Chapter 24. Amines

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Chapter 24. Amines

• Based on McMurrys Organic Chemistry, 6th edition

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Amines Organic Nitrogen Compounds

• Organic derivatives of ammonia, NH3,
• Nitrogen atom with a lone pair of electrons,
  making amines both basic and nucleophilic
• Occur in plants and animals

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24.1 Naming Amines

• Alkyl-substituted (alkylamines) or
  aryl-substituted (arylamines)
• Classified 1 (RNH2), methyl (CH3NH2), 2
  (R2NH), 3 (R3N)

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Quaternary Ammonium Iions

• A nitrogen atom with four attached groups is
  positively charged
• Compounds are quaternary ammonium salts

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Common Names of Heterocyclic Amines

• If the nitrogen atom occurs as part of a ring,
  the compound is designated as being heterocyclic
• Each ring system has its own parent name

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24.2 Structure and Bonding in Amines

• Bonding to N is similar to that in ammonia
• N is sp3-hybridized
• CNC bond angles are close to 109 tetrahedral
  value

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Chirality Is Possible (But Not Observed)

• An amine with three different substituents on
  nitrogen is chiral (in principle but not in
  practice) the lone pair of electrons is the
  fourth substituent
• Most amines that have 3 different substituents on
  N are not resolved because the molecules
  interconvert by pyramidal inversion

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24.3 Properties and Sources of Amines

• Simple methylated amines from reaction of NH3
  with CH3OH and alumina catalyst
• Yields a mixture of monomethylated, dimethylated,
  and trimethylated products that are easily
  separated by distillation

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Amines Form H-Bonds

• Amines with fewer than five carbons are
  water-soluble
• Primary and secondary amines form hydrogen bonds,
  increasing their boiling points

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24.4 Basicity of Amines

• The lone pair of electrons on nitrogen makes
  amines basic and nucleophilic
• They react with acids to form acidbase salts and
  they react with electrophiles

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Relative Basicity

• Amines are stronger bases than alcohols, ethers,
  or water
• Amines establish an equilibrium with water in
  which the amine becomes protonated and hydroxide
  is produced
• The most convenient way to measure the basicity
  of an amine (RNH2) is to look at the acidity of
  the corresponding ammonium ion (RNH3)
• High pKa ? weaker acid and stronger conjugate
  base .

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General Patterns of Basicity

• Table 24.1 pKa values of ammonium ions
• Most simple alkylammmonium ions have pKa's of 10
  to 11
• Arylamines and heterocyclic aromatic amines are
  considerably less basic than alkylamines
  (conjugate acid pKa 5 or less)

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Amides

• Amides (RCONH2) in general are not proton
  acceptors except in very strong acid
• The CO group is strongly electron-withdrawing,
  making the N a very weak base
• Addition of a proton occurs on O but this
  destroys the double bond character of CO as a
  requirement of stabilization by N

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Amines as Acids

• Loss of the NH proton requires a very strong base

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24.5 Basicity of Substituted Arylamines

• The N lone-pair electrons in arylamines are
  delocalized by interaction with the aromatic ring
  ? electron system and are less able to accept H
  than are alkylamines

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Substituted Arylamines

• Can be more basic or less basic than aniline
• Electron-donating substituents (such as ?CH3,
  ?NH2, ?OCH3) increase the basicity of the
  corresponding arylamine
• Electron-withdrawing substituents (such as ?Cl,
  ?NO2, ?CN) decrease arylamine basicity

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24.6 Synthesis of Amines

• Reduction of nitriles and amides (review)

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Reduction Aryl Nitro Compounds

• Arylamines are prepared from nitration of an
  aromatic compound and reduction of the nitro
  group
• Reduction by catalytic hydrogenation over
  platinum is suitable if no other groups can be
  reduced
• Iron, zinc, tin, and tin(II) chloride are
  effective in acidic solution

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SN2 Reactions of Alkyl Halides

• Ammonia and other amines are good nucleophiles

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Uncontrolled Multiple Alkylation

• Primary, secondary, and tertiary amines all have
  similar reactivity, the initially formed
  monoalkylated substance undergoes further
  reaction to yield a mixture of products

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Selective Preparation of Primary Amines the
Azide Synthesis

• Azide ion, N3? displaces a halide ion from a
  primary or secondary alkyl halide to give an
  alkyl azide, RN3
• Alkyl azides are not nucleophilic (but they are
  explosive)
• Reduction gives the primary amine

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Gabriel Synthesis of Primary AMines

• A phthalimide alkylation for preparing a primary
  amine from an alkyl halide
• The N-H in imides (?CONHCO?) can be removed by
  KOH followed by alkylation and hydrolysis

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Reductive Amination of Aldehydes and Ketones

• Treatment of an aldehyde or ketone with ammonia
  or an amine in the presence of a reducing agent

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Reductive Amination Is Versatile

• Ammonia, primary amines, and secondary amines
  yield primary, secondary, and tertiary amines,
  respectively

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Mechanism of Reductive Amination

• Imine is intermediate

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Reducing Step

• Sodium cyanoborohydride, NaBH3CN, reduces CN but
  not CO
• Stable in water

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Hofmann and Curtius Rearrangements

• Carboxylic acid derivatives can be converted into
  primary amines with loss of one carbon atom by
  both the Hofmann rearrangement and the Curtius
  rearrangement

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Hofmann Rearrangement

• RCONH2 reacts with Br2 and base
• Gives high yields of arylamines and alkylamines

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Curtius Rearrangement

• Heating an acyl azide prepared from substitution
  an acid chloride
• Migration of ?R from CO to the neighboring
  nitrogen with simultaneous loss of a leaving group

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Reactions of Amines

• Alkylation and acylation have already been
  presented

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Hofmann Elimination

• Converts amines into alkenes
• NH2? is very a poor leaving group so it converted
  to an alkylammonium ion, which is a good leaving
  group

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Silver Oxide Is Used for the Elimination Step

• Exchanges hydroxide ion for iodide ion in the
  quaternary ammonium salt, thus providing the base
  necessary to cause elimination

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Orientation in Hofmann Elimination

• We would expect that the more highly substituted
  alkene product predominates in the E2 reaction of
  an alkyl halide (Zaitsev's rule)
• However, the less highly substituted alkene
  predominates in the Hofmann elimination due to
  the large size of the trialkylamine leaving group
• The base must abstract a hydrogen from the most
  sterically accessible, least hindered position

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Steric Effects Control the Orientation
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Definition of Phase Transfer Catalysis

• The transfer of an inorganic ion such as OH? from
  one phase to another is called phase transfer,
  and the tetraalkylammonium salt is a
  phase-transfer catalyst

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