Download 19.7 Reversible Addition Reactions of Aldehydes and Ketones

Organic Chemistry, 5th ed.
Marc Loudon
Chapter 19
The Chemistry of Aldehydes and Ketones.
Carbonyl-Addition Reactions
Eric J. Kantorowski
California Polytechnic State University
San Luis Obispo, CA
Chapter 19 Overview
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19.1 Nomenclature of Aldehydes and Ketones
19.2 Physical Properties of Aldehydes and Ketones
19.3 Spectroscopy of Aldehydes and Ketones
19.4 Synthesis of Aldehydes and Ketones
19.5 Introduction to Aldehyde and Ketone Reactions
19.6 Basicity of Aldehydes and Ketones
19.7 Reversible Addition Reactions of Aldehydes and Ketones
19.8 Reduction of Aldehydes and Ketones to Alcohols
19.9 Reactions of Aldehydes and Ketones with Grignard and
Related Reagents
• 19.10 Acetals and Their Use of Protecting Groups
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Chapter 19 Overview
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19.11 Reactions of Aldehydes and Ketones with Amines
19.12 Reduction of Carbonyl Groups to Methylene Groups
19.13 The Wittig Alkene Synthesis
19.14 Oxidation of Aldehydes to Carboxylic Acids
19.15 Manufacture and Use of Aldehydes and Ketones
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Carbonyl Compounds
• Aldehydes and ketones have the following
general structure
19.1 Nomenclature of Aldehydes and Ketones
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Carbonyl Compounds
19.1 Nomenclature of Aldehydes and Ketones
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Common Nomenclature
19.1 Nomenclature of Aldehydes and Ketones
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Prefixes Used in Common Nomenclature
19.1 Nomenclature of Aldehydes and Ketones
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Common Nomenclature
19.1 Nomenclature of Aldehydes and Ketones
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Substitutive Nomenclature
19.1 Nomenclature of Aldehydes and Ketones
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Substitutive Nomenclature
19.1 Nomenclature of Aldehydes and Ketones
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Physical Properties
• Most simple aldehydes and ketones are liquids
19.2 Physical Properties of Aldehydes and Ketones
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IR Spectroscopy
• Strong C=O stretch: 1700 cm-1
19.3 Spectroscopy of Aldehydes and Ketones
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IR Spectroscopy
• Conjugation with a p bond lowers the
absorption frequency
19.3 Spectroscopy of Aldehydes and Ketones
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IR Spectroscopy
• The C=O stretching frequency in small-ring
ketones is affected by ring size
19.3 Spectroscopy of Aldehydes and Ketones
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1H
NMR Spectroscopy
• The reason for the large d value for aldehydic
protons is similar to that for vinylic protons
• However, the electronegative O increases this
shift farther downfield
19.3 Spectroscopy of Aldehydes and Ketones
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13C
NMR Spectroscopy
• Aldehyde and ketone C=O: d 190-220
• a-Carbons: d 30-50
19.3 Spectroscopy of Aldehydes and Ketones
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UV/Vis Spectroscopy
• p → p*: 150 nm (out of the operating range)
• n → p*: 260-290 nm (much weaker)
19.3 Spectroscopy of Aldehydes and Ketones
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UV/Vis Spectroscopy
19.3 Spectroscopy of Aldehydes and Ketones
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Mass Spectrometry
19.3 Spectroscopy of Aldehydes and Ketones
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Mass Spectrometry
• What accounts for the m/z = 58 peak?
