HETEROCYCLIC

COMPOUNDS
UNIT - II
Classification Of Organic Compounds:
IN
D
ET
AI
L
 INTRODUCTION
 Heterocyclic compound is the branch of Organic Chemistry dealing with the synthesis,
properties, and applications of these heterocycles.
 A heterocyclic compound or ring structure is a cyclic compounds that has atoms of at least two
Different elements as members of its ring.
 Eg:
* Nucleic acids,
* Majority of drugs,
* Biomass (cellulose and related materials)
* Natural and synthetic dyes.

and so on.,
Classification Of Heterocyclic Compounds
 SYNOPSIS
Dealt by.,
1. Aromaticity - Mukundha Balan S

2. Pyrrole - Santhosh S

3. Thiophene - Aparnasakthi V
4. Furan - Lakshminarayanan S
5. Furfural - Kanishkaa
Rithami A R
6. Tetrahydrofuran - Aniz P
7. Indole - Madhiarasu S
8. Pyridine - Vasanth Kanna
AROMATICITY
-MUKUNDHA BALAN S
INTRODUCTION
 Aromaticity is a property of Cyclic, Planar structures with π bonds in resonance (those
containing delocalized electrons) that gives increased stability compared to other geometric or
connective arrangements with the same set of atoms.
 Aromatic rings are very stable and do not break apart easily.
 Organic compounds that are not aromatic are classified as aliphatic compounds - they might
be cyclic, but only aromatic rings have enhanced stability.
 There are four conditions, if any of these conditions are violated then no aromaticity is possible.
* It must be cyclic.
* Every atom in the ring must be conjugated.
* The molecule must have [4n+2] π electrons.
* The molecule must be flat.
 CONDITIONS FOR AROMATICITY
1. The Molecule must be Cyclic:
2. Every atom in the ring must be conjugated:
 Being cyclic isn’t a sufficient condition for aromaticity.
 Every atom around the ring must be capable
of Conjugation with each other .
 Every atom in the ring must have an available p orbital
or every atom in the ring must be able to participate
in resonance.
 This condition applies not just to atoms that are part
of a pi bond, but also atoms bearing a lone pair,
a radical, or an empty p orbital (e.g. carbocation).
 Sp3 hybridized atoms cannot participate in resonance.
3. The Molecule must have [4n+2] π electrons:
 Conjugated molecule must have the correct number of pi electrons.
 Benzene and cyclooctatetraene are both cyclic and conjugated, but benzene is aromatic and
cyclooctatetraene is not.
 Benzene has [4n+2] pi electrons and cyclooctatetraene does not.
 This rule is known as Huckel’s rule ie., [4n+2] π electrons.

4. The molecule must be flat

PYRROLE
-SANTHOSH S
INTRODUCTION
• PYRROLE is a Heterocyclic Aromatic Compound, a
five membered ring with the formula C4H4NH.
• Colorless volatile liquid – darkens when gets exposed
to air.
• Naturally found in,
Vitamin B12
Bile Pigments
Heme
Chlorophyll.
• Constituent of coal tar.
• Constituent of Tobacco smoke.
 METHODS OF PREPARATION
1. From Ammonia and Furan:
 Prepared by treatment of furan with ammonia in the presence of solid acid catalyst
like Al2O3, SiO2 etc.

 Industrial method of preparation.

 Occurs at High temperature around 500oC.

 Obtained in large amount.

2. From Acetylene and Ammonia:
Pyrrole can be obtained by heating acetylene and ammonia over red hot tube.

3. Reaction between Ammonium Mucate and Glycerol:

 By heating ammonium mucate with glycerol at 200oC.
 At this temperature, ammonium mucate is dissociated into mucic acid and ammonia.
 The acid then undergoes dehydration, decarboxylation and ring closure with ammonia.
4. By heating Succinimide with zinc dust:
Succinimide undergoes tautomerism and reacts with Zinc dust gives Pyrrole.

