Section 9: Amines – Chapter 20

Practice Problems:

None! (yay!)

N

Amines: Nomenclature

H3CN

HH

H3CN

HCH3

H3CN

CH3CH3

1o amine 2o amine 3o amine

H3CN

CH3CH3

CH3

X

a quaternary ammonium salt

NH2

t-butylamine

NH2

cyclohexylamine

NH2

aniline

N

diisopropylethylamine( Hünig's base )

OHH3C

H3CH3C NH2

H3C

H3CH3C

a 3o alcohol a 1o amine

Don't be confused...

Amines: Heterocyclic Amines

NN

H

N

N

N

H

NH

N

N

N

H

NH

Pyridine Pyrrole

QuinolineImidazole

Indole

Pyrimidine

Pyrrolidine

Piperidine

Amines: Structure

RN

R''R'

close to 109o

sp3 ~ tetrahedral

note: if R, R’, R’’ are different, the amine is technically chiral, but…

RN

R''R'

fast RN

R''R'

Amines: Smell

Et3Ntriethylamine - "fishy smell"

H2N NH2

cadaverine

H2NNH2

putrescine

H2N

HN NH2

spermidine

Amines: Basicity

N H A N H A

RNH3+ + H2O RNH2 + H3O

+

K a =[RNH2][H3O

+]

[RNH3+]

pK a = log K a

Basicity is often reported as the pKa of the conjugate acid:

Amines: Basicity

Some representative pKa values:

Et3N NH3 Ph NH2 NH

10.8 9.3 4.6 0.4pKa of

conjugate acid:

triethylamine ammonia aniline pyrrole

Don't be confused...

N H

pKa of the amineitself ~ 35

pKa of theconjugate acid

~ 11

Amines: in Biology

NH3C OCH3

O

O

OCocaine

N

NN

NH3C

CH3

CH3

O

O

Caffeine

O

NH

HN

HN

O

NH

O

O

HN

O

NH

HN

O

NH

O

O

HN

NH

OHN

O

O

NH

OOH

NH

OH

OH

NH2

NH

NH2HN

NH2O

NNH

OHO

Protein

N

S

OOH

OO

HN

Penicillin

Amines: in Biology

N

NH

CH3

N O

H

Lysergic acid diethylamide

N

NN

N

NH H

O

O

O

P OON N

H

O

O

CH3

N

NO

O

O

P OO

N

N

O

H

N

H

H

N N

N

O

H

Hadenine

thymine

guanine

cytosineO

O

O

PO O

O

O

O

PO O

DNA

NH

O

H H

H

NHO

Propecia

O

HO

HO

H

H H

NCH3

Morphine

OCH3

H

NH3C

Dextromethorphan

Amines: Preparation

A. Reduction of nitriles / amides / nitro compounds

RC

N 1. LiAlH4

2. H3OR NH2

R N

O

R'

R''

1. LiAlH4

2. H3O

R N

R''

R'

NO2SnCl2

H3ONH2

Amines: Preparation

B. SN2 reactions

H3N + R X R NH3

X

baseR NH2

X = Cl, Br, I...

H2N + R X R NH2

X

baseR NH

R R R

But...

Hard to stop here!!

R X

NRR

R

OK to stop here

R XR4N

X

If you want to go from a 2o amine to a 3o amine, rxn with R-X is usually OK. Otherwise, consider an alternative approach.

Amines: Preparation

C. Attack with NaN3

R X

X = Cl, Br, I...

Na N3+SN2

R NN

N R NH2or

LiAlH4

PPh3

D. Gabriel Synthesis

R X

X = Cl, Br, I...

+SN2

NH

O

Ophthalimide

N

O

O

KOH

R N

O

O

R NH2or

H2NNH2

MeOH

NaOHH2O

Amines: PreparationE. Reductive amination

R R'

O

ketoneor aldehyde

H2NR''

NaBH3CN

CH3OHR R'

NR''H

BH2CNH (i.e. "H ")

R H

N HHR'

Great reaction!!

e.g.

H

O

NaBH3CN

CH3OH

NH

CH3H2NCH3

O

NaBH3CN

CH3OH

H3N

NH2

O

HNH

CH3H3C

NaBH3CN

CH3OH

N

H

H3C CH3

CH3

CH3

Ch. 20 - 14

4D. Preparation of Primary Amines through the Hofmann and Curtius Rearrangements

O

R NH2

Br2, NaOH

H2OR NH2

+ NaBr + Na2CO3

Hofmann rearrangement

Ch. 20 - 15

(1) NH2

O

Br2

NaOH

NH2

Examples

(2)

NH2

O

NH2Br2

NaOH

Ch. 20 - 16

Mechanism

O

R N

H

HOH O

R N

H

Br Br O

R N

H

Br

HO

O

R NBr

O C NR (Hofmann

rearr.)(isocyanate)

HOO C

N

OH

R

O C

N

O

R

H

+ CO2H

NR

H OHR NH2

Ch. 20 - 17

Curtius rearrangement

O

R Cl

NaN3O

R N N NO C N

R+ N2 (g)

heat

R NH2

H2O

CO2 (g) +

O

Cl 1. NaN3

2. heat3. H2O

NH2

e.g.