Chapter 25: Amines

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Chapter 25 Amines

• Introduction (25.1)
• Structure and Bonding (25.2)
• Nomenclature (25.3)
• Spectroscopic Properties (25.5)
• Interesting and Useful Amines (25.6)
• Preparation of Amines (25.7)
• Amines as Bases (25.9)
• Relative Basicity of Amines (25.10)
• Amines as Nucleophiles (25.11)
• Hofmann Elimination (25.12)
• Reactions of Amines with Nitrous Acid (25.13)
• Substitution Reactions of Aryl DiazoniumCompounds
  (25.14)
• Coupling Reactions of Aryl DiazoniumSalts (25.15)

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I. Introduction

• Amines are bases.
• Amines are nucleophiles.

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II. Structure and Bonding

• Trigonal pyramidal geometry
• High negative potential on N

• Amine N can be stereogenic center.

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• Enantiomers rapidly interconvert.

• Enantiomers of quaternary ammonium salts

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III. Nomenclature A. Primary Amines
1. IUPAC Name Find longest chain and
replace e ending with amine. 2.
Common Name Name alkyl group attached to
N and add amine.
CH3CH2CH2CH2NH2
butanaminebutylamine
B. 2 3 Amines with Identical Substituents
diethylamine triethylamine
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B. 2 3 Amines with Different Substituents
1. Find longest chain or largest ring.
2. Name other groups in alphabetical order,
with N prefix for each.
N,N-dimethybenzenamimeN,N-dimethylaniline
N-ethyl-N-methyl-1-propanamimeN-ethyl-N-methylpro
pylamine
C. Other Prominent Amines
pyridine pyrrole pyrrolidine
piperidine
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IV. Spectroscopic Properties A. Mass
Spectrometry
Amines with odd of Ns give molecular ion with
odd m/z.
Figure 25.2 Mass Spectrum of Butylamine
B. IR Spectroscopy
CH3CH2CH2CH2NH2
CH3CH2NHCH2CH3
Figure 25.3 IR Spectra of Amines
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C. NMR Spectroscopy

• NH signal between 0.5 and 5.0 ppm.
• a-CH absorbs between 2.3 and 3.0 ppm.
• No HC-NH spin-spin splitting.
• a-C absorbs at 30-50 ppm in 13C spectrum.

Figure 25.4 1H NMR Spectrum of N-methylaniline
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V. Interesting Amines A. Alkaloids
nicotine coniine (from
hemlock)
B. Phenylethylamines
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C. Excitatory Neurotransmitters
Dopamine controls movement involved in
cognition (perception, emotions)
serotonin
LSD
Acetylcholine involved in cognition and
intelligence
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VI. Preparation of Amines A. Nucleophilic
Substitution 1. Direct Nucleophilic
Substitution

• RX limited to methyl and 1 alkyl halides.
• Complicated by polyalkylation.
• Useful for preparing 1 amines and quaternary
  ammonium salts.

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2. Gabriel Synthesis of 1 Amines
phthalimidepKa 10

• R Me or 1 alkyl

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B. Reduction of Nitrogen-containing Functional
Groups 1. From Nitro Compounds
(Section 18.14C)
reduce
RNO
2
Reducing Agents H2/Pd-C 1) Fe, HCl
2) OH- 1) Zn, or Sn, or SnCl2
HCl 2) OH-
2. From Nitriles (Section 22.18B)
Nitriles from alkyl halides
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3. From Amides (Section 20.7B)
C. Reductive Amination
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Examples
Retrosynthetic Analysis
ephedrine
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VII. Amines as Bases
Figure 25.8 Separation of Cyclohexylamine and
Cyclohexanol by Extraction
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VIII. Relative Basicity of Amines
Compare basicities by using conjugate acid
pKa values. A. An Amine and Ammonia
H-NH3 pKa 9.3 NH3 (weaker
base) CH3CH2-NH3 pKa 10.8
CH3CH2NH2 ? Alkyl amines are stronger
bases than NH3. ? Electron-donating alkyl
groups increase electron density on
N.
B. An Alkylamine and an Arylamine
pKa 4.6 pKa 10.8
Aniline is a weaker base that ethylamine.Why?
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etc.
resonance delocalized lone pair
localized lone pair

• Electron donors increase basicity.
• Electron withdrawers decrease basicity.

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C. An Alkylamine and an Amide
Lone pair on N is resonance delocalized.

• Amides are less basic than alkyl amines.
• Preferred site of protonation is on oxygen.

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D. Heterocyclic Aromatic Amines
pKa 5.3 pyridine pKa
0 pyrrole

• Pyridine stronger base lone pair localized
• Pyrrole weaker base lone pair delocalized

E. Effects of Hybridization
pKa 5.3 pyridine pKa
11.1 piperidine

• Pyridine weaker base lone pair in sp2
  orbital
• Piperidine stronger base lone pair in sp3
  orbital

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IX. Amines as Nucleophiles A. With
Aldehydes and Ketones (Sections
21.11-21.12)
B. With Acid Chlorides and Anhydrides
(Sections 22.8-22.9)
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C. Friedel-Crafts Reactions of ArNH2
Strategy 1) protect 2) do desired reaction
3) deprotect
pyridine
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X. Hofmann Elimination A. General Features

• SN2 amine alkylation
• Anion exchange
• E2 elimination

Elimination Mechanism
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Example
cyclohexylamine
cyclohexene
B. Regioselectivity

• Less substituted product is favored.
• Contrasts with Zaitsev elimination.

CH3CH2O-CH3CH2OH
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XI. Reaction of Amines with HNO2 A.
Generation of HNO2 and NO
B. Reaction of NO with 1 AminesExample

• Aryl diazonium salts are stable at 0 C.
• Alkyl diazonium salts generally are not useful.

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substitution and elimination products
Mechanism
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C. Reaction of NO with 2 Amines

• N-nitrosamines formed from 2 amines are
  relatively stable and carcinogenic.

Mechanism
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XII. Substitution Reactions of Aryl
Diazonium SaltsA. Synthesis of Phenols
B. Sandmeyer Reactions
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C. Synthesis of Aryl Fluorides

• Aryl fluorides cannot be prepared by EAS
  reactions.

D. Synthesis of Aryl Iodides

• Aryl iodides cannot be prepared by EAS
  reactions.

E. Synthesis of Benzonitriles

• Nitriles can be converted to carboxylic acids,
  aldehydes, ketones, or 1 amines (Section
  22.18)

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F. Reduction to Benzene
G. Synthesis with Diazonium Salts
Retrosynthetic Analysis
Synthesis
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XIII. Coupling Reactions of Aryl
Diazonium Compounds
Example
Mechanism