this ppt include introduction synthesis, physical ,chemical properties, and uses of pyrrole furan and thiophene also include introduction of 5 membered heterocyclic compound and fused heterocyclic compounds

1. BY – VISHAL SINGH SOLANKI
CORPORATE INSTITUTE OF PHARMACY, BHOPAL
VISIT MY YOUTUBE CHANNEL – PHARMA RISING
OR VISHAL SINGH SOLANKI
BY – VISHAL SINGH SOLANKI
PHARMA RISING

2. 1. INTRODUCTION
2. 5 MEMBERED HETEROCYCLIC COMPOUNDS
3. PYRROLE
4. FURANE
5. THIOPHENE
CONTENT
BY – VISHAL SINGH SOLANKI
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3. Heterocyclic compounds possess a cyclic structure with two or more different
kinds of atoms in the ring.
This work is devoted to organic heterocyclic compounds in which the ring
contains at least one carbon atom; all atoms other than carbon are considered
as heteroatoms.
Heterocyclic compounds are cyclic compounds with the ring containing carbon
and other element, the component being oxygen, nitrogen and sulfur.
The simplest of the five membered heterocyclic compounds are pyrrole, furan
and thiophene, each of which contains single heteroatoms.
The five membered ring contains more than one or two heteroatoms also such
as azole, pyrrole, thiazole, thiadiazole, oxadiazole, triazene, etc.
INTRODUCTION
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5. 5 MEMBERED HETEROCYCLIC COMPOUNDS
BY – VISHAL SINGH SOLANKI
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6. Pyrrole is a heterocyclic aromatic
organic compound, a five-membered
ring with the formula C4H4NH.
It is a colorless volatile liquid that
darkens readily upon exposure to air.
Substituted derivatives are also called
pyrroles, e.g., N-methylpyrrole,
C4H4NCH3.
PYRROLE
Chemical formula C4H5N
Molar mass 67.091 g·mol
−1
Density 0.967 g cm
−3
Melting point −23 °C (−9 °F; 250 K)
Boiling point 129 to 131 °C (264 to 268 °F; 402
to 404 K)
BY – VISHAL SINGH SOLANKI
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7. 1. FROM FURAN
2. Hantzsch pyrrole synthesis
3. Knorr pyrrole synthesis
4. Paal–Knorr pyrrole synthesis
SYNTHESIS OF PYRROLE
BY – VISHAL SINGH SOLANKI
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8. Pyrrole is prepared industrially by treatment of furan with ammonia in the presence of solid
acid catalysts, like SiO2 and Al2O3
Pyrrole can also be formed by catalytic dehydrogenation of pyrrolidine.
1. FROM FURAN
BY – VISHAL SINGH SOLANKI
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9. The Hantzsch pyrrole synthesis is the reaction of β-ketoesters (1) with ammonia (or primary
amines) and α-haloketones (2) to give substituted pyrroles(3)
2. Hantzsch pyrrole synthesis
BY – VISHAL SINGH SOLANKI
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10. The mechanism starts with the amine (1)
attacking the β carbon of the β-ketoesters
(2), and eventually forming an enamine (3).
The enamine then attacks
the carbonyl carbon of the α-haloketone (4).
This is followed by the loss of H2O, giving
an imine (5). This intermediate undergoes an
intramolecular nucleophilic attack, forming a
5-membered ring (6). Finally, a hydrogen is
eliminated and the pi-bonds are rearranged
in the ring, yielding the final product (7).
An alternative mechanism has been
proposed in which the enamine (3) attacks
the α-carbon of the α-haloketone (4) as part
of a nucleophilic substitution, instead of
attacking the carbonyl carbon.
MECHANISM
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11. The Knorr pyrrole synthesis involves the reaction of an α-amino ketone or an α-amino-β-ketoester with an
activated methylene compound. The method involves the reaction of an α-aminoketone (1) and a compound
containing a methylene group α to (bonded to the next carbon to) a carbonyl group (2).
3. Knorr pyrrole synthesis
BY – VISHAL SINGH SOLANKI
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12. In the Paal–Knorr pyrrole synthesis, a 1,4-dicarbonyl compound reacts with ammonia or a primary
amine to form a substituted pyrrole.
