CHE2201, Chapter 5 Learn, 1 Stereochemistry at Tetrahedral Centers Chapter 5 Suggested Problems - 1-25,32-35,37-8,35,42- 4,47,56-7

CHE2201, Chapter 5Learn, 1

Stereochemistry at Tetrahedral

Centers

Chapter 5

Suggested Problems - 1-25,32-35,37-8,35,42-4,47,56-7


Isomers

Compounds that have the

same molecular formula but

different structures.


Constitutional Isomers

Constitutional isomers differ in the way the atoms are connected.


Cis–Trans Isomers

Cis–trans isomers result from restricted rotation.

Cis: The substituents are on the same side of the ring.

Trans: The substituents are on opposite sides of the ring.

Cyclic structures restrict rotation.


Double bonds restrict rotation.

Cis: The hydrogens are on the same side of the double bond.

Trans: The hydrogens are on opposite sides of the double bond.

Cis–Trans Isomers


Cis–trans isomers have different physical properties.

Cis–Trans Isomers


Some Alkenes Do Not Have Cis–Trans Isomers


Different Conformations

Compounds with different conformations (conformers) cannot be separated.


Different Configurations

Compounds with different configurations can be separated.

Cis–trans isomers have different configurations.


• Some objects are not the same as their mirror images (technically, they have no plane of symmetry)– A right-hand glove is

different from a left-hand glove. The property is commonly called “handedness”

• Organic molecules (including many drugs) have handedness that results from substitution patterns on sp3 hybridized carbon

Stereochemistry


Chiral and Achiral Objects

Chiral objects – not superimposable on their mirror image

Achiral objects – superimposable on their mirror image


Chiral Molecules

Chiral molecules have an asymmetric center.

An asymmetric center is an atom that is attached to

four different groups.


Compounds with an Asymmetric Center

Asymmetric centers are also called chirality centers.


Enantiomers

The two isomers are called enantiomers.

Enantiomers are different compounds: they can be separated.

Enantiomers have the same physical and chemical properties.


Enantiomers are nonsuperimposable mirror images.

Enantiomers


Chiral and Achiral Molecules

Chiral compounds have nonsuperimposable mirror images.

Achiral compounds have superimposable mirror images (they are identical molecules).


Asymmetric Center versus Stereocenter

Asymmetric center: an atom attached to four different groups

Stereocenter: an atom at which the interchange of two groups produces a stereoisomer


• Molecules that have one carbon with 4 different substituents have a nonsuperimposable mirror image – enantiomer

• Which of the following are enantiomers?

Examples of Enantiomers


• Molecules that are not superimposable with their mirror images are chiral (have handedness)

• A plane of symmetry divides an entire molecule into two pieces that are exact mirror images

• A molecule with a plane of symmetry is the same as its mirror image and is said to be achiral (See Figure 5.4 for examples)

The Reason for Handedness: Chirality


Plane of Symmetry


• The plane has the same thing on both sides for the flask

• There is no mirror plane for a hand

Plane of Symmetry


• Groups are considered “different” if there is any structural variation (if the groups could not be superimposed if detached, they are different)

• In cyclic molecules, we compare by following in each direction in a ring

Asymmetric (Chirality) Centers inChiral Molecules


• Light restricted to pass through a plane is plane-polarized

• Plane-polarized light that passes through solutions of achiral compounds retains its original plane of polarization

• Solutions of chiral compounds rotate plane-polarized light and the molecules are said to be optically active

Optical Activity


Plane-Polarized Light


An Achiral Compound is Optically Inactive

An achiral compound does not rotate the plane of polarization of plane-polarized light.


A Chiral Compound is Optically Active

A chiral compound rotatesthe plane of polarization of plane-polarized light.


• A polarimeter measures the rotation of plane-polarized light that has passed through a solution

• The source passes through a polarizer and then is detected at a second polarizer

• The angle between the entrance and exit planes is the optical rotation.

Measurement of Optical Rotation


A Polarimeter

• Rotation is measured in degrees, []• Clockwise rotation is called dextrorotatory = (+)• Counterclockwise rotation is levorotatory = (-)


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

• []D = observed rotation/(pathlength x concentration)

= /(l x C) = degrees/(dm x 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 nm)

Specific Rotation


• Characteristic property of a compound that is optically active – the compound must be chiral

• The specific rotation of the enantiomer is equal in magnitude but opposite in sign

Specific Rotation and Molecules


• Louis Pasteur discovered that sodium ammonium salts of tartaric acid crystallize into right handed and left handed forms

• The optical rotations of equal concentrations of these forms have opposite optical rotations

• The solutions contain mirror image isomers, called enantiomers and they crystallized in mirror image shapes – such an event is rare

Pasteur’s Discovery of Enantiomers


How to Draw Enantiomers

Perspective formulas

Fischer projections


• A general method applies to the configuration at each chirality center (instead of to the whole molecule)

• The configuration is specified by the relative positions of all the groups with respect to each other at the chirality center

• The groups are ranked in an established priority sequence and compared

• The relationship of the groups in priority order in space determines the label applied to the configuration, according to a rule

Sequence Rules for Specification of Configuration


Rule 1:• Look at the four atoms directly attached to the chirality

center, and rank them according to atomic number. • With the lowest priority group pointing away, look at

remaining 3 groups in a plane• Clockwise is designated R (from Latin word for “right”)• Counterclockwise is designated S (from Latin word for

“left”)

Sequence Rules (IUPAC)


Rule 2:• If a decision cannot be reached by ranking the first atoms

in the substituents, look at the second, third, or fourth atoms until difference is found

Sequence Rules (Continued)


Rule 3:• Multiple-bonded atoms are equivalent to the same

number of single-bonded atoms

Sequence Rules (Continued)


Naming Enantiomers

Assign relative priorities to the four groups.


if the lowest priority group is on a hatched wedge, then

clockwise = R

counterclockwise = Sand

Naming Enantiomers

draw an arrow from 1 to 2 to 3


If the lowest priority group is not on a hatched wedge, switch a pair so it is on a hatched wedge.

