Chapter 19 The Chemistry of Aldehydes and Ketones. Carbonyl-Addition Reactions Organic Chemistry, 5th ed. Marc Loudon Eric J. Kantorowski California Polytechnic State University San Luis Obispo, CA
Jan 12, 2016
Chapter 19The Chemistry of Aldehydes and Ketones.
Carbonyl-Addition Reactions
Organic Chemistry, 5th ed.Marc Loudon
Eric J. KantorowskiCalifornia Polytechnic State UniversitySan Luis Obispo, CA
Chapter 19 Overview
• 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
• 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
419.1 Nomenclature of Aldehydes and Ketones
Carbonyl Compounds
519.1 Nomenclature of Aldehydes and Ketones
Common Nomenclature
619.1 Nomenclature of Aldehydes and Ketones
Prefixes Used in Common Nomenclature
719.1 Nomenclature of Aldehydes and Ketones
Common Nomenclature
819.1 Nomenclature of Aldehydes and Ketones
Substitutive Nomenclature
919.1 Nomenclature of Aldehydes and Ketones
Substitutive Nomenclature
1019.1 Nomenclature of Aldehydes and Ketones
Physical Properties
• Most simple aldehydes and ketones are liquids
1119.2 Physical Properties of Aldehydes and Ketones
IR Spectroscopy
• Strong C=O stretch: 1700 cm-1
1219.3 Spectroscopy of Aldehydes and Ketones
IR Spectroscopy
• Conjugation with a bond lowers the absorption frequency
1319.3 Spectroscopy of Aldehydes and Ketones
IR Spectroscopy
• The C=O stretching frequency in small-ring ketones is affected by ring size
1419.3 Spectroscopy of Aldehydes and Ketones
1H NMR Spectroscopy
• The reason for the large value for aldehydic protons is similar to that for vinylic protons
• However, the electronegative O increases this shift farther downfield
1519.3 Spectroscopy of Aldehydes and Ketones
13C NMR Spectroscopy
• Aldehyde and ketone C=O: 190-220• -Carbons: 30-50
1619.3 Spectroscopy of Aldehydes and Ketones
UV/Vis Spectroscopy
• → *: 150 nm (out of the operating range)• n → *: 260-290 nm (much weaker)
1719.3 Spectroscopy of Aldehydes and Ketones
UV/Vis Spectroscopy
1819.3 Spectroscopy of Aldehydes and Ketones
Mass Spectrometry
1919.3 Spectroscopy of Aldehydes and Ketones
Mass Spectrometry
• What accounts for the m/z = 58 peak?
2019.3 Spectroscopy of Aldehydes and Ketones
Mass Spectrometry
• The McLafferty rearrangement involves a hydrogen transfer via a transient six-membered ring
• There must be an available -H
2119.3 Spectroscopy of Aldehydes and Ketones
Summary of Aldehyde and Ketone Preparation
1. Oxidation of alcohols2. Friedel-Crafts acylation3. Hydration of alkynes4. Hydroboration-oxidation of alkynes5. Ozonolysis of alkenes6. Periodate cleavage of glycols
2219.4 Synthesis of Aldehydes and Ketones
Carbonyl-Group Reactions
• Reactions with acids
• Addition reactions
• Oxidation of aldehydes
2319.5 Introduction to Aldehyde and Ketone Reactions
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 -hydroxy carbocations
2419.6 Basicity of Aldehydes and Ketones
Basicity of Aldehydes and Ketones
• -hydroxy and -alkoxy carbocations are significantly more stable than ordinary carbocations (by ~100 kJ mol-1)
2519.6 Basicity of Aldehydes and Ketones
Addition Reactions
• One of the most typical reactions of aldehydes and ketones is addition across the C=O
2619.7 Reversible Addition Reactions of Aldehydes and Ketones
Mechanism of Carbonyl-Addition Reactions
2719.7 Reversible Addition Reactions of Aldehydes and Ketones
Addition Reactions
• The addition of a nucleophile to the carbonyl carbon is driven by the ability of oxygen to accept the unshared electron pair
2819.7 Reversible Addition Reactions of Aldehydes and Ketones
Addition Reactions
• The nucleophile attacks the unoccupied * MO (LUMO) of the C=O
2919.7 Reversible Addition Reactions of Aldehydes and Ketones
Addition Reactions
• The second mechanism for carbonyl addition takes place under acidic conditions
3019.7 Reversible Addition Reactions of Aldehydes and Ketones
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 aldehydes2. Addition is more favorable if EN groups are
near the C=O3. Addition is less favorable when groups that
donate electrons by resonance to the C=O are present
3119.7 Reversible Addition Reactions of Aldehydes and Ketones
Equilibrium Constants for Hydration
3219.7 Reversible Addition Reactions of Aldehydes and Ketones
Relative Carbonyl Stability
3319.7 Reversible Addition Reactions of Aldehydes and Ketones
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
3419.7 Reversible Addition Reactions of Aldehydes and Ketones
Carbonyl Stability
• Resonance can also add stability to the carbonyl group
• However, EN groups make the addition reaction more favorable
3519.7 Reversible Addition Reactions of Aldehydes and Ketones
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
3619.7 Reversible Addition Reactions of Aldehydes and Ketones
Reduction with LiAlH4 and NaBH4
3719.8 Reduction of Aldehydes and Ketones to Alcohols
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
3819.8 Reduction of Aldehydes and Ketones to Alcohols
Reduction with LiAlH4
• Like other strong bases, LiAlH4 is also a good nucleophile
• Additionally, the Li+ ion is a built-in Lewis-acid
3919.8 Reduction of Aldehydes and Ketones to Alcohols
