Chemistry > Aldehydes and Ketones > 12.0 Addition of Nitrogen Nucleophiles
Aldehydes and Ketones
1.0 Introduction
2.0 Methods of Preparation
2.1 Aldehydes by Oxidation of 1° Alcohol
2.2 Ketones by Oxidation of 2° Alcohol
2.3 Aldehydes by Reduction of Acyl Chlorides, Esters and Nitriles
2.4 Aldehydes from Acyl Halides
2.5 Aldehydes from Esters and Nitriles
2.6 By heating calcium salt of fatty acids
2.7 Hydroboration of Alkynes
2.8 Hydration of Alkynes
2.9 Gattermann-Koch Reaction
2.10 Gattermann Reaction
2.11 Freidel Crafts Acylation
2.12 By Oxidation of Alkyl Benzenes
2.13 Etard’s Reaction
3.0 Physical Properties
4.0 Relative Reactivities of Carbonyl Compounds
4.1 Relative Reactivities towards Nucleophilic addition
4.2 Rate of Nucleophilic Substitution
4.3 Reactivitiy Considerations
5.0 Addition of Carbon Nucleophiles
6.0 Haloform Reactions
7.0 Aldol Condensations
8.0 Claisen Condensation
9.0 Intramolecular Claisen Condensation
9.1 Dieckmann Condensation
9.2 Perkin Reaction
9.3 Mechanism:
9.4 Knoevenagel Reaction
9.5 Mechanism
10.0 Cannizzaro Reaction
11.0 Reformatsky Reaction
12.0 Addition of Nitrogen Nucleophiles
12.1 Mechanism and pH dependence of Rate of Reaction of Imine (>C = N-) Formation
12.2 Addition of Secondary Amines: Formation of Enamine
12.3 Mechanism for Enamine Formation
12.4 Addition of Ammonia: Reductive Amination
13.0 Addition of Oxygen Nucleophile
13.1 Addition of Water
13.2 Mechanism
13.3 Mechanism for Acid-Catalysed Hydrate Formation
13.4 Addition of Alcohols
13.5 Mechanism for the Reaction
13.6 Acid-Catalyzed Hemiacetal Formation
13.7 Base-Catalyzed Hemiacetal Formation
13.8 Acid-Catalyzed Acetal Formation
13.9 Acetals are Protecting Groups
14.0 Addition of Sulphur Nucleophile
15.0 Oxidation of Aldehydes And Ketones
15.1 Tollen’s Reagent
15.2 Fehling Solution
15.3 Benedict’s Solution
15.4 Schiff’s Reagent
15.5 Baeyer-Villiger Oxidation
15.6 Oppenauer Oxidation
15.7 Oxidation of Aldehydes And Ketones With $S{O_2}$
16.0 Reduction of Aldehyde and Ketones
16.1 Addition of Hydride Ion
16.2 Meerwein-Ponndorf-Verley Reduction
16.3 The Wolf Kishner Reduction
16.4 Mechanism for Wolff-Kishner
16.5 Clemmensen Reduction
17.0 Other Reactions Of Aldehydes And Ketones
17.1 Wittig Reaction
17.2 Pinacol-Pinacolone Rearrangement
17.3 Benzoin Condensation
17.4 Schimdt Reaction
17.5 Benzilic acid Rearrangement
17.6 The Beckmann Rearrangement
17.7 Reaction of Formaldehyde with Ammonia
12.1 Mechanism and pH dependence of Rate of Reaction of Imine (>C = N-) Formation
2.2 Ketones by Oxidation of 2° Alcohol
2.3 Aldehydes by Reduction of Acyl Chlorides, Esters and Nitriles
2.4 Aldehydes from Acyl Halides
2.5 Aldehydes from Esters and Nitriles
2.6 By heating calcium salt of fatty acids
2.7 Hydroboration of Alkynes
2.8 Hydration of Alkynes
2.9 Gattermann-Koch Reaction
2.10 Gattermann Reaction
2.11 Freidel Crafts Acylation
2.12 By Oxidation of Alkyl Benzenes
2.13 Etard’s Reaction
4.2 Rate of Nucleophilic Substitution
4.3 Reactivitiy Considerations
9.2 Perkin Reaction
9.3 Mechanism:
9.4 Knoevenagel Reaction
9.5 Mechanism
12.2 Addition of Secondary Amines: Formation of Enamine
12.3 Mechanism for Enamine Formation
12.4 Addition of Ammonia: Reductive Amination
13.2 Mechanism
13.3 Mechanism for Acid-Catalysed Hydrate Formation
