Download Ch 16 Aldehydes and Ketones I

Ch 16 Aldehydes and Ketones I
Introduction
• All aldehydes have a carbonyl group bonded
on one side to a carbon and on the other to a
hydrogen
• Examples:
• Ketone have carbons bonded to both sides of
the carbonyl
• Examples:
Introduction
• The chemistry of the carbonyl group is central
to the chemistry of most of the chapters to
follow
• In this chapter, we will focus on naming
aldehydes/ketones, preparing them, their
physical properties, and on nucleophilic
addition reactions that take place at their
carbonyl groups
Introduction
• In the next chapter, we will study the
chemistry of aldehydes and ketones that
results from the acidity of the hydrogen atoms
on the carbon atom adjacent to their carbonyl
group
Nomenclature
• Aldehydes– Drop the –e of the alkane name
– Add –al
– Since aldehydes are always at the end of the
chain, no need to number
– When other substituents are present, the carbonyl
carbon is assigned position 1
– Examples:
Nomenclature
• Aldehydes attached to a ring system are
named by adding –carbaldehyde to the end of
the regular name
• Example
Nomenclature
• IUPAC names for Ketones– Drop the –e of the alkane name
– Add –one
– The chain in numbered to give the carbonyl
carbon the lowest possible number
• Common names for Ketones
– Name the two groups attached to carbonyl
followed by the word ketone
– examples
Nomenclature
• Some ketones have common names that are
retained in IUPAC:
• Examples:
• When it is necessary to name the aldehyde group as
a prefix, it is the methanoyl group
• Ketones are named as prefixes as the alkanoyl
group.
• Examples:
Physical Properties
• The carbonyl group is polar, therefore
aldehydes and ketones are polar and have
higher BP’s than hydrocarbons of similar MW
• Since ald/ket can not hydrogen bond to each
other they have lower BP’s than
corresponding alcohols
Physical Properties
• The carbonyl oxygen can form hydrogen bonds
with water, so low MW ald/ket show
appreciable water solubility
Synthesis of Aldehydes
• 1) Aldehydes by oxidation of primary alcohols
– Covered in reactions of alcohols
– Uses PCC
– examples
• 2) Aldehydes by reduction of Acyl chlorides,
esters, and nitriles
– Carboxylic acids are reduced all the way to the
alcohol because any aldehyde produced is
immediately reduced.
Synthesis of Aldehydes
– By using a derivative of the carboxylic acid, we can use a
less powerful reducing agent, thus stopping at the
aldehyde
– There are 2 derivatives of LAH that are less reactive:
– Lithium tri-tert-butoxyaluminum hydride
– Diisobutylaluminum hydride (DIBAL-H)
– Examples:
Synthesis of Aldehydes
i) Aldehydes from acid chlorides:
Recall that we learned how to make acid chlorides in
the last chapter
We can then use lithium tri-tert-butoxy aluminum
hydride to reduce the acid chloride to the aldehyde:
Mech:
Synthesis of Aldehydes
ii) Aldehydes from Esters and nitrilesBoth esters and nitriles can be reduced to aldehydes
by the use of DIBAL-H
Carefully controlled amounts of DIBAL-H must be
used to avoid over-reduction
The ester reduction must additionally be done at low
temperatures
Synthesis of Aldehydes
• Mechanism for reduction of esters
• Mechanism for reduction of Nitriles
• Note: the oxygen in the aldehyde comes from
added water!
• examples
Synthesis of Ketones
• Previously covered 3 ways:
– 1) Ketones (and aldehydes) by ozonolysis of Alkenes
– 2) Ketones from arenes by Freidel Crafts Acylations
– 3) Ketones from secondary alcohol oxidation
Synthesis of Ketones
• Ketones from Alkynes– Alkynes can undergo hydration similar to double
bonds
– The reaction is usually done with HgSO4 and
aqueous sulfuric acid
– However, after the first addition of water, a very
unstable vinylic alcohol is formed.
