Chemeketa Community College Stereoisomerism Chapter 26 Larry Emme Chemeketa Community College

Historical Scientists

In 1848, Louis Pasteur conducted an experiment in which he produced crystals of the sodium ammonium salt of what was (at the time) known as racemic acid. The crystals were of two kinds, known as "+" and “–" forms, which were mirror images of one another. Pasteur separated out the two kinds of crystals and then made two solutions, one from the "+" form crystals, and one from the “–" form crystals. He shone polarized light through each solution, and found that the two solutions had equal but opposite optical activity. That is, the angle of polarization was rotated in each case by the same amount, but in opposite directions. If polarized light was shone through the original solution from which the crystals had been formed there was no rotation, the solution was optically inactive. Pasteur correctly concluded that racemic acid was a mixture of two different substances with opposite optical activity. Racemic acid was optically inactive because it was a mixture of two substances (actually different forms of tartaric acid) with equal and opposite optical activities which cancelled out.

Louis Pasteur Sodium Ammonium Tartrate

Hermann Kolbe

In 1877, Hermann Kolbe, one of the most eminent organic chemists of the time, wrote the following: “Not long ago, I expressed the view that the lack of general education and of thorough training in chemistry was one of the causes of the deterioration of chemical research in Germany . . . Will anyone to whom my worries seem exaggerated please read, if he can, a recent memoir by a Herr van’t Hoff on ‘The Arrangements of Atoms in Space,’

A document crammed to the hilt with the outpourings of a childish fantasy . . . This Dr. J.H. van’t Hoff, employed by the Veterinary College at Utrecht, has, so it seems, no taste for accurate chemical research. He finds it more convenient to mount his Pegasus (evidently taken from the stables of the Veterinary College) and to announce how, on his bold flight to Mount Parnassus, he saw the atoms arranged in space.”

Kolbe, nearing the end of his career, was reacting to a publication of a 22-year-old Dutch scientist. This publication had appeared two years earlier in September 1874, and in it, van’t Hoff had argued that the spatial arrangement of four groups around a central carbon is tetrahedral. A French scientist, J.A. Le Bel, had independently advanced the same idea in a publication in November 1874.

Within 10 years after Kolbe’s comments, however, abundant evidence had accumulated to substantiate the “childish fantasy” of van’t Hoff, and in 1901 he was named the first recipient of the Nobel Prize for chemistry.

Jacobus van't Hoff http://www.youtube.com/watch?v=bj13zmUE7y0 Freshman Organic Chemistry with Professor J. Michael McBride, Fall 2008

Joseph Achille LeBel

Patti LaBelle

Review of Isomerism

What are isomers? 1. Isomers are molecules that have the same chemical formula but differ in either : (a) how the atoms are connected or, (b) how the connected atoms are arranged in space. 2. Isomers that differ only in their connectivity are called structural isomers, e.g., butane and isobutane. 3. while those that differ in the spatial arrangement of their atoms are stereoisomers

There are two types of stereoisomers

Plane-Polarized Light

What is plane-polarized light? It is light that has passed through a special filter called a polarizer and consequently vibrates in a single plane as shown. Polarized light is used in a polarimeter to analyze optical isomers. Diagram of ordinary light vibrating in all possible directions (planes) Diagram of plane-polarized light vibrating in a single plane. The beam of light is coming toward the viewer.

Plane-polarized light is produced only when the Polaroid filters are parallel. With no light emerging, the filters appear black.

A polarimeter is used to analyze optical isomers which are also called enantiomers. The measurement gives the observed rotation of plane-polarized light which is then adjusted to a specific rotation.

Optical Activity

What is optical activity? Optical activity is the ability of a substance to rotate plane-polarized light to the right or left. Rotation of polarized light to the right (i.e. clockwise) is called dextrorotatory (+) Rotation of polarized light to the left (i.e. counterclockwise) is called levorotatory (-)

Optical Activity A substance that can rotate plane-polarized light is said to be optically active. A necessary condition for optical activity is the property chirality.

Chirality Chirality is a property present in an object that cannot be superimposed on its mirror image. Chiral objects or chiral molecules do not have a plane of symmetry, i.e. they are asymmetric. Your right hand is chiral because its mirror image, your left hand, are not superimposable on each other.

Chirality and Asymmetry Chirality is typically seen in molecules that have a chiral or asymmetric carbon atom. Chiral or asymmetric carbons have four different atoms or four different group attached to it.

