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Chapter 20
Amines
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1. Nomenclature
1o Amines
2o Amines
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3o Amines
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1A. Arylamines
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1B. Heterocyclic Amines
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2. Physical Properties and Structure of Amines
2A. Physical Properties
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2B. Structure of Amines
N: sp3 hybridized
Trigonal pyramidal
Bond angles close to 109.5o
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3. Basicity of Amines: Amine Salts
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The aminium ion of a more basic amine will have a larger pKa than the aminium ion of a less basic amine
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>
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By releasing electrons, R— stabilizes the alkylaminium ion through dispersal of charge
>
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3A. Basicity of Arylamines
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Five resonance structures
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Only two resonance structures
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15. 3C. Amines versus Amides
Amides are far less basic than amines (even less basic than arylamines). The pKa of the conjugate acid of a typical amide is ~zero
Larger resonance stabilization
Smaller resonance stabilization
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3D. Aminium Salts and Quaternary Ammonium Salts
Cannot act
as bases
However, R4N⊕ ⊖OH are strong bases (as strong as NaOH)
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3E. Solubility of Amines in Aqueous Acids
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4. Preparation of Amines
4A. Through Nucleophilic Substitution Reactions
Alkylation of ammonia
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Alkylation of azide ion and reduction
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The Gabriel synthesis
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Alkylation of 3o amines
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4B. Preparation of Aromatic Amines through Reduction of Nitro Compounds
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4C. Preparation of 1o, 2o, & 3o Amines through Reductive Amination
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Mechanism
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Examples
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4D. Preparation of 1o, 2o, & 3o Amines through Reduction of Nitriles, Oximes, and Amides
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Examples
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Examples
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4E. Preparation of Primary Amines
through the Hofmann and Curtius Rearrangements
Hofmann rearrangement
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Examples
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Mechanism
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Curtius rearrangement
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5. Reactions of Amines
Acid-base reactions
Alkylation
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Acylation
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Electrophilic aromatic substitution
NH2: powerful activating group, ortho-para director
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5A. Oxidation of Amines
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6. Reactions of Amines with Nitrous Acid
Nitrous acid (HONO) is a weak, unstable acid
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40. 6A. Reactions of Primary Aliphatic Amines with Nitrous Acid
1o aliphatic amine
(aliphatic diazonium salt)
(highly unstable)
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41. 6B. Reactions of Primary Arylamines with Nitrous Acid
(arenediazonium salt)
(stable at <5oC)
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Mechanism
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Mechanism (Cont'd)
diazonium ion
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6C. Reactions of Secondary Amines with Nitrous Acid
N-Nitroso-
amines
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6D. Reactions of Tertiary Amines with Nitrous Acid
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7. Replacement Reactions of Arenediazonium Salts
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7A. Syntheses Using Diazonium Salts
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7B. The Sandmeyer Reaction: Replacement of the Diazonium Group by —Cl, —Br, or —CN
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7C. Replacement by —I
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7D. Replacement by —F
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7E. Replacement by —OH
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7F. Replacement by Hydrogen: Deamination by Diazotization
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8. Coupling Reactions of Arenediazonium Salts
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Examples
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Examples
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Examples
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9. Reactions of Amines with Sulfonyl Chlorides
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9A. The Hinsberg Test
Sulfonamide formation is the basis for a chemical test, called the Hinsberg test, that can be used to demonstrate whether an amine is primary, secondary, or tertiary
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1o Amine
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2o Amine
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3o Amine
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10. Synthesis of Sulfa Drugs
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11. Analysis of Amines
11A. Chemical Analysis
Dissolve in dilute aqueous acid
Moist pH paper
 basic
Hinsberg test
1o aromatic amines
 azo dye formation with 2-naphthol
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12. Eliminations Involving Ammonium Compounds
12A. The Hofmann Elimination
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Although most eliminations involving neutral substrates tend to follow the Zaitsev rule, eliminations with charged substrates tend to follow what is called the Hofmann rule and yield mainly the least substituted alkene
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12B. The Cope Elimination
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13. Summary of Preparations and Reactions of Amines
Preparation of amines
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Reactions of amines
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