Amines

1

• Amines

Chapter 23
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23.1 Structure Classification

• Amines are classified as
• 1 2 or 3 amines amines in which 1 2 or
  3 hydrogens of NH3 are replaced by alkyl or aryl
  groups.

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Structure Classification

• Amines are further divided into aliphatic
  aromatic and heterocyclic amines
• aliphatic amine an amine in which nitrogen is
  bonded only to alkyl groups.
• aromatic amine an amine in which nitrogen is
  bonded to one or more aryl groups.

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Structure Classification

• heterocyclic amine an amine in which nitrogen is
  one of the atoms of a ring.

5
Structure Classification

• Example classify each amino group by type.

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Structure Classification

• Aliphatic amines replace the suffix -e of the
  parent alkane by amine.

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22.2 A. Nomenclature

• The IUPAC system retains the name aniline.

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Nomenclature

• Among the various functional groups discussed in
  the text -NH2 is one of the lowest in order of
  precedence.

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B. Nomenclature

• Common names for most aliphatic amines are
  derived by listing the alkyl groups bonded to
  nitrogen in one word ending with the suffix
  amine.

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Nomenclature

• When four groups are bonded to nitrogen the
  compound is named as a salt of the corresponding
  amine.

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22.3 Chirality of Amines

• if we consider the unshared pair of electrons on
  nitrogen as a fourth group then the arrangement
  of groups around N is approximately tetrahedral.
• an amine with 3 different groups bonded to N is
  chiral and exists as a pair of enantiomers and
  in principle can be resolved.

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Chirality of Amines

• in practice however they cannot be resolved
  because they undergo pyramidal inversion which
  converts one enantiomer to the other.

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Chirality of Amines

• pyramidal inversion is not possible with
  quaternary ammonium ions and their salts can be
  resolved.

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22.4 Physical Properties

• Amines are polar compounds and both 1 and 2
  amines form intermolecular hydrogen bonds.
• N-H- - -N hydrogen bonds are weaker than O-H- -
  -O hydrogen bonds because the difference in
  electronegativity between N and H (3.0 - 2.1
  0.9) is less than that between O and H (3.5 -
  2.1 1.4).

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Hydrogen Bonding in Amines
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22.5 Basicity

• All amines are weak bases and aqueous solutions
  of amines are basic.
• it is common to discuss their basicity by
  reference to the acid ionization constant of the
  conjugate acid.

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Basicity

• using values of pKa we can compare the acidities
  of amine conjugate acids with other acids.

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A. Basicity-Aliphatic Amines Table 23.2

• Aliphatic Amines

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B. Basicity-Aromatic Amines Table 23.2
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Basicity-Aromatic Amines

• aromatic amines are considerably weaker bases
  than aliphatic amines.

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Basicity-Aromatic Amines

• Aromatic amines are weaker bases than aliphatic
  amines because of two factors.
• 1. Resonance stabilization of the free base
  which is lost on protonation.

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Basicity-Aromatic Amines

• 2. The greater electron-withdrawing inductive
  effect of the sp2-hybridized carbon of an
  aromatic amine compared with the sp3-hybridized
  carbon of an aliphatic amine also decreases
  basicity.
• Electron-releasing such as alkyl groups
  increase the basicity of aromatic amines.
• Electron-withdrawing groups such as halogens
  the nitro group and a carbonyl group decrease
  the basicity of aromatic amines by a combination
  of resonance and inductive effects.

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Basicity-Aromatic Amines

• 4-nitroaniline is a weaker base than
  3-nitroaniline.

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C. Basicity-Aromatic Amines

• Heterocyclic aromatic amines are weaker bases
  than heterocyclic aliphatic amines.

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Basicity-Aromatic Amines

• in pyridine the unshared pair of electrons on N
  is not part of the aromatic sextet.
• pyridine is a weaker base than heterocyclic
  aliphatic amines because the free electron pair
  on N lies in an sp2 hybrid orbital (33 s
  character) and is held more tightly to the
  nucleus than the free electron pair on N in an
  sp3 hybrid orbital (25 s character).

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Basicity-Aromatic Amines

• Imidazole.

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D. Basicity-Guanidine

• Guanidine is the strongest base among neutral
  organic compounds.
• its basicity is due to the delocalization of the
  positive charge over the three nitrogen atoms.

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22.6 Reaction with Acids

• All amines whether soluble or insoluble in
  water react quantitatively with strong acids to
  form water-soluble salts.

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Extraction Flow Sheet
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Extraction Flow Sheet
A carboxylic acid B phenol C amine
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22.7 Preparation of Amines

• We have already covered these methods
• nucleophilic ring opening of epoxides by ammonia
  and amines (11.9B).
• addition of nitrogen nucleophiles to aldehydes
  and ketones to form imines (Section 16.8).
• reduction of imines to amines (16.8A).
• reduction of amides by LiAlH4 (18.10B).
• reduction of nitriles to a 1 amine (18.10C).
• nitration of arene2 followed by reduction of the
  NO2 group to 1 amines (22.1B).