Then, name the new compound.

Naming Enantiomers


if the lowest priority group is on a vertical bond, then

clockwise = R

counterclockwise = S

and

Naming Enantiomers


if the lowest priority group is on a horizontal bond, then

counterclockwise = R

clockwise = Sand

Naming Enantiomers


R and S Versus (+) and (–)

Some R enantiomers are (+) and some are (–).

Some S enantiomers are (+) and some are (–).


If One Enantiomer Is (+), the Other Is (–)


Compounds with Two Asymmetric Centers

maximum # of stereoisomers = 2n

(n = # of asymmetric centers)

1 and 2 are enantiomers. 3 and 4 are enantiomers.


Diastereomers

1 and 2 are enantiomers. 3 and 4 are enantiomers.

Diastereomers are stereoisomers that are not enantiomers.

1 and 3 are diastereomers.




Diastereomers have different physical and chemical properties.


Let’s Examine 2-amino-3-hydroxybutanoic acid


Two Asymmetric Centers, Four Stereoisomers

The cis stereoisomers are a pair of enantiomers.

The trans stereoisomers are a pair of enantiomers.


Identifying an Asymmetric Center

An asymmetric center is attached to four different groups.

two asymmetric centers, four stereoisomers


No Asymmetric Centers

There are only two stereoisomers: cis and trans.


There are only two stereoisomers: cis and trans.

No Asymmetric Centers


• Tartaric acid has two chirality centers and two diastereomeric forms

• One form is chiral and the other is achiral, but both have two chirality centers

• An achiral compound with chirality centers is called a meso compound – it may have a plane of symmetry

• The two structures on the right in the figure are identical so the compound (2R, 3S) is achiral

Meso Compounds


Two Asymmetric Centers: Three Stereoisomers

(a meso compound and a pair of enantiomers)


A Meso Compound Has a Superimposable Mirror Image

Meso compounds are optically inactive even though they have asymmetric centers.


A Meso Compound Has a Plane of Symmetry


A Meso Compound

A compound with two asymmetric centers that have the same four groups bonded to each asymmetric center will have three stereoisomers:

a meso compound and a pair of enantiomers.


A Meso Compound

For cyclic compounds with the same substituent bonded to two asymmetric centers,

cis = a meso compoundand

trans = a pair of enantiomers.


Naming Stereoisomers






• A 50:50 mixture of two chiral compounds that are mirror images does not rotate light – called a racemic mixture (named for “racemic acid” that was the double salt of (+) and (-) tartaric acid)

• The pure compounds need to be separated or resolved from the mixture (called a racemate)

• To separate components of a racemate (reversibly) we make a derivative of each with a chiral substance that is free of its enantiomer (resolving agent)

• This gives diastereomers that are separated by their differing solubility

• The resolving agent is then removed

Racemic Mixtures and The Resolution of Enantiomers


Racemic Mixtures (Continued)


Racemic Mixtures (Continued)


Physical Properties of Stereoisomers


Separating Enantiomers

separating by hand

separating by chromatography


Physiological Properties of Enantiomers

Enantiomers can have very different physiological properties.


Oranges and Lemons

found in oranges found in lemons


Enantiomeric Excess

Enantiomeric excess tells us how much of an excess of one enantiomer is in a mixture.


• The flowchart summarizes the types of isomers we have seen

A Review of Isomerism

alkenes


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

Constitutional Isomers


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

• Includes cis, trans, configurational

Stereoisomers


• N, P, S commonly found in organic compounds, and can have chirality centers

• Trivalent nitrogen is tetrahedral• Does not form a chirality center since it rapidly flips• Individual enantiomers cannot be isolated

Chirality at Nitrogen, Phosphorus, and Sulfur


• May also apply to phosphorus but it flips more slowly

Chirality at Nitrogen, Phosphorus, and Sulfur (Continued)


Nitrogen and Phosphorus Can Be Asymmetric Centers

If nitrogen and phosphorus contain four groups, chirality endures.


• A molecule that is achiral but that can become chiral by a single alteration is a prochiral molecule

Prochirality

Attack by hydride from the top “re” face produces (S)-2-butanol


• An sp3 carbon with two groups that are the same is a prochirality center

• The two identical groups are distinguished by considering either and seeing if it were increased in priority in comparison with the other

• If the center becomes R the group is pro-R and pro-S if the center becomes S

Prochiral Distinctions: Faces


• Biological reactions often involve making distinctions between prochiral faces or groups

• Chiral entities (such as enzymes) can always make such a distinction

• Example: addition of water to fumarate

Prochiral Distinctions in Nature


• Stereoisomers are readily distinguished by chiral receptors in nature

• Properties of drugs depend on stereochemistry• Think of biological recognition as equivalent to 3-

point interaction

Chirality in Nature and Chiral Environments


Erythronolide B is the biological precursor of erythromycin, a broad-spectrum antibiotic. How many chirality centers does erythronolide B have?

Let’s Work a Problem


Answer

The key to navigating this question is to apply the rules learned in this chapter on chirality and apply them to EVERY carbon atom in the ring system. When we examine under these terms we should come to the finding that there are 10 chiral carbons in Erythronolide B.

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CHE2201, Chapter 5 Learn, 1 Stereochemistry at Tetrahedral Centers Chapter 5 Suggested Problems - 1-25,32-35,37-8,35,42- 4,47,56-7