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Synthesis of pyridine 1 – By heating the hydrochloride of pentamethylene diamine and oxidizing the product piperidine with concentrated sulphuric acid at 300 cº.

CH2

CH2 - CH2 - NH2 .HCl

CH2 - CH2 - NH2 .HCl -NH4Cl-HCl

CH2

CH2 - CH2

NH

CH2 - CH2

NH2SO4300 co

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2 – from 1,5 – dicarbonyl compounds and ammonia : -

HH

H

OO+ N - H

H

H

-2H2O

NH

H

Oxidation

N

1,4 - dihydropyridine Pyridine

Ammonia react with 1,5 – dicarbonyl compounds to give 1,4 dihydropyridine which are easily dehydrogenated to pyridines .The reaction proceed via loss of two molecules of water .

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NaOEt

CH2Cl2EtOOC - C C-COOEt

CH2

CH3CH3 HO HO

Oxide EtOOC - C

N

C-COOEt

CH3CH3

EtOOC CH2 | C = O CH3

EtOOC CH2 | O = C CH3

EtOOC H || CCH3 OH

HC-COOEt || COH CH3

NH3-H2O

EtOOC - C C-COOEt CH2

CH3CH3 NH2 HO

-H2OEtOOC - C

NH

C-COOEt

HH

CH3CH3

EtOOC-

3- From ethyl acetoacetate two mole with dichloromethane in presences of ammonia .

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CH3 C = O | CH2O = C | CH3

+ CH2

CN

C = O

H2N

C

C = O C =O

CCH

H

OHCH3H

H2NCH3

CN

acetylacetone cyanoacetamide

C

C C =O

CCH

OHHH

H2NCH3

CN

OH

-2H2OCH

CH3 -C NH

C = O

C - CNCH

CH

CH3 -C N

C - OH

C - CNCH

4 – From 1,3 – dicarbonyl compound and cyanoacetamide

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Chemical reactions

Basicity of pyridine

Pyridine behaves as abase , It react with acids to from fairly stable salt . The reason for the basic character of pyridine is that the nitrogen lone pair being in sp2 hybrid orbital is not involve in the delocalized π molecular orbital .It is readily

available for the formation of a new p N – H bond with proton. Pyridine is a stronger base than pyrrole in which the basicity is reduced by delocalization of the nitrogen lone pair

NH

NRNH2

Basicity increase

Pyrrole < Pyridine < aliphatic amine

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Addition and ring – opening reaction

The acid derivatives combine with the pyridine to give a quaternary salt (e.g 2) .Which have been isolated as acidchlorides .This salt react with hydroxyl group

yielding the Acyl derivative ; the liberated acid is taken up as the pyridine salt (3) .Quaternary salts as (2) are immediately decomposed by water to pyridine hydrochloride and the organic acid but with etheylcyanoacetate the ring open

yielding (4)

N

PhCoCl+ Cl-

( 2 )

R+/OH- PhCOOR + N

H

+ Cl-

( 3 )

CoPhN

EtCOOCH2CN

NHC(CN)CO2Et

|Ph - C = C(CN)CO2Et

( 4 )

H2O

N+ Cl- PhCOOH

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The ring is comparatively easily opened by nucleophilic reagent 2,4 – Dinitrophenylpyridinum chloride (5) is a colourless crystalline solid which is formed from pyridine and 2,4 – dinitrochlorobenzene at 100 cº this reaction is reversed at 200 cº with water at 150 cº yield pyridine hydrochloride and 2,4 – dinitrophenol , but with cold aqueous alkali a deep red compound (6) is formed which on successive treatment with dilute aniline and acid yields 2,4 –

dinitroaniline and glutaconic aldehyde dianil (7) .

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N

NO2

NO2Cl

100 c0

200 c0 NNO2

NO2

Cl-

cold aquKOH

( 5 )

150 c0H2O

N H

+ Cl-

PridiniumChloride

2.4 - dinitrophenylpyridinumchlorid

OHNO2

NO2

+

2.4 - dinitrophenol

CH

CH CH

CH

HC

NNO2

NO2

+ KCl

( 6 )

aniline Acid

OHNO2

NO2

CH

CH CH = NPh

CH

HC

Ph - NH -

( 7 )

glutaconic aldehydedianil

+

PhNH2PhNH2

+

HO-

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Reduction

N

Me3Si HPd catalyst

+ -

NSiMe3

0.1% KOHMeOH

NH

Pyridine is easily reduce to hexahydropyridin or piperidine by a variety of method including hydrogen over Raney nickel , rubidium at 60 ºc palladium charcoal with acetic acid .1,4 – dihydropyridine has however been obtained by the reduction of pyridine with trimethylsilane .

