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Chapter 18 – Ketones and Aldehydes

 Nomenclature

o Ketones have priority over alcohols

. Find the longest chain with the carbonyl in it.

. Name the parent and replace the “e” with “one”

. Say where the carbonyl is.

O

octan-3-one

. When the ketone is not the high-priority group, you call the carbonyl “oxo” to name it.

. Common names: Name the two pieces coming off the carbonyl and call it “ketone”

O

ethyl butyl ketone

o Aldehydes have priority over ketones

. Find the longest chain with the carbonyl at the end.

. Name the parent and replace the “e” with “al.”

O

O

3-oxo-octanal

 Synthesis of ketones and aldehydes o Oxidation of alcohols

Chromic Acid KMnO4 PCC Swern 1° ROH RCOOH RCOOH RCHO RCHO 2° ROH Ketone Ketone Ketone Ketone 3° ROH NR NR NR NR

o Ozonolysis of alkenes

1) O3 O

2) DMS O

. See Chapter 8 for review

o Friedel-Crafts Acylation

O O

Cl

AlCl3

. See Chapter 17 for review

o Hydration of alkynes

. Acid-catalyzed

H2SO4 (aq) H HgSO4 O

. Hydroboration-oxidation

O 1) Sia2BH H - 2) H2O2, OH

. See Chapter 8 for review o Synthesis from carboxylic acids and acid chlorides

. Acids are first converted to acid chlorides.

O O SOCl2 OH Cl

. Acid chlorides are reduced to aldehydes with LiAlH(OtBu)3

O O 1) LiAlH(OtBu)3

Cl 2) H2O

 LiCuR2

o LiCuR2 is like a specialty version of a Grignard that only replaces the Cl of acid chlorides.

O O

LiCu(CH2CH3)2 Cl

 Wittig Reactions

o Overall reaction: turn a carbonyl into a carbon-carbon double bond.

. The carbon of the alkyl halide replaces the oxygen of the carbonyl.

O

Br Ph3P BuLi

CH3

o Step one: Triphenylphosphine attacks an alkyl halide

H Ph + Ph ·· CH3 P H Ph P Br Ph Ph Ph H

o Step two: Grignard deprotonates to form the ylide . What’s an ylide?

 An ylide is when you have two atoms next to each other where one has a negative charge, the other has a positive charge, and they both have full octets.

Ph H Bu Li Ph + + - P H P H Ph Ph H Ph H Ph o Step 3: ylide attacks the carbonyl

Ph Ph + Ph3 P – O O Ph P +

- H H o Step 4: O- forms bond with P+

Ph3

+ P Ph3 P – O O

o Ring collapses – fun with arrows

Ph3

H H H P O H o Considerations: You want alkyl halide to be methyl or primary because they are best for

SN2

 Hydration

o Acid-catalyzed

H H + O + O + OH H OH O OH H

H2O

o Base-catalyzed

O OH – OH OH O H2 O

-OH

o Rates

. This reaction doesn’t happen to a large degree with most ketones

. It happens a little more with aldehydes

. Keq for formaldehyde is 40

 Formation of Cyanohydrins

o HCN is a toxic gas, so most often it is made in situ from excess NaCN and HCl.

o Step one: cyanide ion attacks the carbonyl.

O CN – O

-CN

o Step two: protonation

CN – CN O H--CN OH o Things you can do with cyanohydrins.

. Catalytic hydration

H H H H N O O CN H2/Pt

. Hydrolysis

H H O + O + H3O NH4 CN COOH +

 Formation of imines

o Overall: The nitrogen replaces the oxygen of the carbonyl, forming a carbon- nitrogen double bond.

. It should be mildly acidic; pH between 4 and 5.

H O N + NH3, H

o Mr. Baker said that you are not responsible for the mechanism, but here it is in case you want to look at it.

o Step one: protonation of the carbonyl

H O O+ H+

o Step two: Amine attacks the activated carbonyl H H + O OH H + N H

H ·· H N

H o Step three: Deprotonation

H H OH H + OH N N H H

o Step four: Protonation of hydroxyl

H H H + H+ OH OH N N H H

o Step five: Loss of water

H H H H + H H OH N+ N N: H + o Step six: Deprotonation

H H H + N N  Formation of acetals

o You could call an acetal a geminal diether

. A hemiacetal is what you have when you’re halfway there.

. It is one hydroxyl and one alkoxy group coming off the same carbon.

o Step one: protonation of the carbonyl

H O O+ H+

o Step two: the alcohol attacks the activated carbonyl

H H O+ H O O+

O H

o Step three: deprotonation to give the hemiacetal

H

+ H O O H O O

o Step four: Protonation of the hydroxyl

H H+ + H O O H O O o Step five: water falls off

H + H O O + O

o Step six: another alcohol adds

H O+ + O O

O H

o Step seven: deprotonation gives the acetal

H + O O O O

 Removing acetals

o Use very dilute acid

o The mechanism of hydrolysis of an acetal is just the same thing going backwards.

 Acetals and hemiacetals in sugars

o Sugars exist in their cyclic forms as hemiacetals . The carbon which is the hemiacetal or acetal is called the anomeric carbon.

. When the OH is up, it’s Beta; when it’s down, it’s alpha.

OH

OH O OH OH

anom eric carbon OH

o When they link up to become polysaccharides, they become acetals.

OH

OH O OH

O OH OH O OH OH

OH

o Something you don’t need to know for this class, but the MCAT expects you to know:

. Sugars that differ by only one chiral center are called epimers.

CHO CHO

H OH H OH H OH HO H H OH H OH H OH H OH

CH2OH CH2OH

D-allose D-glucos e

 Protecting groups

o Requirements of a good protecting group

. Easy to put on . Nonreactive under the reaction conditions

. Easily removable

 Oxidation of aldehydes

o Aldehydes are oxidized to carboxylic acids by KMnO4 and chromic acid

 Reductions of ketones and aldehydes

o The following reductions which have already been seen work on ketones and aldehydes:

NaBH4 LiAlH4 H2/ Raney Zn(Hg)/HCl N2H4/base Ni (aq)

Ketone 2° ROH 2° ROH 2° ROH Alkane Alkane

Aldehyde 1° ROH 1° ROH 1° ROH Alkane Alkane

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