Aldehydes and Ketones - carbonyl compounds carbonyl group - structure, bonding and physical...

Aldehydes and Ketones - carbonyl compounds

carbonyl group -structure, bonding and physical

properties

Review of methods of preparation of aldehydes and ketones

hydration of alkynesFriedel-Crafts acylation of

aromatic compounds

Overview of reactions of carbonyl compounds

reduction to alcoholsaddition of organometallic

reagentsaddition of oxygen, nitrogen, sulfur

and phosphorus nucleophilesreduction of carbonyl to methylene

(Clemmensen or Wolff-Kishner)

Nucleophilic addition to carbonyls

Nucleophilic addition to carbonyls

Synthesis of Alcohols

Reduction of Carbonyl Compounds

Synthesis of Alcohols

Reduction of Carbonyl Compounds

H2/cat., NaBH4, LiAlH4

Synthesis of Alcohols

Reduction of Carbonyl Compounds

CO

reducing agent COH

H

lithium aluminum hydride (LAH)

OHO1. LiAlH4/ether2. H2O

-+LiAlH3

HO

Li+

-O H

AlH3-

+LiAlH3

HO

CH3CH2CCH2CH2COCH2CH3

O O

2. H2O

1. LiAlH4/ether

CH3CH2CHCH2CH2CH2OH

OH

sodium borohydride

CH3CH2CCH2CH2COCH2CH3

O O

NaBH4/H2O

CH3CH2CHCH2CH2COCH2CH3

OH

O

Synthesis of Alcohols Using Organometallic Reagents

++-

RMgX C

O MgX

RCO

C

OH

R

H3O

MgX

RCO

++-

RMgX C

O MgX

RCO

C

OH

R

H3O

+2. H3O

1. ether

CH3(CH2)8CH2MgBr +

CH3(CH2)8CH2CH2OH

HCHO

+

CCH3

OH

CH3

COCH3 + O

2. H3O

1. ether

2 CH3MgBr

CH3

OC OCH3

+MgBr-

CH3 MgBr

COCH3 O

-OCH3CH3

OC

CH3

OC OCH3

+MgBr-

CH3 MgBr

COCH3 O

CH3

OCCH3

CH3 MgBr

CH3

OC

+MgBr-

+H

CH3

OCCH3

CH3 MgBr

CH3

OC

+MgBr-

CCH3

OH

CH3

CH2CH2OHMgBr+

1. THF

2. H3O+

O

Hydration of aldehydes and ketones

An example

Addition of alcohols: hemiacetal and acetal formation

Addition of alcohols: hemiacetal and acetal formation

hemiacetalor hemiketal

O

+ROH H3O+

OH

OR

Addition of alcohols: hemiacetal and acetal formation

hemiacetalacetal

+ROH H3O+

OH

OR

OR

OR

Mechanism of acetal formation

O H OH2+ OH

+

O R

H

O

OHH

R

+

OR+

OR

H

Mechanism of acetal formation

OR+

OR

H

OR

OR

H+

OHHOR

ORH3O

++

An example

O +

HO

HO

pTosOH

tolueneO

O

Addition of ammonia and amines: imine and enamine formation

O+ R NH2

H+

NH

OH

R

NR

Examples

N

O

+CH3NH2

H3O+

N

N CH3

Examples

Examples

The Wittig Reaction

R CH2X + Ph3P: RCH2 PPh3+

X-

B:

RCH PPh3+

YLIDE

O

R

H

An example

The mechanism

Br Ph3P:+PPh3

HBr

Mechanism, cont.

PPh3 ylidePPh3

HBr

OH

Mechanism, cont.

+

O

O

PPh3

oxaphosphetane

PPh3

Mechanism, cont.

O

PPh3

Formation of cyanohydrins

O1) CN

-

2) H3O+

C

OH

N

Example

Glc Glc O

H C N

Reduction of carbonyls to alkanes

Clemmensen reductionWolff-Kishner reductionDesulfurization of thioketals

Nucleophilic Addition to a,b-Unsaturated Carbonyls

O

+ Nuc

Nuc

OH

Nuc OH

Nucleophilic Addition to a,b-Unsaturated Carbonyls

Strong nucleophiles add 1,2 kinetic control

Weaker nucleophiles add 1,4thermodynamic control

Nucleophilic Addition to a,b-Unsaturated Carbonyls

O

KCN

H2O

Nucleophilic Addition to a,b-Unsaturated Carbonyls

NC

OHO

KCNH2O

O

NC

Nucleophilic Addition to a,b-Unsaturated Carbonyls

O

+ CH3CH2( )2CuLiEt2O

H2O

Nucleophilic Addition to a,b-Unsaturated Carbonyls

O

CH3CH2

O

+ CH3CH2( )2CuLiEt2O

H2O