N

ultrasound 2 CH CH + HCN

The pyridine is cleaved by ultrasonic waves giving acetylene and hydrogen cyanide .

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Electrophilic subistitution reactions .

Toward electrophilic subistitution pyridine resembles a deactivated benzene derivative it is often compared to nitrobenzene in reactivity

N NN

N = O

O

N

O ON

O ON

OO

N( + )

( + )

( - ) ( - ) ( - )

( + )( + )

( + )

( + )

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when the reaction take place the attack at β position can be understood in term of the resonance forms shown above in which ( α ) and ( γ ) position have a positive

charge , this orientation can be understood also by comparison of the intermediate resulting from attack at various position

N

EHH

.. N

E HH

.. N

EH

..

Attack at γ position

N

HH

E

..

H

EH N..

H

EN H..

Attack at β position

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N

NO2

3 - nitropyridine

KNO3H2SO4

370 c0

N

300 c0

Br2

Rx or RCoxAlCl3 No reaction

HgSO4H2SO4

N

SO3H

3 - pyridinesulphonicacid

3 - bromo pyridine N

Br

three resonance can be written for each intermediate but one of these in the case of attack at the γ ( or α ) leaves positive charge on nitrogen this must be regarded as an unfavorable structure as

compared to one in which carbon has a positive charge for nitrogen more electronegative than carbon .

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Nucleophilic subistitution in pyridine

The reactivity of pyridine toward nucleophilic subistitution is so great even the powerfully basic hydride ion , H- , can be displaced .Two important example of this reaction are amination by sodium amide and Alkylation by organolithium

compounds .

N+ NaNH2

+ -heat NH3

N

H

NH2

-

NaN NH2

+ NaNH2+ -

N NHNa+ NH3

Sod salt of 2 - amino pyriine

N

H

Ph

-

LiN Ph

+ LiH

2 - phenylpyridine

N+ C6H5Li

+ -heat

N

KOH

320 N OH NH

O

The attack take place at α – position because the positive charge arises in α – position

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Pyrylium salt and pyrans

Very few simple derivatives of the aromatic pyrylium cation (1) are known , although benzopyrylium are widely distributed as flower petal colouring

matters .The potentially very reactive 4-pyran (3) has been obtained recently and the pyranes ( 4 and 5 ) are well known .2,3 – Dihydro – 4 – pyran (6) has

received some attention now it is easily available , and tetrahydropyran ( 7 ) is used as a synthetic intermediate .The sulphur analogues of these compounds

have received little attention until very recently

O+

1

2

3

4

5

6

Pyriliumcation

O O O O O

O

O O

1 2 3 4 5 6 7

2pyrone 4 pyrone

5

62

3

4

1

O+

4

3

2

1

5

6

7

8

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Pyrylium salts

CH

CH = O

CHCH

CH- +

H ClO4-2O

CHHO

CH

CH = OH

CHCH

ClO4-

+0 c 0

O1

2

34

5

6ClO4

)8 ( Pyrylium perchlorate

sod . salt of glutaconic aldehyde Oxonium salt

-

-H 2ONa O

The sodium salt of glutaconic aldehyde with perchloric acid at – 20 cº gives ared oxonium salt , which on standing at o cº cyclizes to the colourless pyrylium perchlorate (8) .This perchlorate has received little attention ,but with ammonia it yields 2,4,6 – triphenylpyrylium ferrichloride ( 9 ) can be prepared easily . It is stable in acid solution and nitrates . with ammonia it yields 2,4,6 – triphenylpyridine while with alkali the ring is opened , yielding (II) through the intermediate (10 )

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O = C-Ph

CH2

C = O

1 - phenyl- 2 - benzoyl ethylene

CHCHPh+

Ph -

FeCl3

phenyl- methyl ketone

H

C= O

CH2CH2

CHPh

C = OPh Ph

2,4,6 - triphenylPyrylium ferricchloride

O

Ph

PhPh+

FeCl4-

NH3

)A(

N

Ph

PhPh

NaHCO 3 NaOAC orr aq ( B )

O

Ph

PhOH

PhCH2CH

CHPh

C = OPh Ph

OC

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CH2

C = O

CHCHPh+

Ph -

FeCl3

H

-- +

O = C-Ph

keto form

C= O

CH2CH2

CHPh

C = OPh Ph

enol form

C - OH

CH CHCHPh

Ph PhHO -C

-H 2O

HC

CO

C

CHC

Ph

PhH

Ph

HC

CO

C - Ph

CHCH

Ph

Ph

+FeCl4-

)A (

NH 3

HC

CO

C - Ph

CHCH

Ph

Ph

+

-H

NH 2

Mechanism

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HC

C C - Ph

CHCH

Ph

Ph

OHNHH

-H 2O

NH

Ph

PhPh

N

Ph

PhPh

+HC

C C - Ph

CHCH

Ph

Ph

N:H2

HO ++

O

Ph

PhPh+

FeCl4-

BNaOaCNaHCO3aq O

Ph

Ph Ph+

H+/ OH-

O

Ph

OHPhPh

O

Ph

OHPhPh - +

PhOH

Ph

Ph OPh

Ph

O

Ph

O

enol form keto form1,3,5 - triphenylglutaconicdialdehyde

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Reaction of pyrylium cation

A–Reaction with electrophilic reagent 2,4,6 –Triphenyl-pyrylium undergoes exchange at 3 – and 5 – position in hot deuteroacetic acid

