1. Synthesis of indole Fischer's synthesis
This the most important method of preparing indole is carried out by heating the phenylhydrazone or subistituted phenylhydrazone of an aldehyde or ketone with zinc chloride as catalyst .The mechanism is uncertain but a highly favored is that Robinson .According to him acetone phenyl hydrazone form 2 – methyl indole by first tautomerising the tautomer then undergoing the O – benzidine rearrangement and the diamine compound so produced eliminating a molecule of ammonia with ring closure
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2. Mechanism
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3. Madelung synthesis
It is the cyclisation of O – acetamide toluene by an alkaline reagent
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4. Indole itself is prepared from O – formamide toluene when heated with potassium t-butoxide at 350 cº
K.T.butoxide -H 2
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5. Lipp synthesis
This is carried out by heating O – aminochlorostyrene with sodium ethoxide
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6. Reissert synthesis
This is a very good method and is carried out with o- nitrotoluene (or its derivative ) and ethyloxalate as follows .
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7. Bischler's synthesis α |
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8. Benzothiophene Physical properties and structure
Thianaphthene (1) also known as benzothiophene was first obtained by difficult synthesis in and in 1902 it was isolated from coal tar Thianaphthene has little commercial value , but derivatives in the form of thioindigo dyes have great value and have been much investigated Thianaphthene is colourless solid , m.p 32º , bp 220 – 221 .it is best presented as
a resonance hybrid of 1 and charged structure 1a , 1b and 1c in order of decreasing important
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9. S H C = l
KOH
2 - ( 2 - chlorovinyl) thiophenol
Chemical Reaction
The electrophilic substitution of these system is much less regioselective than that of indole(effectively complete selectivity for attack at carbon – 3 ) .for example nitration gives mixture of more than half of the product is the 3 – nitro , 2,4,6 and 7 are also produced
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10. Treatment of benzothiophene with halogene
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11. Reduction :
The sulphur – containing ring can be opened in several ways the most useful being desulphurization with Range nickel
Oxidation
Thianaphthene doesn't react with methyl iodide but with hydrogen peroxide in refluxing acetic acid yield a 1,1 – dioxide or sulphone (2)
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12. Addition reaction :
Dioxide is much more stable than thiophene 1,1 – dioxide .It under goes a Diels – Alder reaction with it self only at 220 cº
Sulphur dioxide is lost giving 3 , the structure of wich was proved by conversion to 4
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13. The Thianaphthene 1,1 – dioxide also give (5) with butadiene , the 2,3 double bond of (2) has the very interesting property of adding
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14. General method for preparation of benzothiophene and benzofuran
Synthetic methods
General method for preparation of benzothiophene and benzofuran
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15. 2-
3 –Thianaphthene is possibly prepared from ethyl benzene in the vapour phase
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16. 4 – I can also be prepared in 71% yield from thiophenol and acetylene at 600 – 650 cº
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17. 5-
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18. 6 – Diels – Alder reaction
malic anhydride O + S H 2
C = H C
decarboxylation
dehydrogenation
2 - vinyl thiophene
- CO -H
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