Chapter 9 Stereochemistry

Stereochemistry is the study of the physical and chemical consequences of 3D molecules.

I. Isomers are molecules with the same formula but different structural or special features.

1. Structural (Constitutional) ~ same formula, different structurea. Compounds which differ in the connectivity of atoms; the skeleton is different. b. Are different compounds with different physical and chemical properties.

i. Tautomers are constitutional isomers which spontaneously interconvert and that differ in the placement of a hydrogen atom

a. Keto-Enol Tautomerism

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2. Sterioisomers —compounds whose atoms are connected in the same order, but with different geometry

a. Conformational Isomers—spontaneously interconvert through a rotation about a sigma bond

b. Enantiomers—pair of molecules which , even though they reflect one another, are non-superimposable mirror images that exhibit identical physical properties

c. Diasteromers—pair which are not enantiomers (those which are not mirror images of each other) that exhibit different physical and chemical properties

i. Cis/Trans isomerism

Enantiomers have opposite configurations at ALL chiral centers, while Diasteromers have opposite configurations at SOME chiral centers

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II. Chirality

A Plane of Reflection is an imaginary plane, which bisects a molecule such that there is a reflection within a molecule. All molecules belong to two classes

1. Achiral—a plane of reflection exists if a molecule is achiral, it has a plane of reflection; its mirror image is an identical molecule

2. Chiral—no plane of reflection if a molecule is chiral, its mirror image is non-superimposable meaning the molecule and its mirror image are enantiomers

An atom with tetrahedral geometry (carbon is sp3 hybridized) and has four different ligands (atoms, groups, electrons) is called the chiral center

If a molecule has a chiral center, this molecule and its mirror image WILL BE ENANTIOMERS

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Compounds that are ACHIRAL, yet contain chirality centers are called meso compounds- Even though there are chiral centers in the molecule, because of a symmetrical plane, the

molecule contains one less enantiomers and is called meso

III. R/S Classification for Chiral Carbons1. Assign Priority of Atoms/Groups attached to a tetrahedral seteriocenter

a. For different elements, higher atomic number takes priorityi. X > O > N > C >H

b. In the case of carbon vs. carbon—differentiate at nearest point of differencei. A carbon with a heteroatom attached beats one without

ii. For carbons with no heteratoms, one with the more Hs losesc. Handling double and triple bonds

i. Double and triple bonds are treated as if each of the bonds has extra C’s attached

2. If lowest priority group is in the back, trace a path from 1—2—3a. If path goes clockwise, steriocenter is Rb. If path goes counterclockwise, steriocenter is S

3. If lowest priority group is in the front, trace a patha. If path goes clockwise, steriocenter is Sb. If the path goes counterclockwise, steriocenter is R

4. If lowest priority group is to the left or right, exchange it with the group in the back and trace the resulting figure

a. If the path goes clockwise, the steriocenter is Sb. If the path goes counterclockwise, the steriocenter is R

5. In Fisher projections, since H is always in front, clockwise is S and counterclockwiseis R

Fisher Projections are planar representations, but with specific meaning:a. Horizontal bonds are coming OUT of the planeb. Vertical bonds are BEHIND the plane, so:

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Position of lowest Priority Clockwise CounterclockwiseBack R SFront S R

Left/Right ExchangeS ExchangeRFisher S R

IV. Consequences of ChiralityEnantiomers exhibit identical physical and chemical properties except under chiral conditions

Basic Chiral Rules with hands as examples1. Right and left hand are chiral, non-superimposable mirror images; they are akin to a pair

of enantiomers2. Both hands can do the same things; under achiral conditions the right can’t be

distinguished from the lefta. Achiral: a box—you put both hands into a box and they both fit equallyb. Achiral: Flat mittens can be work on either handc. Chiral: A right handed glove; the glove selects for the right hand

i. Enzyme drug interactions are often specific as a hand-in-a-gloveii. Enzymes ‘select’ which enantiomers to react with

Separation of enantiomers

Generally, when separating components, we use Silica Gel (Column Chromatography); however we can’t use it in this case. Therefore, we have to use chiral silica

To separate enantiomers, their reflection plane must be broken.

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Example:

In general, the number of sterioisomers possible = 2n; where n = number of chiral centerSo, in the above examples there were two chiral centers, so 22 = 4 sterioisomers possible

Example:3 chiral centers 8 sterioisomers possible (4 pairs)

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IV. Optical Activity

1. Plane Polarized Light

One physical property where enantiomers differ is their rotation of plane polarized light. Plane polarized light, which is generated by a polarimiter, vibrates in only one plane

2. Interactions of plane polarized light with chiral moleculesa. Chiral molecules are optically active because of their interactions with plane polarized

lightb. A pair of enantiomers are sometimes called optical isomersc. Under identical conditions, R and S enantiomers have rotations that are equal in

magnitude, but opposite in sign

d. Neither the direction nor the magnitude can be predicted; they have to be determined experimentally

e. Achiral molecules give zero rotationf. A 50:50 mixture of R and S will give zero rotation; such a mixture is called a racemate

or racemic mixtureg. Nomenclature

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i. (+)- or (-)- is designated before the nameii. d = dextrorotary (rotates to the right ; +)

iii. l = levorotatory (rotates to the left; -)

3. Specific Rotation is the optical rotation of a sample; it is given by the formula ¿ where α = observed rotation c = concentration (g/mL) l = pathlength (dm)

Example: A 20g sample of R enantiomers is dissolved in 10mL of water. This solution gives a rotation of +100 degrees when using a 1dm polarimiter tube.

a. What is the specific rotation of this enantiomers?b. What is the specific rotation of its S enantiomers?

4. Optical Purity (Enantiomeric Excess) is a measure of the molar ratio of enantiomers present in a mixture

V. Reactions at Chiral Centers

1. Inversion of configuration due to a backside attack like in an SN2 Reaction

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2. Racemization is the loss of the chiral center like in a SN1 Reaction (the partial conversion of one enantiomers into another; the intermediate is not chiral)

3. Retention of configuration

4. Enrichment (results in an R/S mixture that is something other than racemic)

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