Reactivity

Question 1

Reactivity of Carbonyls

Answer 1

Reactivity of carbonyls depends on heteroatom (X) attached. If heteroatom has a lone pair, it will delocalise into system, therefore more stable and raising the energy of LUMO.

e- Rich X = High Stability/Not Very Reactive/High LUMO E
e- Poor X = Unstable/Very Reactive/Low LUMO E

Question 2

Why is the LUMO energy important when considering reactivity of an electrophile such as the carbonyl functional group?

Answer 2

LUMO energy is important as if it is lower in energy it means that it is closer in energy to the HOMO which means that these orbitals can form an interaction with each other and succeed with a reaction (successful nucleophilic attack).

Question 3

Reactivity of Carbonyls (Ketones vs Aldehydes)

Answer 3

The size of the group attached in this case R vs H, matters to the reactivity of the carbonyl. If the group is larger it means that it sterically hinders the nucleophilic attack on the carbonyl.

This means that ketones (X=R) are less reactive than aldehydes (X=H).

Question 4

Carbonyl groups as nucleophiles (Alpha carbon)

Answer 4

Acidic proton attached to alpha Carbon to be attacked by base.

1) Form Enolate ion
2) Oxygen comes back in to break alkene bond, nucleophilic alpha carbon goes off to attack electrophile.

Question 5

Reactivity of enols vs alkenes

Answer 5

The main reason is because an enol has an oxygen whereas an alkene does NOT.

1) Oxygen higher in energy and mixes with HOMO easier. This makes it more nucleophilic.
2) Bear in mind that this is actually more of a resonance effect rather than an inductive effect, please see notes for the resonance structures.

Question 6

Rationalising pKa values

Answer 6

pka = -log(Ka)

• Me = Electron Releasing therefore alpha carbon proton more acidic (LOWER pKa)
• N/O = Electron Withdrawing therefore alpha carbon proton less acidic (HIGH pKa)

Good exam note to have is that the lone pair on these heteroatoms (O/N) destabilise the conjugate base which increases the pKa value and makes for a weaker acid).

Question 7

Kinetic Control of Enolates

Answer 7

Deprotonation occurs the fastest at the least substituted (number of carbons directly attached to carbon which proton is attached to) alpha carbon.

Question 8

Nucleophilic substitutions (relative reactivities)

Answer 8

This is NOT due to electronegativity, it is due to resonance effects where there is more C=O character reactivity increases and viceversa.

Question 9

pKaH values

Answer 9

R = 50
NR2 = 35
RO = 16
RCO2(-) = 5
Cl(-) = -7

Question 10

Weird pKaH values

Answer 10

NR2H = 10 (Nitrogen binding)
ROH = -2 (Oxygen binding)