Aldehydes - IR

Aldehydes, Ketones - MS

Aldehydes - 1H-NMR

C9H10O - IR at 1690 cm-1

C9H10O isomer - IR at 1730 cm-1

C4H7ClO - IR at 1715 cm-1

C7H14O - IR at 1710 cm-1

C9H10O2 - IR at 1695 cm-1

C10H12O - IR at 1710 cm-1

C6H12O3 - IR at 1715 cm-1

C4H6O - IR at 1690 cm-1

Preparative methodology for aldehydes.

"something" 1° alcohol aldehyde

H3O+

OHPCC

H

O

1. B2H6 / THF CrO3 H

O

2. H2O2 / OH-OH

H

N

Br1. Mg / ether PCC H

O

2. CH2O / H3O+

OH

+ 1 Carbon

Br1. Mg / ether

2. oxirane / H3O+

OH

CrO3

N

H

O

From alkenes

From halides

+ 2 Carbons

Preparative methodology for ketones.

"something" 2° alcohol ketone

H3O+

OH O

1. Hg(OAc)2 /H2ONa2Cr2O7

O2. NaBH4

OH

O

HgSO4 / H3O+

Br

Mg / ether

2. H3O+

Mg+Br-

O

From alkenes

From halides

+ 2 Carbons

CrO3

H3O+

H3O+

From alkynes

OHOCrO3

H3O+

Oxidation of aldehydes; ketones do not oxidize.

Ag2O / NH3OH

O

OH

O

MnO4- / H3O

+

H

O

Tollen's Reagent

Mild permanganateoxidation

H

O

OH-

Ag2O / NH3

OH-

OH

O

H3CO

O

H Cu2+ / OH- H3CO

O

OHFehling's Reagent

H

O

Reaction Scheme for the Carbonyl Group Reacting as an Electrophile with Nucleophiles

Reaction Scheme for the Carbonyl Group Reacting as a Nucleophile with Electrophiles

Nucleophile Reaction Conditions Reaction mode(Purpose)

BH4 - 1. NaBH4 / OH-

2. H3O+

Intermolecular 1,2-addition(reduction of aldehydes and

ketones; synthesis of alcohols)

AlH4 - 1. LiAlH4 / THF2. H3O

+

Intermolecular 1,2-addition(reduction of aldehydes,

ketones and esters;synthesis of alcohols)

[ (CH3)2CHCH2 ]2AlH1. [(CH3)2CHCH2]2AlH

in THF2. H3O

+

Intramolecular 1,2-addition(reduction of aldehydes,ketones and acyl halides;

synthesis of alcoholsand aldehydes)

H2

H2 / (Me/C)Me = Pd, Pt, Ni

Intermolecular 1,2-addition(reduction of aldehydes,

ketones and esters;synthesis of alcohols

and alkanes)

H2

Zn/Hg amalgamin HCl

Clemensen Reduction(reduction of aryl ketones toalkyl aromatic compounds)

Summary of H-centered nucleophiles in 1,2-additionsto C=O groups.

For both the BH4- and AlH4

- anions the stoichiometry is 4:1 in the substrate.

O

Al-

H

H

H

H+

OAl-

H

H

H

H

OAl-

H

H

H

H

OH

+ H3AlO3

H3O+

H

+ 3 more mol

O

AlR4-

HR =

AlR4-

Reducing agents are selective for different functional groups.

BH4- LiAH

H2 Pd/C

O H

O

O

O

O

CH2OH

HOH2C

CH2OH

HOH2C

CH2OH

Ester functional group is first reduced to an aldehyde, then to alcohol.

O

O

HOH2C

Al-

H

H

H

H+

O

OAl-

H

H

H

H

O

OAl-

H

H

H

HH

O

+ Al-

H

H

H

OCH3

H

O

AlH4-

4 mol 4 mol+ H3AlO3H3O

+

Because the R2AlH is a Lewis Acid the reaction is intramolecular.

