CHM-102 –Lecture 2

Conformaons of acylic and cyclic systems: Deviaons from bond angles, cyclopropane, cyclobutane, strain energy etc, High energy materials from cyclic strained systems, propellanes, staffanes, cubanes etc. Natural product examples on cyclic small rings, (natural product drugs, thymine photodimerizaon, etc,); Renewable energy models from small strained cyclic systems (examples, photoirradiaon of norbornadiene, tetramethyldioxetanes, light eming examples etc) (3 hr) Bond rotaon (single bonds) allows chains of atoms to adopt a number of conformaons / shapes

Pea moth pheromone Different shapes of same molecule

RT in soluon, all Rotate about single bonds in the arrowed bonds molecule constantly rotate No two molecules - chances of 2 More rotaons exactly the same molecules with shape at any one exactly same shape More rotaons me, they are sll at any one me are all the same quite small. chemical compound—

• Overall shape different, but local structure is same. sp3, sp2 etc. • Double bonds cannot rotate Conformaon and configuraon Structures that can be interconverted by rotang about single bonds: (no breaking - all different conformaons of the same molecule

Each compound in two conformaons

The following pairs can only be interconverted by breaking a bond. This means that they have different configuraons—configuraons can be interconverted only by breaking bonds. Three pairs of stereomers: each member of a pair has a different configuraon Some conformaons are more stable than others

• Structures that can be interconverted simply by rotaon about single bonds are conformaons of the same molecule • Structures that can be interconverted only by breaking one or more bonds have different configuraons, and are stereoisomers Barrier to rotaon

Rate of a chemical process - associated with an energy barrier (this holds both for reacons and simple bond rotaons): the lower the rate, the higher the barrier.

• 73 kJ mol–1 - one rotaon every second at 25 °C (that is, the rate is 1 s–1) • 6 kJ mol–1 - the rate at 25 °C by about a factor of 10 • For conformaons to interconvert slowly enough for them to exist as different compounds, the barrier must be over 100 kJ mol–1. • The barrier to rotaon about a C=C double bond is 260 kJ mol–1—which is why we can separate E and Z isomers Conformaons of ethane Why should there be an energy barrier in the rotaon about a single bond

staggered

eclipsed

Newman projecon

Staggered conformaon is lower in energy than the eclipsed by 12 kJmol–1, the value of the rotaonal barrier. Energy level diagram of conformaon as a funcon of potenal energy minimum Why is the eclipsed conformaon higher in energy than the staggered conformaon Steric – 10%

Eclipsed Staggered

Stabilising interacon beteween filled C-H σ bond Filled orbitals repel and empty C-H σ* of other C

Rotaonal barrier is slightly higher than for ethane: 14 kJ mol–1 as compared to 12 kJ mol–1. greatest when the two orbitals are exactly parallel - staggered Conformaons of butane

• Steric factors- significant contribuon • Not all the staggered / all eclipsed conformaons are same • Barrier -20 kJ mol–1 corresponds to a rate at RT of 2 x 109 s–1. Ring strain

sp3 hybridized, each bond angle would ideally be 109.5° Planar ring causes strain, bonds curve good measure of the strain in real rings is obtained using heats of combuson. Difference between any two in the series is very nearly constant at around –1 –660 kJ mol contribuon of each extra methylene group, –CH2– Strain Energy in Cycloalkanes o o o ∆Hf ∆Hf ∆∆Hf (calc) (exp) -29.6 -29.9 0.3 -24.7 -18.3 6.4 -19.7 +6.7 26.4 -14.8 +12.7 27.5 n Strain Energy n Strain Energy 3 27.5 10 12.4 Small Ring Medium 4 26.3 11 Rings 11.3 5 6.2 12 4.1 6 Common 0.1 13 5.2 Rings 7 6.2 14 Large 1.9 Rings 8 Medium 9.7 15 1.9 9 Rings 12.6 16 2.0 Strain in ring compounds

The greatest strain is in the three-membered ring, cyclopropane (n = 3) Strain decreases rapidly with ring size but reaches a minimum for cyclohexane, reaches a maximum at around n = 9 Cyclohexane (n = 6) and the larger cycloalkanes (n > 14) - heats of combuson –1 per –CH2– group of around 658 kJ mol , strain free Cyclopropane

• 3 carbon atoms in cyclopropane lie in a plane since it is always possible to draw a plane through any three points. • All the C–C bond lengths are the - the three carbon atoms are at the corners of an equilateral triangle. • Large heat of combuson per methylene group - considerable strain in this molecule – due to the bond angles deviang greatly from the ideal 109.5°. • Further cause of strain—not possible to rotate any of the C–C bonds and so all the C–H bonds are forced to eclipse Cyclobutane

• Ring distorts from a planar conformaon in order to reduce the eclipsing interacons • Reduces the bond angles further and so increases the bond angle strain. • Cyclobutane adopts a puckered or ‘wing-shaped’ conformaon. Cyclopentane

‘half-chair’ or an ‘envelope’.

1. Strain in planar cyclopentane caused by the eclipsing of adjacent C–H bonds. 2. Ring distorts to reduce the eclipsing interacons but this increases the angle strain. 3. Cyclopentane adopts a shape of an ‘open envelope’, with four atoms in a plane and one above or below it. 4. Atoms in the ring rapidly take turns not to be in the plane 5. Cyclopentanes have much less well-defined conformaonal properes than cyclohexanes, Cyclohexane Cyclohexane is virtually strain-free in chair conformaon

• C-atoms are not in a plane all the bond angles are 109.5° • No eclipsing of C–H bonds, all the bonds are fully staggered in chair conformaon Boat form

• All the C–H bonds are eclipsed • Bad interacon between the ‘flagstaff’ C–H bonds • Eclipsing interacons in the boat 25 kJ mol–1 higher in energy than the chair conformaon. • Twist-boat conformaon is lower in energy (by 4 kJ mol–1) • Chair form is approximately 21 kJ mol–1 lower in energy than the twist-boat form. Ring inversion (flipping) of cyclohexane

Ring inversion interconverts the axial and equatorial protons

• Barrier to ring inversion of cyclohexane is 43 kJ mol–1, or a rate at 25 °C of about 2 x 105 s–1 • Ring inversion also interconverts the axial and equatorial protons, exchanging at a rate of 2 x 105 s–1 at 25 °C—too fast for them to be detected individually Equatorial conformer present increase in the order Me < Et < i-Pr < t-Bu

Equilibrium constant does not depend on the actual size of the substuent, but on its interacon with the neighbouring axial hydrogens More than one substuent on the ring: stereoisomerism

Both forms equivqlent

1,4 disubstuted 1,3 -disubstuted

2 or 3 different substuents Fused rings – Decalin Two diastereomers

Ring inversion Steroids regulang growth (anabolic steroids) and sex hormones, self-defence mechanism in plants, frogs, and even sea cucumbers Axial and equatorial substuents react differently

Nucleophilic substuon Direcon of approach of the nucleophile: Nucleophile must aack the σ* of the leaving group, directly behind the C–X bond.

Rings containing sp2 hybridized carbon atoms: cyclohexanone and cyclohexene • Conformaon is not significantly altered by the presence of just one sp2 centre in a ring • Barrier for ring inversion of cyclohexene is around 22 kJ mol–1 Mulple rings Boat structures are important in some bicyclic compounds

Adamantane Polycyclic Systems Transannular Strain in Cyclodecane Synthesis of mulple ring compounds