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Benzofuran (coumarone)General properties

Benzo furan (1) some times called coumarone , is a colourless liquid b.p.137cº which may be isoleted from coal tar .Its structure has not been investigated in detail ,but it has aromatic properties and is best treated as a resonance hybrid to which 1 is the major contributor ; minor contribution are made by charged structure such as (1a) and (1b). Benzofuran is much more stable to chemical attack than furan.

6

5

1

O17

43

2O+

-

1a 1b

O

-

+

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Chemical reaction OxidationBenzofuran is much less easily opened than that of furan , but it can be spilt

by the two routes outlined.

OO3

O

OO2

C -RO

OHMixtureR = H , OHC CH

ONa

Na

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2 – Electrophilic subistitution. Benzofuran display a lesser tendency for 3 – subistitution for- mylation of benzofuran reportedly gives only the 2-formly derivative and nitric acid nitration produced 2 – nitrobenzofuran ;alater study using dinitrogen tetroxide give 3 – nitrobenzofurane as amajor product togother with smaller percentage of the 2 –

isomer.

ON2O4PhH 10c0 O

NO2

+

OHNO3CH3COOH

O NO2

O NO2

59 % 14%

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Treatment of benzofuran with halogens result in 2,3 – addition product with initial electrophilic attacke taking place at c -2

O

X2

O

x

x

2,3 - dihalobenzofuran

O

(CH3CO)2O BF3

O C - CH3

O

This is in very marked contrast to indole and thianphthene , where attack takes place predominantly at position 3 , and has been attributed to the much

greater electronegative of oxygen than that of nitrogen or sulphur.

Some benzofurans even form 2,3 – epoxides with perbenzoic acid.

O OO

epoxide

C6H5COOH

O

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ReductionBenzofuran is easily reduced by hydrogen over Palladium or sodium and alcohol the 2,3 – dihydroderivative ,which is also known as coumaran

O O

2,3 - dihydroderiv(coumaran)

redH2/Pd

-H2

coumaran -2-one is the lacton of 2 – hydroxyphenyl acetic acid

CH2 - COOH

OHO O

coumaran - 2 - one(lactone )

-H2O

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Synthesis of Benzofuran1 -A useful laboratory synthesis starts with coumaran ,and is generally applicable

O O

Br2

O O

H BrBr

H

HO- K+

K / OH

-HBr

+ -

OH

CHC - CO2KBr

+ H

-HBr O COOH

Distile , CaO

-CO2 O

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COR

O Na

C =O

O

R

CH2CO2Et

Br CH2CO2Et

-NaBr

NaOEt

-H2O

O COOEt

RDecarboxylation

+H2O O

R

+ CO2 + EtOH

2 -An internal claisen reaction may be used to bring about ring closure.

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3 -When the sodium derivative of etheyl salicylate is used the product is ethyl coumaran -3-one -2-carboxylate which can be decarboxylated giving the best synthesis of coumaran -3-one

C =O

ONa

OEt

Br CH2CO2Et

-NaBr

NaOEt

-EtOH

C = OCH - COOEt

O

Decarboxylation

H2O

C =O

O

OEt

CH2- CO2Et

O

O

Coumaran-3-one-2-carboxylate Coumaran-3-one

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Heterocyclic Analogues of benzen with one hetero atom

The most important ring system of this class , that of pyridine , can be derived from benzene by the replacement of a carbon and hydrogen atom by one of nitrogen .This change leaves the aromatic structure of the rings essentially unaltered .A similar replacement of carbon and halogen atoms by one of oxygen cannot be envistigated because of valency consideration unless

Oxygen atom subsequently bears appositive charge .

N O O OPyridine Pyrylium

cation1,2 - Pyran 1,4 - Pyran

S

1 - R - Thia (IV) benzene R+

SS

Thiapyryliumcation

1,4 - Thiapyuran

S1,2-Thiapyuran

+

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This is the case with the pyrylium cation , which has aromatic properties , Reduction of the pyrylium cation could lead to the non – aromatic 1,2 and 1,4 – pyrans and derivatives of both are known .Sulphur analognes of the pyrylium salt and pyrans which are called thiapyrulium salt and thiapyrans, respectively, and some unstable tetravalent sulphur containing compound , the thia (IV)

benzenes , have been prepared recently.

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PyridinePyridine was discover by Anderson , he isolated this base from bone oil an he obtained pure picoline (methyl pyridine ) and Lutidine (dimethylpyridine ) from the same source .Compound containing the pyridine ring are widely distribute in nature , examples being Vatamine B6 and the nicotinamide, adenine , dinucleotide phosphate are of great biochemical importance , it also feature in the structure of many drugs , dyes andalkaloide .

Pyridine is an aromatic compound similar to benzene .The asymmetry of the ring , greatly increase the number of structural isomers in comparison with the benzene .

N.. +

-

N....

+

-

N..

.. -

N..

..

N

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N CH3 N

CH3

N

CH3

CH3

There is only one monomethylbenzene ,but there are three monomethylpyridine .

Pyridine has 19 possible methyl substitution while benzene gives rise to only 12 methylsub . benzene.

The position of subistituent around the pyridine ring are numbered (1) or (2).The cation is called pyridinum and hexa hydropyridine is known as piperidine.

NH

N

2

N1

2

3

4

5

6

1 Pyridinum

+

NH

Piperidine

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Structure of pyridine

In pyridine all ring atoms (five carbon and one nitrogen ) , are sp2hybriization .Two of the sp2 orbitals in each atom overlap with each other to

from C – C an C – N σ bonds. The third sp2 orbitals on each carbon atom overlap with an S orbital of hydrogen to form the C – H σ bonds; the third sp2 orbital on nitrogen is occupied by two electron (lone pair electrone ) i.e .sp2 orbital containing Nitrogen lone pair .All the six bond in pyridine lie in one plane and the bond angles are approximately equal to 120 cº .Also each ring atom in pyridine possesses an unhybridized p orbital containing one electron and these are perpendicular to the plane containing the σ

bonds .

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The latter overlap between two p orbitals produced a delocalized π molecular orbital containing six electrons (Aromatic character ) one half of this π molecular orbital lies above and the other half below the plane of σ bonds . Pyridine show some aromatic properties because the resulting molecular orbitals satisfies the

Huckel's rule ( n = 1 in 4n+2).

According to the resonance theory ,pyridine is considered to be hybrid of five structure as shown before.

Measurement of bond length by x – ray confirms the hybrid nature of the pyridine molecule .The C – C and C – N bond lengths of 1.39 Aº an 1.57 Aº are

intermediate between those corresponding to a single and double bond.

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Physical properties Pyridine is a colour less liquid , b.p 115Cº . It has a very pungent dour , pyridine is miscible with water and most organic solvent it is very hygroscopic .Pyridine react with Na and so should be dried over solid potassium hydroxide or barium oxide .Almost all classes of organic compound are soluble in pyridine , even many of high melting solids which scarcely dissolve in solvents such as ethanol and benzene .It is consequently used as a solvent