Aromatic amines topic includes basicity of the aromatic amine. It also includes the comparison of the basicity. It is designed according to new PCI syllabus of B. Pharmacy.

1. Aromatic AminesAromatic Amines
Kumar Pratyush

2. Introduction
• Organic derivatives of ammonia
• Many are biologically active.
2
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3. Biological Activity
• Neurotransmitters: dopamine
• Bioregulators: epinephrine
• Vitamins: niacin, B6
• Alkaloids: nicotine, morphine, cocaine
• Amino acids
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3

4. Aromatic Amines
Amino group is bonded to a benzene
ring. Parent compound is called
aniline.
4
NH2
aniline
N
CH3
CH3
N,N-dimethylaniline
=>
NH2
H3C
4-methylaniline
or p-toluidine

5. Basicity of Amines
• Lone pair of electrons on nitrogen can
accept a proton from an acid
• Aqueous solutions are basic to litmus.
• Ammonia pKb = 4.74
• Alkyl amines are usually stronger bases
than ammonia. Increasing the number of
alkyl groups decreases solvation of ion,
so 2° and 3° amines are similar to 1°
amines in basicity.
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5

6. Basicity-Aliphatic Amines
• Aliphatic Amines
– note that pKa + pKb = 14
Tertiary Amines
diethylamine
dimethylamine
cyclohexylamine
ethylamine
methylamine
Secondary Amines
Primary Amines
Ammonia
pKaStructureAmine
trimethylamine
triethylamine
9.26
10.64
10.81
10.66
10.73
10.98
9.81
10.75
pKb
4.74
3.36
3.34
3.19
3.27
3.02
4.19
3.25
CH3 NH2
NH3
CH3 CH2 NH2
C6 H1 1 NH2
( CH3 ) 2 NH
( CH3 CH2 ) 2 NH
( CH3 ) 3 N
( CH3 CH2 ) 3 N
Stronger
bases
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7. Basicity-Aromatic Amines
NH2CH3
NH2Cl
NH2O2N
NH2
N
N
N
H
Heterocyclic Aromatic Amines
Aromatic Amines
StructureAmine
Aniline
4-Chloroaniline
4-Nitroaniline
4-Methylaniline
Pyridine
Imidazole
4.63
5.08
4.15
1.0
5.25
6.95
pKa of Conjugate Acid
Weaker
bases
Intermediate
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8. Basicity-Aromatic Amines
– Aromatic amines are considerably
weaker bases than aliphatic amines.
NH2 H2 O
H2 ONH2
NH3
+
OH-
NH3
+
OH-
Cyclohexylamine
pKa = 4.63
Aniline
pKa = 10.66+
+
Cyclohexylammonium
hydroxide
Anilinium hydroxide
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9. The greater the availability of the lone pair electrons on nitrogen, the greater the base.
Kb = [RNH3
+
] [OH-
] / RNH2
In the old days, pKb was a measure of base strength.
pKb = - log Kb
The stronger the base the lower the pKb
EFFECTS ON AMINE BASICITY
1. INDUCTIVE EFFECT - ALKYL SUBSTITUTION
CH3-NH2 < CH3-NH
CH3
METHYL GROUP INCREASES ELECTRON DENSITY ON N
3.36 3.28 2 METHYLS ARE BETTER THAN ONE
WATCH OUT THREE METHYL GROUPS DECREASES
BASICITY pKb = 4.26 - Steric inhibition of solvation of HOH
with the NH+
of the R3NH+
cation.
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10. Basicity-Aromatic Amines
• Aromatic amines are weaker bases
than aliphatic amines because of two
factors:
– Resonance stabilization of the free
base, which is lost on protonation.
N
HH
H
HH
H
H
..
. .
. .
. .
unhybridized 2p orbital of N
nitrogen is sp2
hybridized
N N N
H H H H
H N
H HH
+++
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11. Basicity-Aromatic Amines
– The greater electron-withdrawing inductive
effect of the sp2
-hybridized carbon of an
aromatic amine compared with that of the
sp3
-hybridized carbon of an aliphatic amine.
And note the effect of substituents
• Electron-releasing groups, 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. 11

12. Example: Basicity-Aromatic
Amines
3-nitroaniline is a stronger base than
4-Nitroaniline.
NH2
O2 N
NH2O2 N
pKa 1.0pKa 2.47
4-Nitroaniline3-Nitroaniline
delocalization of the nitrogen
lone pair onto the oxygen atoms
of the nitro group
++
-
-
-
N NH2 NH2
+
N
O
O
O
O
Cannot do this kind of resonance in 3 nitroaniline
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13. Energy Diagram
Alkyl groups are electron-donating and
stabilize the cation.
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14. Resonance Effects
Any delocalization of the electron pair
weakens the base.
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15. Electrophilic Substitution
of Aniline
• -NH2 is strong activator, o-,p-directing.
• May trisubstitute with excess reagent.
• H+
changes -NH2 to -NH3
+
, a meta-directing
deactivator.
• Attempt to nitrate aniline may explode.
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16. Aniline Substitution
16
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17. 17

18. 18

19. 19

20. 20

21. Arenediazonium Salts
• Stable in solution at 0°–10°C.
• Diazotizing reagent :- NaNO2 + 2HCl
• The -+
N≡N group is easily replaced by
many different groups.
• Nitrogen gas, N2, is a by-product.
21
HBF4 (KI)
H3O
+
CuCl (Br)
CuCN
H3PO2
H Ar'
Ar N N
+
Ar OH
Ar Cl
Ar C N
Ar F
Ar H
Ar N N Ar'
(Br)
(I)
phenols
aryl halides
benzonitriles
aryl halides
benzene
azo dyes =>