13.4 Addition of Alcohols
13.5 Mechanism for the Reaction
13.6 Acid-Catalyzed Hemiacetal Formation
13.7 Base-Catalyzed Hemiacetal Formation
13.8 Acid-Catalyzed Acetal Formation
13.9 Acetals are Protecting Groups
15.2 Fehling Solution
15.3 Benedict’s Solution
15.4 Schiff’s Reagent
15.5 Baeyer-Villiger Oxidation
15.6 Oppenauer Oxidation
15.7 Oxidation of Aldehydes And Ketones With $S{O_2}$
16.2 Meerwein-Ponndorf-Verley Reduction
16.3 The Wolf Kishner Reduction
16.4 Mechanism for Wolff-Kishner
16.5 Clemmensen Reduction
17.2 Pinacol-Pinacolone Rearrangement
17.3 Benzoin Condensation
17.4 Schimdt Reaction
17.5 Benzilic acid Rearrangement
17.6 The Beckmann Rearrangement
17.7 Reaction of Formaldehyde with Ammonia
The addition of nitrogen nucleophile to the aldehyde or ketone is unlike the addition of hydrogen or carbon nucleophile, more than a simple addition reaction. The addition of a carbon or hydrogen nucleophile to an aldehyde or a ketone forms a stable tetrahedral compound. Because the nitrogen atom in the tetrahedral compound formed when a nitrogen nucleophile adds to an aldehyde or a ketone still has a non-bonding pair of electrons, the tetrahedral compound is not stable. The non-bonding electrons on nitrogen cause water to be eliminated. Loss of proton from a resulting imine(protonated) results in stable imine. Overall the reaction is a nucleophilic addition – elimination reaction: nucleophilic addition of an amine followed by loss of water. Aldehydes and ketones undergo a nucleophilic addition reaction with a carbon and hydrogen nucleophile and undergo nucleophilic addition – elimination reaction with a nitrogen nucleophile.
The pH at which imine formation is carried out, must be carefully controlled. There must be sufficient acid present to protonate the tetrahedral intermediate so that ${H_2}O$ rather than the much more basic $OH$ is the leaving group. However, if too much acid is present, it protonates the reactant amine. Protonated amine are not nucleophiles, so they cannot react with carbonyl groups.
A plot of the observed rate constant for the reaction of acetone with $N{H_2}OH$ as a function of pH of the reaction mixture is shown in figure. This type of a plot is called pH – rate profile. The pH rate profile is a bell shaped curve with maximum rate occurring at pH = 4.5. As the acidity
increases below pH = 4.5, the rate of the reaction decreases because more and more of the amine becomes protonated. As a result less and less amine is present in the nucleophilic non-protonated form. As the acidity decreases above pH = 4.5, the rate decreases because the less and less of the tetrahedral intermediate is present in the reactive protonated form. The pKa of protonated hydroxylamine is 4.5. Apparently, the maximum rate is obtained at a pH at which half of the amine is active as a nucleophile and the other half is protonated.
Imine formation is a reversible reaction. In aqueous acidic solutions, imines are hydrolysed back to the carbonyl compound and amine. In an acidic solution, amine is protonated and is unable to participate in the reverse reaction.
Imine hydrolysis is a necessary step in the conversion of a nitrile to a ketone. Reaction of a nitrile with a Grignard reagent forms an imine that is hydrolysed to a ketone.
