Carbonyl & Acyl Mechanisms — formula sheet

Nucleophilic addition: a nucleophile bonds to the carbonyl carbon, the π electrons move onto oxygen, and the carbon changes from trigonal sp² to tetrahedral sp³. The product is an alkoxide (from an anionic nucleophile) or, after proton transfer, an alcohol.

The structure-correlation principle: a set of static structures scattered along a deformation coordinate maps out the reaction path for that deformation. Nature samples the low-energy valley; a family of crystal structures is a series of snapshots along its floor.

Hemiacetal: R₂C(OH)(OR′) — one hydroxyl, one alkoxyl on the same carbon. Formed reversibly under acid or base catalysis.Acetal: R₂C(OR′)₂ — two alkoxyls, no hydroxyl. Formed only under acid catalysis.

Specific acid catalysis: rate = k[S][H₃O⁺]. Protonation is a fast pre-equilibrium; only the hydronium concentration matters.General acid catalysis: rate = Σk_HA[S][HA] over every acid in solution. The proton is in flight in the rate-determining transition state, so each acid contributes according to its own strength (the Brønsted relation).

The one-way rule: you can convert any acid derivative into one lower on the ladder directly, but never into one higher. Acid chloride → ester → amide is straightforward; amide → ester requires going back through the acid, and acid → acid chloride requires a special reagent (SOCl₂, oxalyl chloride, PCl₅) that works by a different mechanism.

Nucleophilic catalysis: the catalyst forms a covalent bond to the substrate, creating a more reactive intermediate, and is released afterwards. Contrast general base catalysis, where the catalyst merely removes a proton in the transition state and never bonds to the substrate. Distinguishing the two is a standard physical-organic exercise; the classic test is whether the reaction is accelerated by a catalyst that is nucleophilic but not especially basic.

Tautomers: constitutional isomers that interconvert rapidly by the movement of a proton (and the associated π bonds). They are different molecules with different atomic positions, different energies, different spectra, and an equilibrium constant between them.Resonance forms: different drawings of one molecule, differing only in where electrons are shown. No atom moves; there is no equilibrium.

The idea: an enol or enolate (nucleophile, from G.7) adds to a carbonyl carbon (electrophile, from G.1) to give a tetrahedral alkoxide. What happens next is the G.4 question: is there a leaving group on that carbon?— No (the electrophile was an aldehyde or ketone) → the alkoxide is protonated. Product: a β-hydroxy carbonyl. This is the aldol.— Yes (the electrophile was an ester) → the alkoxide collapses, expelling R′O⁻. Product: a β-keto ester or 1,3-diketone. This is the Claisen.