Chapter 19 The Chemistry of Aldehydes and Ketones. Carbonyl-Addition Reactions Organic Chemistry,...

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


Common Nomenclature


Prefixes Used in Common Nomenclature


Common Nomenclature


Substitutive Nomenclature


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


IR Spectroscopy

• The C=O stretching frequency in small-ring ketones is affected by ring size


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


13C NMR Spectroscopy

• Aldehyde and ketone C=O: 190-220• -Carbons: 30-50


UV/Vis Spectroscopy

• → *: 150 nm (out of the operating range)• n → *: 260-290 nm (much weaker)


UV/Vis Spectroscopy


Mass Spectrometry


Mass Spectrometry

• What accounts for the m/z = 58 peak?


Mass Spectrometry

• The McLafferty rearrangement involves a hydrogen transfer via a transient six-membered ring

• There must be an available -H


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


Addition Reactions

• The addition of a nucleophile to the carbonyl carbon is driven by the ability of oxygen to accept the unshared electron pair


Addition Reactions

• The nucleophile attacks the unoccupied * MO (LUMO) of the C=O


Addition Reactions

• The second mechanism for carbonyl addition takes place under acidic conditions


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


Equilibrium Constants for Hydration


Relative Carbonyl Stability


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


Carbonyl Stability

• Resonance can also add stability to the carbonyl group

• However, EN groups make the addition reaction more favorable


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


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



• Like other strong bases, LiAlH4 is also a good nucleophile

• Additionally, the Li+ ion is a built-in Lewis-acid



• Each of the remaining hydrides become activated during the reaction


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


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


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


Reduction by Catalytic Hydrogenation

• Hydride reagents are more commonly used• However, catalytic hydrogenation is useful for

selective reduction of alkenes


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


Organolithium and Acetylide Reagents

• These reagents react with aldehydes and ketones analogous to Grignard reagents


Importance of the Grignard Addition

• This reaction results in C-C bond formation

• The synthetic possibilities are almost endless


Importance of the Grignard Addition


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


• Use of a 1,2- or 1,3-diol leads to cyclic acetals• Only one equivalent of the diol is required



• 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


Hemiacetals

• Hemiacetals normally cannot be isolated• Exceptions include simple aldehydes and

compounds than can form 5- and 6-membered rings


Hemiacetals


Protecting Groups

• A protecting group is a temporary chemical disguise for a functional group preventing it from reacting with certain reagents


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


Derivatives

• Before the advent of spectroscopy, aldehydes and ketones were characterized as derivatives


Some Imine Derivatives


Reactions with Secondary Amines

• Like imine formation, enamine formation is reversible


Reactions with Secondary 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


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


• The Wolff-Kishner reduction takes place under highly basic conditions

• It is an extension of imine formation



• Clemmensen reduction:

• This reduction occurs under acidic conditions• The mechanism is uncertain


The Wittig Alkene Synthesis

• This reaction is completely regioselective, assuring the location of the alkene

6819.13 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


Preparation of the Wittig Reagent

• Any alkyl halide that readily participates in SN2 reactions can be used



• Retrosynthetically

• Stereochemistry


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

Chapter 19 The Chemistry of Aldehydes and Ketones. Carbonyl-Addition Reactions Organic Chemistry,...

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