types using tweezers, Louis Pasteur discovered that solutions of each type had specific rotations that were equal in degree, but opposite in sign. Louis Pasteur had discovered optical isomers. Optical isomers are also called enantiomers

Isomers

You will recall that isomers are molecules having the same molecular formula but different structural formulas.

n-n-

Optical Isomers

Optical isomers also fall under the general definition of isomerism, but the difference in their structural formulas is much more subtle! A pair of optical isomers have structural formulas that are related as "nonsuperimposable mirror images.“They have the same relationship as do your two hands

In fact, after separating the two types of crystals, Louis Pasteur noticed that their shapes had this same relationship 

Mirror Images and Optical Isomers

Every molecule has a mirror image. Only if the mirror image of a molecule is nonsuperimposable on the original do the two structures represent a pair of optical isomers. Only if the mirror image of a molecule is nonsuperimposable on the original do the two rotate plane polarized light to the same # of degrees but in opposite directions. The criterion of sameness in chemistry is"superimposability".

If two structures are superimposable, then they represent the same molecule

Criteria for Optical Isomerism

In order for a molecule to exist as a pair of optical isomers it must meet the following two criteria:

It must contain at least one carbon bonded to four different groups

It must not contain a plane of symmetry

Mirror-image Forms of Lactic Acid When H and

OH substituents match up, COOH and CH3 don’t

when COOH and CH3 coincide, H and OH don’t

Optical Isomers (Enantiomers) and Chirality Chirality: a pair of optical isomers (or enantiomers)

are related as are your two hands. They are nonsuperimposible mirror images of one another. Therefore, a pair of enantiomers have the structural property of "opposite handedness". The Greek word for hand is “cheir" and from this we get the words "chiral" and "chirality". We may therefore call a pair of enantiomers "chiral" or say they posses"chirality". The opposite of chiral is achiral

Facts About Optical Isomers

. Physical Properties of Optical Isomers: Although they are different substances, the structures of a pair of enantiomers are so similar that their physical properties are identical (bp, mp, density, etc.).

Racemic mixtures: a mixture that is a 50:50 mix of each member of a pair of optical isomers. This mixture is optically inactive because the optical effect of each isomer cancels the other.

If a molecule possesses n chiral centers, then the max number of optical isomers is 2n

1 chiral center = 21 = 2 optical isomers 

Reactions of Optical Isomers

Chemical reactions for a pair of enantiomers are identical if the enantiomers are reacted with achiral (non- optically active) reagents right hand + ski pole = ski pole in hand left hand + ski pole = ski pole in hand

Two different reaction products are observed for each member of an optically active pair if they are forced to react with a chiral reagent. right hand + right glove = R hand R glove left hand + right glove = Left hand in R. glove

The Biochemistry of Chirality

Many of the sensory receptors in the human body are chiral Therefore, the biochemical effect of each member of an enantiomeric pair is quite different.

Bitter-Sweet Story of Asparagine

Asparagine is an amino acid and furthermore two enantiomers of asparagine exist.

C

HH N

COOH

CH

mirror

C

H

COOH

2

C == ONH 2

2

N H 2

CH

C == ONH 2

2

These two represent a pair of enantiomers. ie. They are nonsuperimposable mirror images of one another. Each of these two has a different biochemistry. One tastes bitter, one is sweet

Chirality Centers

As mentioned earlier, the most common cause of chirality in a molecule is a carbon that is attached to four different groups. Such a carbon is referred to as a chiral center

Detecting chiral centers in a complex molecule can be difficult because it is not always apparent that 4 different groups are bonded to a given carbon. The differences do not necessarily appear right next to the carbon centers .

Chirality Centers in Cyclic Molecules

Groups are considered “different” if there is any structural variation

In cyclic molecules, we compare by following in each direction of the ring

Identifying Specific Enantiomers

The arrangement of groups around a chiral carbon is different for each member of an enantiomeric pair. We need a way of verbally identifying each member of an enantiomer pair

We need a set of rules for specifying the exact configuration around a chiral carbon

Sequence Rules for Specification of Configuration These rules allow us to specify the exact

arrangement of atoms about each chiral carbon without having to draw a perspective structural formula

Sequence Rules (IUPAC)

Assign each group that is attached to the chiral carbon a priority according to the Cahn-Ingold-Prelog scheme; highest = #1 and lowest = #4

If, when the thumb of your left hand points in the direction of the lowest priority group(4), your fingers curl in the direction of descending priority (1-2-3), then your molecule has an S Configuration

If your right hand is needed to accomplish the above, then the configuration is R

Right Hand; R ConfigurationRight Hand; R Configuration

Left Hand; S ConfigurationLeft Hand; S Configuration

Diastereomers If a molecule contains one chiral center,

then 2 stereoisomers exist for this molecule. The two stereoisomers represent a pair of enantiomers. 

If a molecule contains more than one chiral center, then more than 2 stereoisomers exist for that molecule (actually the max number is 2n where n = number of chiral centers). These stereoisomers usually exist as pairs of enantiomers. One member of each enantiomer pair is the mirror image of the other member and has the opposite coniguration at each chiral center. What is the relationship between two members of different enantiomeric pairs. These molecules are still stereoisomers of one another but they are not related as object and its mirror image. These molecules are called Diastereomers (2R,3R and 2R,3S or 2S,3S and 2R,3S)

2R,3S 2S,3R

2R,3R 2S,3S

Meso Compounds Compounds having n chiral centers have a max number of 2n

stereoisomers. These stereoisomers exist as pairs of enantiomers that have opposite configuration at each chiral center. If a pair of enantiomers is seen to have a plane of symmetry then both structures represent the same molecule (the two structures are superimposable). Any compound that contains both chiral centers and a plane of symmetry is called a Meso compound.

Meso compounds have different physical properties than their enantiomers. ** Meso compounds are achiral .

Physical Properties of Stereoisomers

Enantiomeric molecules differ in the direction in which they rotate plane polarized but their other common physical properties are the same

Daistereomers have a complete set of different common physical properties

A Brief Review of Isomerism

The flowchart summarizes the types of isomers we have seen

Constitutional Isomers

Different order of connections gives different carbon backbone and/or different functional groups

Stereoisomers

Same connections, different spatial arrangement of atoms Enantiomers (nonsuperimposable mirror images) Diastereomers (all other stereoisomers)

Includes cis, trans and configurational