Chapter 24 Amines

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Chapter 24 Amines
R
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R-NH2 R-NH-R
R-N-R R-N-R
R
R
Primary, 10 Secondary, 20
Tertiary, 30 Quaternary ammonium
Structure
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ammonia
triethylamine H-N-H angle 1070 C-N-C angle
1080
An amine may be chiral, but if so, it is in rapid
equilibrium with its mirror-image enantiomer.
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Transition state
(R)ethylmethylamine
(S)ethylmethylamine
2
Note Transition State is planar with an Ea of 6
kcal/mol. This low Ea means that
these mirror images rapidly interconvert. This
process is termed pyramidal inversion

• Physical Properties of Amines
• They stink!!!!
• 10 and 20 amines self H-bond since they
  possess N-H groups
• 30 amines cannot self H-bond - no N-H
  group.
• Consequence 10 and 20 amines will
  have higher boiling points
• 30 amines if the same molecular weight
• 10, 20 and 30 amines can all accept a H-bond
  from water or an alcohol.
• Thus they are all H-bond acceptors

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This H-bond with water increases the
amines solubility in water. Most low MW amines
are highly soluble in water.
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Basicity an extremely important property of
amines.
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RNH2 H2O R-NH3
OH
Kb RNH3 OH- RNH2 H2O
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RNH2 R2NH R3N
pKb 3-5 Alkyl amines
ArNH2 ArNHR pKb 8-13 Aryl amines
ArNR2
Heterocyclic Amines pKb 3-15
Why are the arylamines (anilines) so much weaker
bases than the alkylamines?
Answer Resonance!!!! The lone pair in anilines
is delocalized into the aromatic Ring. This
resonance effect stabilizes the molecule and
makes it less basic.
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Molecular Orbital Picture of Aniline
The nonbonding pair of electrons on the N atom
exist in the highest occupied molecule orbital
(HOMO) of the molecule. AM1 calculations of this
orbital reveal that the electrons in the HOMO
are shared with the ring as shown below.
Top View Side
View
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Substituent Effects in Aryl Amines
pKb 9.40
Electron-withdrawing groups make aniline less
basic. Electron-donating groups make aniline
more basic. Why?? The nonbonding pair of
electrons is conjugated with the aromatic ring.
Any substituent that donates electrons to the
ring, increases the electron density on the N.
This makes the N more basic relative to aniline.
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Resonance Forms of p-nitroaniline illustrated
this effect.
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Heterecyclic Amines
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pyrrole
pyrrolidine piperidine
pyridine N hybridization sp2
sp3 sp3
sp2 Basicity pKb 15
2.73 2.88
8.75
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• Why this order of basicity among the heterocyclic
  amines?
• To explain, examine
• The type of orbital of the nonbonded electrons
• Hybridization of N atom
• Whether the nonbonded electrons are delocalized
  or not.

For pyrrole, the N is sp2 and the nonbonded pair
of electrons resides in a p orbital, which
overlaps with the pi system. Thus the electrons
are delocalized, making it a weaker base than
the others.
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p orbital electrons delocalized in pi system
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AM1 HyperChem Calculations on Pyrrole
-.196
-.196
-.146 -.146
.181
Charge on C and N Atoms
HOMO shows nonbonded electrons on carbon atoms
For pyridine, the N is sp2 as well, but the
nonbonded electrons reside in an sp2 orbital.
Therefore the nonbonded electrons are not
delocalized and it is a stronger base than
pyrrole.
sp2 orbital electrons localized on N atom

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Finally, why is pyridine a weaker base than
piperidine and pyrrolidine. In all molecules,
the nonbonded electrons are not delocalized. So
what is the difference?
The difference is due to hybridization of the
nitrogen.


sp2 sp3
pyridine
piperidine
More tightly held electrons
Loosely held electrons pKb 8.75
pKb 2.88
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Q How would you make a 30 amine by this method?
Predict these products
3. Reduction of Nitro Compounds
Catalyst Ni, Pd, Pt Active metal Fe, Zn, Sn
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R may be alkyl or aryl in nature
4. Reduction of Azides and Nitriles
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Azide ion
or N3
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Nitriles
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cyanide ion
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Notice that one carbon has been added to the
alkyl halide
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LAH
5. Gabriel Synthesis
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6. Hofman Rearrangement
Where X2 Cl2, Br2
Mechanism Blackboard
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Reactions of Amines
1. As Bronsted Bases
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RNH2 HCl ? RNH3
Cl
Examples
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pyridinium chloride
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Tripropylammonium chloride
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• Properties of ammonium salts
• High solubility of water
• Used as phase transfer catalysts due to
  solubility in both organic
• and water phases.

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Ephedrine
Ephedrine hydrochloride Low water
solubility Water
soluble
Aliquat 336 - used as a phase transfer catalyst
to shuttle water soluble reagents
into an organic phase so they can react
with something that is solely organic
soluble.
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Aliquat 336 and Phase-Transfer Catalysis
insoluble in organic phase
complex soluble in organic phase
octyl groups are hydrophobic!
Aliquat 336
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2. Reactions with ketones/aldehydes
or NH3
H2O
H
imine
H2O
H
enamine
3. Alkylation of Amines
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neutralize
10 20 30
40
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This reaction is not that useful for synthesis of
an amine except when a large excess of ammonia
is used with an alkyl halide.
excess
10 amine
good yield
4. Amines as Leaving Groups Synthesis of
Alkenes
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Now heat to obtain E2 elimination
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• Excess CH3I
• Ag2O
• Heat

Write the mechanisms for the above reaction
sequence.
When more than on alkene can form, which one
prodominates?

• Excess CH3I
• Ag2O

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3. Heat
5 95
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OH
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Why is the Hofmann (least stable) the major
product? It relates to the bulky leaving
group.
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OH
3 2
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?-hydrogen and LG Must be anti-coplanar
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2-butene
Gauche interaction unstable conformation
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OH
1 2
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1-butene
No severe Gauche interaction more stable
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5. Cope Elimination
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30 amine
amine oxide
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This reaction is an intramolecular E2 syn
elimination.
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6. Reactions of aryl amines with nitrous acid
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00 C
aniline
benzene diazonium chloride
These aryl diazonium salts, unlike those derived
from 10 alkyl amines, is relatively stable at 00
C.
Once formed, the diazonium salt can be reacted
with a variety of reagents to other aromatic
derivatives.
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Phenol Aryl chloride or bromide Benzonitrile
Aryl fluoride Aryl iodide Benzene
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benzene diazonium chloride