Title: Chapter 24. Amines
1Chapter 24. Amines
- Based on McMurrys Organic Chemistry, 6th edition
2Amines 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
324.1 Naming Amines
- Alkyl-substituted (alkylamines) or
aryl-substituted (arylamines) - Classified 1 (RNH2), methyl (CH3NH2), 2
(R2NH), 3 (R3N)
4Quaternary Ammonium Iions
- A nitrogen atom with four attached groups is
positively charged - Compounds are quaternary ammonium salts
5Common 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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824.2 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
9Chirality 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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1224.3 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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14Amines Form H-Bonds
- Amines with fewer than five carbons are
water-soluble - Primary and secondary amines form hydrogen bonds,
increasing their boiling points
1524.4 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
16Relative 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 .
17General 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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23Amides
- 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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25Amines as Acids
- Loss of the NH proton requires a very strong base
2624.5 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
27Substituted 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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2924.6 Synthesis of Amines
- Reduction of nitriles and amides (review)
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31Reduction 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
32SN2 Reactions of Alkyl Halides
- Ammonia and other amines are good nucleophiles
33Uncontrolled 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
34Selective 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
35Gabriel 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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37Reductive Amination of Aldehydes and Ketones
- Treatment of an aldehyde or ketone with ammonia
or an amine in the presence of a reducing agent
38Reductive Amination Is Versatile
- Ammonia, primary amines, and secondary amines
yield primary, secondary, and tertiary amines,
respectively
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42Mechanism of Reductive Amination
43Reducing Step
- Sodium cyanoborohydride, NaBH3CN, reduces CN but
not CO - Stable in water
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47Hofmann 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
48Hofmann Rearrangement
- RCONH2 reacts with Br2 and base
- Gives high yields of arylamines and alkylamines
49Curtius 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
50Reactions of Amines
- Alkylation and acylation have already been
presented
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57Hofmann 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
58Silver 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
59Orientation 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
60Steric Effects Control the Orientation
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63Definition 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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