Transcript Les amines - University of Alberta

Amines - classification
RNH 2
R2NH
1o
2o
R 3N
R4N+ X-
3o
quaternary
ammonium
salts
© E.V. Blackburn, 2011
Nomenclature
To name aliphatic amines, name the alkyl groups
bonded to the amine nitrogen and then add the suffix
“amine”:
(CH3)3CNH2
t-butylamine
C2H5NHCH3
ethylmethylamine
Systematic nomenclature adds the suffix to the name of
the hydrocarbon:
CH3CH2NH2
C2H5NHCH3
ethanamine
N-methylethanamine
© E.V. Blackburn, 2011
Nomenclature
In the IUPAC system, the -NH2 group is called the amino
group. The prefix “amino” (or “methylamino”,
“diethylamino” etc.) is therefore used in naming complex
molecules.
H2NCH2CH2CH2CO2H
H2NCH2CH2OH
H H
H3C N C (CH2)4CH3
CH3
4-aminobutanoic acid
-aminobutyric acid
2-aminoethanol
ethanolamine
2-methylaminoheptane
© E.V. Blackburn, 2011
Nomenclature
H3C
NH 2
N
C2H5
NO 2
m-nitroaniline
3-nitrobenzenamine
N-ethyl-N-methylaniline
N-ethyl-N-methylbenzenamine
© E.V. Blackburn, 2011
Nomenclature
Salts of amines are named by replacing the suffix amine
by ammonium:-
+
(C2H5NH 3)2 SO42ethylammonium sulfate
+
(CH3)3NH NO 3trimethylammonium nitrate
+
C6H5NH 3 Clanilinium chloride
© E.V. Blackburn, 2011
Physical Properties
Tertiary amines, having no N-H bonds, cannot form
hydrogen bonds (N-H-------N).
1o and 2o amines can! Their intermolecular association
by hydrogen bonding reduces their volatility relative to
hydrocarbons of similar molecular weight.
Amines having less than six carbon atoms show an
appreciable water solubility.
© E.V. Blackburn, 2011
Preparation - alkylation
RX
NH 3
RX
RX
RNH 2
1o
R3N
3o
RX
R2NH
2o
R4N+ X-
tetraalkylammonium
salt
© E.V. Blackburn, 2011
Preparation - reduction of nitro
compounds
ArNO 2
or
RNO 2
metal, H +
or H2/catalyst
ArNH 2
or
RNH 2
1º amine
NH 2
NH 2
Sn/HCl

NO 2
NH 2
© E.V. Blackburn, 2011
Preparation - reductive
amination
O
R
H
NH 3
R'
R
aldehyde
or ketone
H2/Ni
N
R'
an imine
H
R C NH 2
R'
or
NaBH 3CN
H2N
O
NH 3
H2/Ni
amphetamine
© E.V. Blackburn, 2011
Preparation - reduction of
nitriles
R C N
H2
catalyst
CN 1. LiAlH
4
RCH2NH 2
CH2NH 2
2. H+
© E.V. Blackburn, 2011
Preparation - Hofmann
degradation
-
OBr
RCONH 2 or ArCONH 2
RNH 2 or ArNH 2 + CO32-
amide
O
Cl2/OH-
NH 2
NH 2
phentermine - an
appetite
suppressant
© E.V. Blackburn, 2011
Hofmann degradation
O
R
N
H
HO -
O
H
R
N
-
H
R
Br-Br
O
R
O
-
N
Br
O
OH
H
R
-
OH
R-N=C=O
N
Br
H + Br-
HO
C O
R N
-
NBr
R-N=C=O
-
O
C O
R N H-O-H
H
© E.V. Blackburn, 2011
Reactions - basicity
+
RNH 2 + H3O
stronger
base
+
RNH 3 + OH-
+
RNH3 + H2O
weaker
base
RNH2 + H2O
© E.V. Blackburn, 2011
Reactions - basicity
RNH 2 + H2O
Kb =
+
RNH 3 + OH-
+
[RNH 3][OH-]
[RNH 2]
RNH 2 > NH3 > ArNH 2
Kb: CH3NH2 = 4.75x10-4, NH3 = 1.78x10-5, C6H5NH2 = 4.26x10-10
© E.V. Blackburn, 2011
Reactions - basicity
H
R>N: + H+
H
H+
R>N H
H
Kb: CH3NH2 = 4.75x10-4, NH3 = 1.78x10-5
© E.V. Blackburn, 2011
Reactions - basicity
H+
:NH 3
NH 4+
Kb = 1.78x10-5
NH 2
NH 3+
NH 2
NH 3+
H+
Kb = 4.26x10-10
NH 2
+ NH
2
+ NH2
-
+ NH2
-
© E.V. Blackburn, 2011
Reactions - basicity
NH 3 + H+
E
+
NH 4
+
ArNH 3
ArNH 2 + H+
Reaction coordinate
© E.V. Blackburn, 2011
Substituent effects
Substituents attached to the aromatic ring which are
electron attracting reduce the basicity of amines.
Electron-repelling substituents increase amine basicity.
NH 2
NH 2
CH3
NO 2
Kb = 1.2x10-9
Kb = 10-13
© E.V. Blackburn, 2011
Action of nitrous acid
RNH 2 + NaNO 2 + HX
RNH2
RN 2+ X-
N2
1. NaNO2/H+
ROH