O PhPh

Ph

+ACDO

+ (ACO -)O PhPh

Ph

OAC

O PhPh

Ph

OAC

DH

+5

D +

B – No nitration of pyrylium are known

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Synthesis of α – pyrones

6 – hydroxyl – α – pyron can be prepared by heating a glutaconic acid with acetic anhydride .

H2C

O = C OH

C = O

CHCH

OH

- H2O

( CH3CO)2O OHO O

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Synthesis of γ – Pyrones

+ 2 (COOEt ) 2O = C

CH3

CH3

O = C

CH2CO . COOEt

CH2CO . COOEt

C2H5ONa

-2(EtOH)

O = C

CH = C- COOEtOH

CH = C - OH

COOEt

heat

COOEt

O = C

CH = C O

CH = C- COOEt

heat

chelidonic acid

O

O

Pyrone γ -

1- γ – pyrone may be prepared by heating chelidonic acid just above its melting point .chelidonic acid may be prepared from acetone and ethyl oxalate

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2 – The dimethyl γ – pyrone may be prepared from the copper salt of ethylacetoacetate as follows

CH3 -CO - CH - COOEt

Cu

CH3 -CO - CH - COOEt

CoCl2

CH3 -CO - CH - COOEt

C = O

CH3 -CO - CH - COOEt

hydheat

CH3 -CO - CH2

C = O

CH3 -CO - CH2

CH3 -C = CH

C = O

OH

CH3 -C = CH OH

heat-H2O

C CH

C = O

CHC

O

CH3

CH3

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H+O

O

NaOH2 -

OHOH

O O

O O

O O

- pyrone

NaOH

COONaONa

HCl

COOHOH

1 -

α

3 -O O

+ NH2NH2

NH|NH2

-H2O

N O|NH2

1 - amino pyridone

OOHOH

ONH|NH2

Reaction of α and γ – Pyrone .

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5 -O

O

CH3CH3

NH3 -H2O

2,6 - di methyl - 4 - pyrone NH2

CH3 CH3

O

OH NH

O

CH3CH3

6 -O O

RR

+ CH3MgBrO

R

R

CH3

OH

HClO4

O

O

CH3CH3

7 - + CH3MgBr

O CH3CH3

CH3HO

-H2OO CH3CH3

CH3

+

ClO4-

pyrylium salt

..

HClO4

O

O

CH3CH3

8-

O CH3CH3

OCH3

-H I O CH3CH3

OCH3

+

ClO4-

..

CH 3I

+I-

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9 - P2S5

O

R

R O O

R

R S

O

O

RR

10 - P2S5

O

S

RR

O

R

R OO

R

R O

Br11 - Br2 / ACOH

3 -bromo - 2 - pyrone

O

O

CH3CH3 O

O

CH3CH3

Br12- Br 2 / ACOH

3- bromo - 4 - pyrone

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O

O

CH3CH3 O

O

CH3CH3

NO214 - HNO3 / ACOH

3 -bromo - 4 - pyrone

O

R

R O O

R

R O

NO213 - HNO3 / ACOH

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Sulphur – containing analogues

S ClCl S S+

Cl240

PhNMe2

(1) (2)

S

Ph

PhPh+ ClO4- PhLi

S

Ph

PhPhPh

isomerize

S

Ph

PhPh

(4) (5)(3)

4 H – Thiopyran ( 1 ) has been obtained in asimilar way to its oxygen analogue and has b.p 30 cº at 12 mm it is readily oxidized by chlorine to thiapyrylium (2) chloride , and an alternative way of making this class of

compound is outlined 2,4,6 triphenylthia pyrylium perchlorate (3) with phenyllithum gives the deep purple 1,2,4,6 – tetraphenylthia (IV)

benzene (4) . On standing it isomerizes to colurless 4H - thiapyran (5)

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S

PhPh

+

O Me-

( 6 )

1- methyl – 3,5 – diphenylthia(IV)benzene 1- oxide (6) has been obtained as indicated below .It has m.p 148º and can be sublimed at near this temperature at 0 – 0.5 mm pressure .The compound is therefore very much more stable than (IV) benzene such as (4)