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 solu'on, all Rotate about single bonds in the arrowed bonds molecule constantly rotate No two molecules - chances of 2 More rota(ons exactly the same molecules with shape at any one exactly same shape More rota(ons 'me, they are s'll 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 reac'ons 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 projec'on 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 func'on of poten'al energy minimum Why is the eclipsed conformaon higher in energy than the staggered conformaon Steric – 10% Eclipsed Staggered Stabilising interac'on 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 contribu'on • 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 contribu'on 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 combus'on –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 combus'on 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 interac'ons • 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 interac'ons 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 proper'es 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 interac'on between the ‘flagstaff’ C–H bonds • Eclipsing interac'ons 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 subs'tuent, but on its interac'on with the neighbouring axial hydrogens More than one subs'tuent on the ring: stereoisomerism Both forms equivqlent 1,4 disubs'tuted 1,3 -disubs'tuted 2 or 3 different subs'tuents 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 subs'tuents react differently Nucleophilic subs'tu'on Direc'on 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 Mul'ple rings Boat structures are important in some bicyclic compounds Adamantane Polycyclic Systems Transannular Strain in Cyclodecane Synthesis of mul'ple ring compounds .