4. Paal–Knorr pyrrole synthesis
protonated carbonyl is attacked by the amine to form
the hemiaminal. The amine attacks the other carbonyl
to form a 2,5-dihydroxytetrahydropyrrole derivative
which undergoes dehydration to give the
corresponding substituted pyrrole.
The reaction is typically run under protic or Lewis acidic
conditions, with a primary amine. Use of ammonium
hydroxide or ammonium acetate (as reported by Paal)
gives the N-unsubstituted pyrrole.
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13. 1. Basic Character:
Pyrrole reacts with dilute hydrochloric acid to give a crystalline hydrochloride.
CHEMICAL PROPERTIES OF PYRROLE
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14. Pyrrole is not only a weak base but also a very weak acid. This is shown by its reactions with potassium hydroxide and Grignard reagents.
2. Acidic Character
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15. Pyrrole undergoes electrophilic
substitution reactions at C-2
because three resonance forms
can be written for the
intermediate obtained from
attack at C-2, whereas only two
such forms are possible for
substitution at C-3.
Consequently the C-2
intermediate is more stable and
the product with a substituent
at C-2 predominates.
Substitution at C-3 occurs only
when both the 2-positions (that
is, α and α') are blocked.
3. Electrophilic Substitution Reactions
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16. BY – VISHAL SINGH SOLANKI
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17. Pyrrole is oxidized by chromium trioxide in acetic acid to give the imide of maleic acid.
4. Oxidation
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18. Mild reduction of pyrrole with zinc and acetic acid yields 3-pyrroline (2,5- dihydropyrrole). Catalytic reduction completely hydrogenates the ring system and
produces pyrrolidine.
5. Reduction
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19. When treated with sodium methoxide and Methylene iodide, pyrrole undergoes ring expansion forming pyridine.
6. Ring Expansion Reaction
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20. When treated with hot ethanolic hydroxylamine, pyrrole undergoes ring opening forming the dioxime of succindialdehyde
7. Ring Opening Reaction
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21. Pyrrole reacts with aqueous potassium carbonate at 100°C to give pyrrole2-carboxylic acid.
7. Kolbe-Schmitt Carboxylation
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22. Pyrrole reacts with chloroform in the presence of alkali to yield pyrrole-2- aldehyde (2-formylpyrrole) and 3-chloropyridine.
8. Reimer-Tiemann Formylation
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23. Pyrrole couples with benzenediazonium chloride in a weakly acidic solution to give 2-phenylazopyrrole.
9. Diazo Coupling
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24. Polypyrrole is of some commercial value.
N-Methylpyrrole is a precursor to N-methylpyrrolecarboxylic acid, a building-block in
pharmaceutical chemistry.
Pyrroles are also found in several drugs, including atorvastatin, ketorolac, and sunitinib.
Pyrroles are used as lightfast red, scarlet, and carmine pigments
USES OF PYRROLE
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25. Furan is a heterocyclic organic compound,
consisting of a five-membered aromatic ring
with four carbon atoms and one oxygen atom.
Chemical compounds containing such rings are
also referred to as furans.
Furan is a colorless, flammable, highly volatile
liquid with a boiling point close to room
temperature.
It is soluble in common organic solvents,
including alcohol, ether, and acetone, and is
slightly soluble in water
FURAN
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26. Chemical formula C4H4O
Molar mass 68.075 g·mol
−1
Appearance Colorless, volatile liquid
Density 0.936 g/mL
Melting point −85.6 °C (−122.1 °F; 187.6 K)
Boiling point 31.3 °C (88.3 °F; 304.4 K)
CONTI…
Its odor is "strong, ethereal; chloroform-like".
It is toxic and may be carcinogenic in humans.
BY – VISHAL SINGH SOLANKI
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27. 1. Industrially, furan is manufactured by the palladium-catalyzed decarbonylation of furfural, or by
the copper-catalyzed oxidation of 1,3-butadiene
In the laboratory, furan can be obtained from furfural by oxidation to 2-furoic acid, followed
by decarboxylation. It can also be prepared directly by thermal decomposition of pentose-containing
materials, and cellulosic solids, especially pine wood.
Synthesis of Furan
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28. The Feist–Benary synthesis is an organic reaction between α-
halogen ketones and β-dicarbonyl compounds to produce
substituted furan compounds.
