MCAT Chemical Processes: Alpha-Carbon Chemistry

aldol reaction

2 Equivalents of reactants are needed. The product of this reaction contains a carbonyl and alcohol group. The reagents for this reaction are NaOEt (or NaOH) and H2O

aldol condensation

Aldehyde + Aldehyde

Ketone + Ketone

Aldehyde + Ketone

Catalyzed by an acid or base (base used here). with water and heat

1) Deprotonation: base deprotonates α-H, leaving the enolate ion.

2) Nucleophilic attack: enolate ion as the nucleophile attacks the carbonyl carbon to form an alkoxide ion.

3) Protonation: alkoxide ion is a stronger base than a hydroxide ion (b/c EDG alkyl attached to O) and deprotonates water to complete the aldol.

4) Condensation: strong base (OH-) does E2 dehydration rxn by deprotonation of the α-C to make the enal (subsequent double bond and original carbonyl).

-> Aldol is unstable and is easily dehydrated by heat or a base to an enal which is stabilized by conjugated double bonds.

result: alpha, beta unsaturated aldehyde

*VERY important on MCAT.

retro-aldol reaction

The reverse of an aldol condensation reaction, in which a carbon-carbon bond is cleaved with heat and base, yielding two aldehydes, two ketones, or one of each.

small pka

strong acid

large pka

weak acid

large ka

strong acid

small ka

weak acid

enolate

-results from deprotonation of alpha-carbon

-stabilized by resonance with the carbonyl

carbanion left, enolate right

kinetic enolate

-less substituted enolate

-formed quickly

-removal of a acidic alpha hydrogen

made with strong base like LDA

thermodynamic enolate

-more substituted double bond

-higher activation energy

-more thermodynamically stable

make with weak base like hydride anion

aldol addition

A reaction between two molecules of an aldehyde or two molecules of a ketone with NaOH and H20 to form an aldol

mixed aldol condensation

Four Products Possible

start with 2 different aldehyde/ketone

catalyzed by NaOEt/NAOH and heat

intramolecular aldol condensation

The formation of an ß-hydroxycarbonyl compound and subsequent dehydration to an alpha, ß-unsaturated carbonyl compound utilizing ONLY the functional groups within a molecule.