AMINES, AMIDES and AMINES, AMIDES and ANILINEANILINE

Amines

• An amine is a base as well as a nucleophile

• Some amines are heterocyclic compounds (or heterocycles)

• Most drugs, vitamins, and many other natural products are heterocycles

• A natural product is a compound synthesized by a plant or an animal

H N H

H

R N H

H

R N H

R

R N R

R

Ammonia Primary (1o) Amine

Secondary (2o) Amine Tertiary (3o) Amine

Organic bases are amines

Amines are derivatives of ammonia

N 1s2, 2s2 2p1 2p1 2p1----------- lone pair occupies an sp3 orbital

NH2

H Cl

N

H

H

H Cl

Base + Acid = Ammonium Salt

Amines are bases because of the lone pair on the Amines are bases because of the lone pair on the nitrogen atom -nitrogen atom - red litmus paper to bluered litmus paper to blue

O

O HO

OHN(CH2CH3)3

O

OO

O

HN(CH2CH3)3

+ 2 +2

oxalic acid triethylaminetriethylaminium oxalate

The lone-pair electrons on nitrogen allows an amine to turn “inside out” rapidly at room temperature

H2NNH2

Putrescine(found in decaying meat) NH2

Amphetamine(dangerous stimulant)

N

H Piperidine

N

Triethylamine NH2

Isopropylamine

1,4-butanediamine

Some Common Amines

Both upper amines are 1o

This amine is are 2o This amine is 3o

This amine is 1o

NH2 N NNaNO2, HCl

benzenediazonium chloride

+Cl-

0 C

Aniline can be converted into useful diazonium salt

N N

N N

Nuc+Cl- Nuc-

-

Relative Reactivity of Amine

The leaving group of a protonated amine cannotdissociate to form a carbocation or be replaced by ahalide ion

RCH2F > RCH2OH ~ RCH2OCH3 > RCH2NH2

most reactive least reactive

HF H2O RCH2OH NH3

pKa = 3.2 pKa = 15.7 pKa = 15.5 pKa = 36

Reactions of Amines

nucleophilic substitution reactions

CH3CH2Br + CH3NH2

Br

CH3CH2NHCH3 + HBrCH3CH2NH2CH3

nucleophilic acyl substitution reactions

CH3CH2

C

O

ClCH3NH2+ 2

CH3CH2

C

O

NHCH3

+ CH3NH3Cl

Oxidation of Amines

R NH2 R NH OH R N O R N+

O-

Ooxd oxd oxd

R NH

R

+ H2O2 R N+

R

OH

H + OH- R N

R

OH

+ H2O

R N

R

+ H2O2 R N+

R

OH

R + OH- R N

R

O_

+ H2O

R R

a hydroxylamine a nitroso compound

Nitrite Ion, Nitrous Acid, and Nitrosyl Nitrite Ion, Nitrous Acid, and Nitrosyl CationCation

HH++

––OO••••••••

••••NN OO

•••• ••••••••

OO•••• ••••

NN OO•••• ••••

••••HH

HH++

OO••••NN OO

•••• ••••

HH

HH

++••••++

••••NN OO

•••• ••••++OO ••••

HH

HH

••••

ExampleExample

(CH(CH33))22NNHH•••• NaNONaNO22, HCl, HCl

HH22OO(88-90%)(88-90%)

••••(CH(CH33))22NN

••••NN OO

•••• ••••

CH3NH2+HNO2 CH3OH+N2+H2O

Nitrosation of Secondary AlkylaminesNitrosation of Secondary Alkylamines

++••••NN OO

•••• ••••••••NN

HH

++

NN••••NN OO

•••• ••••++

HH++

HH

++

NN••••NN OO

•••• •••••••• nitrosation of nitrosation of secondary amines secondary amines gives an gives an NN-nitroso -nitroso amineamine

Nitrosation of Primary ArylaminesNitrosation of Primary Arylamines

gives aryl diazonium ionsgives aryl diazonium ions

aryl diazonium ions are much more stable aryl diazonium ions are much more stable thanthanalkyl diazonium ionsalkyl diazonium ions

most aryl diazonium ions are stable under the most aryl diazonium ions are stable under the conditions of their formation (0-10°C) conditions of their formation (0-10°C)

ArArNN NN++

RRNN NN++ fastfast

slowslow

RR++ ++ NN22

ArAr++ ++ NN22

Example:Example: (CH(CH33))22CHCH NNHH22

NaNONaNO22, H, H22SOSO44

HH22O, 0-5°CO, 0-5°C (CH(CH33))22CHCH NN NN

++HSOHSO44

––

Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts

ArAr NN NN++

ArAr HH

ArAr OOHH

ArAr II

ArAr FF

ArAr BrBrArAr ClCl

ArAr CNCN

Azo CouplingAzo Coupling

Diazonium salts are weak electrophiles.Diazonium salts are weak electrophiles.React with strongly activated aromatic React with strongly activated aromatic compounds by electrophilic aromatic compounds by electrophilic aromatic substitution.substitution.

ArAr NN NN++

Ar'Ar' HH++ ArAr NN NN Ar'Ar'

an azo compoundan azo compound

Ar'Ar' must bear a strongly electron-releasing group must bear a strongly electron-releasing group such as OH, OR, or NR such as OH, OR, or NR22..

ExampleExample OHOH

++ CC66HH55NN NN++ OHOH

NN NCNC66HH55

ClCl––

NC R

R'

O

NC R

R'

O

Amides

Features of a Peptide Bond

1. Usually inert2. Planar to allow delocalisation3. Restricted Rotation about the amide bond4. Rotation of Groups (R and R’) attached to the

amide bond is relatively free

------------- Not acids or bases