2. H2O/
© E.V. Blackburn, 2011
Aromatic diazonium salts
-5C
ArNH 2 + NaNO 2 + 2HX
+
ArN
HONO + H 3O+
H
Ar N :
H
Ar
NO
H+ Ar
N N=OH +
H
+
Ar-N=N-OH
2H2O + +NO
H2O: H
+
N
Ar
NO
H
+
N N=O
H
H2O:
N: X- + NaX + 2H 2O
H
Ar
N N=O
H
Ar-N=N-OH
+
Ar-N=N-OH 2
© E.V. Blackburn, 2011
Sandmeyer reaction
NO 2
HBr
NH 2
NaNO 2
-5C
NO 2
NO 2
CuBr
N2+ Br-
Br
© E.V. Blackburn, 2011
Gattermann reaction
NO 2
HCl
NH 2
NaNO 2
-5C
NO 2
Cu/HCl
N2+ Cl-
NO 2
Cl
© E.V. Blackburn, 2011
Aromatic diazonium salts
ArN 2+
ArN 2+
-
X
-
-
X +I
HBF 4
ArN2+
ArN 2+
-
X
KI
ArI + N2 + X-
BF4-

ArF + BF3 + N2
CuCN
ArCN + N 2
© E.V. Blackburn, 2011
Aromatic diazonium salts
Synthesis of phenols
ArN 2+ X-
H2O
H2SO4
ArOH + N2

Substitution by H
ArN 2+ X- + H3PO2 + H2O
ArH + N 2 +
H3PO3 + HX
© E.V. Blackburn, 2011
Synthesis of the three
bromotoluenes
CH3
CH3
CH3
Br
FeBr3
+
Br2
bp = 182 o
Br
bp = 185 o
oops
© E.V. Blackburn, 2011
Synthesis of the bromotoluenes
CH3
CH3
CH3
NO 2
+
HNO 3
H2SO4
NO 2
bp = 222 o
CH3
bp = 238 o
1. Sn/H+
2. NaNO 2/HBr/-5 o
3. CuBr
CH3
Br
Br
© E.V. Blackburn, 2011
Synthesis of m-bromotoluene
CH3
CH3
HNO 3
Sn/H +
CH3
CH3
(CH3CO) 2O
H2SO4
NO 2
CH3
Br2/FeBr3
OH-
Br
NHCOCH 3
NHCOCH 3
CH3
NH 2
CH3
NaNO 2
Br
NH 2
CH3
H+
-5C
Br
N2+ Cl-
H3PO2
Br
© E.V. Blackburn, 2011
Coupling Reactions of
Diazonium Compounds
An electrophilic attack......
N2+ Cl+
N(CH 3)2
(H3C)2N
N N
p-(dimethylamino)azobenzene
© E.V. Blackburn, 2011
HO
HO 2C
N N
NO 2
alizarin yellow
SO3Na
N N
NH 2
H2N
N N
congo red
NaO 3S
© E.V. Blackburn, 2011
Preparation of substituted
amides
© E.V. Blackburn, 2011
Nomenclature of Substituted
Amides
CH3CNHC 2H5
O
N-ethylacetamide
O
NHCCH 3
acetanilide
N(CH 3)2
O
N,N-dimethylbenzamide
O
NHC
benzanilide
© E.V. Blackburn, 2011
Sulfanilic acid
+
NH 3
NH 2
?
SO3-
SO3H
mp > 280-300o
OH- - soluble
H+ - insoluble
dipolar ion
-a
zwitterion
“zwitter” - hermaphrodite
© E.V. Blackburn, 2011
Sulfa drugs
NH 2
NHCOCH 3
NHCOCH 3
ClSO 3H
(CH3CO) 2O
SO2Cl
NH 3
NH 2
NHCOCH 3
H2O/H+
sulfanilimide
SO2NH 2
SO2NH 2
© E.V. Blackburn, 2011
Spectroscopic Properties
N-H - stretching
3300 - 3500 cm-1
1o amines show 2 high intensity peaks
NMR - the amino H gives a peak which can be found almost
any where in the spectrum (similar to the -O-H proton).
© E.V. Blackburn, 2011