REACTIVE INTERMEDIATES IN SYNTHETIC ORGANIC CHEMISTRY
Carbon atoms in stable - hence relatively unreactive - carbon compounds have the following characteristics:
(1) Closed (i.e. octet) valence shells - 8 electrons in the carbon valence shell - 4 covalent bonds - hence no vacant or singly-filled low energy orbital to allow attack by electron-donors.
(2) Neutral, i.e. no overall charge - hence no very strong electrostatic driving force for attack by nucleophiles or electrophiles.
(3) Bond angles appropriate for the hybridisation involved - i.e. ca. 109° 28' for sp3, ca. 120° for sp2 and 180° for sp - hence no serious bond-strain.
Moderate deviations from these criteria lead to compounds with greater-than-normal reactivity:
Species with large deviations from these criteria - such as carbanions, R–, or carbocations, R+, are usually too unstable to allow isolation - but may show synthetically useful reactivity when generated as short-lived reactive intermediates in chemical reactions.
The three reactive intermediates studied in this course are:
Free radicals
Carbenes and
Arynes.
ORGANIC FREE RADICALS:
Organic Free Radicals: organic compounds which contain at least one unpaired electron. In the simplest cases an atom in the compound has only seven electrons in its valence shell and the unpaired electron is localised on either a carbon atom or on a heteroatom. Note the characteristic 'yl' termination of the systematic names for free radicals and the representation of the unpaired electron by a dot at the appropriate atom:
Preparation of Free Radicals:
(1) Homolytic cleavage of weak single covalent bonds.
Note the use of 'fish-hook' single-headed curved arrows, i.e. to indicate the movement of a single electron.
Thermal cleavage:
N-N, O-O, S-S, Cl-Cl, Br-Br, C-N, N-Cl, O-Cl, O-Br
Photolytic cleavage - compounds with low-energy electronic absorptions only:
(2) Redox reactions of non-radical precursors:
Reduction.
Oxidation:
Detection of Free Radicals:
(1) Electron Spin Resonance (ESR) Spectroscopy.
The degeneracy of spin of an unpaired electron is lifted in a strong magnetic field. DE corresponds to microwave radiation. Hyperfine splitting due to electron-proton spin coupling aids structural interpretation.
(2) Matrix Isolation:
Free radicals generated and trapped in a radiation-transparent solid argon matrix at very low temperature may be studied spectroscopically:
Stability of Free Radicals:
allylic ≈ benzylic > 3° alkyl > 2° alkyl > 1° alkyl
Substitution effect - radical centres are electron-deficient, hence stabilised by attached electron releasing alkyl groups.
Resonance effect:
The combination of electronic and steric effects can result in very stable - and, in suitable circumstances, even isolable - free radicals:
Characteristic Reaction Pathways of Free Radicals:
(1) Dimerisation:
Leads to non-radical products - termination steps in radical chain-reactions.
(2) Radical abstraction:
Ease of abstraction = I ≈ Br > H > Cl
This can be a chain transfer process in radical mechanisms.
(3) Disproportionation - one radical is oxidised by another:
Hydrogen abstraction from one n-propyl radical by the other results in the radical accepting hydrogen being reduced to an alkane. The radical losing hydrogen is simultaneously oxidised to an alkene.
This leads to non-radical products - i.e. is a termination step in radical chain-reactions.
(4) Radical addition to unsaturated structures:
This is a chain propagation step in radical chain-reactions.
(5) Rearrangement:
Despite what we might expect, simple free radicals do not normally undergo rearrangement:
The transition states for both rearrangements are very similar:
Consider the orbitals involved in the transition state: H 1s and 2 C 2p.
Combination of the H 1s and 2 C 2p atomic orbitals gives three molecular orbitals:
(A) is bonding for the hydrogen atom and both carbon atoms.
(B) is bonding for the two C atoms but antibonding for the C2-H interaction.
(C) is antibonding for the two C atoms. In addition there is no net interaction between the hydrogen atom and the two carbon atoms.
(A) is the lowest energy orbital while (B) and (C) are approximately equivalent in energy.
bg-Unsaturated free radicals will undergo rearrangement with migration of the unsaturated group:
(6) Fragmentation:
FREE RADICALS IN ORGANIC SYNTHESIS
(1) Free Radical Substitution of Hydrogen by Other Atoms.
(a) Photochemical halogenation of saturated hydrocarbons