19.3 Spectroscopy of Aldehydes and Ketones
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Mass Spectrometry
• The McLafferty rearrangement involves a
hydrogen transfer via a transient sixmembered ring
• There must be an available g-H
19.3 Spectroscopy of Aldehydes and Ketones
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Summary of Aldehyde and Ketone Preparation
1. Oxidation of alcohols
2. Friedel-Crafts acylation
3. Hydration of alkynes
4. Hydroboration-oxidation of alkynes
5. Ozonolysis of alkenes
6. Periodate cleavage of glycols
19.4 Synthesis of Aldehydes and Ketones
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Carbonyl-Group Reactions
• Reactions with acids
• Addition reactions
• Oxidation of aldehydes
19.5 Introduction to Aldehyde and Ketone Reactions
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Basicity of Aldehydes and Ketones
• The carbonyl oxygen is weakly basic
• One resonance contributor reveals that
carbocation character exists
• The conjugate acids of aldehydes and ketones
may be viewed as a-hydroxy carbocations
19.6 Basicity of Aldehydes and Ketones
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Basicity of Aldehydes and Ketones
• a-hydroxy and a-alkoxy carbocations are
significantly more stable than ordinary
carbocations (by ~100 kJ mol-1)
19.6 Basicity of Aldehydes and Ketones
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Addition Reactions
• One of the most typical reactions of aldehydes
and ketones is addition across the C=O
19.7 Reversible Addition Reactions of Aldehydes and Ketones
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Mechanism of Carbonyl-Addition Reactions
19.7 Reversible Addition Reactions of Aldehydes and Ketones
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Addition Reactions
• The addition of a nucleophile to the carbonyl
carbon is driven by the ability of oxygen to
accept the unshared electron pair
19.7 Reversible Addition Reactions of Aldehydes and Ketones
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Addition Reactions
• The nucleophile attacks the unoccupied p*
MO (LUMO) of the C=O
19.7 Reversible Addition Reactions of Aldehydes and Ketones
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Addition Reactions
• The second mechanism for carbonyl addition
takes place under acidic conditions
19.7 Reversible Addition Reactions of Aldehydes and Ketones
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Equilibria in Carbonyl-Addition Reactions
• The equilibrium for a reversible addition
depends strongly on the structure of the
carbonyl compound
1. Addition is more favorable for aldehydes
2. Addition is more favorable if EN groups are
near the C=O
3. Addition is less favorable when groups that
donate electrons by resonance to the C=O are
present
19.7 Reversible Addition Reactions of Aldehydes and Ketones
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Equilibrium Constants for Hydration
19.7 Reversible Addition Reactions of Aldehydes and Ketones
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Relative Carbonyl Stability
19.7 Reversible Addition Reactions of Aldehydes and Ketones
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Carbonyl Stability
• Any feature that stabilizes carbocations will
impart greater stability to the carbonyl group
• For example, alkyl groups stabilize
carbocations more than hydrogens
• Hence, alkyl groups will discourage addition
reactions to the carbonyl group
19.7 Reversible Addition Reactions of Aldehydes and Ketones
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Carbonyl Stability
• Resonance can also add stability to the
carbonyl group
• However, EN groups make the addition
reaction more favorable
19.7 Reversible Addition Reactions of Aldehydes and Ketones
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Rates of Carbonyl-Addition Reactions
• Relative rates can be predicted from
equilibrium constants
• Compounds with the most favorable addition
equilibria tends to react most rapidly
• General reactivity: formaldehyde > aldehydes
> ketones
19.7 Reversible Addition Reactions of Aldehydes and Ketones
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Reduction with LiAlH4 and NaBH4
19.8 Reduction of Aldehydes and Ketones to Alcohols
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Reduction with LiAlH4
• LiAlH4 serves as a source of hydride ion (H:-)
• LiAlH4 is very basic and reacts violently with
water; anhydrous solvents are required
19.8 Reduction of Aldehydes and Ketones to Alcohols
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Reduction with LiAlH4
• Like other strong bases, LiAlH4 is also a good
nucleophile
• Additionally, the Li+ ion is a built-in Lewis-acid
19.8 Reduction of Aldehydes and Ketones to Alcohols
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Reduction with LiAlH4
• Each of the remaining hydrides become
activated during the reaction
19.8 Reduction of Aldehydes and Ketones to Alcohols
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Reduction with NaBH4
• Na+ is a weaker Lewis acid than Li+ requiring
the use of protic solvents
• Hydrogen bonding then serves to activate the
carbonyl group
19.8 Reduction of Aldehydes and Ketones to Alcohols
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Reduction with LiAlH4 and NaBH4
• Reactions by these and related reagents are
referred to as hydride reductions
• These reactions are further examples of
nucleophilic addition
19.8 Reduction of Aldehydes and Ketones to Alcohols
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Selectivity with LiAlH4 and NaBH4
• NaBH4 is less reactive and hence more
selective than LiAlH4
• LiAlH4 reacts with alkyl halides, alkyl tosylates,
and nitro groups, but NaBH4 does not
19.8 Reduction of Aldehydes and Ketones to Alcohols
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Reduction by Catalytic Hydrogenation
• Hydride reagents are more commonly used
• However, catalytic hydrogenation is useful for
selective reduction of alkenes
19.8 Reduction of Aldehydes and Ketones to Alcohols
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Grignard Addition
• Grignard reagents with carbonyl groups is the
most important application of the Grignard
reagent in organic chemistry
19.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents
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Grignard Addition
• R-MgX reacts as a nucleophile; this group is
also strongly basic behaving like a carbanion
