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mines

1

Reference: Organic Chemistry, Seventh Edit ion, Francis A. Carey, 2008, McGraw Hill

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Primar Alk lamines

(R(RNNHH : one carbon directl attached to: one carbon directl attached to NN))

CHCH33CHCH22NHNH22 ethylethylamineamine

NHNH22 cyclohexylcyclohexylamineamine

CHCH33CHCHCHCH22CHCH22CHCH33 11--methylbutylmethylbutylamineamine

222

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Primary Arylamines (ArNH )

ame as ervatves o an ne.

22

NHNH22FF BrBr CHCH22CHCH33

pp--fluorofluoroanilineaniline oo

44--fluorofluoroanilineaniline

55--bromobromo--22--ethylethylanilineaniline

3

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Amino Grou s as Substituents

Amino rou s rank below OH rou sand higher oxidation states of carbon.

substituent.

OO

NHNH22HCHCHOCHHOCH22CHCH22NHNH22

--aminoaminobenzaldeh debenzaldeh de22--aminoaminoethanolethanol

4

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Secondary and Tertiary Amines

CHCH33NNHCHHCH22CHCH33 NN--methylethylmethylethylamineamine

NNHCHHCH22CHCH33

4--chlorochloro--NN--eth leth l--33--nitronitroanilineaniline

NONO22

ClCl CHCH33

CHCH33NN

--5

,,

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Ammonium Salts

A nitro en with fou substituents is ositivelcharged and is named as a derivative of

+

CHCH33NNHH33++

ClCl

NN

33++

CFCF COCO

HH

methylmethylammoniumammonium NN--ethylethyl--NN--methylcyclopentylmethylcyclopentylammoniumammonium

6chloridechloride trifluoroacetatetrifluoroacetate

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Ammonium Salts

When all four atoms attached to N are carbon,t e on s ca e a qua ernary ammon um on an

salts that contain it are called quaternaryammonium salts.

CHCH33

CHCH22 NN CHCH33 II

CHCH33

7benzyltrimethylbenzyltrimethylammoniumammoniumiodideiodide

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Physical Properties

CHCH33CHCH22NNHCHHCH33CHCH33CHCH22CHCH22NNHH22 (CH(CH33))33NN

boilingboiling

point:point:

5050 CC 3434 CC 33 CC

Boiling points of isomeric amines decrease in

going fromprimary to secondary to tertiary amines.

of being involved in intermolecular hydrogen bonding.

Secondary amines have one.

8Tertiary amines cannot be involved in intermolecularhydrogen bonds.

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Basicit of Amines

It is more useful to describe the basicity of amines

in terms of the K s of their con u ate acids thanas basicity constants Kb.

The more basic the amine, the weakeritsconjugate acid.

The more basic the amine, the largerthe pK of itsconjugate acid.

9

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Citing amine basicity according to the pKa of the

-reactions of amines according to the usual Brnsted.

Amines are converted to ammonium ions by acetic acid.

10

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Adding sodium hydroxide to an ammonium saltcoverts it to the free amine.

11

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Effect of Structure on Basicity

(1)(1)AlkylaminesAlkylamines areare slightly strongerslightly stronger bases thanbases thanammona.ammona.

. a

NH NH + .

CH3CH2NH2 CH3CH2NH3+ 10.8

++ ++33 22 33 44

therefore,therefore, CHCH33CHCH22NHNH22 is a stronger baseis a stronger base

12

33..

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Effect of Structure on Basicity

(2)(2)ArylaminesArylamines areare much weakermuch weaker bases thanbases thanammonia.ammonia.

. a

+

CH3CH2NH2 CH3CH2NH3+ 10.8

(CH3CH

2)2NH (CH

3CH

2)2NH

2

+ 11.1

(CH3CH2)3N (CH3CH2)3NH+ 10.8

13C6H5NH2 C6H5NH3+

4.6

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Decreased Basicity of Arylamines

by delocalization into the system of the aromatic ring.

14

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Decreased Basicity of Arylamines

diphenylamine a weaker base than aniline,an rp enyamne a wea er ase andiphenylamine.