Fischer Projection Formulas

What is a Fischer projection formula? A Fischer projection is a two-dimensional structural formula used to represent a three-dimensional image on paper.

This is a comparison of two-dimensional and three-dimensional representations of lactic acid.

A 180 rotation within the plane of the paper is the only permissible movement used in determining if two Fischer projections represent the same or different molecules. Example: Are molecules A and B the same molecule?

To answer this question you would perform an in-plane 180 rotation and then determine if the rotated molecule is superimposable on the other molecule. A and B are not the same molecules because they are non-superimposable mirror images.

Enantiomers

What are enantiomers? Enantiomers are optically active, non-superimposable mirror image molecules that have the property of chirality. A molecule that has a non-superimposable mirror image is chiral. Most chiral molecules consist of enantiomer pairs where (+) is assigned to the enantiomer that rotates polarized light to the right and (-) is assigned to the one that rotates polarized light to the left . (e.g. (+) lactic acid and (-) lactic acid)

These molecules are enantiomers These molecules are enantiomers. They are non-superimposable mirror images of each other. (–)-Lactic acid rotates plane-polarized light to the left while (+)-lactic acid rotates plane-polarized light to the right. .

Key Characteristics of Enantiomers Same chemical properties in an achiral environment Different chemical properties in a chiral environment ( e.g. only the (+)-glucose enantiomer can be used in the body for energy, however the (-)-glucose enantiomer has no biological activity.) Same physical properties (except for optical rotation) Rotates plane-polarized light in equal but opposite directions.

Racemic Mixtures

Racemic Mixtures A racemic mixture is a 50:50 mixture of an enantiomer pair. These mixtures are optically inactive (i.e. no observed rotation in a polarimeter) because each enantiomer rotates the plane of polarized an equal amount but in opposite directions so that each rotation cancels each other and the observed rotation for the 50:50 mixture is zero.

Racemic Mixtures Racemic mixtures are generally prepared in a laboratory synthesis while the single enantiomer is produced in a biological synthesis. The reaction shown below is a typical synthesis ran in the laboratory.

Examples of common chiral drugs Examples of common chiral drugs. Many drugs are racemic mixtures but due to safety considerations more drugs are being prepared as the single enantiomer .

Diastereomers and Meso Compounds

Diastereomers Diastereomers are non-mirror image stereoisomers which are classified as either R,S or cis-trans diastereomers.

The number of stereoisomers for a molecule can be determined using 2n where n is the number of chiral carbons.

Meso Compounds A meso compound is a stereoisomer that is superimposable on its mirror image due to an internal plane of symmetry. Meso compounds are optically inactive.

The isomers in this table with an enantomeric relationship are easily identified because all properties are identical except the specific rotation. Those with a diastereomeric relationship will have differences in the other physical properties.

Terms to Know 1. Steroisomers. Compounds that have the same structural formulas but differ in their spatial arrangements. Types: cis-/trans- or geometric & optical (rotates plane-polarized light). 2. Dextrorotary. A substance that rotates plane-polarized to the right (clockwise). 3. Levorotary. A substance that rotates plane-polarized to the left (counterclockwise).

Terms to Know 4. Asymmetric Carbon Atom. A carbon atom with four different atoms or functional groups bonded to it. 5. Superimposable. When one object is placed upon another, all parts of both objects coincide exactly. 6. Chiral. A molecule or object that has the property of handedness and so is not superimposable on its mirror image.

Terms to Know 7. Achiral. A Molecule or object that is superimposable on its mirror image. 8. Asymmetric Carbon. A chiral carbon atom or chiral center. 9. Enantiomers. Meaning “opposite”. Chiral molecules that are mirror images of each other.

Terms to Know 10. Diastereomers. Stereoisomers that are not enantiomers (not mirror images of each other). 11. Meso Compounds. Stereoisomers that contain chiral carbon atoms and are superimposable on their own mirror images. 12. Racemic Mixtures. A mixture containing equal amounts of a pair of enantiomers.

Terms to Know 13. Projection Formulas. Molecules represented by drawing a cross and attaching the four groups in their proper positions. The chiral carbon is understood to be in the located where the lines cross. It is also understood that the horizontal lines are coming out of the plane of paper toward the observer (like a hug), and the groups attached to the vertical bonds are projected back behind the paper. 14. Resolution. Separation of a racemic mixture into its optically active forms.

The End