Radicals in Synthesis Flashcards
What is a radical?
Atoms or molecules possessing a single electron in a reactive orbital. This makes most radicals very reactive.
How can radicals be detected and observed?
Via EPR, a very sensitive technique for detecting radicals at low concentrations. Radicals with lifetimes considerably less than 1s can be deteced. It provides information on the nature and structure of the unpaired electron.
Describe radical stability.
It’s related to the rate of radical formation and disappearance.

Describe thermodynamic stability of a radical.
The bond dissociation energy (BDE) e.g. of R-H depends on the themodynamic stability of R•.
A lower BDE/weaker R-H bond means that the carbon centred radical is more stable. Carbon radical stability decreases in the order:
tertiary > seconday > primary > methyl

What are the contributing factors to thermodynamic stability of a radical?
- Induction - more +I groups means more stable a radical, because the carbon is 1 e- deficient (7 instead of 8)
- Hyperconjugation - the interaction of the p-orbital of the radical with a pair of bonding electrons in a neighbouring sigma bond. Electrons in the sigma bond are donated to the p-orbital of the radical.
- Resonance - interaction of the p-orbital on a radical with a pi-bond or lone pair (3-electron bonding).
- Hybridisation - increasing p-character of the orbital increases radical stabilisation. Homolysis of double bond C-H leaves the unpaired electron with a lot of s-character and lying at a right angle to the p-orbitals (e.g. C-H on benzene). This is not stabilised by delocalisation.
sp3 > sp2 > sp (stability)
Describe the lifetime of a radical.
Usually determined by steric factors. The larger the substituents attached to the radical centre, the more stable the radical and the longer the lifetime.
Usually reported as half-lives (t1/2), aka the time taken for the concentration of radicals to fall to half the initial value.
What are the different kinds of chain reactions?
- Initiation - formation of radicals.
- Propagation - formation of a different radical.
- Termination - destruction of radicals.
Describe initiation via thermolysis. Show how this occurs for peroxides and azo compounds.
Compounds with relatively weak covalent bonds undergo homolysis below 150ºC.

Describe initiation via photolysis. Show how it occurs for halogens, organometallics and carbonyls.
Works if the compound absorbs light of an appropriate wavelength and the excited state undergoes dissociation/fragmentation. The energy of the photon must be enough to rupture a bond.
The mechanism for peroxides is the same as for thermolysis.

Describe initiation via radiolysis. Show how it works for H2O.
Uses high energy x-rays or gamma-radiation.

Give the general process for initiation via oxidation.

Show how initiation via oxidation occurs for carboxylic acids and carbonyls.

Give the general process for initiation via reduction.

Show how initiation via reduction occurs for peroxides, halides, carbonyls and diazonium salts.

Give a general scheme demonstrating intermolecular radical abstraction.

Give a general scheme demonstrating intramolecular radical abstraction.

Give a general scheme demonstrating intermolecular radical addition to alkenes and alkynes.

Give a general scheme demonstrating intramolecular radical addition to make rings and to aromatic rings.

Give a general scheme demonstrating radical fragmentation.

Describe the different termination reactions.
- Recombination or coupling - the reverse of bond homolysis, the joining of two radicals (dimerisation).
- Disproportionation - transfer of hydrogen atoms.
- Electron transfer - oxidation (removal of an electron from a radical to form a cation) and reduction (addition of an electron to form an anion).
Describe how enthalpy affects radical reactivity.
We can predict if a reaction will take place by considering the energies of the bonds broken and formed. Exothermic reactions result in strong bond formation and occur rapidly. Endothermic reactions resulting in products with weaker bonds are slow.
Enthalpy change = total energy of bonds broken - total energy of bonds formed
Describe how entropy affects radical reactivity.
Reactions resulting in an increase in entropy by increasing the number of molecular species from reactants to products are favoured.
Describe how steric effects affect radical reactivity.
Reactions with sterically hindered radicals require very strained TS’s with high enthalpy of activation and are disfavoured.
Steric effects explain the regioselective addition of radicals to alkenes (add to least hindered end) and sometimes the stereoselective formation of adducts.
Describe how stereoelectronic effects affect radical reactivity.
For a radical to react, the single occupied orbital must overlap with either another of its own orbitals (intramolecular) or another molecule orbital (intermolecular).
In SH2, a radical and a non-radical can orientate themselves to give a linear TS.












