Reactive Intermediates II — Radicals, Carbenes, Nitrenes & Arynes — formula sheet

Free radical: a species with at least one unpaired electron. In organic chemistry this almost always means a carbon-centred radical with seven valence electrons — three bonds and one unpaired electron in a singly occupied molecular orbital (SOMO).

Radicals racemise. A radical generated at a stereogenic carbon loses its stereochemical information, because the planar (or rapidly inverting) radical is attacked with equal probability from both faces. A radical reaction at a stereocentre therefore gives a racemic product, exactly as an S_N1 reaction does — and for the same geometric reason.

Bond-dissociation energy (BDE), D(A–B): the enthalpy change for the gas-phase homolysis A–B → A• + B• at 298 K. It is always positive. A lower BDE for a C–H bond means the resulting carbon radical is more stable, because the hydrogen atom produced is the same in every case.

Stabilised radical: low in energy relative to its precursor — a thermodynamic statement, measured by BDE.Persistent radical: long-lived in solution — a kinetic statement, usually the result of steric shielding of the radical centre so that dimerisation is slow.

Kinetic chain length ν: the number of propagation cycles completed per initiation event — equivalently, moles of product formed per mole of radicals generated.

Reactivity–selectivity principle (RSP): the more reactive a reagent, the less selective it is. Justified through Hammond’s postulate: a more reactive reagent has a more exothermic reaction, therefore an earlier transition state, therefore less product-like character and less discrimination.

Carbene: a neutral divalent carbon species, R₂C:, with six valence electrons — four in the two σ bonds and two non-bonding. It is neither a cation nor an anion nor a radical, and depending on its electronic state it can behave like any of the three.

Singlet carbene: σ²p⁰. All electrons paired, total spin S = 0, multiplicity 2S+1 = 1. Bond angle around 100–110°. Diamagnetic.Triplet carbene: σ¹p¹. Two unpaired electrons, S = 1, multiplicity 3. Bond angle around 130–150°. Paramagnetic — detectable by ESR.

α-Elimination: loss of a proton and a leaving group from the same carbon atom, generating a carbene. Contrast β-elimination, which removes them from adjacent carbons and generates an alkene.

Carbenoid: a reagent that transfers a carbene-like fragment to a substrate without a free carbene ever being formed. Structurally it is a carbon bearing both a metal (or other electropositive group) and a leaving group.

Nitrene: a neutral, monovalent nitrogen species R–N:, with six valence electrons on nitrogen — two in the R–N bond and four non-bonding. It is the nitrogen analogue of a carbene and is isoelectronic with it.

The unifying statement. Hofmann, Curtius, Lossen and Schmidt all do the same thing: they place a leaving group on the nitrogen of an amide-like nitrogen bearing a lone pair, and then the group R migrates from the carbonyl carbon to that nitrogen at the same time as the leaving group departs. The product is always an isocyanate, R–N=C=O, which is then captured by whatever nucleophile is present. The four reactions differ only in how the leaving group is installed.

The settled position. In the thermal Hofmann, Curtius, Lossen and Schmidt rearrangements the migration is concerted with departure of the leaving group and no free nitrene is formed. In photochemical Curtius reactions a genuine free acyl nitrene can be produced, and it can be trapped and observed spectroscopically — so photolysis and thermolysis of the same acyl azide are not mechanistically equivalent.

Aryne (benzyne): a benzene ring in which two ortho hydrogens or substituents have been removed, leaving an extra bond formed by the sideways overlap of two in-plane sp² orbitals. Formally 1,2-didehydrobenzene. The aromatic sextet is untouched.

Cine substitution: substitution in which the incoming group attaches to the carbon adjacent to the one that carried the leaving group. It is impossible by any addition–elimination or S_NAr route and is diagnostic of an aryne intermediate.

Ylide: a species with a negatively charged carbon directly bonded to a positively charged heteroatom, both atoms having complete octets. R₃P⁺–C⁻R₂, R₂S⁺–C⁻R₂, R₃N⁺–C⁻R₂.

Radical anion: a species carrying both a negative charge and an unpaired electron, formed by adding one electron to a neutral molecule.Radical cation: the same idea with one electron removed.