classes winter09 30bid18 30b-ch16-pt2

8/2/2019 Classes Winter09 30BID18 30B-Ch16-Pt2

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Chapter 16: Aldehydes and Ketones

Lecture 20

Chem 30B


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Oxidation of Aldehydes

Aldehydes are oxidized to carboxylic acids by avariety of oxidizing agents, including H2CrO4.

They are also oxidized by Ag+.

CHO H2 CrO4 COOH

Hexanal Hexanoic acid

Vanillic acidVanillin

++

CH

HO

CH3 O

O O

CH3 O

HO

COH

Ag2 OTHF, H2 O

NaOHAgHCl

H2 O


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Oxidation of Aldehydes

Aldehydes are oxidized by O2 in a radicalchain reaction.

Liquid aldehydes are so sensitive to air thatthey must be stored under N2.

Benzoic acidBenzaldehyde

+CH

O O

COH2O22


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Oxidation of Ketones

Ketones are not normally oxidized by chromicacid.

They are oxidized by powerful oxidants at

high temperature and high concentrations ofacid or base.

Hexanedioic acid(Adipic acid)

Cyclohexanone(keto form)

Cyclohexanone(enol form)

HNO3

O

HO OH

OO OH


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Reduction

Aldehydes can be reduced to 1 alcohols.

Ketones can be reduced to 2 alcohols.

The C=O group of an aldehyde or ketone can be

reduced to a -CH2- group.

AldehydesCan BeReduced to Ketones

Can BeReduced to

O OOH

RCH

RCH2 OH

RCH3

RCR'RCHR'

RCH2 R'


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Metal Hydride Reduction

The most common laboratory reagents forthe reduction of aldehydes and ketones areNaBH4 and LiAlH4. Both reagents are sources of hydride ion, H:-, a

very powerful nucleophile.

Hydride ionLithium aluminum

hydride (LAH)

Sodium

borohydride

H

H H

H

H-B-H H-Al-HLi +Na+ H:


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NaBH4 Reduction

Reductions with NaBH4 are most commonlycarried out in aqueous methanol, in puremethanol, or in ethanol.

One mole of NaBH4 reduces four moles ofaldehyde or ketone.

4RCH

O

NaBH4

( RCH2O) 4B-

Na+ H2O

4RCH2OH

A tetraalkyl borate

boratesalts

+

+methanol


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NaBH4 Reduction

The key step in metal hydride reduction istransfer of a hydride ion to carbon of the C=Ogroup to form a tetrahedral carbonyl addition

compound.

Na+

H

H

H-B-H

O

R-C-R'

O BH3

H

R-C-R'

Na+

H2O

O-H

H

R-C-R'

This H comes from waterduring hydrolysis

This H comes from thehydride reducing agent

+


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LiAlH4 Reduction

Unlike NaBH4, LiAlH4 reacts violently withwater, methanol, and other protic solvents.

Reductions using it are carried out indiethyl ether or tetrahydrofuran (THF).

4RCR LiAlH4 ( R2 CHO)4Al- Li+ H2OH

+or OH

-

OH

4RCHR+ + aluminumsaltsA tetraalkyl

aluminate

ether

O


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Catalytic Reduction

Catalytic reductions are generally carried out at

from 25 to 100C and 1 to 5 atm H2.

+ 25 oC, 2 atm

Pt

Cyclohexanone Cyclohexanol

O OH

H2


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Catalytic Reduction

A carbon-carbon double bond may also bereduced under these conditions.

1-Butanoltrans- 2-Butenal

(Crotonalde hyde)

2 H2

NiH

O

OH


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Catalytic Reduction

O OH

RCH=CHCR' RCH=CHCHR'1. NaBH4

2. H2O

O

RCH=CHCR' H2Rh

RCH2 CH2CR'

O

+

By careful choice of experimentalconditions, it is often possible toselectively reduce a carbon-carbon doublein the presence of an aldehyde or ketone.


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Clemmensen Reduction

Refluxing an aldehyde or ketone withamalgamated zinc in concentrated HClconverts the carbonyl group to a methylenegroup.

Zn(Hg), HCl

OH O OH


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Wolff-Kishner Reduction

In the original procedure, the aldehyde or ketoneand hydrazine are refluxed with KOH in a high-boiling solvent.

The same reaction can be brought about usinghydrazine and potassium tert-butoxide in DMSO.

+

diethylene glycol

(reflux)

KOH

N2

Hydrazine

+ H2 NNH2

+ H2 O

O


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Racemization

Racemization at an -carbon may becatalyzed by either acid or base.

O

Ph

OH

Ph

O

PhAn achiral

enol(R)-3-Phenyl-2-

butanone(S)-3-Phenyl-2-

butanone


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Deuterium Exchange

Deuterium exchange at an -carbonmay be catalyzed by either acid or

base.

+

Acetone-d 6Acetone

+

O O

CH 3 CCH 3 6 D2 O CD 3 CCD 3 6 HODD

+

or OD

-


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-Halogenation

-Halogenation: aldehydes and ketones withat least one -hydrogen react at an -carbonwith Br2 and Cl2 .

Reaction is catalyzed by both acid and base.

O

Br2 CH3COOH

OBr

HBr

Acetophenone

++

-Bromo-acetophenone


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-Halogenation Acid-catalyzed -halogenation

Step 1: Acid-catalyzed enolization.

Step 2: Nucleophilic attack of the enol on halogen.

Step 3: (not shown) Proton transfer to solvent

completes the reaction.

H

R

R'-C-C-R

O

R'

C C

H-O R

R

slow

C

R

RH-O

C

R'

Br BrR'

C C

O Br

R

R

H

Br:-+fast+


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-Halogenation

Base-promoted

-halogenationStep 1: Formation of an enolate anion.

Step 2: Nucleophilic attack of the enolate

anion on halogen.

+-

-

Resonance-stabilized enolate anion

+slow

O H

R

O

C C

R'R'

C C

O:

R'-C-C-R-:OH H2O

R

R

R

R

+fast

R'

C C

O Br

R

R BrBr Br +

-

R'

C C

O: R

R


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-Halogenation

Acid-catalyzed halogenation: Introduction of a second halogen is slower than the first.

Introduction of the electronegative halogen on the -carbon decreases the basicity of the carbonyl oxygen

toward protonation. Base-promoted -halogenation:

Each successive halogenation is more rapid than theprevious one.

The introduction of the electronegative halogen on the

-carbon increases the acidity of the remaining -hydrogens and, thus, each successive -hydrogen isremoved more rapidly than the previous one.

classes winter09 30bid18 30b-ch16-pt2

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