Transcript Overview of the Reactions of Carbonyl Compounds

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
Chapter 09. Aldehydes and Ketones:
Nucleophilic Addition Reactions
Aldehydes
• Aldehydes are carbonyl compounds having at least
one hydrogen attached to the carbonyl carbon.
O
O
O
C
H
CH3 CH2 CH
propanal
Benzaldehyde
C
H
H
formaldehyde
Ketones
• Ketones are carbonyl compounds having two
alkyl fragments attached to the carbonyl carbon.
O
O
CH3
CH3 C CH3
2-propanone
O
CH3 C CH2 CH3
acetophenone
2-butanone
Naming Aldehydes and Ketones
• Aldehydes are named by replacing the terminal -e
of the corresponding alkane name with –al
• The parent chain must contain the CHO group
– The CHO carbon is numbered as C1
• If the CHO group is attached to a ring, use the
suffix carbaldehyde
Names of more Complex
Aldehydes
Naming Ketones
• Replace the terminal -e of the alkane name with –
one
• Parent chain is the longest one that contains the
ketone group
– Numbering begins at the end nearer the carbonyl
carbon
Ketones with Common Names
• IUPAC retains well-used but unsystematic names
for a few ketones
Preparation of Aldehydes and
Ketones
Preparing Aldehydes
•
• We have already discussed two of the best methods of
aldehyde synthesis. These are oxidation of primary
alcohols, and oxidative cleavage of alkenes. Oxidize
primary alcohols using pyridinium chlorochromate
Preparing Ketones
• Ketones may be prepared by the oxidation of
secondary alcohols. A wide range of oxidizing can
accomplish this purpose. Some of these are: Jones
reagent (CrO3 in aqueous sulfuric acid), sodium
chromate (Na2CrO4) and potassium permanganate
(KMnO4).
OH
O
Na2CrO4
acetic acid
C(CH3)3
4-tert-butylcyclohexanol
C(CH3)3
4-tert-butylcyclohexanone
(90%)
Prep. Of Ketones by Ozonolysis
of Alkenes
• Ozonolysis of alkenes yields ketones if one of the
doubly bonded carbons is itself bonded to two
alkyl groups.
Prep. Of Ketones by Hydration of
Terminal Alkynes
• Methyl ketones can be prepared by the
Markovnikov addition of water to a terminal
alkyne. The reaction needs to be catalyzed by
Hg+2 ion. See Section 4.13 of text.
Aryl Ketones by Acylation
• Friedel–Crafts acylation of an aromatic ring with
an acid chloride in the presence of AlCl3 catalyst
(see Section 5.6)
Oxidation of Aldehydes and Ketones
• Aldehydes are readily oxidized to carboxylic acid but
ketones are unreactive towards oxidation except under the
most vigorous conditions. This difference in reactivity
towards oxidation lies in the structural difference between
the two types of carbonyl compounds. Aldehydes are
more easily oxidized because they posses a hydrogen
atom bonded to the carbonyl carbon. This hydrogen atom
can be removed as a proton with the final result being the
oxidation (loss of hydrogen) from the original aldehyde.
Ketones have no expendable carbonyl-hydrogen bond.
Oxidation of Aldehydes and Ketones
• Many oxidizing agents will convert aldehydes to carboxylic
acids. Some of these are Jones reagent, hot nitric acid and
KMnO4.
O
O
CH3(CH2)4
C
H
Jones
CH3(CH2)4
C
OH
• One drawback to the Jones reagent is that it is acidic. Many
sensitive aldehydes would undergo acid - catalyzed
decomposition before oxidation if Jones reagent was used
A Milder Oxidizing Agent
• For acid sensitive molecules a milder oxidizing
agent such as the silver ion (Ag+) may be used. A
dilute ammonia solution of silver oxide, Ag2O,
(Tollens reagent) oxidizes aldehydes in high yield
without harming carbon-carbon double bonds or
other functional groups.
Tollens Oxidation
•Note; In this reaction the oxidizing agent is Ag+ and it is
ultimately reduced to Ag(s).
•A shiny mirror of metallic silver is deposited on the inside
walls of the flask during a Tollens oxidation: observation of
such a mirror forms the basis of an old qualitative test for the
presence of an aldehyde functional group in a molecule of
unknown structure.