Synthesis of Ketones
– This vinylic alcohol can rearrange to form a ketone
– The rearrangement is acid catalyzed and involves
the loss of a proton from the hydroxyl group, the
addition of a hydrogen to the other carbon of the
double bond and the relocation of the double
bond.
– Mechanism:
Synthesis of Ketones
– This kind of rearrangement is called a
tautomerization.
– Vinylic alcohols are often called enols.
– Since the product of the rearrangement is a
ketone, these types of rearrangements are often
called keto-enol tautomerizations
– Example:
Synthesis of Ketones
– The addition of water to alkynes follows
Markovnikov’s rule, so when using terminal triple
bonds, you will always get the ketone, only
exception is ethyne.
– With internal alkynes, you usually get mixed
results.
– Examples:
Synthesis of Ketones
• Ketones from Lithium Dialkylcuprates
– This is a variation of the Corey-Posner-WhitesideHouse alkane synthesis done at very low
temperature
– The dialkyl cuprates are mixed with an acid
chloride in ether to yield the ketone
– example
Synthesis of Ketones
• Ketones from Nitriles
– Treating a nitrile with either a grignard reagent or
an organolithium reagent followed by hydrolysis
yields a ketone
– Examples:
– Note: Reminder, nitriles can be made by adding
NaCN to an alkyl halide via Sn2 reaction
Synthesis of Ketones
• See solved problem 16.5 and practice problem
16.4 on page 731
Nucleophilic Addition to the CarbonOxygen Double Bond
• The most characteristic reaction of aldehydes
and ketones is nucleophilic addition to the
carbon-oxygen double bond
• Examples:
• Because the carbonyl is trigonal planar, the
nucleophilic attack may occur from the top or
the bottom, so therefore if a stereogenic is
formed, it is racemic
Nucleophilic Addition to the CarbonOxygen Double Bond
• The partial positive charge on the carbonyl
carbon makes it suseptible to nucleophilic
attack
• The first mechanism takes place with strong
nucleophiles
Nucleophilic Addition to the CarbonOxygen Double Bond
• The second mechanism shows that the reaction can
also be acid-catalyzed
• This mechanism occurs when the carbonyl is
treated with strong acid in presence of weak
nucleophile
Nucleophilic Addition to the CarbonOxygen Double Bond
• Many nucleophilic additions to the carbonyl are
reversible
• The results of the reaction depend on the
equilibrium
• Relative Reactivity
– In general, aldehydes are more reactive than ketones
– This is due to both steric and electronic factors
Nucleophilic Addition to the CarbonOxygen Double Bond
• Addition of Alcohols– Hemi-acetals- a compound that contains a carbon
bonded to both an –OR group and –OH group
– General Reaction
– Most open-chain hemiacetals are not sufficiently
stable to allow their isolation
– Cyclic hemiacetals with 5 or 6 membered rings are
much more stable
Nucleophilic Addition to the CarbonOxygen Double Bond
– Most simple sugars exist primarily in a cyclic
hemiacetal form
– Example
– Ketones can form hemiacetals as well
– We can show both an acid catalyzed and base
catalyzed mechanism
– Examples:
Nucleophilic Addition to the CarbonOxygen Double Bond
– Once a hemiacetals form, the addition of another
alcohol is possible to form an acetals
– Acetal- has two –OR groups bonded to the same
carbon atom:
– Like hemiacetals, open chain acetals are not
favored but cyclic acetals are.
– Acetals as protecting groups:
Nucleophilic Addition to the CarbonOxygen Double Bond
• Addition of primary and secondary amines
– Primary amines react with ald/ket to form imines
– An imine has a C-N double bond
– Secondary amines react with ald/ket to form enamines
– An enamine has an amino group bonded to carboncarbon double bond.