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A. Preparation

• Alkylation of ammonia and amines by SN2.
• unfortunately such alkylations give mixtures of
  products through a series of proton transfer and
  nucleophilic substitution reactions.

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B. Preparation via Azides

• Attaching an alkyl group to an azide (alkylation)
  followed by reduction.

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Preparation via Azides

• Formation of an alkylazide then reduction.

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22.8 Reaction of amines with HNO2

• Nitrous acid a weak acid is most commonly
  prepared by treating NaNO2 with aqueous H2SO4 or
  HCl.
• In its reactions with amines nitrous acid
• participates in proton-transfer reactions
• is a source of the nitrosyl cation NO a weak
  electrophile.

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Formation of NO

• NO is formed in the following way.
• we study the reactions of HNO2 with 1 2 and
  3 aliphatic and aromatic amines.

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A. B. 3o Amines with HNO2

• 3 aliphatic amines whether water-soluble or
  water-insoluble are protonated to form
  water-soluble salts.
• 3 aromatic amines NO is a weak electrophile
  and as such participates in EAS.
• 2 aliphatic and aromatic amines react with NO
  to give N-nitrosoamines.

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C. 2o Amines with HNO2

• Reaction of a 2 amine to give an N-nitrosamine.
• Step 1 reaction of the 2 amine (a nucleophile)
  with the nitrosyl cation (an electrophile).
• Step 2 proton transfer.

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D. 1o Amines (RNH2) with HNO2

• 1 aliphatic amines give a mixture of
  unrearranged and rearranged substitution and
  elimination products all of which are produced
  by way of a diazonium ion and its loss of N2 to
  give a carbocation.
• Diazonium ion an RN2 or ArN2 ion.
• Aromatic diazonium ions are more stable than
  aliphatic ones.

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1 RNH2 with HNO2

• Formation of a diazonium ion
• Step 1 reaction of a 1 amine with the NO.
• Step 2 protonation followed by loss of water.

H












N
O


A diazotic acid
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1 RNH2 with HNO2

• Aliphatic diazonium ions are unstable and lose N2
  to give a carbocation which may
• 1. lose a proton to give an alkene.
• 2. react with a nucleophile to give a
  substitution product.
• 3. rearrange and then react by 1 and/or 2.

(5.2)

(25)
(13.2)

(25.9)
(10.6)
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1 RNH2 with HNO2

• Tiffeneau-Demjanov reaction treatment of a
  -aminoalcohol with HNO2 gives a ketone and N2.

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1 RNH2 with HNO2

• reaction with NO gives a diazonium ion.
• concerted loss of N2 and rearrangement followed
  by proton transfer gives the ketone.

N
N
(A diazonium ion)




O

O
H
O
H

Cycloheptanone
A resonance-stabilized cation
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E. 1 ArNH2 with HNO2

• The -N2 group of an arenediazonium salt can be
  replaced in a regioselective manner by these
  groups. The aromatic diazonium salt is more
  stable than the aliphatic due to resonance.

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1 ArNH2 with HNO2

• A 1 aromatic amine can be converted to a phenol.

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1 ArNH2 with HNO2

• Problem what reagents and experimental
  conditions will bring about this conversion

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1 ArNH2 with HNO2

• Problem Show how to bring about each conversion.

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22.9 Hofmann Elimination

• Hofmann elimination thermal decomposition of a
  quaternary ammonium hydroxide to give an alkene.
  Step 1 formation of a 4 ammonium hydroxide.

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Hofmann Elimination

• Step 2 thermal decomposition of the 4 ammonium
  hydroxide.

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Hofmann Elimination

• Hofmann elimination is regioselective - the major
  product is the least substituted alkene.
• Hofmanns rule any -elimination that occurs
  preferentially to give the least substituted
  alkene as the major product is said to follow
  Hofmanns rule.

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Hofmann Elimination

• the regioselectivity of Hofmann elimination is
  determined largely by steric factors namely the
  bulk of the -NR3 group.
• hydroxide ion preferentially approaches and
  removes the least hindered hydrogen and thus
  gives the least substituted alkene.
• bulky bases such as (CH3)3CO-K give largely
  Hofmann elimination with haloalkanes.

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22.10 Cope Elimination

• Cope elimination thermal decomposition of an
  amine oxide.
• Step 1 oxidation of a 3 amine gives an amine
  oxide.
• Step 2 if the amine oxide has at least one
  hydrogen it undergoes thermal decomposition to
  give an alkene.

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Cope Elimination

• Cope elimination shows syn stereoselectivity but
  little or no regioselectivity.
• mechanism a cyclic flow of electrons in a
  six-membered transition state.

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Amines
End Chapter 23