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Heterocyclic Chemistry

Heterocyclic Chemistry

N

O

S Benzopyridines

Quinoline andIsoquinoline:

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Heterocyclic Chemistry

Introduction:Introduction:

N

N

QuinolineBenzo[b]pyridine IsoquinolineBenzo[c]pyridine

N

Quinolizinium ionBenzo[a]pyridinium

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Heterocyclic Chemistry

Quninoline and isoquinoline are two fusedheterocycles derived by fusion of pyridine ringwith a benzene ring.

Quinoline is high boiling liquid (b.p. 23!"# ands$ells li%e pyridine while isoquinoline is a low$elting solid ($.p. 2&.'!" b.p. 2)3!"#.

Both quinoline and isoquinoline are planar *+,-electron aro$atic syste$s  in which all ato$s aresp2 hybridized and contribute one electron each inorthogonal p-orbitals for delocalization over therings with resonance energies of */ and *)301$ol respectively

Introduction :Introduction :

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esonance structures of Quinoline and isoquinolineesonance structures of Quinoline and isoquinoline

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Heterocyclic Chemistry

  Both ring syste$s occur naturally and were

originally isolated fro$ coal tar.

4ccurrence of quinoline4ccurrence of quinoline

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Heterocyclic Chemistry

5$etine is a drug used as both ananti-protozoal and to induce vomiting

It is a toxic crystalline alkaloid

It inhibits protein synthesis andmay inhibit ascorbic acidbiosynthesis

it serves some interest in the study o

certain yeasts

4ccurrence isoquinoline4ccurrence isoquinoline

http://en.wikipedia.org/wiki/Anti-protozoalhttp://en.wikipedia.org/wiki/Anti-protozoal

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BasicityBasicity

Heterocyclic Chemistry

Quinoline and isoquinoline areQuinoline and isoquinoline are wea% baseswea% bases butbutslightlyslightly  $ore basic than pyridine (why6#$ore basic than pyridine (why6# butbut lesslessbasic than anilinesbasic than anilines  since the nitrogen in quinolinesince the nitrogen in quinolineand isoquinoline is $ore electronegative being spand isoquinoline is $ore electronegative being sp22 

hybridized co$pared to sphybridized co$pared to sp33

 hybridized nitrogen ofhybridized nitrogen ofanilines.anilines.

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7reparation of Quinoline7reparation of Quinoline

!" #riedl$nder %ynthesis

2-8$inobenzene-2-8$inobenzene-carbo9aldehydecarbo9aldehyde

5nolizable5nolizablecarbonylcarbonylco$poundco$pound

/'/'

HH22O, NaOH, 50O, NaOH, 50 ºCºC

Paul Friedländer

(1857 - 1923) 

&'

(

N')

;

'

(

N

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2-

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 Bischler-?apierals%i

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@he nitrogen of the quinoline and isoquinoline has@he nitrogen of the quinoline and isoquinoline has deactivatingdeactivatingeffect on the ring towards electrophilic substitutioneffect on the ring towards electrophilic substitution as in caseas in caseof pyridine. Aowever electrophilic substitution of quinoline andof pyridine. Aowever electrophilic substitution of quinoline andisoquinoline requires less vigorous conditions than pyridine.isoquinoline requires less vigorous conditions than pyridine."onsequently"onsequently electrophilic aro$atic substitution occurs at theelectrophilic aro$atic substitution occurs at the

benzene ring at positions ' and /.benzene ring at positions ' and /.

5lectrophilic aro$atic substitution in quinoline andIsoquinoline

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5lectrophilic aro$atic substitution in quinolineand isoquinoline

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5lectrophilic aro$atic substitution in quinoline andIsoquinoline

 Aowever nitration can ta%e place at pyridine ring usingnitric acid and acetic anhydride at position 3 in case ofquinoline and at position ) in case of isoquinoline

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eduction of quinolineeduction of quinoline

Heterocyclic Chemistry

@he pyridine ring is $ore easily reduced@he pyridine ring is $ore easily reduced

Quinoline can be selectively reduced at *2-bond by reactionQuinoline can be selectively reduced at *2-bond by reactionwith lithiu$ alu$iniu$ hydride but the *2-dihydro quinolineswith lithiu$ alu$iniu$ hydride but the *2-dihydro quinolinesare unstable and disproportionate easily to give quinoline andare unstable and disproportionate easily to give quinoline and*23)-tetrahydroquinoline.*23)-tetrahydroquinoline.

 Quinoline can be converted to *23)-tetrahydroquinolineQuinoline can be converted to *23)-tetrahydroquinolineby catalytic hydrogenation or with tin and hydrochloric acidby catalytic hydrogenation or with tin and hydrochloric acid

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Quinoline and isoquinolineQuinoline and isoquinoline undergo o9idative cleavageundergo o9idative cleavage  withwith

al%alian potassiu$ per$angnate to give pyridine-23-al%alian potassiu$ per$angnate to give pyridine-23-dicarbo9ylic acid and pyridine-3)-dicarbo9ylic aciddicarbo9ylic acid and pyridine-3)-dicarbo9ylic acidrespectively.respectively.

 Aowever pyridine-23-dicarbo9ylic acid is not stable andAowever pyridine-23-dicarbo9ylic acid is not stable andundergoes decarbo9ylation to give nicotinic acid. Quinolineundergoes decarbo9ylation to give nicotinic acid. Quinoline

and isoquinoline both for$ ?-o9ides when treated withand isoquinoline both for$ ?-o9ides when treated withhydrogen pero9ide in acetic acid or with organic peracids.hydrogen pero9ide in acetic acid or with organic peracids.

49idations

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Heterocyclic Chemistry

@han%s for your attention@han%s for your attention