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Heterocyclic Compounds

3rd Year Students Special Chem, Chem-Phys, Geo-chem, Zoo-Chem, Bot-Chem,

Synthesis Of Furan

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1. From cyclodehydration of 1, 4-diketones by acidic reagents, e.g., H2SO4, ZnCl2, Ac2O and P2O3

O H3CH3CEtOOC

C

COHH3C

CC

OH

CH3

COOEtH2SO4

EtOOCHC

C

O

CH3

HCC

O

CH3

COOEt2CH3COCH2COOEt + 2C2H5ONa

Na+

I2CH3COCHCOOEt

2. From knorr-pyrrole synthesis

Synthesis Of Furan

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3. Feist’s synthesis

O CH3

H3CH3C C

CH2Cl

O C

CH Cl

H3C OH HC COOEt

C CH3

OH

E.A.A

Chloroacetone

4. From decarboxylation of furoic acid.

O COOHO

+ CO2

Synthesis Of Furan

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5. Furfural (furan 2-carboxaldehyde)

O

HO OH

CHO

OHOH

CHO

OHOHCHO

Furfural is commercially obtained from pentose (occurred in oat hulls) by stream distillation

6. By treatment of α-hydroxyketones and acetylenic compounds

O

OH

R

CO2CH3

CO2CH3

O CO2CH3

CO2CH3RK2CO3 H+

-H2O

R

H2COH

C

C

CO2CH3

CO2CH3

C=O

Synthesis Of Pyrrole

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Reactions Of Furan

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1. Ring opening of furan:

The mildest acidic conditions required to affect the hydrolysis of furan into succinaldehyde to prevent the polymerization

O OH

H+ H2O

OHC CHO

2. Addition reactions of furuan:

a) Reduction:

O O

+ H2

THF

Reactions Of Furan

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b) Diels-Alder reaction:

O O

HC

CH

OO

O

O

+

O

O

c) Addition of carbenes (with diazomethane):

O O

CH2N2

-N2

Reactions Of Furan

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d) Furanis not stable in presence of air and usually stabilized by addition of small amount of hydroquinone. Air oxidation takes place by 2, 5 addition forming peroxide. Hydrogenation of furan peroxide gives succinaldehyde.

O O

O2O O

[H] H2C

OHC

CH2

CHO

3. Electrophilic substitution of furan:

*Furan cannot be directly nitrated with nitric acid (is very readily attack by oxidizing agents). 2-Nitrofuran may be prepared by nitrating furan with acetyl nitrate (CH3COONO2). Similarly, furan cannot be directly sulphonated, but 2-sulphonic acid may be prepared by action of SO3/pyridine on furan. *If (-I) group is present in the ring, then sulphonation can be carried out directly, e.g., furoic acid gives furoic 5-sulphonic acid. *Furan reacts readily with halogen, but the liberated (HX) causes polymerization, because of this halogenated furan prepared by indirect method, e.g., by brominating furoic acid and decarboxylating the product, 5-bromofuroic acid to 2-bromofuran by heating in quinolone in the presence of copper bronze. Aluminum chloride attacks furan ring, and Friedel-Crafts is best carried with SnCl4.

Reactions Of Furan

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O

NH

O

O

O

O O

SO3H

COR

HgOAc Br

HO(CH2)4OH

+

H2O/H+

Br2

2-Bromofuran

TetramethyleneglycolTetrahydrofuran

2,5-dinitrofuran2-nitrofuran

2-acylfuran

furan-2-sulphonic acid

Furan

NH3/Al2O3

450°C

SO3/pyridine

RCOCI/SnCl2

CH3COONO2

0°C

H2/Ni

Hg(OAC)2

O NO2O NO2

O2N

O Li O COOH

C4H9Li 1-CO2

2-HCl

HCl/HCN

O CHO

Synthesis Of Furfural

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1. From dehydration of aldopentoses

HCl

OCHO

CH2OH-(CHOH)3-CHO

CHO

OHH

HHO

OHH

CH2OH

- H2O

CHO

C OH

C H

OHH

CH2OH

CHO

C O

HC H

OHH

CH2OH

CHO

C O

C

CH

CH2OH

H

H

H

CHO

OH - H2O

CHO

Synthesis Of Furfural

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2. From Gattermann’s reaction:

OO

+ HCl/HCN

OCHO

+ H2OCH=NH2

O

+ HCl + H-CN

H-C=NH

ClO

CH=NH

H2O

OCHO

Reactions Of Furfural

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Furfural is chemically very similar to benzaldehyde as the following

1. It undergoes oxidation (KMnO4) to furoic acid.

2. When it was submitted to react with sodium hydroxide it undergoes cannizzaro reaction

and gives a mixture from furfuryl alcohol and sodium salt of furoic acid.

3. It under goes benzoin condensation and gives furoin.

4. It reacts with aniline in the presence of acetic acid and gives Schiff’s base.

NH2

aniline

O

O

furfural

+2Ph-NHCH=CH-CH

C

HO

NPhSchiff 's baseBrilliant red

Reactions Of Furfural

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5. It reacts with acetone and yields furfurylidene acetone.

O

O

furfurylidene acetone

6. It reacts with CaO/400ºC, it loses carbon monoxide and gives furan by steam decomposition.

7. With ammonia and ammonium chloride gives 3-hydroxypyridine.

NH3/NH4Cl

H2NO

C

O

H OH

CHO

Reactions Of Furfural

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furfuryl alcohol

tetrahydrofurfuryl alcoholfurfural

H2/CuO

H2/Ni

furfuryl alcohol

(cannizzaroreaction)

+

furoic acid

furoic acid

OCHO

O CH2OH

O CH2OH

O CH2OH O COOH

O COOH

KMnO4

NaOH

Reactions Of Furfural

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furylacrylic acidfurfural

AC2O/AcONa

Alc./KCN

(perkinreaction)

(benzoincondensation) furoin

furil

2

furilic acid

OCHO

O CH CH COOH

O OCH

O OH

O O

O O

O

OH

COOH

OXID

NaOH