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ALDEHYDES AND KETONES I.

NUCLEOPHILIC ADDITION TO CARBONYL

Chapter 16

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Reading Assignment

• DO: Sections 16.0 through 16.7

• SKIP: Section 16.8

• DO: 16.9 through 16.18

• SKIP: Section 16.19

• DO: Section 16.20

• Organic Nomenclature: Aldehydes and Ketones

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Problem Assignment

• In-Text Problems– 16.1 through 16.27

• End-of-Chapter– 1 through 6– 7a; 7c through 7j– 8 b, c, d– 9 through 10– 12 through 14

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Aldehyde

Ketone

O

CR H

R = H, alkyl, aryl

O

CR R'

R and R' = alkyl or arylR and R' cannot be hydrogen!

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IUPAC Nomenclature of Ketones

• Choose the longest continuous carbon chain that contains the carbonyl carbon

• Number from the end of the chain closest to the carbonyl carbon

• Ending is -one

• Do the ketones section of Organic Nomenclature -- Assignment!

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Example

CH3

CCH2

CH2CH3

O

2-Pentanone

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Another...

O

CCH2 CH

CH3 CH2

CH2

CH3

CH3

4-Ethyl-3-hexanone

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And another...O

CH

CH3

CH3

3-Isopropylcyclopentanone

or 3-(1-Methylethyl)cyclopentanone

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Common, or Trivial, Names

• Name each group attached to the carbonyl group as an alkyl group

• Combine into a name, according to:– alkyl alkyl’ ketone

• NOTE: This is not all one word!

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Example of a Common Name

CH3

CCH2

CH2CH3

O

Methyl propyl ketone

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Another example...

O

CCH2 CH2

CH3 CH3

Diethyl ketone

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Important example!

O

CCH3 CH3

Dimethyl ketone

Acetone

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Another Important Common Name

C CH3

O

Acetophenone

(Methyl phenyl ketone)

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IUPAC Nomenclature of Aldehydes

• Choose the longest continuous carbon chain that contains the carbonyl carbon

• Number from the end of the chain closest to the carbonyl carbon (this will automatically be carbon #1!)

• Ending is -al• Note: The carbonyl carbon is not identified by number

in the final name.• Do the aldehydes section of Organic Nomenclature --

Assignment!

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Example

CH3

CH2CH2

CH2CH2

CH

O

Hexanal

Notice that there is no “-1-” in the name!

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… another:

CH3

CHCH2

CH2CH2

CH

CH3 O

5-Methylhexanal

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One more:

CH2CH2

CH

O

3-Phenylpropanal

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For cyclic molecules, the ending is -carbaldehyde

C

O

H

Cycloheptanecarbaldehyde

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Two acceptable alternative names:

CH

O

2

3

4

5

6

Benzenecarbaldehyde (official IUPAC name)Benzaldehyde (acceptable IUPAC name)

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Common Names of the AldehydesO

CH H

O

CCH3 H

O

CCH2 HCH3

O

CCH2 HCH2CH3

O

CCH2 HCH2CH2CH3

O

CCH2 HCH2CH2CH2CH3

Formaldehyde Acetaldehyde Propionaldehyde

Butyraldehyde Valeraldehyde

Caproaldehyde

1 2 3

4 5

6

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Forming Common Names of Aldehydes

C

C C C C C C H

O

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Also: “Iso” names:

• Whenever there is a -CH(CH3)2 group, an alternative common name is an “iso” name.

• The “iso” name includes all of the carbon atoms in the molecule.

• The “iso” name isn’t used if there are other substituents.

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Example

CH3

CHCH2

CH

CH3 O

-MethylbutyraldehydeIsovaleraldehyde

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Another example...

CH2

CH2CH2

CH2CH2

CH

O

Br

-Bromocaproaldehyde-Bromocaproaldehyde

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Benzaldehyde

CH

O

o-

o-

m-

m-

p-

ortho (o-) meta (m-) para (p-)1,2- 1,3- 1,4-

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More than one subsituent:

CH2

CH2CH2

CH

O

HO

4-Hydroxybutanal-HydroxybutyraldehydeThe prefix for -OH is hydroxy

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Also...

CH2

CH2CH

CH

O

OCH3

CH3

2-Methoxypentanal-Methoxyvaleraldehyde

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CCH3

CH3

CH3

CH2CH2

CH

O

Bourgeonal

Bourgeonal is thought to be a chemoattractant emitted by the egg and detected by an odor receptor on the sperm cell. This guides the sperm to the egg

Science, 299, 2054 (2003)

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Structure of the Carbonyl Group

C O

•Hybridization of the carbonyl carbon is sp2.•Geometry of the carbonyl carbon is trigonal planar•Attack by nucleophiles will occur with equal ease from either the top or the bottom of the carbonyl group.•Hybridization of the oxygen is “nominally” sp2.

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ProchiralThe carbonyl carbon is prochiral. That is, the carbonyl carbon is not the center of chirality, but it becomes chiral as the reaction proceeds.

C O

R

R'

:Nu

:Nu

C OH

Nu

RR'

C OH

Nu

RR'

These two products are enantiomers.

In general, both enantiomers are formed in equal amount.

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Reaction of the Carbonyl Group with Acids

O

C+ H+

O

C

H

Typical behavior

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Reaction of the Carbonyl Group with Bases

O

C

+

B:

C

O

B

Typical behavior

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Nucleophilic Addition to Carbonyl -- General Mechanism

+ :Nuslow

: ::..