O

Al

H

+

H3O+

O

Al-

H

OAl-

H

OAl

H

OAl

H

HO H

Nucleophile Reaction Conditions Reaction mode(Purpose)

NH31. NH3 / H3O

+

2. H2 / NiIntermolecular 1,2-addition

(reductive amination;synthesis of imines

and 1° amines)

RNH21. RNH2 / H3O

+

2. H2 / Ni

RNH2 / ethanol

Intermolecular 1,2-addition(reductive amination;

synthesis of Schiff basesand 2° amines)

Intermolecular 1,4-addition(synthesis of β-aminocarbonyl

compounds)

R2NH R2NH / H3O+ Intramolecular 1,2-addition

(synthesi sof enamines)

N2H4a nd derivatives

1. N2H4 / H3O+

2. OH- / DMSOIntermolecular 1,2-addition(Wol -ff Kishner reduction of

aldehydes, ketones;synthesi sof hydrazones, alkanes

and alkyl benzene)s

Summary of N-centered nucleophiles in 1,2- and 1,4-additionsto C=O groups.

O

H

O

CH3NH2

NH3

H3O+

H3O+

N

H

H

H2

Ni NH2

1° AmineImine

N

Schiff Base

H2

NiNH

2° Amine

O

(CH3)2NH

H3O+

N N

Enamine, 3° Amine

Preparation of imines, Schiff bases, and 1°, 2° and 3° amines.

H

Example of the use of 1,4-addition in synthesis of complex amines.

Br

O HN

NH

Br

O

OH- / MeOH

O

CH3NH2

ethanol

O

NH

CH3NH2

H3O+

N

NH

H2 Ni

HN

NH

Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2-additions.

Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2-additions.

O

Hal

eliminationO

1,4-addition

ONu1,4

1,2-addition

OHNu1,4

Nu1,2Nu1,4

Nu1,2 elaborationXNu1,4

Nu1,2

Intrachain

Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2-additions.

Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2-additions.

O

Hal

elimination O1,4-addition

O

Nu1,4

1,2-addition

OH

Nu1,4

Nu1,2

Nu1,4

Nu1,2 elaboration

Exo-ring.

X

Nu1,4Nu1,2

Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2-additions.

Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2-additions.

O

elimination

O

Hal1,4-addition

O

Nu1,4

OH

Nu1,4

Nu1,2

Nu1,4

1,2-addition

Nu1,2

elaboration

X

Nu1,4

Nu1,2

Endo-ring.

H2N

HN

N

HO

Br

H

O

NO

13

1

3

1

3

Examples closely following the templates - one elaboration step.

N

N

H

Br

Br

H

N

O

13

13

1

3

Examples closely following the templates - multiple elaboration steps.

OH

O

O

Br

O

O

NH2

NH2

NH2

Use of 1,3-template for inducing multiple Hoffman eliminations.

1

3

1 1

11

3 3

33

OBr

Use of 1,3-template for making fused rings via Michael Addition.

1

111

3

33 3

O O N

Tms O N

-O

+13

Tms O

N

O

13

Cl

N

O

Nucleophile Reaction Conditions Reaction mode(Purpose)

H2O

H3O+

orOH-

Intermolecular 1,2-addition(hydration)

ROH

ROH / H3O+

excess ROH / H3O+

Intermolecular 1,2-addition(synthesis of hemiacetals

and hemiketals)

(synthesis of acetals and ketals)

1,2- or 1,3-diols diol / H3O+

Intramolecular 1,2-addition(synthesis of cyclic acetals

and ketals;protecting group for aldehydes

and ketones)

aldehyde or ketonepolyols equilibrium in H2O Intramolecular 1,2-addition

(cyclic carbohydrates)

Summary of O-centered nucleophiles in 1,2-additionsto C=O groups.

Hydration equilibrium favors the carbonyl compound for both stericelectronic (inductive) reasons).

OH

H3CCH3

OHH3C

O

CH3

H2O

However, sterically incongested carbonyls with electron-withdrawingsubstituents favor hydrates.

OH

HH

OHH

O

H

H2O

OH

Cl3CH

OHCl3C

O

H

H2O

ChloralChloral hydrate

The most important applications of acetals and ketals is in a conceptof C=O protecting groups using diols.

