Organic Chemistry Carbonyl Reactions: Mechanisms, Products & Synthesis

Aldol Condensation

NaOH, H2O, Δ

Aldol Addition

NaOH, H2O (low/room temp)

Retro-Aldol

NaOH, H2O (reverse reaction)

Alkylation of α-Carbon (Kinetic / Less Substituted)

1) LDA, -78°C 2) R-X

Alkylation of α-Carbon (Thermodynamic / More Substituted)

1) NaH, 25°C 2) R-X

Alpha-Halogenation of Ketones (Acidic Conditions)

[H3O+], Br2

Alpha-Halogenation of Ketones (Basic Conditions)

OH-, Br2

Hell-Volhard-Zelinsky (HVZ) Reaction

1) Br2, PBr3 2) H2O

Haloform Reaction (Alpha-Halogenation w/ NAS)

1) NaOH, Br2 2) H3O+

Claisen Condensation

1) NaOEt 2) H3O+

Michael Addition (Base-Catalyzed, 1,4-Addition)

1) KOH 2) α,β-unsaturated carbonyl 3) H3O+

Gilman Conjugate Addition (1,4-Addition)

1) R2CuLi 2) H3O+

1,2-Addition

1) RMgBr 2) H3O+ OR 1) LiAlH4 2) H3O+

Malonic Ester Synthesis

1) NaOEt 2) R-Br 3) H3O+, Δ (starting with diethyl malonate)

Acetoacetic Ester Synthesis

1) NaOEt 2) R-Br 3) H3O+, Δ (starting with ethyl acetoacetate)

Stork Enamine Synthesis

1) R2NH, [H+] (-H2O) 2) Michael acceptor or R-X 3) H3O+

Robinson Annulation

1) NaOH / NaOEt / KOH 2) NaOH / NaOEt / KOH, Δ

Tautomerization (Acidic Conditions)

H3O+, H2O

Tautomerization (Basic Conditions)

OH-, H2O

Aldol Condensation (Mechanism)

DR. NaP "Ed-ish" (Crossed/Intramolecular: DR. NaP "Ed-ish" -> 1OR. Love)

Aldol Addition (Mechanism)

DR. NaP

Retro-Aldol (Mechanism)

DR. Love Problems

Alkylation of α-Carbon (Mechanism)

DR. SN2

Alpha-Halogenation - Acidic Ketones (Mechanism)

PROuD + NAKeD

Alpha-Halogenation - Basic Ketones (Mechanism)

DR. SN2

Hell-Volhard-Zelinsky / HVZ Reaction (Mechanism)

DR. SN2

Haloform Reaction (Mechanism)

DR. SN2 + NL

Claisen Condensation (Mechanism)

DR. Nelly & DR. Pele

Michael Addition - Base-Catalyzed (Mechanism)

DR. NaRP

Gilman Conjugate Addition (Mechanism)

NaRP + taut.

1,2-Addition - Grignard / LiAlH4 (Mechanism)

NaP

Malonic & Acetoacetic Ester Synthesis (Mechanism)

DR. SN2 + PaNDn PLaD + Δ (decarb + Taut)

Stork Enamine Synthesis (Mechanism)

2° amine to enamine + NaP + PaNDn PLaD

Robinson Annulation (Mechanism)

Michael addition + aldol condensation (forms ring)

Tautomerization - Acidic (Mechanism)

PROuD

Tautomerization - Basic (Mechanism)

DRiP

Aldol Condensation (Reactant -> Product)

2 carbonyls -> α,β-unsaturated aldehyde or ketone (trans is major)

Aldol Addition (Reactant -> Product)

2 carbonyls -> β-hydroxy aldehyde or ketone (favored if aldehyde)

Retro-Aldol (Reactant -> Product)

β-hydroxy aldehyde or ketone -> 2 carbonyl compounds (favored if ketone)

Alkylation of α-Carbon (Reactant -> Product)

Carbonyl compound + alkyl halide -> α-substituted carbonyl compound

Alpha-Halogenation - Acidic Ketones (Reactant -> Product)

Ketone -> monohalogenated α-bromo ketone

Alpha-Halogenation - Basic Ketones (Reactant -> Product)

Ketone -> polyhalogenated α-bromo ketone (watch for polyhalogenation on non-methyl ketones)

Hell-Volhard-Zelinsky / HVZ Reaction (Reactant -> Product)

Carboxylic acid -> α-bromo carboxylic acid

Haloform Reaction (Reactant -> Product)

Methyl ketone -> carboxylic acid (+ CHX3)

Claisen Condensation (Reactant -> Product)

2 esters -> β-keto ester

Michael Addition - Base-Catalyzed (Reactant -> Product)

Doubly stabilized carbonyl (Michael donor) + α,β-unsaturated carbonyl (Michael acceptor) -> 1,5-dicarbonyl compound

Gilman Conjugate Addition (Reactant -> Product)

α,β-unsaturated carbonyl + Gilman reagent -> β-substituted carbonyl compound

1,2-Addition (Reactant -> Product)

α,β-unsaturated aldehyde/ketone -> allylic alcohol (1° for ald & 2° for ket w/ LiAlH4; 2° for ald & 3° for ket w/ Grignard)

Malonic Ester Synthesis (Reactant -> Product)

Diethyl malonate + alkyl halide -> carboxylic acid

Acetoacetic Ester Synthesis (Reactant -> Product)

Ethyl acetoacetate + alkyl halide -> methyl ketone

Stork Enamine Synthesis (Reactant -> Product)

Aldehyde/ketone -> 1,5-dicarbonyl (if Michael acceptor) OR α-alkylated carbonyl (if alkyl halide)

Robinson Annulation (Reactant -> Product)

Ketone + α,β-unsaturated ketone -> 6-membered α,β-unsaturated cyclic ketone

Tautomerization (Reactant -> Product)

Keto

Synthesis Strategy: C-C bond forming reactions that yield products with 2 functional groups

1. Aldol reaction/condensation, 2. Claisen condensation, 3. Stork enamine synthesis (Michael reaction)

Synthesis Strategy: Which reactions produce 1,5-dicarbonyl compounds?

Stork enamine synthesis (with a Michael acceptor) and Base-catalyzed Michael addition

Synthesis Strategy: Which reactions produce 1,3-difunctional compounds?

Aldol addition (β-hydroxy carbonyl) and Claisen condensation (β-keto ester)