Nucleophilic Addition Reactions of
Aldehydes and Ketones
• Nu- approaches 45° to the plane of C=O and adds to the
Carbonyl Carbon
• A tetrahedral alkoxide ion intermediate is produced and
ultimately protonated
Nucleophiles
• Nucleophiles can be negatively charged ( : Nu) or neutral
( : Nu-H)
• If neutral, the nucleophile usually carries a hydrogen atom
that can subsequently be eliminated and carry away the
positive charge.
Relative Reactivity of Aldehydes and Ketones
• Aldehydes are generally much more reactive than ketones.
There are two reasons for this;
– Aldehydes are less sterically hindered than ketones. In
other words the carbonyl carbon of aldehydes is more
accessibly to attack. The presence of two relatively large
substituents in ketone hinders the attacking nucleophile
from reaching the carbonyl carbon.
–
The + on the carbonyl carbon is reduced in ketones
because of the ability of the extra alkyl group to stabilize
a + charge. This ability is emphasized in the stability
order of carbocations. 3o>2o>1o
Aldehydes Have A Greater
Electrophilicity Than Do Ketones
• Aldehyde C=O is more polarized than ketone C=O
• As in carbocations, more alkyl groups stabilize + character
• Ketone has more alkyl groups, stabilizing the C=O carbon
inductively
Addition of H-Y to C=O
• Reaction of C=O with H-Y, where Y is electronegative,
gives an addition product (“adduct”) and the reaction is
readily reversible because the electronegative Y is a
good leaving group.
Nucleophilic Addition of Alcohols:
Acetal Formation
• Two equivalents of ROH in the presence of an acid
catalyst add to C=O to yield acetals, R2C(OR)2
• Alcohols, ROH, fall under the category of Y-H and
therefore the reaction is reversible.
• Mechanism for
Formation of
Acetals
Uses of Acetals
• Acetals can serve as protecting groups for
aldehydes and ketones-remember the rxn. is
reversible.
• It is convenient to use a diol, to form a cyclic
acetal (the reaction goes even more readily)
Nucleophilic Addition of Grignard Reagents and
Hydride Reagents: Alcohol Formation
• Treatment of aldehydes or ketones with Grignard
reagents yields an alcohol
– Nucleophilic addition of the equivalent of a carbon
anion, or carbanion. A carbon–magnesium bond is
strongly polarized in the direction of the carbon atom, so
a Grignard reagent reacts for all practical purposes as R:
and MgX +.
Mechanism of Addition of Grignard
Reagents
• R- attacks the carbonyl carbon. The alkoxide
anion is then protonated by dilute acid.
• Grignard additions are irreversible because a
carbanion is not a leaving group
Hydride Addition
• H- attacks the carbonyl carbon. The alkoxide anion
is then protonated by dilute acid.
• Hydride additions are irreversible because a
hydride is not a good leaving group
• LiAlH4 and NaBH4 react as donors of hydride ion
(H-)
Nucleophilic Addition of Amines: Imine Formation
Primary amines (RNH2) add to C=O to form imines, R2C=NR
(after loss of HOH)
• Mechanism of
Imine Formation
Imine Derivatives
• Addition of amines that have an adjacent atom containing a
lone pair of electrons occurs very readily, giving useful,
stable imines
• For example, hydroxylamine forms oximes and 2,4dinitrophenylhydrazine readily forms 2,4dinitrophenylhydrazones
– These are usually solids and help in characterizing liquid ketones
or aldehydes by melting points
Spectroscopy of Aldehydes and
Ketones
• Infrared Spectroscopy
• Aldehydes and ketones show a strong C=O peak 1660 to
1770 cm1
• aldehydes show two characteristic C–H absorptions in the
2720 to 2820 cm1 range.
C=O Peak Position in the IR
Spectrum
• The precise position of the peak reveals the exact
nature of the carbonyl group
Summary
• Aldehydes are from oxidative cleavage of alkenes
or oxidation of 1° alcohols
• Ketones are from oxidative cleavage of alkenes or
oxidation of 2° alcohols.
• Aldehydes and ketones are reduced to yield 1° and
2° alcohols , respectively
• Grignard reagents also gives alcohols
• 1° amines add to form imines
• Alcohols add to yield acetals