:_

:..

:

+ H2O

:..

fast

_

O

CC

O

Nu

C

O

Nu

C

OH

Nu

NOTE: Reversible reaction

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Nucleophilic Addition to Carbonyl -- in Acid (General Mechanism)

+ :Nuslow

::..

+

: :

+ H+

fast

+:

OH

CC

OH

Nu

OH

C

O

C

NOTE: Reversible reaction

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The carbocation intermediate has resonance.

O

C

HO

C

H

The positive charge character on carbon makes this an excellent site for attack by Lewis bases (nucleophiles).

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Once we have the intermediate, what happens to it?

Case 1: The Addition Product is Stable.

R C R

OH

Nu

The reaction stops here. This happens most often when the nucleophilic atom is carbon, oxygen, or sulfur.

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Case 2: Addition-Elimination

R C R

OH

NuH

C

Nu

R R+ O

HH

The addition product is unstable with respect to loss of a molecule of water. This is observed most often when the nucleophilic atom is nitrogen or phosphorus.

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Case 3: Loss of Leaving Group

R C X

O

Nu

R C

Nu

O

+ X

This process is observed when X is a potential leaving group. In this case we have nucleophilic acyl substitution (see Chapter 19).

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What are the stereochemical requirements?

• The hybridization of carbon in the carbonyl group is sp2

• The geometry around carbon is trigonal-planar.• Nucleophile can attack the carbonyl group equally

easily from top or bottom (see model)• BUT: aldehydes react faster than ketones in

nucleophilic addition!

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Why?• Aldehydes have a hydrogen attached to the carbonyl group,

whereas ketones have an alkyl group.– Alkyl groups are much more bulky than hydrogens -- hence

ketones should show some steric hindrance.

• Alkyl groups have a small electron-releasing inductive effect.– This should make the carbonyl carbon less favorable by attack by

nucleophile.

• The answer is that there is a combination of steric hindrance and inductive effects that makes ketones react slower than aldehydes.

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Addition of Cyanide (16.6)

+ CN_

+ H+

: : : :

: : :

..

..

_

_

R C R

O

R C R

O

CN

R C R

O

CN

R C R

OH

CN

..

A cyanohydrin

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MechanismO

CR R

C N

slowR C R

O

C

N

1)

2)

R C R

O

C

N

+ H+ R C R

O

C

N

H

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ExampleO

+ C N

(NaCN)

Na2CO3

O

C N

H2O, H+

OH

C N

•Notice that the cyanide ion and the acid are added in two separate steps!

•Sodium carbonate is used to keep the reaction medium basic.

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So, what’s it good for?

CH2 C H

ONaCN

H2OCH2 C C

OH

H

N

H2O, H+

heat

CH2 C C

OH

H

OH

O

Nitriles can be hydrolyzed to form carboxylic acids.

This affords us with an important method of synthesizing -hydroxy-carboxylic acids -- important intermediates in biochemical processes.

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Reaction with Organometallic Compounds (16.7)

+..

:.. MgX

+R MgX R C

R

R

O_ H2Oether

O

CR R

R C OH

R

R

The products of this sequence are always alcohols.

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Addition of Organometallic Reagents

+

(R-MgBr)

M

_+

H2O

H +

R M

+ M (OH)x

: : : :

:

..

..

O

CR R

R C R

O

R

R C R

OH

R

The products of the addition are always alcohols.

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Crude outline of the mechanism of organometallic addition

"R:-"

(from R-MgX)

C O

R'

R

R C O

R

R'

H+

R

C

R'

OHR

R, R' = H, alkyl, or aryl

+slow

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Whatever is attached to the carbonyl group will be attached to the resulting alcohol carbon.

R M + C O

H

H

R C OH

H

Hformaldehyde primary alcohol

R M + C O

H

R

R C OH

R

Hsecondary alcohol

R M + C O

R'

R

R C OH

R

R'ketones tertiary alcohol

other aldehydes

(M = Li or MgX)

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Example

CH3 CH2 C CH2 CH3

O

CH3MgI

etherCH3 CH2 C CH2 CH3

O

CH3

MgI

H2O, H+

CH3 CH2 C CH2 CH3

O

CH3

H

Organometallics react with ketones to yield tertiary alcohols.

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And another...

CH3 CH2 CH2 C H

O MgBr

ether

CH3 CH2 CH2 CH

OH

1-Phenyl-1-butanol

H2O

H+

Organometallics react with aldehydes to form secondary alcohols

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Summary of Reactions of Organometallics with Carbonyl

Compounds

• Organometallics with ketones yield tertiary alcohols

• Organometallics with aldehydes yield secondary alcohols

• Organometallics with formaldehyde yield primary alcohols.

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Ethynylation

C CH HNaNH2

H C C Na

O

CR R'

H C C Na

CR R'

HO C C H

H+

H2O

One can also use a Grignard reagent to do an ethynylation.

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To make an alkynyl Grignard...

CH3 CH2 BrMg

etherCH3 CH2 MgBr

R C C H + CH3 CH2 MgBrether

R C C MgBr + CH3 CH2 H

This is an acid-base reaction (the proton is transferred from the stronger acid to the stronger base).

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A Practical ApplicationOCH3

HO

Estrone

H C C Na

CH3

HO

OHC CH

Ethynylestradiol

Used in oral contraceptives