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Overview of the Reactions of
Carbonyl Compounds
• Topical Outline of Coverage
– I. Kinds of Carbonyl Compounds.
– II.Polarity of the Carbonyl Functional
Group.
– III.General Reactions of Carbonyl
Compounds
• A.
• B.
Nucleophilic Addition Reactions
Nucleophilic Substitution Reactions
Kinds of Carbonyl Compounds
• All carbonyl compounds contain the acyl group
O
C
R
• where the (R) residue bonded to the carbonyl
maybe alkyl, aryl, alkenyl, or alkynyl. The
different kinds of carbonyl compounds arise from
the nature of the other residue bonded to the
carbonyl group.
Kinds of Carbonyl Compounds
O
C
R
X
X = H then aldehyde
X= R then ketone
X = OH then carboxylic acid
X = Cl then acid chloride
X = OR then ester (cyclic esters = lactones)
X = OCOR then acid anhydride
X = N then amide (cyclic amides = lactams)
Categories of Carbonyl Compounds
• Carbonyl
Compounds
may be
grouped into
two broad
categories
based upon
whether or
not they take
part in
Nucleophilic
Substitution
Reactions
Aldehydes and Ketones
O
C
R
R
XX
• Aldehydes and Ketones - X = H and R
respectively ; these carbonyl compounds do
not undergo nucleophilic substitution
reactions. That is to say, the H and R groups
are never substituted by other groups. Both Hand R- make poor leaving groups.
Carboxylic Acids and their Derivatives
O
C
R
X
• Carboxylic acids and their derivatives –
X = some heteroatom (O, Cl, or N).
Nucleophilic substitution reactions are
possible for these carbonyl compounds
because the electronegative heteroatom can
stabilize a negative charge and form good
Leaving Groups.
Polarity of the Carbonyl
Groups
• The carbon-oxygen double bond of the
carbonyl group is extremely polarized in the
direction of the highly electronegative oxygen.
This polarization is responsible for the
characteristic reactions of carbonyl compounds
- :O:
nucleophilic oxygen reacts with
acid and other electrophiles
+ C
electrophilic carbon reacts with
bases and other nucleophiles
General Reactions Of
Carbonyl Compounds
• Nucleophilic Addition Reactions
• Nucleophilic Acyl Substitution
Nucleophilic Addition Reactions –
Chapter 09
• There are two different ways in which a nucleophile can add
to a carbonyl compound. Each way leads to a different
nucleophilic addition reaction but the mechanisms for both
reactions involves the same 1st step.
• In this step, the nucleophile bonds to the carbonyl carbon
and thereby causes a carbon-oxygen bond to break. The
carbonyl carbon rehybridizes from sp2 to sp3 and the
carbonyl oxygen becomes negatively charged. At this point
the tetrahedral intermediate can either be protonated to form
an alcohol (NaBH4, LiAlH4, or Grignard Reduction) or a
non-bonded e- pair on the nucleophile can be used to form a
second bond to the carbonyl carbon. The new bond
formation causes expulsion of the carbonyl oxygen as H2O.
First Type of Nucleophilic
Addition
• Alcohol Formation –
Ketones and
Aldehydes react with
NaBH4, LiAlH4, and
Grignard reagents to
form alcohols
Second Type of Nucleophilic Addition
• Imine formation Ketones and
Aldehydes react
with 1o amines to
form imines .
Nucleophilic Acyl Substitution –
• Theses reactions do not apply to aldehydes
and ketones. These reactions involve the
substitution of the nucleophile for the X
residue of the carbonyl compound.
R
O
C
NuX
R
O
C
+
Nu
X-
Nucleophilic Acyl Substitution
Carboxylic Acid Derivatives
O
C
R
X
X = H then aldehyde
X= R then ketone
X = OH then carboxylic acid
X = Cl then acid chloride
X = OR then ester (cyclic esters = lactones)
X = OCOR then acid anhydride
X = N then amide (cyclic amides = lactams)
Carboxylic Acid Derivatives
• These all have an acyl group bonded to Y, an
electronegative atom or leaving group
• Includes: Y = halide (acid halides), acyloxy
(anhydrides), alkoxy (esters), amine (amides).
General Reaction Pattern
• Nucleophilic acyl substitution
Nucleophilic Acyl Substitution-The
Mechanism
• Carboxylic acid
derivatives have an acyl
carbon bonded to an
electronegative group
Y that can leave
• A tetrahedral
intermediate is formed,
then the leaving group
is expelled to generate a
new carbonyl
compound, leading to
substitution
Substitution in Synthesis
• We can readily convert a more reactive acid
derivative into a less reactive one
• Reactions in the opposite sense are possible but
require more complex approaches
Found in Nature
Reactions of Acid Halides
•
•
•
•
Nucleophilic acyl substitution
Halogen replaced by OH, by OR, or by NH2
Reduction yields a primary alcohol
Grignard reagent yields a tertiary alcohol
Reactions of Acid Anhydrides
• Similar to acid chlorides in reactivity
Reactions of Esters
• Less reactive toward nucleophiles than are acid
chlorides or anhydrides
• Cyclic esters are called lactones and react
similarly to acyclic esters