ALDEHYDES AND KETONES I' NUCLEOPHILIC ADDITION TO CARBONYL

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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
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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
2-Pentanone
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Another...
4-Ethyl-3-hexanone
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And another...
3-Isopropylcyclopentanone or 3-(1-Methylethyl)cy
clopentanone
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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
Methyl propyl ketone
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Another example...
Diethyl ketone
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Important example!
Dimethyl ketone
Acetone
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Another Important Common Name
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
Hexanal
Notice that there is no -1- in the name!
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another
5-Methylhexanal
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One more
3-Phenylpropanal
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For cyclic molecules, the ending is
-carbaldehyde
Cycloheptanecarbaldehyde
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Two acceptable alternative names
Benzenecarbaldehyde (official IUPAC
name) Benzaldehyde (acceptable IUPAC name)
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Common Names of the Aldehydes
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Forming Common Names of Aldehydes
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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 isnt used if there are other
  substituents.

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Example
b-Methylbutyraldehyde Isovaleraldehyde
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Another example...
e-Bromocaproaldehyde w-Bromocaproaldehyde
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Benzaldehyde
ortho (o-) meta (m-) para
(p-) 1,2- 1,3-
1,4-
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More than one subsituent
4-Hydroxybutanal g-Hydroxybutyraldehyde The
prefix for -OH is hydroxy
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Also...
2-Methoxypentanal a-Methoxyvaleraldehyde
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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

• 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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Prochiral
The carbonyl carbon is prochiral. That is, the
carbonyl carbon is not the center of chirality,
but it becomes chiral as the reaction proceeds.
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
Typical behavior
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Reaction of the Carbonyl Group with Bases
Typical behavior
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Nucleophilic Addition to Carbonyl -- General
Mechanism
NOTE Reversible reaction
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Nucleophilic Addition to Carbonyl -- in Acid
(General Mechanism)
NOTE Reversible reaction
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The carbocation intermediate has resonance.
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.
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
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
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)
A cyanohydrin
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Mechanism
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Example

• 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, whats it good for?
Nitriles can be hydrolyzed to form carboxylic
acids. This affords us with an important method
of synthesizing a-hydroxy-carboxylic acids --
important intermediates in biochemical processes.
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Reaction with Organometallic Compounds (16.7)
The products of this sequence are always alcohols.
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Addition of Organometallic Reagents
The products of the addition are always alcohols.
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Crude outline of the mechanism of organometallic
addition
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Whatever is attached to the carbonyl group will
be attached to the resulting alcohol carbon.
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Example
Organometallics react with ketones to yield
tertiary alcohols.
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And another...
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
One can also use a Grignard reagent to do an
ethynylation.
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To make an alkynyl Grignard...
This is an acid-base reaction (the proton is
transferred from the stronger acid to the
stronger base).
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A Practical Application
Used in oral contraceptives