AMINES Compounds in which one or more of the H atoms of ammonia have been replaced by an organic group.

Can be: a) Primary amines RNH2 b) Secondary amines R2NH c) Tertiary amines R3N Can also be classified as: a) Alkyl amine the organic substituents on N are all alkyl groups. b) Aryl amine if one or more of the substituents on N is an aryl group.

Physical properties of amines: BPs of amines are higher than alkanes but lower than alcohols of comparable MW. Compound Pentane Butylamine n-Butanol MW 72 73 74 118
o BP C 36 78

1o, 2o and 3o amines in which the organic groups are small are soluble in water. Basicity of amines: Basicities of amines are determined by the relative availability of the nonbonding electrons on N to a proton donor or Lewis acid and by the stabilization of the positively charged N by solvation or by resonance. Order of basicity: In CH3NH2 and (CH3)2NH, the methyl groups increases basicity. (CH3)3N is more basic than NH3 because of the methyl groups. It is less basic than CH3NH2 and (CH3)2NH because the 3 methyl groups interfere with protonation and with stabilization of the cation by solvation. Aryl amines are less basic than ammonia because the nonbonding pair of electrons of N is less available to acids. The nonbonding electrons of N can be delocalized to the aromatic ring. Order of basicity: 2o amine > 1o amine > 3o amine > NH3 > aryl amine Substituent effects on the basicity of aryl amines: Electron-withdrawing groups on an aryl amine decreases the basicity of an aryl amine. Electron-donating substituents on an aryl amine increases the basicity of an aryl amine. Reactions of Amines: 1. Reaction with carboxylic acid derivatives to form amides
O R C Cl O + O R'NH2 O R C N R' + HCl H O R C N R' + RCOOH H R C O C R + R'NH2

2. Reaction with HONO nitrosation reaction of amines HONO nitrous acid; generated as needed from NaNO2 and a strong mineral acid (usually HCl).
+ + Na + NO2 + H3O + Cl -

H2O 0o C
H2O
+

HO N O + Na + Cl

HO N O +

H3 O

N O

H2 O + N O

Nitrosonium ion:
a) Nitrosation of 2o amines
R R N .. H
+

+ :

.. N O:
R R N
+

+ :N O ..

R H R N N O N-nitrosamine

N O N O

CH3 CH3 N H

NaNO2 HCl

CH3 CH3 N N O

b) Nitrosation of 1o amines
B H R N .. H
+ -

H R N
+

.. R N .. O .. .. N B .. R N N OH .. B H
-

N O N O .. .. .. + R N N O H H

.. + H2O R N N alkyldiazonium ion

Alkyldiazonium ion can lose N2 spontaneously even at low To. N2 may also be displaced by a nucleophile in an SN2 reaction or lost as a leaving group in an E2 reaction.
CH3CH2CH2CH2 N Cl
+

CH3CH2CH2CH2Cl + N2 alkyl halide

H

CH3CH2CH2CH2 N H O H H H CH3CH2 B
-

CH3CH2CH2CH2 O

+ N2

H CH3CH2CH2CH2 alcohol C C N H H
+

OH

E2

H C CH2 + N2 + HB

CH3CH2

c)

Nitrosation of aryl amines 1o aryl amines form aryldiazonium ions, while 2o aryl amines form nitrosamines.
NaNO2, HCl H2O, 0oC
+

NH2

N N

N H CH3

NaNO2, HCl H2O, 0oC

N N O CH3

Reactions of Aryldiazonium Ions:

KI CuCl I

Cl Br CN OH

CuBr CuCN H2O

Coupling Reactions of Aryldiazonium Ions:

N
+

N +

OH

N N

OH

N +

N(CH3)2

N N

N(CH3)2

3.