Reduction with LiAlH4
• Each of the remaining hydrides become activated during the reaction
4019.8 Reduction of Aldehydes and Ketones to Alcohols
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
4119.8 Reduction of Aldehydes and Ketones to Alcohols
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
4219.8 Reduction of Aldehydes and Ketones to Alcohols
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
4319.8 Reduction of Aldehydes and Ketones to Alcohols
Reduction by Catalytic Hydrogenation
• Hydride reagents are more commonly used• However, catalytic hydrogenation is useful for
selective reduction of alkenes
4419.8 Reduction of Aldehydes and Ketones to Alcohols
Grignard Addition
• Grignard reagents with carbonyl groups is the most important application of the Grignard reagent in organic chemistry
4519.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents
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
4619.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents
Organolithium and Acetylide Reagents
• These reagents react with aldehydes and ketones analogous to Grignard reagents
4719.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents
Importance of the Grignard Addition
• This reaction results in C-C bond formation
• The synthetic possibilities are almost endless
4819.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents
Importance of the Grignard Addition
4919.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents
Preparation and Hydrolysis of Acetals
• Acetal: A compound in which two ether oxygens are bound to the same carbon
5019.10 Acetals and Their Use of Protecting Groups
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
5119.10 Acetals and Their Use of Protecting Groups
Preparation and Hydrolysis of Acetals
5219.10 Acetals and Their Use of Protecting Groups
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
5319.10 Acetals and Their Use of Protecting Groups
Hemiacetals
• Hemiacetals normally cannot be isolated• Exceptions include simple aldehydes and
compounds than can form 5- and 6-membered rings
5419.10 Acetals and Their Use of Protecting Groups
Hemiacetals
5519.10 Acetals and Their Use of Protecting Groups
Protecting Groups
• A protecting group is a temporary chemical disguise for a functional group preventing it from reacting with certain reagents
5619.10 Acetals and Their Use of Protecting Groups
Protecting Groups
5719.10 Acetals and Their Use of Protecting Groups
Reactions with Primary Amines
• Imines are sometimes called Schiff bases
5819.11 Reactions of Aldehydes and Ketones with Amines
Reactions with Primary Amines
• The dehydration of water is typically the rate-limiting step
5919.11 Reactions of Aldehydes and Ketones with Amines
Derivatives
• Before the advent of spectroscopy, aldehydes and ketones were characterized as derivatives
6019.11 Reactions of Aldehydes and Ketones with Amines
Some Imine Derivatives
6119.11 Reactions of Aldehydes and Ketones with Amines
Reactions with Secondary Amines
• Like imine formation, enamine formation is reversible
6219.11 Reactions of Aldehydes and Ketones with Amines
Reactions with Secondary Amines
6319.11 Reactions of Aldehydes and Ketones with Amines
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
6419.11 Reactions of Aldehydes and Ketones with Amines
Reduction of Aldehydes and Ketones
• Complete reduction to a methylene (-CH2-) group is possible by two different methods
• Wolff-Kishner reduction:
6519.12 Reduction of Carbonyl Groups to Methylene Groups
Reduction of Aldehydes and Ketones
• The Wolff-Kishner reduction takes place under highly basic conditions
• It is an extension of imine formation
6619.12 Reduction of Carbonyl Groups to Methylene Groups
Reduction of Aldehydes and Ketones
• Clemmensen reduction:
• This reduction occurs under acidic conditions• The mechanism is uncertain
6719.12 Reduction of Carbonyl Groups to Methylene Groups
The Wittig Alkene Synthesis
• This reaction is completely regioselective, assuring the location of the alkene
6819.13 The Wittig Alkene Synthesis
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
6919.13 The Wittig Alkene Synthesis
The Wittig Alkene Synthesis
7019.13 The Wittig Alkene Synthesis
Preparation of the Wittig Reagent
• Any alkyl halide that readily participates in SN2 reactions can be used
7119.13 The Wittig Alkene Synthesis
The Wittig Alkene Synthesis
• Retrosynthetically
• Stereochemistry
7219.13 The Wittig Alkene Synthesis
Carboxylic Acids from Aldehydes
• The hydrate is the species oxidized
7319.14 Oxidation of Aldehydes to Carboxylic Acids
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
7419.14 Oxidation of Aldehydes to Carboxylic Acids
Production and Use of Aldehydes
• The most important commercial aldehyde is formaldehyde
• Its most important use is in the synthesis of phenol-formaldehyde resins
7519.15 Manufacture and Use of Aldehydes and Ketones
Production and Use of Ketones
• The most important commercial ketone is acetone
• It is co-produced with phenol by the autoxidation-rearrangement of cumene
7619.15 Manufacture and Use of Aldehydes and Ketones