hetero cyclic s

8/10/2019 Hetero Cyclic s

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Heterocycles

Ring compounds with elements other than carbon in the

ring. The most common elements to appear in

heterocyclic compounds are oxygen, nitrogen and sulfur.

The aliphatic heterocycles are similar to the open chain

analogues, ethers, amines and sulfides.

The aromatic heterocycles are similar to other aromatic

compounds.


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Heterocyclic Nomenclature

Replacement nomenclature (IUPACrecommended 1957)

Oxygen oxa

Sulfur thia

Nitrogen aza

Lowest number assigned to the hetero atom with the highest

precedence: O > S > N

S

thiacyclobutane

O NH

1-oxa-3-azacyclopentane


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Hantzsch-Widman(1888)

Suffixes

ring with nitrogen ring without nitrogen

Ring members unsatd satd unsatd satd

3 -irine -iridine irene irine

4 ete etidine ete etane

5 ole olidine ole olane

6 ine perhydro__ine in ane7 epine perhydro__epine epin epane


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O S N

H

*oxiraneethylene oxide

oxacyclopropane

* thiiraneethylene sulfide

thiacyclopropane

* aziridineethylene imineazacyclopropane

N

N

N O

NH

diazirane 1-azirine oxaziridineoxazacyclopropane

You must know the * names


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O S NH

N N

oxetaneoxacyclobutane

thietanethiacyclobutane

azetidineazacyclobutane

azeteazacyclobutadiene

1-azetine1-azacyclobutene


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O

O NH

O

O S NH

* furanoxoleoxacyclopentandiene

* thiophenethiolethiacyclopentandiene

* pyrrole

1,3-dioxolane

1,3-dioxacyclopentane

* tetrahydrofuran

* pyrrolidineazacyclopentane


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N

O

N

SON

NH

N

N

NH

N

NH

N

pyrazole imidazole 1,2,4-triazole

oxazole isooxazole thiazole


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O O O

O

O

NH NH

HN

O

O

4-hydropyran 2-pyrone 4-pyrone

* 1,4-dioxane * piperidine piperazine


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6

7

8

5

N1

2

34

6

7

8

5

1

N 2

34

NH

*quinoline * isoquinoline

* indole


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Aliphatic heterocyclics, chemistry

Ethers

Amines

sulfides

O

conc. HBr

heatBrCH2CH2CH2CH2Br

HNCH3 C

Cl

O

+ CH3 C

N

O

2o

amine


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Three-membered rings undergo additions due to angle

strain, eg. epoxides

O

O

+ HBr

+ NH3

HOCH2CH2Br

HOCH2CH2NH2


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NH NH CH=O

NH

C

NH

Br

pyrrole

CHCl3, KOH

HCN, HClH2O

(CH3CO)2O

250o

CH3

O

Br2, EtOH0o

BrBr

Br


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O

furan

CH3CO2NO2

O NO2

pyridine:SO3

O SO3H

C6H5N2+

O NN

(CH3CO)2O, BF3

O CO

CH3


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O

furan

O CH=O

O Br

O HgCl OI

1. HCN, HCl

2. H2O

Br2

dioxane

HgCl2

CH3CO2Na

I2

CH3COCl

O CO

CH3


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S

less reactive, can use acids

H2

SO4

S SO3H

CH3CO2NO2

(CH3CO)2O SNO

2

Br2, benzene

S BrBr

I2, HgO

S I


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NH

O

H2, Ni

250o

H2, Ni

50o

NH

O

Kb = 10-14 Kb = 10-3

2o

amine

THF


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Pyridine

N N N6 pi electrons,

sp2, flat

aromatic, resonance stabilization energy ~ 23 Kcal/mole

Kb = 2.3 X 10-9

3

2 N1

6

54

N

N

CH3

-picoline


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Pyridine important solvent & base (~ 3oamine)

Reactions:

1) EAS (much less reactive than benzene ~ nitro)

N

KNO3, H2SO4, 370o

N

NO2

3% yield

H2SO4, SO3, HgSO4220o, 24 hours

N

SO3

H

Br2, 300o

N N

Br Br Br

+

Friedel-Craftsno reaction


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N

N

N

H Y

Y

H

Y

HN

Y

HN

Y

H

N

Y

H

N

Y

H

N

HY

N

HY

Deactivated to EAS due to electronegativity of NitrogenDirects beta due to destabilization of alpha and gamma


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Pyridine, reactions

2) Nucleophilic aromatic substitution

N

NaNH2

N NH2

phenyl lithium H2O

NN


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N

N

N

Br

Cl

Br

NH3, 200o

NH3, 200o

NH3, 200o

NR

N NH2

N

NH2

N

N

H Z

Z

H

activated to nucl. arom. subts.directs alpha & gamma


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Pyridine, reactions

3) As base

Kb = 2.3 X 10-9

N

N

HBr

CH3I

N

H

Br

N

CH3

I

4osalt


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Pyridine, reactions

4) reduction

N

H2, Pt

HCl, 25o, 3 atm. NH

piperidine

Kb = 2 X 10-3

aliphatic 2oamine


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Polynuclear Heteroaromatics

6

7

8

5

N1

2

34

6

7

8

5

1

N 2

34

quinolineisoquinoline

EAS EAS

NAS

NAS

5

6

7

4

NH 1

2

3

indole

EAS


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HC

H2C

H2C

OH

OH

OH

H+

-H2O

HC

CHCH2

O

acrolein

NH2

+

NH

CH2

CH2

C

O

H

H+

NH

CH2

CH2C

OH

HEAS

NH

H OH

NH

NO2

N

NH2

+

-H2O


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Heterocycles as you would expect!

O NH

S angle strain

O

O O

ethers

NH

NH

NH

amines


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N

NNH

N

NH2

NH

NNH

N

O

NH2

N

NH

NH2

O

NH

NH

O

O

adenine guanine

cytosine thymine

hetero cyclic s

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