Tab 1
Overall Chemistry
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Chapter 19 - Ketones and Aldehydes
Chapter 20 - Carboxylic Acids
Chapter 21 - Carboxylic Acid Derivatives
Chapter 22 - Enols, Enolates, α,β-unsaturated compounds
Chapter 19
Chapter 19 - Ketones and Aldehydes
19.1 - Structure of Aldehydes and Ketones
Aldehydes =
Ketones =
19.2 - Nomenclature
19.3 - Physical Properties of Aldehydes and Ketones
19.4 - Spectroscopy of Aldehydes and Ketones
19.5 - Introduction to Reactions of Aldehydes and Ketones
19.6 - Basicity of Aldehydes and Ketones
19.7 - Reversible Addition Reactions
19.8 - Reduction of Aldehydes and Ketones to Alcohols
19.9 - Reactions of Aldehydes and Ketones with Grignard Reagents
19.10 - Protecting Groups for Aldehydes and Ketones
19.11 - Reactions of Aldehydes with Amines
19.13 - The Wittig Reaction
19.14 - The Oxidation of Aldehydes to Carboxylic Acids
Chapter 20
Chapter 20 - Carboxylic Acids
Chapter 21
Chapter 21 - Carboxylic Acid Derivatives
21.1 Nomenclature:
Esters and Lactones
Ex: ethyl acetate
Acid Halides
Add -yl and name of halide
Ex: acetyl chloride
Anhydrides
Ex: acid anhydride
Nitriles
Ex: acetonitrile
Me-C☰N:
Amides and Lactams
Acetamide
Primary amine + carboxylic acid
Important CA derivatives
Urea and phosgene
21.2 Structures of CA Derivatives
Amides and resonance
Amides are stable linkages > esters
21.3 Physical Properties of CA Derivatives
Esters
Insoluble in H2O
Name
Propanoic Acid
2-Butanone
Methyl Acetate
Boiling Point
141˚C
80˚C
57˚C
Acid Halides
Water insoluble, Reacts with water
Name
Acetyl Chloride
Methyl Acetate
Acetic Acid
Boiling Point
51˚C
57˚C
118˚C
Nitriles
Somewhat water soluble
Name
Acetonitrile
Propyne
Boiling Point
82˚C
-23˚C
Amides
Water soluble (mostly and depending on the substituent)
Name
Acetamide
Acetic Acid
Acetone
Boiling Point
221˚C
118˚C
57˚C
Melting Point
82˚C
17˚C
-97˚C
At RT
solid
liquid
liquid
Highest Boiling Point 1˚ > 2˚ > 3˚ Lowest Boiling Point
21.4 Spectroscopy of CA and Derivatives
IR Spectra
Name
Ketone
Aldehyde
Carboxylic Acid
Acid Chloride
Amide
CO Stretch
1710
1720
1710
1800
1650
Triple bond (Ex RCN) Stretch at 2200
Strong bonds = strong stretch
21.5 Basicity of CA Derivatives
Generally, CA derivatives are not basic. Low pKa = more acidic
Name
Esters
Amides
Nitriles
PKa
-6
-1 (most basic)
-10
Base-Promoted Hydrolysis of Esters (saponification)
NaOH (inxs) in H2O and RT
Remove MeOH then acid workup (H3O) to replace ester with OH
Acid-Catalyzed Ester Hydrolysis
Acid Catalyzed Hydrolysis is the reverse Fischer Esterification
H+ (catalytic)
Remove ester and replace with OH
Steps:
1. Protonation of Carbonyl of Ester
2. Attack with water and proton transfer
3. Loss of Alcohol and regeneration of catalyst
Microscopic Reversibility: The mechanism of a reversible reaction is exactly the same in both forward and backward directions.
Hydrolysis and Formation of Lactones
Saponification (reverse is fischer esterification)
Hydrolysis of Amides
H2SO4 and ∆
Hydrolysis of Nitriles
Acid-Mediated Hydrolysis
H2SO4 (inxs) in H2O and ∆
Mechanism:
1. Protonation of nitrile
2. Attack of water
3. Proton Transfer and Regeneration of Acid
4. Protonation of Amide and Attack of Water
5. Proton Transfer and Collapse of Tetrahedral Intermediate
Base-Mediated Hydrolysis
KOH (inxs) in H2O and ∆
Mechanism:
1. Attack of Hydroxide
2. Formation of Primary Amide
3. Hydrolysis of Amide
Theory of Everything
(Nucleophilic Substitutions on Carboxylic Acid Derivatives)
Nitrile
Amides
Esters
Carboxylic Acids
Anhydrides
Acid Chloride
—------ Increasing Electrophilicity —------>
21.8 Reactions of CA Derivatives with Nucleophiles
Reactions of Acid Chlorides with Nucleophiles
Acetyl Chloride + Benzyl Amine – RT (THF or DCM) → Amide and Conj. Acid
Mechanism:
1. Addition of Nucleophile to Acid Chloride
2. Collapse of Tetrahedral Intermediate
3. Deprotonation with 2nd Equivalent of Amine
Biphasic Reaction of Acid Chlorides and Amines
Scholten-Bowmann Reaction
Reaction with two organic compounds (soluble in organic solvent) -> organic soluble and water soluble
Tetrahedral Intermediate formed in organic layer then moves to H2O layer
Reaction of Anhydrides with Nucleophiles
Nucleophile breaks C=O bnd to separate anhydride to two CA
Reactions of Esters with Nucleophiles
21.9 Reduction of Carboxylic Acid Derivatives
Ester to a Primary Alcohol
(esters cannot be reduced by NaBH4)
Ex:
Ethyl 2-methyl benzoate + LiAlH4 – THF or Et2O → –H3O→ ROH
Amides to Amines
1. THF and Et2O
2. H3O and OH
Mechanism:
1. Deprotonation of Amide with LAH
2. Complexation of AlH3 and Transfer of H-
3. Loss [Al]
4. Reduction of Imine to Amine
21.10 Reaction of Esters with Grignards
THF or Et2O then H3O
C=O reduced to OH
Ester reduced to methyl
+ Me-MgBr → Tertiary Alcohol
Chapter 22
Chapter 22 - Enols, Enolates, α,β-unsaturated compounds
Enolate
(requires addition of base)
Enol
(occurs spontaneously)
α,ß - unsaturated compounds
22.1 Acidity of Carbonyl Compounds
Enolates
Enolate ions are bronsted bases
Name
Butane
Acetone
Ethyl Acetate
pKa
50 (Very stable)
19.2 (more acidic)
25
Intro to reactions of enolate anions
Protonation of optically active enolate ion leads to racemate
Ex: amino acids are difficult to be synthesized because protonation causes loss of chirality
22.2 Enolization of Carbonyl Compounds
Carbonyl compounds are in equilibrium with their enol isomers.