CC66HH55NNHH22 (C(C66HH55))22NNHH (C(C66HH55))33NN

ppKKaa

of conjugate acid:of conjugate acid:

4.64.6 0.80.8 --55

15

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Effect of Substituents on

as c y o ry am nes

y groups on t e rng ncrease as c ty, u

only slightly (less than 1 pK unit).

XX NNHH22

aa

HH 4.64.6

16

..

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Effect of Substituents on

as c y o ry am nes

,

and/or para to amine group, decrease basicityan can ave a arge e ec .

XX NNHH22

XX KK of conu ate acidof conu ate acidHH 4.64.6CFCF 3.53.5

17OO22NN 1.01.0

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p-Nitroaniline

OO

OO

NHNH22NN NN NHNH22

OO OO

Lone air on amine nitro en is conu atedwith p-nitro groupmore delocalized than

18

.

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Heterocyclic Amines

Wh ?19

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The nitrogen lone pai occupies an sp3-hybridizedorbital in i eridine verus an s 2-h bridized onein pyridine.

Electrons in orbitals with more s characterare

y wcharacter.

Thus, nitro en holds on to its unshared airmore strongly in pyridine than in piperidine and

20

.

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Alkylation of Ammonia

Desired reaction is:Desired reaction is:

22 NNHH33 ++ RRXX RRNNHH22 ++ NNHH44XX

via:via:

HH33NN

RR XX HH33NN RR++

XX++ ++

then:then:HH HH

HH33NN ++ HH NN RR++

HH33NN HH ++ NN RR

21HH HH

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Alkylation of Ammonia

''

, ,, ,

and tertiary amines, plus the quaternary salt.and tertiary amines, plus the quaternary salt.

RXRX RXRX

RXRX

RR NNRXRX++

XX

22

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Exam le

NNHH3333 22 66 22 33 22 66 22 22

45%45%

++

CHCH33(CH(CH22))66CHCH22NNHCHHCH22(CH(CH22))66CHCH33

(43%)(43%)

s oc yamne s orme , compe es wammonia for the remaining 1-bromooctane.

23

eac on o oc yamne w - romooc ane

gives N,N-dioctylamine.

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Pre aration of Amines b Reduction

-

be reduced to an amine, including:azides

nitro-substituted benzene derivatives

24

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Synthesis of Amines via Azides

SN2 reaction, followed by reduction, gives a.

CHCH22CHCH22BrBr CHCH22CHCH22NN33aa 33

Azides may also be..

2. H2. H22OO

hydrogenation.

CHCH22CHCH22NNHH22

25(89%)(89%)

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Synthesis of Amines via Nitriles

SN2 reaction, followed by reduction, gives a.

CHCH33CHCH22CHCH22CHCH22BrBraa

CHCH33CHCH22CHCH22CHCH22CNCN

Nitriles may also be

HH22 (100 atm), Ni(100 atm), Ni

aluminum hydride.

CHCH33CHCH22CHCH22CHCH22CHCH22NHNH22

26

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Synthesis of Amines via Nitroarenes

ClCl NONO22Nitro rou s ma also

(88(88--95%)95%)

be reduced with tin (Sn)

1. Fe1. Fe HClHCl

hydrogenation.

2.2. NaOHNaOH

ClCl NHNH22

27(95%)(95%)

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S nthesis of Amines via Amides

OO OO

COHCOH

1. SOCl1. SOCl22

CCNN(CH(CH33))22(86(86--89%)89%)

.. 33 22

1. LiAlH1. LiAlH44

4appropriate reducing

2. H2. H22OOagen or s reac on.

CHCH22NN(CH(CH33))22

28

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Synthesis of Amines via

is subjected tois subjected to catalytic hydrogenationcatalytic hydrogenation in thein the

..

29

M h i f

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Mechanism of

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Ammonia Gives a

r mary m ne

OO ++ NNHH33

HHHH22, Ni, Ni

(80%)(80%)22

Synthesis ofamphetamine () (a central nervous system stimulant)

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Primary Amines Give Secondary Amines

++

HH22, Ni, Ni ethanolethanol

CHCH CHCH CHCH NNHH

(65%)(65%)

32

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Secondary Amines Give Tertiary Amines

33

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Synthesis ofynthesis ofUsing Reductive Amination!

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