JBC Stereochemistry

Define empirical formula

Simplest whole number ratio of elements present in a substance.

Define molecular formula

Actual number of each element in a molecule

Define constitution

Molecular connectivity of a molecule

Define configuration

Permanent spatial arrangement within a molecule

Define conformation

Spatial arrangement within a molecule caused by rotation/torsion

Define conformation

Spatial arrangement within a molecule caused by rotation/torsion.

Configuration isomers

Stereoisomers which can be interconverted by breaking and making bonds

Conformational isomers

Stereoisomers which can be interconverted by rotation about single bonds

What is the Newman Projection

Alternative to dash-wedge notation. Drawing the molecule as if looking down the c-c bond.

Define hyperconjugation

Repulsion between H atom electron clouds

Define heat of combustion

Change in thermal energy from conversion of alkanes to co2 and h2o. Can be measured by calorimetry.

Define heat of formation

Change in thermal energy from formation of 1 mole of a substance under standard conditions. Can be calculated from known enthalpy of combustion and enthalpy of formation.

Define Hess’ Law

Entropy changes are additive

Why are cyclopropane and cyclobutane unstable?

Due to ring strain

What does ring strain mainly come from?

• Angle strain

• Tortional strain

Structure of cyclopropane

• Planar molecule

• Angle strain - bond angles 60, so 49.5 degrees away from ideal (109.5 tetrahedral)

• Torsional strain - 3 eclipsed c - c bonds so 2×2.8kcalmol^-1

• Total strain - 27.6 Kcalmol^-1

Structure of cyclobutane

• Angle strain - Bond angles approx 90 so 19.5 away from ideal

• Tortional strain - 4 x nearly eclipsed c - c, 4 x 2.8kcalmol^-1

• Total strain = 26.3 kcalmol^-1

Cyclohexane (chair)

In the chair confirmation, eclipsing of the hydrogens is completely prevented, the c-c-c bond angles are very nearly tetrahedral and the molecule is nearly strain free.

Cyclohexane (boat)

A second less stable conformation of the cyclohexane.

Less stable than the chair formation by 6.9kcalmol^-1

Higher energy is due to the eclipsing of the 8 hydrogens at the base of the boat and the transannular (steric crowding across a ring) strain between the 2 H’s at the top.

Axial and Equatorial positions on cyclohexane (chair)

In the chair form cyclohexane has 2 types of hydrogens:

• Axial - 6 H parallel to the principle molecular axis

• Equatorial - 6 H perpendicular to the principle molecular axis

How to draw cylohexane (chair)

Flipping cyclohexane

• The conformational flipping between 2 chair forms interconverts the equatorial and axial positions

• If Ea low enough for rapid interconversion at room temp, substituents may favour one conformation, affecting stereochemistry and reactivity.

Monosubstituted cyclohexanes

• Lowest energy chair formation - the substituent in an equatorial position

• Chair flipping equilibrium shifts towards equatorial conformation

• Equilibrium shift determined by size and nature of its substituent.

Chirality

Non super imposable on its mirror image

Enantiomers

Pair of non superimposable mirror images of a chiral molecule.

Same chemical properties

Stereocentres

• A chiral molecule has at least one stereogenic centre

• Organic chiral molecules usually have an atom that is connected to 4 different substitute group

• This atom is called the asymmetric carbon or a stereocentre

How to identify chirality?

Symmetry helps to distinguish chiral structures from achiral ones

For most organic molecules a sufficient test for chirality is absence of a plane symmetry.

Experimentally identifying chirality

• Enantiomers have the same physical properties (mp, bp, solubility etc) but they interact with plane polarised light differently

• The rotation can be measured using a polarimeter to give the observed rotation.

• The rotation is affected by path length (l) and concentration (c)

Dextrorotary enantiomers rotate light…

clockwiseA

Levorotary enantiomers rotate light…

counterclockwise

Define racemic/racemate

Equal amounts of both enantiomers

No net rotation in polarised light ([a]=0)

Equilibration of enantiomers is called racemisation

Diasteromers

Two or more stereocentres

When do diastereomers typically arise

When there is more than one asymmetric centre (stereocentre) in a molecule

E/Z isomers of double bonds are always diasteromers.

Enantiomer vs diastereomer