Stereochemistry and Optical Activity:

What is Stereochemistry?

the study of the three-dimensional structure of molecules

Chirality

Handedness. A chiral molecule has a different (non-identical/non-superimposable) mirror image.

What is an achiral object/molecule?

An object/molecule whose mirror image is identical to the object (superimposable).

Do all chiral compounds have enantiomers?

Yes. Achiral compounds do not.

How is an asymmetric or chiral carbon designated?

With an asterisk (*).

What makes a carbon atom asymmetric (chiral)?

It must be bonded to 4 different groups.

If a molecule possesses an internal mirror plane of symmetry (σ), can it be chiral?

No, if a molecule possesses an internal mirror plane of symmetry, it cannot be chiral.

Does the absence of a mirror plane necessarily imply chirality?

No.

Provide an example of an achiral molecule despite having asymmetric carbons.

cis-1,2-dichlorocyclopentane (it has an internal mirror plane of symmetry).

Do enantiomers have identical physical properties?

Nearly identical (e.g., same Boiling points, Melting points, Density)

What are the apparent differences between enantiomers?

Their interactions with other chiral molecules and with plane-polarized light.

What is polarimetry used for?

To distinguish between enantiomers and measure their purity.

How do enantiomers interact with plane-polarized light?

They rotate the plane of polarized light in opposite directions.

Define unpolarized light.

Light vibrating randomly in all directions.

Define plane-polarized light.

Light composed of waves that vibrate in only one plane.

How is plane-polarized light produced from unpolarized light?

Unpolarized light is passed through a polarizing filter, which filters randomly vibrating light waves, allowing most of the light to vibrate in one direction.

Can two enantiomers have different biological properties?

Yes, they may have totally different biological properties.

How do enzymes in living systems interact with enantiomers?

Enzymes are chiral and are capable of distinguishing between enantiomers. Usually, only one enantiomer fits properly into the chiral active site.

What is the specific example given for a drug where enantiomers have different effects?

Thalidomide. S-thalidomide was an effective drug, but R-thalidomide was dangerous and caused disabilities in babies. The body racemizes it, making even pure S-thalidomide dangerous.

How do all amino acids rotate plane-polarized light?

To the right.

Which isomer of Ibuprofen is effective, and how is it marketed?

Only the S-isomer is effective, but the drug is marketed as a racemate (racemic mixture). The body slowly converts the R-isomer to the S-isomer.

What do a pair of enantiomers represent in terms of configuration?

The two possible spatial arrangements (configurations) about the asymmetric carbon of the compound.

What is the Cahn-Ingold-Prelog (CIP) Convention used for?

To give (R) and (S) designations to each chiral carbon to distinguish between enantiomers.

What are the two main steps to assigning (R) or (S) to an enantiomer?

1. Assignment of "priority" to each of the 4 substituents bonded to the asymmetric carbon. 2. Using the "priority" to decide on (R) or (S).

How are priorities assigned to groups directly bonded to the asymmetric carbon?

By the atomic number of the atom directly attached to the asymmetric carbon. Higher atomic number gets higher priority (1 for highest, 4 for lowest).

How do you assign priority if the atoms directly attached to the chiral carbon are the same?

The atomic number of the next atom along the chain of each group is used to assign priority.

How are double and triple bonds treated when assigning priorities in the CIP system?

They are treated as if each bond were to a separate atom (e.g., C=O is like C bonded to two O's).

How is the molecule arranged for (R) and (S) assignment after priorities are set (for a perspective drawing)?

The molecule is drawn in 3D and arranged so the bond between the chiral carbon and the lowest priority group (priority 4) points back into the paper (away from the viewer).

After setting priorities and orienting the molecule with the lowest priority group to the back, how do you determine (R) or (S)?

Draw an arrow from priority 1 to 2 to 3. If the arrow is clockwise, it's (R). If the arrow is counter-clockwise, it's (S).

What is typically the lowest priority group in Fischer projections?

Hydrogen (H).

In Fischer projections, where is the lowest priority group (H) usually located, and what does this mean about its orientation?

It will be on the horizontal axis, sticking out of the page (opposite to the normal convention for R/S assignment).

How do you assign R/S directly from a Fischer projection if the lowest priority group is on the horizontal axis?

gnore the lowest priority group (H). Draw an arrow from 1 to 2 to 3. If the arrow is clockwise, the configuration is (S). If the arrow is counter-clockwise, the configuration is (R). (It's the reverse of the normal rule because H is facing out).

How can you verify R/S from a Fischer projection (alternative method)?

Mentally turn the molecule/arrow around so the lowest priority group is in the back, then apply the normal (R = clockwise, S = counter-clockwise) rule.

What is a racemic mixture (racemate)?

A mixture containing equal amounts of a pair of enantiomers.

Is a racemic mixture optically active?

No, it is optically inactive.

Can a reaction using optically inactive reactants and catalysts produce an optically active product mixture?

No. Any chiral products formed will be formed as a racemate (equal amounts of enantiomers).

Are chiral molecules are optically active? Yes or no?

yes

Molecules without a plane of symmetry

are optically active

Molecules with a plane of symmetry

are optically inactive. They don't rotate plane-polarized light.