WWU -- Chemistry Aldehydes and Ketones II. Oxidation and Reduction: Synthesis Chapter 17.

WWU -- ChemistryWWU -- Chemistry

Aldehydes and Ketones II. Aldehydes and Ketones II. Oxidation and Reduction: Oxidation and Reduction:

Synthesis Synthesis

Chapter 17


Assignment for Assignment for Chapter 17Chapter 17

• Sections 17.0 through 17.2• Section 17.3 -- SKIP• Sections 17.4 through 17.12• Section 17.13 through 17.15 --

SKIP• Sections 17.16 through 17.20• Problems


Problem AssignmentProblem Assignment

• In-Text Problems– 17-1 through 17-11– 17-15 through 17-18

• End-of-Chapter Problems– 1 through 4 (all parts)


Reduction of a Carbonyl Group to an Alcohol


What If We Had the What If We Had the World’s Simplest World’s Simplest

Nucleophile?Nucleophile?

R C R

O

H

R C R

O

H

R C R

OH

H

:_

: : : :.. _

H2O


•If we could make this work, we would have means of reducing the carbonyl group.

•Go back and re-read the Special Topics box at the beginning of Chapter 14.


Lithium Aluminum Lithium Aluminum HydrideHydride

H Al H

H

H

Li

Lithium aluminum hydride, LiAlH4, is a very powerful hydride donor, and thus it is an excellent reducing agent.


OutlineOutline

Al H

O

CR R

R C R

O

H


Lithium Aluminum HydrideLithium Aluminum HydrideReduction of AldehydesReduction of Aldehydes

and Ketonesand Ketones

These reactions typically go in very high yield.

O

CR R

H C O

R

R

Al Li+

H C O

R

R

Al Li+

R C R

O

H

H

LiAlH4 + 4

4

4

+ 4 H2O 4 + Al(OH)3

+ LiOH


Learn it this way:Learn it this way:

O

CR R

LiAlH4R C R

O

H

H2OR C R

OH

H


Aluminum is required to coordinate with the oxygen of the carbonyl group.

For example, in the absence of aluminum (using sodium hydride, NaH as the reducing agent), there is no reduction.


You Must Be Careful!You Must Be Careful!

LiAlH4 + 4 H2O LiOH + Al(OH)3 + 4 H2


A similar, but less A similar, but less reactive, reducing agent reactive, reducing agent is is sodium borohydride, sodium borohydride,

NaBHNaBH44..

H B H

H

H

Na


Sodium Borohydride Reduction Sodium Borohydride Reduction

of Aldehydes and Ketonesof Aldehydes and Ketones

O

CR R

R C R

O

H

Na+

R C R

O

H

H

NaBH4H2O


ExampleExample

ONaBH4

orLiAlH4

H2O

H

OH

In general, the reduction should proceed equally easily from either side, yielding two mirror-image products.


Sodium Borohydride Sodium Borohydride Reduction of CamphorReduction of Camphor

(endo)(exo)

In this case, approach by borohydride from the upper side is sterically hindered by the bridge methyl group. The result is a predominance of exo alcohol.

CH3

CH3

CH3O

CH3

CH3

CH3

OH

H

CH3

CH3

CH3

H

OH

1) NaBH4+

Camphor Borneol Isoborneol (15%) (85%)

2) H2O


Sodium Borohydride Sodium Borohydride Reduction of NorcamphorReduction of Norcamphor

•Here, it is the underside of the molecule that is more sterically hindered, so the favored alcohol is the endo alcohol.

•Similar results are obtained with lithium aluminum hydride.

O OH

H

H

OH

1) NaBH4+

Bicyclo[2.2.1}heptan-2-one endo alcohol exo alcohol (Norcamphor) (86%) (14%)

2) H2O


Another example:Another example:

C H

O

LiAlH4

orNaBH4

CH2 OH


Contrast these two Contrast these two reactionsreactions

CH3

CCH2

CH2

CO

CH2

O

O

CH3

CH3

CCH2

CH2

CO

CH2

O

O

CH3

CH3

CHCH2

CH2

CH2

OH

OH

CH3

CHCH2

CH2

CO

CH2

OH

O

CH3

1) LiAlH4

2) H2O

1) NaBH4

2) H2O

Note that sodium borohydride is more selective.


Catalytic Hydrogenation ofCatalytic Hydrogenation ofAldehydes and KetonesAldehydes and Ketones

O

CR R

R C R

O

H

H

+ H2

Ni

50°(1000 psi)


Reduction of a Carbonyl Group to a Methylene

Group


We are trying to We are trying to accomplish...accomplish...

C

O

CH2


Clemmensen ReductionClemmensen Reduction

Zn(Hg) is a zinc amalgam

R C R

O

R C

H

H

RZn(Hg)

HCl (conc.)


•The mechanism of the Clemmensen reduction involves the formation of some sort of zinc-ketone complex.

•This reaction is a good method for the reduction of acid-stable carbonyl compounds (Note that the reaction takes place in the presence of concentrated HCl).


Example of a Example of a Clemmensen ReductionClemmensen Reduction

C CH2

O

CH2 C OH

O

CH2 CH2 CH2 C OH

O

Zn(Hg)

conc. HCl heat

90% yield

Notice that the reduction does not affect the carboxyl group


Wolff-Kishner ReductionWolff-Kishner Reduction

R C R

O

NH2 NH2OH CH2 CH2 OH

R C R

H

H

+KOH

190 - 200 °C

+ N2 + H2O


• The mechanism involves the formation of a hydrazine adduct, which loses water to form a hydrazone.

• The hydrazone then rearranges to lose a molecule of nitrogen gas, leaving behind a carbanion.

• The carbanion picks up a proton from the solvent to form the product.


This will never show up on any of my This will never show up on any of my exams!exams!

O

CR R

H2N NH2

acidR C R

OH

NH

NH2

- H2O C

N

R R

NH2

rearrange

C

N

R R

N

H

R C R

H

+

N N

H2OR C R

H

H


The Wolff-Kishner reduction is useful for the reduction of carbonyl compounds that are stable in strong base.

(Note that the reaction takes place in the presence of concentrated KOH or other base)


ExampleExample

N

O

O

H

Isatin

H2N NH2

N

N

O

H

NH2

NaOCH2CH3 CH3CH2OH

N

O

H

75% yield


DesulfurizationDesulfurization

O

CR R

HS CH2 CH2 SHC

R R

S S

CH2 CH2

CR R

S S

CH2 CH2

CR R

H HCH3 CH3

+ +

+Raney Ni

+

+

H2O

2 NiS

BF3

diethyl ether

H2


•Advantages: High yields Mild and nearly neutral reaction conditions

•Disadvantages: Stinky! Raney Nickel is

tricky to prepare


Example of a Raney Example of a Raney Nickel DesulfurizationNickel Desulfurization

O

HSCH2

CH2

SH

BF3 ether

S

S

H2 Raney Ni


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WWU -- Chemistry Aldehydes and Ketones II. Oxidation and Reduction: Synthesis Chapter 17.

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