Hetero cyclic Analogues of Naphthalene with one heteroatom

1
Hetero cyclic Analogues of Naphthalene with one
heteroatom
The most investigated compound of this group
contain a nitrogen atom , and theoretically can
be drived from naphthalene by the substation of
carbon or carbon and hydrogen atoms by a nitrogen
atom .The same result can be obtained by fusing a
benzene on to that of pyridine and three
structure result .Derivative of all three ring
system 1 , 2 , 3 occure naturally in the form of
alkaloide
2
These three type of compound are essentially
aromatic in character .The oxygen analogues of
naphthalene which will be considered here are
those derived from benzopyrylium cation (4) and
benzopyranes (5) and (6) derivatives of these
systems occure widely in plants and the
anthocyanins. subistituted benzopyrylium salt are
responsible for most red and blue flower coloure
.very few sulphur analogues are known and at
present they are not of general interest .
3
Physical properties and structure
Quinoline is a colourless liquid its b.p 237cº
it's miscible with most organic solvent ,its
useful high boiling solvent for many types of
organic compound .The structure for quinoline was
first proposed by korner ,and was supported at an
early stage by an oxidation to quinolinic acid
(2) and by several syntheses of which
Friedlander's is shown .
4
ozone attacke quinoline at the 5,6 and 7,8
position the initial product is a diozonide ,
decomposition of diozonide give pyridine 2,3
dicarbaldehyde and glyoxal
The resonance energy of quinoline (47.3) kcal/
mol calculated from heat of combustion data the
position of quinoline ring are usually numbered
as structure .
5
Chemical reaction 1 basicity Quinoline is a
slightly weaker base than pyridine and form many
salt which sparingly soluble in water .
6
Addition and ring opening reactions
Quinoline is a colourless liquid , it form 1
oxide with hydrogen peroxide and acetic acid and
quaternary salt with methyl iodide which
with alkali give the hydroxide these are in
equilibrium with the corresponding bases (3)
which can be tautomerize to an open chain (4)
the oxidation of (3)give (5) .
7
(No Transcript)
8
(No Transcript)
9
Reduction
Quinoline is easily reduced to
tetrahydroquinoline by tin and hydrochloric acid
or by hydrogenation .
10
Oxidation
Oxidation of quinoline opens the ring giving
quinolinic acid (1) the 2 phenyl quinoline (2)
and hydroxide (3) the nitrogen containing ring
can be split
11
Mechanism
12
Substitution reaction The nitrogen atom
deactivates the pyridine ring and so the
subistituent enter the benzene ring .calculation
of charge densities show that position 8 will be
attack by electrophilic reagent and position -2-
by nucleophilic reagents .In practice nitration
and sulphonation give a mixture of 5 and 8
substituted product . In bromination the
heterocyclic rings is subistituted in the 3
position .
13
Quinoline resonance hybrid indicate the same
result for electrophilic and nucleophilic
substituent .
14
Electrophilic subistitution
15
Nucleophilic subistitution
16
Synthesis of quinoline 1 Skraup's synthesis
It is the most useful method for preparing
quinoline from aniline and glycerol in presence
of concentrated sulphuric and nitrobenzene .
17
The following steps seem to be involved
1 Dehydration of glycerol by hot sulphuric
yield the unsaturated aldehyde acroline .
18
2 Nucleophilic addition of aniline to acrolein
to yield ß (phenylamino) propionaldehyde .
19
3 Electrophilic attacke on the aromatic ring by
the electron deficient carbonyl carbon of the
protonated aldehyde .
20
4 Oxidation by nitrobenzene resulting in the
aromatization of the new formed ring
21
2 Friedlander's synthesis
It involves the condensation of a
aminobenzaldhyde with acetaldehyde in the
presence of an alkali
22
3 Dobner Miller synthesis .
consist of heating primary aromatic amine with
aldehyde or ketone in presence of conc . HCl
23
Mechanism
24
4 Condensation between ß ketonic ester and
primary aromatic amine produces quinolines .
25
OR
26
Isoquinoline
Isoquinoline contain a benzene ring fused as
shown with a pyridine ring .It closely resembles
quinoline in physical and chemical properties .
27
It isolated from coal tar in the form of a
sparingly soluble sulphate ,it also found as a
part of the total structure of a number of
alkaloide e.g. papaverine and morphine
.Isoquinoline is one of the very few heterocyclic
compounds in which numbering of the ring atoms
does not start on the hetero atom as in the case
of naphthalene the numbering starts adjacent to
the benzene ring .The bicyclic structure was
first proposed on the basis of oxidation to
phthalic and pyridine 3,4 dicarboxylic acid .
28
The chemical reactions as in the case of
quinoline suggest that the symmetrical double
bond structure is the major contribiotor to the
hybrid .
Calculation of the p electron densities at the
various position in the ring are as follows .
29
Isoquinoline is a resonance hybrid of uncharged
structure (1,1a and 1 b ) and charged structure (
1c and 1d )
30
Chemical reaction Isoquinoline resemble
quinoline in many ways 1 Basicity
Isoquinoline is a stronger base than quinoline
31
2 Addition and ring opening
Isoquinoline reacts with alkylating agents at the
nitrogen atom give quaternary salt such as ( 2 )
the corresponding hydroxide (3) is obtain when
treated with sodium hydroxide which is in
equilibrium with ( 4 ) (1,2 hydro 1- hydroxy
2 methylisoquinoline ) and on oxidation give
isoquinoline ( 5 ) .
32
1,2,3,4 tetrahydroisoquinoline when treated
with excess methyl iodide followed by alkali give
1,2,3,4 tetrahydro 2,2 dimethyl
isoquinolinum hydroxide ( 7 ) which on
degradation by Hofmann's method the rings breaks
between position 2 and 3 giving ( 8 ) .
33
Reduction
34
Electrophilic substation Should give the 5
substituent isoquinoline ( see the p electron
density picture ) . Nitration occurs at position
5 and 8 in isoquinoline the former agrees with
expectation from charge densities , but position
7 would have bean expected to be the next
position to attacked .