2. Feist–Benary synthesis
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29. The Paal–Knorr Synthesis in organic chemistry is a reaction that generates
either furans, pyrroles, or thiophenes from 1,4-diketones.
The furan synthesis requires an acid catalyst:
Mechanism -
3. Paal–Knorr Synthesis
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30. 1. Basic Character: • Furan is a weak base like pyrrole. It forms unstable salts
with mineral acids. These salts may either polymerize to produce a brown resin
or undergo hydrolysis to yield succindialdehyde.
Chemical reactions of furan:
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31. Like pyrrole, it undergoes electrophilic
substitution at C-2. Substitution at C-3
occurs only when both of the C-2
positions (α and ά) are already blocked.
2. Electrophilic Substitution
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32. Furan is reduced by hydrogen in the presence of nickel to produce
tetrahydrofuran
3. Reduction:
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33. Furan undergoes the Diels-Alder reaction. An interesting point about this adduct is that it forms
phthalic acid when heated in hydrobromic acid. This is the general reaction for furan adduct.
4. Diels-Alder reaction:
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34. Furan is used primarily as an intermediate in the synthesis and production of
other organic compounds.
Hydrogenation of furan over a nickel catalyst produces high yields of
tetrahydrofuran and is a source of commercial tetrahydrofuran.
Furan may also be used as a starting material in the commercial production of
thiophene.
Furan is used in the formation of lacquers and as a solvent for resins.
It is also used in the production of agricultural chemicals (insecticides),
stabilizers, and pharmaceuticals.
Uses of Furan
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35. Thiophene is a heterocyclic
compound with the formula C4H4S.
Consisting of a planar five-membered
ring, it is aromatic as indicated by its
extensive substitution reactions.
It is a colorless liquid with a benzene-like
odor.
In most of its reactions, it
resembles benzene.
THIOPHENE
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36. THIOPHENE
Chemical formula C4H4S
Molar mass 84.14 g/mol
Appearance colorless liquid
Density 1.051 g/mL, liquid
Melting point −38 °C (−36 °F; 235 K)
Boiling point 84 °C (183 °F; 357 K)
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37. 1. By passing a mixture of acetylene and hydrogen sulphide through a tube
containing aluminium oxide at 400°C.
SYNTHESIS OF THIOPHENE
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38. The Paal–Knorr Synthesis in organic chemistry is a reaction that generates either furans, pyrroles,
or thiophenes from 1,4-diketones. in that of thiophene for instance the compound phosphorus
pentasulfide
MECHANISM
Thiophene synthesis is achieved via a mechanism very similar to the furan synthesis. The initial diketone is
converted to a thioketone with a sulfurizing agent, which then undergoes the same mechanism as the furan
synthesis.
2. Paal–Knorr Synthesis
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39. 3. By the high-temperature (650 C) reaction of sulphur with butane. (Commercial Method of Preparation).
4. From sodium succinate (Laboratory method): In laboratory thiophene is prepared by heating
sodium succinate with phosphorous trisulphide.
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40. Thiophene is 300 times more reactive than benzene.
Thiophene does not show any basic properties.
It is much more stable to acids than either pyrrole or furan.
Thiophene does not undergo the Diels-Alder reaction.
Chemical properties of Thiophene
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41. Thiophene, like furan and
pyrrole, undergoes
electrophilic substitution
reactions primarily at C-2.
Substitution at C-3 occurs
only when both of the 2-
positions (α and ά) are
already occupied.
(1) Electrophilic Substitutions:
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42. Thiophene may be hydrogenated by means of sodium amalgam and ethanol to
tetrahydrothiophene.
(2). Reduction:
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43. Catalytic reduction of Thiophene with Raney Nickel results in the removal of Sulphur to
form n-butane
(3) Desulphurisation:
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44. Thiophenes are important heterocyclic compounds that are widely used as building
blocks in many agrochemicals and pharmaceuticals.
The benzene ring of a biologically active compound may often be replaced by a
thiophene without loss of activity.
This is seen in examples such as the NSAID lornoxicam, the thiophene analog
of piroxicam, and sufentanil, the thiophene analog of fentanyl.
Uses PHARMA RISING

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