Chapter 19 - Aldehydes and Ketones

Nomenclature of Aldehydes

1) Suffix “-al” indicates aldehyde.

2) Parent chain must include aldehyde.

3) Aldehyde has priority (always position 1).

4) Aldehyde on ring is carbaldehyde.

Nomenclature of Ketones

1) Suffix “-one” indicates ketone.

2) Ketone has priority over alcohol, alkene, alkyne.

3) Ketone as substituent is “oxo.”

Acid-Catalyzed Hydration

Notes:

Acid conditions = H₃O⁺

Adds two -OH to the carbonyl carbon.

Mechanism:

Acid protonates ketone/aldehyde. Water attacks the carbonyl carbon. -OH₂ is deprotonated.

Base-Catalyzed Hydration

Notes:

Acid conditions = OH^-

Adds two -OH to the carbonyl carbon.

Mechanism:

OH^- attacks the carbonyl carbon. -O^- is protonated.

Acetal Formation

Notes:

Acid conditions = H₃O⁺

Adds two -OR to the carbonyl carbon.

Forms a hemiacetal intermediate.

Mechanism:

Acid protonates ketone/aldehyde. Alcohol attacks carbonyl carbon. -ROH⁺ is deprotonated.

-OH is protonated. Reformation of C=O bond kicks out H₂O. Alcohol attacks carbonyl carbon. -ROH⁺ is deprotonated.

Acetal as a Protecting Group

Notes:

Acetal (R-O) bond is inert under basic conditions. Can be used to protect aldehydes and ketones.

Mechanism:

Same as acetal formatiom.

Imine Formation

Notes:

From primary amines (H₂N-R, H₂N-OH, H₂N-NH₂).

pH dependent - Max rate at ~4.5.

Forms imines (C=N double bond).

Carbinolamine intermediate.

Mechanism:

RNH₂ attacks carbonyl carbon. -O^- is protonated. R₂NH₂⁺ is deprotonated. Carbinolamine formed.

-OH is protonated. Formation of C=N bond kicks out H₂O. R=NRH⁺ is deprotonated.

Enamine Formation

Notes:

From secondary amines (HN-R₂)

Forms Enamines (Amine next to C=C).

Carbinolamine intermediate.

Mechanism:

R₂NH attacks carbonyl carbon. -O^- is protonated. R₃NH₁⁺ is deprotonated. Carbinolamine formed.

-OH is protonated. Formation of C=N bond kicks out H₂O. Elimination reaction to form C=C and removes NR₃⁺ charge.

Wolfff-Kishner Reduction

Notes:

Imine fromation using H₂N-NH₂ forms a hydrozone which can undergo Wolff-Kishner Reduction.

Removes =N-NH₂ and replaces it with 2 H.

Mechanism:

=N-NH₂ is deprotonated. Resonance causes C to have - charge. - charge on C protonated. -N=N-H deprotonated. Formation of N=N bond kicks out N₂. - charge on C protonated.

Acid-Catalyzed Hydrolysis of Acetals

Notes:

Acetal stable under basic conditions.

Reverse reaction of acetal formation.

Mechanism:

-OR is protonated. Formation of C=O bond kicks out HOR. H₂O attacks carbonyl carbon. -H2O⁺ is deprotonated. -OR is protonated. Formation of C=O bond kicks out HOR. C=OH⁺ is deprotonated.

Acid-Catalyzed Hydrolysis of Imines

Notes:

Acetal stable under basic conditions.

Reverse reaction of imine formation.

Mechanism:

C=N-R is protonated. H₂O attacks carbonyl carbon. -H₂O⁺ is deprotonated. N is protonated. Formation of C=O bond kicks out H₂NR. C=OH⁺ is deprotonated.

Acid-Catalyzed Hydrolysis of Enamines

Notes:

Acetal stable under basic conditions.

Reverse reaction of enamine formation.

Mechanism:

C=C double bond is protonated. Resonance when N=C reforms. H₂O attacks C=N. -H₂O⁺ is deprotonated. N is protonated. Formation of C=O bond kicks out HNR₂. C=OH⁺ is deprotonated.

Thioacetal Formation

Notes:

Adds two -SR (thiols) to the carbonyl carbon.

Same mechanism as acetal formation.

Mechanism:

Same mechanism as acetal formation.

Desulfurization (Removal of Thioacetal)

Notes:

Cylic thioacetal is a good protecting group because it is stable in both acidic and basic conditions.

Mechanism:

Same mechanism as thioacetal formation.

Reduction of Aldehydes/Ketones

Notes:

3 methods to reduce aldehydes/ketones.

Reduce aldehydes/ketones into alcohols by delivering H.

LiAlH₄⁺ and protic solvents must be used in separate steps.

Mechanism NaBH₄ / LiAlH₄:

H added to carbonyl carbon. -O^- protonated by protic solvent.

Grignard Reagents

Notes:

Reduces aldehydes/ketones into alcohol by delivering an alkyl group.

Grignard reagents synthesize by adding Mg + ether to an alkyl halide.

Mechanism:

High nucleophilic C attacks carbonyl carbon and delivers alkyl group. -O^- protonated by protic solvent.

Cyanohydrin Formation

Notes:

Reduces aldehydes/ketones into alcohols by delivering a CN group.

Mechanism:

CN^- attacks carbonyl carbon. -O^- is protonated.

Wittig Reaction

Notes:

Unstabilized ylids (with alkyl group) = Z isomer (same)

Stabilized ylids (with EWG) = E isomer (opposite)

[2+2] Cycloaddition and retro [2+2] cycloaddition.

Driving force is O=P bond (triphenylphosphine oxide).

Mechanism:

CN^- attacks carbonyl carbon. -O^- is protonated.

Preparation of Ylid Reagents for Wittig Reactions

Notes:

Unstabilized ylids (with alkyl group) = Z isomer (same)

Stabilized ylids (with EWG) = E isomer (opposite)

Must be done on methyl, primary, secondary R-X due to S_N2.

Common bases used → NaH, n-BuLi, PhLi, NaNH₂

Mechanism:

PPh₃ attacks R-X and kicks X out (S_N2). Base deprotonates C, leaving a negative charge on C and a positive charge on PPh₃. Resonance occurs and double bond forms between C and PPh₃

Baeyer-Oxidation Reaction

Notes:

Any peroxyacid can be used (ex: mCPBA).

Migration/irreversible step aptitude:

H > 3° > 2° > Ph > 1° > CH₃

(Theory: Migrating group has ability to stabilzie + charge)

Forms an ester.

Mechanism:

Peroxyacid protonated aldehyde/ketone. Conjugate base of peroxy acid attacks carbonyl carbon. Undergoes migration/rearrangment. C=OH⁺ is deprotonated.