Ch. 20 - 1

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Chapter 20

• Amines

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About The Authors

• These PowerPoint Lecture Slides were created and
  prepared by Professor William Tam and his wife,
  Dr. Phillis Chang.
• Professor William Tam received his B.Sc. at the
  University of Hong Kong in 1990 and his Ph.D. at
  the University of Toronto (Canada) in 1995. He
  was an NSERC postdoctoral fellow at the Imperial
  College (UK) and at Harvard University (USA). He
  joined the Department of Chemistry at the
  University of Guelph (Ontario, Canada) in 1998
  and is currently a Full Professor and Associate
  Chair in the department. Professor Tam has
  received several awards in research and teaching,
  and according to Essential Science Indicators, he
  is currently ranked as the Top 1 most cited
  Chemists worldwide. He has published four books
  and over 80 scientific papers in top
  international journals such as J. Am. Chem. Soc.,
  Angew. Chem., Org. Lett., and J. Org. Chem.
• Dr. Phillis Chang received her B.Sc. at New York
  University (USA) in 1994, her M.Sc. and Ph.D. in
  1997 and 2001 at the University of Guelph
  (Canada). She lives in Guelph with her husband,
  William, and their son, Matthew.

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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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1. 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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• 3o Amines with three different groups

• The two enantiomeric forms interconvert rapidly
• Impossible to resolve enantiomers
• Pyramidal or nitrogen inversion
• Barrier 25 kJ/mol
• Enough to occur rapidly at room temperature

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• Ammonium salts with four different groups

enantiomers can be resolved
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1. Basicity of AminesAmine 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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gt
gt
By releasing electrons, R stabilizes the
alkylaminium ion through dispersal of charge
gt
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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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3B. Basicity of Heterocyclic Amines
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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 about zero

Larger resonance stabilization
Smaller resonance stabilization
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lt
gt
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3D. Aminium Salts and QuaternaryAmmonium Salts
Cannot act as bases
However, R4N? ?OH are strong bases (as strong as
NaOH)
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3E. Solubility of Amines in AqueousAcids
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3F. Amines as Resolving Agents

• Enantiomerically pure amines are often used to
  resolve racemic forms of acidic compounds by the
  formation of diastereomeric salts

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1. 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 Primary, Secondary, and
Tertiary Amines through Reductive Amination
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• Mechanism

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• Examples

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4D. Preparation of Primary, Secondary, or
Tertiary Amines through Reduction of Nitriles,
Oximes, and Amides
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• Examples

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• Examples

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4D. 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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1. 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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1. Reactions of Amines withNitrous Acid

• Nitrous acid (HONO) is a weak, unstable acid

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6A. Reactions of Primary Aliphatic Amines with
Nitrous Acid
1o aliphatic amine
(aliphatic diazonium salt) (highly unstable)
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6B. Reactions of Primary Arylamines with
Nitrous Acid
(arenediazonium salt) (stable at lt5oC)
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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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1. 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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1. Coupling Reactions of Arenediazonium Salts

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• Examples

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• Examples

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• Examples

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1. 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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1. Synthesis of Sulfa Drugs

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1. 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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11B. Spectroscopic Analysis

• IR
• 1o amines
• 3300 3555 cm-1 (NH)
• ? two bands
• 2o amines
• 3300 3555 cm-1 (NH)
• ? one band only
• 3o amines
• No bands at 3300 3555 cm-1 region

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• Aliphatic amines
• 1020 1220 cm-1 (CN)
• Aromatic amines
• 1250 1360 cm-1 (CN)

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• 1H NMR spectra
• 1o and 2o amines
• NH d (0.5 5 ppm), usually broad, exact
  position depends on the solvent, concentration,
  purity and temperature
• NH protons are not usually coupled to protons on
  adjacent carbons
• Protons on the a carbon of an aliphatic amine are
  deshielded by the electron-withdrawing effect of
  the nitrogen and absorb typically in the d
  2.22.9 region

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• Protons on the b carbon are not deshielded as
  much and absorb in the range d 1.01.7

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• 13C NMR spectra

23.0
34.0
14.3
29.7
42.5
13C NMR chemical shifts (d)
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• Mass spectra
• The molecular ion in the mass spectrum of an
  amine has an odd number mass (unless there is an
  even number of nitrogen atoms in the molecule)
• The peak for the molecular ion is usually strong
  for aromatic and cyclic aliphatic amines but weak
  for acyclic aliphatic amines
• Cleavage between the a and b carbons of aliphatic
  amines is a common mode of fragmentation

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1. 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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1. Summary of Preparations and Reactions of Amines

• Preparation of amines

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• Reactions of amines

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? END OF CHAPTER 21 ?