• The addition is irreversible due to this basicity
19.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents
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Organolithium and Acetylide Reagents
• These reagents react with aldehydes and
ketones analogous to Grignard reagents
19.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents
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Importance of the Grignard Addition
• This reaction results in C-C bond formation
• The synthetic possibilities are almost endless
19.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents
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Importance of the Grignard Addition
19.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents
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Preparation and Hydrolysis of Acetals
• Acetal: A compound in which two ether
oxygens are bound to the same carbon
19.10 Acetals and Their Use of Protecting Groups
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Preparation and Hydrolysis of Acetals
• Use of a 1,2- or 1,3-diol leads to cyclic acetals
• Only one equivalent of the diol is required
19.10 Acetals and Their Use of Protecting Groups
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Preparation and Hydrolysis of Acetals
19.10 Acetals and Their Use of Protecting Groups
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Preparation and Hydrolysis of Acetals
• Acetal formation is reversible
• The presence of acid and excess water allows
acetals to revert to their carbonyl form
• Acetals are stable in basic and neutral solution
19.10 Acetals and Their Use of Protecting Groups
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Hemiacetals
• Hemiacetals normally cannot be isolated
• Exceptions include simple aldehydes and
compounds than can form 5- and 6membered rings
19.10 Acetals and Their Use of Protecting Groups
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Hemiacetals
19.10 Acetals and Their Use of Protecting Groups
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Protecting Groups
• A protecting group is a temporary chemical
disguise for a functional group preventing it
from reacting with certain reagents
19.10 Acetals and Their Use of Protecting Groups
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Protecting Groups
19.10 Acetals and Their Use of Protecting Groups
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Reactions with Primary Amines
• Imines are sometimes called Schiff bases
19.11 Reactions of Aldehydes and Ketones with Amines
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Reactions with Primary Amines
• The dehydration of water is typically the ratelimiting step
19.11 Reactions of Aldehydes and Ketones with Amines
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Derivatives
• Before the advent of spectroscopy, aldehydes
and ketones were characterized as derivatives
19.11 Reactions of Aldehydes and Ketones with Amines
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Some Imine Derivatives
19.11 Reactions of Aldehydes and Ketones with Amines
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Reactions with Secondary Amines
• Like imine formation,
enamine formation is
reversible
19.11 Reactions of Aldehydes and Ketones with Amines
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Reactions with Secondary Amines
19.11 Reactions of Aldehydes and Ketones with Amines
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Reactions with Tertiary Amines
• Tertiary amines do not react with aldehydes or
ketones to form stable derivatives
• They are good nucleophiles, but the lack of an
N-H prevents conversion to a stable
compound
19.11 Reactions of Aldehydes and Ketones with Amines
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Reduction of Aldehydes and Ketones
• Complete reduction to a methylene (-CH2-)
group is possible by two different methods
• Wolff-Kishner reduction:
19.12 Reduction of Carbonyl Groups to Methylene Groups
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Reduction of Aldehydes and Ketones
• The Wolff-Kishner reduction takes place under
highly basic conditions
• It is an extension of imine formation
19.12 Reduction of Carbonyl Groups to Methylene Groups
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Reduction of Aldehydes and Ketones
• Clemmensen reduction:
• This reduction occurs under acidic conditions
• The mechanism is uncertain
19.12 Reduction of Carbonyl Groups to Methylene Groups
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The Wittig Alkene Synthesis
• This reaction is completely regioselective,
assuring the location of the alkene
19.13 The Wittig Alkene Synthesis
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The Wittig Alkene Synthesis
• Occurs via an addition-elimination sequence
using a phosphorous ylide
• An ylid (or ylide) is any compound with
opposite charges on adjacent, covalently
bound atoms
19.13 The Wittig Alkene Synthesis
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The Wittig Alkene Synthesis
19.13 The Wittig Alkene Synthesis
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Preparation of the Wittig Reagent
• Any alkyl halide that readily participates in SN2
reactions can be used
19.13 The Wittig Alkene Synthesis
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The Wittig Alkene Synthesis
• Retrosynthetically
• Stereochemistry
19.13 The Wittig Alkene Synthesis
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Carboxylic Acids from Aldehydes
• The hydrate is the species oxidized
19.14 Oxidation of Aldehydes to Carboxylic Acids
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Carboxylic Acids from Aldehydes
• This is known as the Tollen’s test
• A positive indicator for an aldehyde is the
deposition of a metallic silver mirror on the
walls of the reaction flask
19.14 Oxidation of Aldehydes to Carboxylic Acids
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Production and Use of Aldehydes
• The most important commercial aldehyde is
formaldehyde
• Its most important use is in the synthesis of
phenol-formaldehyde resins
19.15 Manufacture and Use of Aldehydes and Ketones
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Production and Use of Ketones
• The most important commercial ketone is
acetone
• It is co-produced with phenol by the
autoxidation-rearrangement of cumene
19.15 Manufacture and Use of Aldehydes and Ketones
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