O

H

H3O+

Br

O

H

CH2OH

O

HBrOH OH

+

HBr

O

O + H2O

1. Mg / ether

2. CH2O / H3O+

HBr

O

O

HHOH2C

O

O

HHOH2C

O

OH3O

+

O

H

CH2OHOH OH

+

use excess diol

use excess water

ProtectingReaction

C=O-sensitiveReaction(s)

De-protectingReaction

Another important applications of acetals and ketals is in thechemistry of carbohydrates and their polymers.

Fisher projection formula for D-glucose

OHH

OH

CH2OH

HOH

H

H

OH

H O

OHH

OH

CH2OH

H

OH

H

H

OH

O

H

H OH

HO H

H OH

H OH

CH2OH

O H

Another important applications of acetals and ketals is in thechemistry of carbohydrates and their polymers.

Cyclic Hemiacetal formed from "top"

OO

H

OH

CH2OH

HOH

H

H

OH

H

OH

H

HOHO

H

H

OH

H

OH

HOH2C

H

OO

H

OH

CH2OH

HOH

H

H

OH

OH

H

H

HOHO

H

OH

H

H

OH

HOH2C

H

OH

H

OH

CH2OH

HOH

H

H

OH

H O

α- or axial epimer

OHH

OH

CH2OH

HOH

H

H

OH

H

OCyclic Hemiacetal formed from " bottom"

β- or axial epimer

O

H

HOHO

H H

H

OH

HOH2C

H

O

H

HO

H

O

H

H

OH

HOH2C

H

O

H

HO

H H

H

OH

HOH2C

H

O

H

HO

H

OH

H

H

OH

HOH2C

H

OOPolymer of all cyclic

β-hemiacetal "

Nucleophile Reaction Conditions Reaction mode(Purpose)

CN - KCN / HCN Intermolecular 1,2-addition(formation of cyanohydrins andα-hydr oxyand α-amino acid )s

R –

( R= alkyl, ally , l vinyl,acetyny l an d ary )l

1. RMg+Br- / ether2. H3O

+

Intermolecular 1,2-addition(Grignard synthesis of alcohols)

RCu –

(R = alkyl, allyl, vinyland aryl)

1. RCu-Li + / ether2. H3O

+

Intermolecular 1,2-and 1,4-addition

(Gilman synthesis of β-alkyl,β-vinyl and β-aryl ketones)

(Ph)3P+-CH-R

(R = alkyl or acylalkoxy)(Ph)3P

+-CH-R / THF Intermolecular 1,2-addition(Wittig synthesis of E-alkenesor Z-α,β-unsaturated carbonyl

compounds)

Summary of C-centered nucleophiles in 1,2- and 1,4-additionsto C=O groups.

Base-catalyzed addition of CN- is used for the synthesis of different classesof organic compounds.

O

HHCN / KCN

OH

HCN

H3O+

or OH-

OH

HCO2H

α-hydroxy acid

O

H

OH

HCN

H3CO H3CO

HCN

O

HHCN / KCN

OH

HCN

H3O+

or OH-

OH

CO2HH

CO2H

NH2

CO2HH

H3O+

ΔNH3Δ

α,β-unsaturated acidα-amino acid

There are two types of ylides: stabilized and unstabilized. They yield alkenes withselect stereochemistry.

P Ph3P

Ph3P : + Br Ph3P+

Br -

BuLi

THF

Ph3P+

Ph3P : +OCH3

Br Ph3P+

Br -

OH-

O

OCH3

O

Ph3P+

OCH3

O

stabilized ylide

unstabilized ylide

There are two types of ylides: stabilized and unstabilized. They yield alkenes withselect stereochemistry.

Ph3P+

Ph3P+

OCH3

O

stabilized ylide

unstabilized ylide

+

O

H

(E)-1-cyclopentyl-4-methyl-2-pentene

+

O

HO

OCH3

methyl (Z)-4-methyl-2-pentenoate

H3O+

O

OH

Organocupper (Gilman) reagents are organometallic compounds with either the alkyl, vinyl or aryl nucleophilic C that react by 1,4-addition.

dialkylcopper lithium (R2CuLi)

+

Br

2 Li

pentane

Li

LiBr CuI

ether Cu-Li+

O

1. R2CuLi / ether

2. H3O+

O

1,4-addition product1. CH3Mg+Br- / ether

2. H3O+

HO CH3

1,2-addition product