– Examples
– Mechanisms:
Nucleophilic Addition to the CarbonOxygen Double Bond
– The pH for these reactions must be monitored
– If it is too low, the primary amine will protonate
– If It is too high, insufficient protons are available
for the reaction
– pH range of 4-5 optimal
• Make sure to review the Oxime, Hydrazones,
and Semicarbozone sections in the book.
Nucleophilic Addition to the CarbonOxygen Double Bond
• Enamines example and mechanism:
• See table 16.2, page 745-746, reactions of
aldehydes and ketones with derivatives of
ammonia
The addition of Hydrogen Cyanide
• The addition of HCN to a carbonyl results in
compounds called cyanohydrins
• Highly hindered ketones do not react
• example.
• Mechanism
• This reaction is very useful in organic synthesis
because the cyano group can be converted to other
functionalities, plus it adds one carbon to the chain
• example
The addition of Ylides: The Wittig
Reaction
• Aldehydes and Ketones react with phosphorus
ylides to give alkenes
• Ylides- a neutral molecule having a negative
charged carbon adjacent to a positive charged
heteroatom.
• Ex.
The addition of Ylides: The Wittig
Reaction
• Although a mixture of E and Z isomers results, the
Wittig Reaction is better than most other alkene
synthesis reactions because there is no ambiguity as
to the location of the double bond.
• The phosphorus ylides are prepared from
triphenylphosphine and a primary or secondary
alkyl halide
• Ex
• Mechanism
The addition of Ylides: The Wittig
Reaction
• The first step is a simple Sn2 reaction with the
phosphorous displacing the halide
• The second step is an acid-base reaction in
which a strong base, usually an alkyllithium or
phenyl lithium, removes a proton from the
carbon attached to the phosphorous
The addition of Ylides: The Wittig
Reaction
• Wittig Reaction mechanism
• Example
The addition of Ylides: The Wittig
Reaction
• A widely used variation of the Wittig reaction
is the Horner-Wadsworth-Emmons
modification
• Instead of using triphenyl phosphine to form
the triphenyl phosphonium salt, a
phosphonate ester is used
• The advantage to this modification is that the
major product is usually the (E)-alkene isomer
The addition of Ylides: The Wittig
Reaction
• The typical bases used are Sodium Hydride,
NaH, potassium t-butoxide, and butyl lithium
• Examples:
The addition of Organometallic
reagents: The Reformatsky Reaction
• Earlier, we saw that Grignard, organolithium, and
sodium alkynides could add to aldehydes and
ketones to give a wide variety of alcohols
• Examples:
• Now, we examine a similar reaction that involves
the addition of an organozinc reagent
• This reaction extends the carbon skeleton of an
aldehyde and ketones and yields a β-hydroxy ester
The addition of Organometallic
reagents: The Reformatsky Reaction
• The reaction involves treating an aldehyde or
ketone with an α-bromo ester in the presence
of zinc metal, typically in Benzene
• Reaction:
• Mechanism:
The addition of Organometallic
reagents: The Reformatsky Reaction
• Because the organozinc is less reactive than a
grignard reagent, it does not add to the ester
group
• The β-hydroxy ester product can easily be
dehydrated to an α,β-unsaturated ester
• examples
Oxidation of Aldehydes and Ketones
• Aldehydes are much easier to oxidize than
ketones.
• Examples:
Baeyer-Villiger Oxidation of Aldehydes
and Ketones
• This reaction converts aldehydes and ketones
to esters, using a peroxycarboxylic acid
(RCO3H) such as m-chloroperoxybenzoic acid
(mCPBA)
• Example
• Mechanism
Baeyer-Villiger Oxidation of Aldehydes
and Ketones
• Notice that we showed the phenyl group
migrating over to the oxygen
• The tendency of a group to migrate is called it
migratory aptitude
• Studies of the Baeyer-Villiger oxidation and
other reactions have shown that the migratory
aptitude of groups is:
• Make sure to check out the synthetic
connections at the end of the chapter.