Stereochemistry - Lecture 3

diastereomer

Stereoisomers that are not mirror images of one another and not identical

same molecular formula and connectivity

differ in 3D arrangement of atoms

different physical and chemical properties

difference between diastereomer and enantiomer

if ALL of the chiral centres are of opposite R/S configuration between 2 stereoisomers, they are enantiomers

if at least one but not all of the chiral centres are opposite between 2 stereoisomers they are diastereomers

meso compounds

a molecule that has chiral centres but has a plane of symmetry rendering the molecule achiral overall

they are superimposable on their mirror images - meaning they are considered to be identical

meso compounds will always have (R,S) or (S,R) configurations but not all compounds with (R,S) or (S,R) configurations will be meso

why are meso compounds achiral

because they have an internal plane of symmetry making the molecule identical to its mirror image.

why is the optical rotation of a meso compound 0

its own symmetry cancels out its chirality

when will a molecule not be chiral

if it possesses a plane of symmetry

What is a plane of symmetry?

an imaginary plane that bisects a molecule in such that the two halves of the molecule are mirror images of each other

what are all molecules with a plane of symmetry in their most symmetric conformation

achiral with an optical rotation of zero

what makes a molecule a meso compound

Any molecule with a plane of symmetry in its most symmetric conformation is achiral and has zero optical rotation. If the molecule also contains more than one stereocenter, it is classified as a meso compound.

R and S

refer to the absolute configuration of the chiral centre base on CIP system

D and L

refer to emil fischer's method for assigning stereochemistry based on analagoy to that of +-glyceraldehyde

+ and -

refer to the direction in which the molecule rotates plane polarized light

+ = clockwise (dextrorotary)

- = counter clockwise (levorotary)

dl-

refers to a racemic mixture

not appropriate for a meso compound

Why are simple amines like R′R″R‴N not typically chiral?

Because nitrogen inversion is extremely rapid; the energy barrier is very small.

What effect does rapid nitrogen inversion have on stereochemistry?

It prevents the isolation or observation of nitrogen-based enantiomers in most amines.

When are stereoisomers observed in nitrogen

When nitrogen is part of a rigid or constrained ring system that prevents inversion.

Example of a ring system that prevents nitrogen inversion?

Three-membered rings such as oxaziridines, where N-stereoisomers can be isolated.

Name a natural product that contains a stereogenic nitrogen.

Quinine, which has a rigid structure that restricts nitrogen inversion.

When else can nitrogen be a stable stereocenter?

When nitrogen is quaternary (positively charged) with four different substituents.

Example of a chiral quaternary ammonium salt.

Ipratropium bromide (a bronchodilator).

Are stereoisomers commonly observed for phosphorus- and sulfur-containing compounds?

Yes, stereoisomers are readily observed.

Can phosphorus and sulfur compounds be isolated as single enantiomers?

Yes, they are often obtained as single enantiomer compounds.

why do phosphorus and sulfur compounds maintain their chirality better than nitrogen compounds?

Because their barrier to inversion is much greater than that of nitrogen.

i.e. it is less likely for them to invert and therefore easier to separate 2 enantiomers

Do phosphorus and sulfur compounds racemize easily?

No, they do not racemize easily due to the high inversion barrier.

racemisation

progressive loss of optical activity with time, usually in a well defined kinetic process

How do UV and NMR spectra of racemic mixtures compare to those of pure enantiomers?

they are indistinguishable

How do racemates and pure enantiomers differ in the solid state?

They have different crystal packing (e.g., like stacking pairs of shoes vs. stacking only left shoes).

Do racemates and pure enantiomers have different physical properties?

Yes—racemates often have different densities and melting points compared to either enantiomer.

What is the process of separating one enantiomer from a racemic mixture called?

resolution

what is a racemic mixture

= racemate

50:50 mixture of (+) and (-) enantiomers Optical rotation = 0

Optical Rotation = -0.10 to +0.10 or -0.05 to +0.05

optical rotation

property displayed by chiral substances of rotating the plane of polarisation of polarised light

angle of optical rotation of a neat liquid

the angle of rotation a, expressed in degrees (°), of the plane of polarisation at the wavelength of the D-line of sodium (λ = 589.3 nm) measured at 20 °C using a layer of 1 dm; for a solution, the method of preparation is prescribed in the monograph

what does specific optical rotation measure

The angle of rotation (α) in degrees of plane-polarized light by a solution of a substance.

At what wavelength is specific optical rotation measured?

At the sodium D-line wavelength, λ = 589.3 nm.

At what temperature is specific optical rotation typically measured?

20C

how is specific optical rotation standardized

it is calculated relative to a 1 dm path length and a conc of 1g/ml

Why must solvent and concentration be specified when reporting specific optical rotation?

Because specific optical rotation always depends on the solvent and concentration used.

formula for specific optical rotation

[a]20 D = 1000a/ l.c