Hinsberg reaction reaction of benzenesulfonyl chloride with amines in the presence of aqueous NaOH. - distinguishes between 1o, 2o and 3o amines. Observations: a) 1o amine will yield a clear solution which, upon acidification, yields an insoluble material. b) 2o amine will yield an insoluble material, which is unaffected by acid. c) 3o amine yields an insoluble material (the unreacted amine itself), which dissolves upon acidification of the mixture.
O S Cl + RNH2 1o amine O x's KOH O S O soluble O S Cl + R2NH 2o amine O x's KOH O S NR2 O sulfonamide insoluble x's KOH H+
-

NR

H+

O S NHR O sulfonamide insoluble O

H+

S NR2 O sulfonamide insoluble R3NH+ soluble

O S O Cl

+ R3N

3o amine

R3N insoluble

Preparation of nitro compounds 1. Reaction between alkyl halides and nitrite ion (nucleophilic substitution) RX + NO2RNO2 + X-

where RX is a primary or secondary alkyl halide and X is Br or I. Example: CH3CH2CH2I + NO2CH3CH2CH2NO2 + I-

2. Nitration of aromatic compounds (Electrophilic aromatic substitution)

HNO3 H2SO4

NO2

Preparation of amines 1. Alkylation of ammonia or amines RX + NH3 RX + RNH2 Example: RNH2 + HX R2NH + HX

H3C

I + NH3
+ -

H3C NH3

+ -

I
+ -

H3C NH3

I + NH3

H3C NH2 + NH4 I

2. Reduction of nitroalkanes Can be carried out using a) Catalytic hydrogenation Pt RNO + 3H

2 2

RNH2

2 H2O

b) Reduction with LiAlH4 Example:

NO2

LiAlH4

H2O

NH2

3. Reduction of nitrobenzenes Can be carried out by: a) using Sn or Fe and HCl, in which case the amine is obtained as its HCl salt. Need to react with NaOH to get the amine. b) Catalytic reduction of a nitro group with H2 and a catalyst.

NO2

Fe, HCl

NH3 Cl

NaOH

NH2

Example:

HOOC

NO2

H2 HOOC Pt/C CH3OH

NH2

NO2 H3C CH3

Fe, HCl H3C

NH3 Cl CH3

NaOH H3C

NH2 CH3
+ -

NO2

+ 3 Sn

+ 14 HCl

NH3 Cl NaOH

+ 3 SnCl4

+ 4 H2O

NH2 + NaCl +H2O

4. Reduction of amides

O R C N R' H Example:
O

LiAlH4

H2O

H R C N R' H H

N C CH3 CH3
5. Reduction of oximes

LiAlH4

H2O

N CH2 CH3 CH3

R C R
Example:

N OH

LiAlH4

H2O

H R C N H R' H

N OH

LiAlH4

H2O

H C N H H

6. Reduction of nitriles Can be carried out by: a) Reaction with LiAlH4, then protonation with water

R C N

LiAlH4

H2O

H R C N H R' H

b) Catalytic hydrogenation

R C N
Example:

H2 Pd

RCH2NH2

CH3CH2CH2

C N

LiAlH4

H2O

H CH3CH2CH2 C N H R' H

7. Reduction of imines

R C R'
Example:

N R''

H2, Pt

H R C N R'' R' H
H H CH3CH2 C N CH3 CH3

CH3CH2 C CH3 N CH3

H2, Pt

8. Gabriel synthesis using potassium phthalimide Useful for the preparation of primary amines. In this synthesis, the nitrogen is protected so that alkylation can take place only once. The H in phthalimide is acidic enough (pKa 7.4) that it can be easily deprotonated to give the anion (can use -OH or CO3 2- as base).
-

O N O + H KOH CH3CH2 OH

O NK O H2 O
+

O N O
-

N O

O N H O
K 2C O3

O N- K+

CH2 Cl

O N CH2 O HCl H2O

O + CH2 NH2 NaOH H2O + CH2 NH3 Cl+ O

The phthalimide synthesis is most useful for making amines that also contain other functional groups.

OH OH

9. Hofmann degradation A primary amide is converted to an amine by Br (or Cl) in NaOH solution Example:
O C NH2

NH2 Cl2, NaOH H2O 70-75oC CH3O OCH3 + NaCl + Na2CO3

CH 3 O OC H3

Mechanism:

O R C N H H
-

O OH R C

..N .. H

Cl

Cl

O R C N Cl H
-

Cl

HO

OH

..O C N .. R

OH

H2O
-

OH O C N R Isocyanate

O R C

..N .. Cl

O C N R H H2O

CO2

H2NR