Thiophene

1
Thiophene 1 1,4 dicarbonyl compound with a
source of sulphur
2
2 The Hinsberg Synthesis The consecutive aldol
condensation between a 1,2 dicarbonyl compound
and diethylthiodiacetate give thiophenes .The
immediate product is an ester acid produced by
a stobbe type mechanism , but the reaction are
often worked up via hydrolysis to offord an
isolated diacid
3
Chemical Reaction Reaction with electrophilic
reagent take place at position 2 3 but at 2
take place much faster yield a stable product
. Nitration
Sulphonation
Use of the pyridine sulfur trioxide complex is
probably the best method
4
Halogenation
Halogenation of thiophene occurs very readily at
room temperatures and is rapid even at 30 cº in
the dark.
5
Acylation
The Friedel crafts acyalation of thiophene is
much used reaction and produced generally to
give good yield under controlled condition ,
adding catalyst to thiophene and acylatting agent
avoid reaction of aluminium chloride with
thiophene to generate tars
6
Reactivity of indoles, benzobthiophenes,
benzobfurans. isoindoles, benzocthiophenes
and isobenzofurans

7
Indoles Indoles are colourless crystalline solids
.Many simple indoles are available commercially
and all of these are produced by synthesis .Most
indoles are stable in air with exception of those
which carry simple alkyl group at c 2
autoxidises easily even in dark brown
bottle. The word indoles derived from the word
India blue dye. chemical degradation of the dye
give rise oxygenated indoles .which named indoxyl
and oxindole indol as first prepared in 1866 by
zinc dust distillation of oxindole
8
Indoles are widely distributed in nature
Tryptophen is an essential amino acid
The formula of indole was proposed by Baeyer in
1869 and was based on the synthesis outlined
9
The resonance energy of indole calculated from
its heat of combustion is (47 49 ) kcal / mol
the increase in resonance energy over pyrrole (23
27 ) is almost identical to the difference
between the resonance energies of naphthalene
(61) and benzene (36)
10
Chemical properties The chemical properties of
indole are quite similar of these of pyrrole 1
The direct oxidation of indole .PhC2 O OH O3 ,
H2ONHRR'CORNHCOR'PhCO2OHO3 , H2ONHCOHNHCOH The
nitrogen containing ring of many substituted
indoles can be opened by the action of peroxy
acid and ozone .
11
2 Addition reaction Indole , like pyrrole is
very weak base and it is polymerized by acid
giving crystalline dimmer
3 Reaction
12
4 Subistitution reactions the hydrogen at
position 1 of indole is acidic and can be
displaced by metallic sodium or pot . hydroxide
at 125 130 c or by Grignard reagent
13
Electrophilic subistitution
attack is more stable at position 3
14
Electrophilic subistitution reaction
NHEHH..NHEH..NHEHmore stablearomatic sextet
preserved attack at position 2 The pyrrole ring
in the indoles readily undergo subistitution
reactions .The general Pattern of reaction is
similar to that observed with Pyrrole itself
except that many of reaction with indole
introduce 3 Subistituents , lead to
3-subistituted indoles .This orientation can be
accounted as follows
15
This orientation agreement with the calculated
change destant for indole
Gattermen reaction
16
Mechanism a -
b
17
Mannich reaction Indol undergo Mannich reaction
with formaldehyde and dimethyl amine to give 3
dimethylamine indole
18
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
19
Mechanism
20
Madelung synthesis
It is the cyclisation of O acetamide toluene by
an alkaline reagent
21
Indole itself is prepared from O formamide
toluene when heated with potassium t-butoxide at
350 cº
22
Lipp synthesis
This is carried out by heating O
aminochlorostyrene with sodium ethoxide
23
Reissert synthesis
This is a very good method and is carried out
with o- nitrotoluene (or its derivative ) and
ethyloxalate as follows .
24
Bischler's synthesis