18 Chapter Reagents : Aldehydes and Ketones Nuc Addition

Making Aldehydes

1) PCC

• 1° Alcohol → Aldehyde

2) 1) DIBAL-H, 2) H2O

• Ester → Aldehyde

3) 1) LiAlH[OC(CH3)3]3 2) H2O

• Acid Chloride → Aldehyde

Making Ketone

1) PCC or Jones Reagent

• 2° Alcohol → Ketone

2) 1) R2CuLi 2) H2O

• Acid Chloride → Ketone

Ozonolysis to make Ketones and Aldehydes

1) O3

2) H3C-S-CH3

Alkene → Ketone + Aldehyde

Nucleophilic Addition Reactions

1) Reagent:

1) NaBH4, CH3OH

OR

1) LiAlH4

2) H2O

Aldehyde/Ketone → Alcohol

2) Reagent:

1) RMgX or RLi

2) H2O

Aldehyde/Ketone → Alcohol

3) NaCN, HCl

Ketone/Aldehyde → Cyanohydrin

Alkoxide gets protonated by the H in HCl

3R)
NaOH (OH-)

Cyanohydrin → Ketone

3b) Hydrolysis:

Cyanohydrin → Alpha Hydroxy Carboxylic Acid

3C Hydrolysis ANION

Cyanohydrin → Alpha Hydroxy Carboxylate Anion

4) Wittig Mechanism

1) PPh3 + 1° Alkyl Halide → Phosphorium Salt

2) Phosphorium Salt + Butyl OrganoLithium → Ylide

3) Ylide + Aldehyde/Ketone → Oxaphosphatene → Final Product

SHORT CUT:

1) Remove Alkyl Halide of Stariting Material

2) Remove Carbonyl of Aldehyde/Ketone

3) Combine both with Alkene to form FINAL PRODUCT

5) 1° Amine + mild acid (H+)

Aldehyde/Ketone → Imine

1) Nuc Addition of Amine

2) 2 Proton transfers to form Hemiaminal intermediate

3) Acid Proton Transfer forming L.G H2O

4) Proton Transfer on Hydrogen ON the nitrogen to form IMINE

5R) 1° Imine Hydrolysis

1) H3O+ Proton Transfer

2) H2O Attaches to Carbon Double Bond to N

3) H2O Deprotonated, then NHR Protonated

4) Form Carbonyl, Amine leaves as L.G

5) Amine L.G deprotonates H from Carbonyl

6) Ketone + Amine NH3+

6) 2° Amine + mild acid (H+)

Aldehyde/Ketone → Enamine

1) Nuc Addition of Amine

2) 2 Proton transfers to form Hemiaminal intermediate

3) Acid Proton Transfer forming L.G H2O

4) Proton Transfer on Hydrogen ADJACENT to nitrogen to form ENAMINE

6R) 2° Enamine Hydrolysis

1) Carbon-Carbon Alkene Proton Transfer

2) H2O Attaches to Carbon Double Bond N

3) Deprotonate H2O and Protonate N

4) Form Carbonyl and Make AMine a Leaving Group

5) Deprotonate OH carbonyl to form Ketone Final Product

7) NEUTRAL Hydration (H2O)

Aldehyde/Ketone → Hydrate: Geminol-Diol

7a) Acidic Hydration (H+) then (H2O)

Aldehyde/Ketone → Hydrate: Geminol-Diol

7b) Basic Hydration (OH-) then H2O

Aldehyde/Ketone → Hydrate: Geminol-Diol

7R) H+ (Acidic) or OH- (Basic)

Hydrate → Ketone/Aldehyde

8) Reagent
1) R’OH (Excess) , TsOH (Acid Catalyst)

Acid: TsOH, H2SO4

Acetal Formation

Ketone/Aldehyde → HemiAcetal → Acetal

1) Proton Transfer from Acid Catalyst on Carbonyl

2) Nuc Attack from ROH

3) 2 ± H+ proton transfers

4) L.G. H2O leaves

5) Nuc Attack from CH3OH

6) Proton Removal to form ACETAL

8R)
1) H2O (excess), H2SO4 (Acid Catalyst)

Acid: TsOH, H2SO4

Acetal → Aldehyde

1) Acid Catalyst Proton Transfer

2) L.G Dissassosciation of ROH

3) Nuc Attack of H2O at Carbonyl

4) Proton Transfer (Deprotonation of H2O and Protonation of ROH)

5) L.G Dissassociation of ROH #2

6) Deprotonate H from OH using H2O

9) Reagent

1) OH-R-OH (Diol), H2SO4 (Acid Catalysst)

Acid: TsOH, H2SO4

Proton Transfer: ROH, HSO4-, H2O

Cyclic Acetal Formation

Ketone/Aldehyde → HemiAcetal → Cyclic Acetal

1) Proton Transfer from Acid Catalyst on Carbonyl

2) Nuc Attack from ROH

3) 2 ± H+ proton transfers

4) L.G. H2O leaves

5) INTRAMOLECULAR Nuc Attack from OH

6) Proton Removal of H from OH to form CYCLIC ACETAL

9R) Reagent

1) H2O (excess), H2SO4 or TsOH (Acid Catalyst)

1) Acid Catalyst Proton Transfer

2) L.G Dissassosciation of ROH INTRAMOLECULARLY (

• still part of the same moleucle

3) Nuc Attack of H2O at Carbonyl

4) Proton Transfer (Deprotonation of H2O and Protonation of ROH)

5) L.G Dissassociation of ROH #2

6) Deprotonate H from OH using H2O to form KETONE and DIOL

8 and 9 TRICK FOR ACETAL FORMATION

8 and 9 TRICK for ACETAL HYDROLYSIS