synthesis of pyridine
DESCRIPTION
Synthesis of pyridine 1 – By heating the hydrochloride of pentamethylene diamine and oxidizing the product piperidine with concentrated sulphuric acid at 300 cº. 2 – from 1,5 – dicarbonyl compounds and ammonia : -. - PowerPoint PPT PresentationTRANSCRIPT
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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)