Bài giảng hoá học hữu cơ amine

Amines
I. Introduction
II. Synthesis
III. Reaction


I. Amines
:NH3
RNH2

1o amine

(R or Ar)

R2NH

2o amine

R3N

3o amine

NR4+

4o ammonium salt


Amines

Antidepressant

Neurotransmitter

Neurotransmitter

Treatment of chronic urticaria
and Allergy


Amines
Mushroo
m
Neurotransmitter

Hallucinogenic


Amines

Ecstasy drug


Dopamine


Nomenclature
Aliphatic amines are named as “alkylamines”

CH3NH2
methylamine
1o

CH3CH2NHCH3
ethylmethylamine
2o

(CH3)2NH
dimethylamine
2o
CH3CH2CHCH3
NH2
sec-butylamine
1o

(CH3)3N
trimethylamine
3o
CH3
CH3CCH3
NH2
tert-butylamine
1o


Nomenclature
NH2
CH2NH2
cyclohexylamine
1o

benzylamine

Complex amines are named by prefixing
"amino"-" ( or N-methylamino, N,N-dimethyl
amino-, etc.) to the parent chain:
CH3CH2CHCH2CH2CH3
NH2
3-aminohexane

CH3NHCH2CH2OH
2-(N-methylamino)ethanol


Nomenclature
Aromatic amines
NH2

NH2

NH2

NH2
CH3

CH3
o-toluidine

aniline

H3C

N

CH3

m-toluidine

p-toluidine

CH3
H
N

N,N-dimethylaniline

diphenylamine


Salts of amines
amine  ammonium + anion
aniline  anilinium + anion

CH3CH2CH2NH3+Cln-propylammonium chloride

(C6H5NH3)2SO4
anilinium sulfate


O
C O

O

C OCH3
N

CH3

cocaine
3o amine
m 98o C
water insoluble
volatile
"free base"
"crack"
smoked
shorter "high"
lower dose, cheaper
5 g = 5 years

HCl

NaHCO3

O
C O

O
C OCH3
H
Cl
N
CH3

cocaine.HCl
HCl salt of 3o amine
m 195o C
water soluble
non-volatile
"powder", "blow"
"snow"
snorted
longer "high"
higher dose, expensive
500 g = 5 years


II. Synthesis of amines
1. Reduction of nitro compounds
Ar-NO2 + H2,Ni  Ar-NH2
2. Ammonolysis of 1o or methyl halides
R-X + NH3  R-NH2
3. Reductive amination
R2C=O + NH3, H2, Ni  R2CHNH2
4. Reduction of nitriles
R-C≡N + 2 H2, Ni  RCH2NH2
5. Hofmann degradation of amides
RCONH

+ KOBr  RNH


Reduction of nitro compounds

NH2

NO2
metal + acid; then OHor H2 + Ni, Pt, or Pd

R NO2
$$$
Chiefly for primary aromatic amines.

R NH2


CH3

HNO3,H2SO4

CH3
+ orthoNO2

H2,Ni

CH3

NH2
p-toluidine


Ammonolysis of 1o or methyl halides
NH3

R-X

RNH2

R-X

R2NH
2o

1o

R-X

R3N
3o
R-X

R-X must be 1o or CH3

R4N+X4o salt

CH3CH2CH2CH2Br

NH3

CH3CH2CH2CH2NH2
n-butylamine


CH3CH2CH2NH2

n-propylamine

NH2

CH3Cl

CH3CH2CH2NHCH3
methyl-n-propylamine

2 CH3CH2Br

aniline

N

Et
Et

N,N-diethylaniline
(xs) CH3I
H2
C NH2

benzylamine

H2 CH3
C N CH3
CH3
I
benzyltrimethylammonium iodide

Ammonolysis of alkyl halides is an SN2 reaction. The
alkyl halide must be primary or methyl. If the alkyl halide
is secondary or tertiary, then an E2 reaction will take place
and the product will be an alkene!
Br

NH2
+ NH3

2o RX


Reductive amination:
O + NH3

O + RNH2

O + R2NH

H2, Ni
or NaBH3CN

CH NH2

1o amine

CH NHR

2o amine

CH NR2

3o amine

H2, Ni
or NaBH3CN

H2, Ni
or NaBH3CN

Avoids E2


Reductive amination via the imine.
O
C

NH3

H2,Ni

H
C
NH2
H2, Ni

OH
C

NH2

- H2O

C
NH
imine


H3C

O
C

NH3, H2/Ni
CH3

NH2
CH3CHCH3
isopropylamine

acetone

O
CCH2CH3 + CH3CH2NH2
propiophenone

O

cyclohexanone

NaBH3CN

CH2CH3
NH
CHCH2CH3

1-(N-ethylamino)-1-phenylpropane
NH3, H2/Ni

NH2

cyclohexylamine


Reduction of nitriles
R-C≡N + 2 H2, catalyst  R-CH2NH2
1o amine
R-X + NaCN  R-CN  RCH2NH2
primary amine with one additional carbon
(R must be 1o or methyl)
CH2Br
benzyl bromide

NaCN

CH2C N

2 H2, Ni

CH2CH2NH2
1-amino-2-phenylethane


Hofmann degradation of amides
O
R C
NH2

KOBr

R-NH2

Removes one carbon!
CH3 O
CH3C C
CH3 NH2

OBr

2,2-dimethylpropanamide

CH3
CH3C NH2
CH3
tert-butylamine


Synthesis of amines
1. Reduction of nitro compounds

1o Ar

Ar-NO2 + H2,Ni  Ar-NH2
2. Ammonolysis of 1o or methyl halides

R-X = 1o,CH3

R-X + NH3  R-NH2
3. Reductive amination

avoids E2

R2C=O + NH3, H2, Ni  R2CHNH2
4. Reduction of nitriles

+ 1 carbon

R-C≡N + 2 H2, Ni  RCH2NH2
5. Hofmann degradation of amides
RCONH2 + KOBr  RNH2

- 1 carbon


Syntheses for each of the following
amines, starting with toluene?
NH2

H3C

aniline

NH2
p-toluidine

CH2CH2NH2
1-amino-2-phenylethane

CH2NH2
benzylamine

H3C

NH2
CHCH3

1-amino-1-(p-tolyl)ethane


Solution
NH2

H3C

1. nitration

5. Hofmann degradation
CH2CH2NH2

4. Reduction of nitrile
CH2NH2

2. ammonolysis

NH2

H3C

NH2
CHCH3

3. Reductive amination