5. By warming Succinic dialdehyde with Ammonia:

Succinic Dialdehyde undergoes tautomerism gives dienediol and reacts with ammonia gives
pyrrole.
6. Paal-Knorr Synthesis:
In the Paal–Knorr pyrrole synthesis, a 1,4-dicarbonyl compound reacts with ammonia or a
primary amine to form a substituted pyrrole.

7. Hantzsch Pyrrole Synthesis:

 The Hantzsch pyrrole synthesis is the reaction of β-keto esters with ammonia or primary
amines and α-halo ketones to give substituted pyrroles.
 Relatively high yields compared to other ie., 60-97% .
 Multicomponent organic reaction.
 Modified version of Feist-Benery synthesis.
 PHYSICAL PROPERTIES
o Density : 0.967 g/cm3
o Explosive Limits : 3.1 – 14.8%.
o o
M.p : -23 C.
o It has a dipole in which positive end lies towards Nitrogen with dipole moment of
1.58 D.
o Flash point : 33.33oC. (The lowest temperature at which a chemical can vaporize
to form an ignitable mixture in air).
o Flash point α 1
flammability
 CHEMICAL PROPERTIES
1. Electrophilic Substitution:
 Pyrrole undergoes electrophilic substitution primarily at C2.
 Number of resonance structures formed in,
*C2 attack – Three
*C3 attack – Two
 C2 intermediate is more stable since 2 substitution product is formed.
 No. of resonance structure α stability of complex.
a) Nitration:
o
Pyrrole reacts with nitric acid and acetic acid at 5 C gives 2 nitropyrrole.

b) Sulphonation:
o o
Pyrrole reacts with SO3 and Pyridine at 90 C - 100 C give pyrrole 2 sulphonic acid
c) Halogenation:
*Chlorination:
Pyrrole reacts with 4 moles Sulphuryl chloride and Et 2O gives 2,3,4,5 tetra chloro
pyrrole.

*Bromination:
o
Pyrrole reacts with 4 moles of Bromine and ethanol at 0 C gives 2,3,4,5 tetra
bromo pyrrole.
d) Friedel crafts Acylation:
 Pyrrole reacts with acetic anhydride at 250 oC gives 2 acetyl pyrrole and acetic acid.
 No catalyst is required.
2. Kolbe-Schmitt carboxylation:
o
Pyrrole reacts with aq.K2CO3 at 100 C gives pyrrole 2 carboxylic acid.

3. Riemer-Teimen Formylation:
Pyrrole reacts with chloroform in the presence of alkali gives pyrrole-2-aldehyde and 3-
chloropyridine
4. Diazo coupling:
Pyrrole reacts with benzene diazonium chloride gives 2-phenylazopyrrole.
5. Oxidation:
Pyrrole undergoes oxidation in presence of Cr2O3 gives maleic-imide.

6. Reduction:
Pyrrole undergoes,
* Partial reduction in presence of Zinc and acetic acid gives 3 pyrroline.
* Complete reduction in presence of H2, Pt gives pyrrolidine.
7. Ring Expansion Reaction:
When pyrrole reacts with sodium methoxide and methylene iodide, it undergoes ring expansion
forms pyridine.

8. Ring Opening Reaction:

Pyrrole reacts with hydroxylamine in presence of ethanol undergoes ring opening reaction gives
succinaldoxime.
 APPLICATIONS OF PYRROLE
 Pyrrole and its derivatives are widely used as an intermediate in synthesis of,
• Pharmaceuticals.
• Agro chemicals.
• Dyes.
• Photographic Chemicals.
• Perfumes.
 Used as catalysts for polymerization process, Corrosion inhibitors, solvents for resin and
terpenes.
 Used as a standard of chromatographic analysis.
 Treatment of dyslipidaemia (Abnormal level of cholesterol in blood)
and prevention of cardiac diseases. Pharmaceutical
 Antibacterial agent. Importance
 Antipsychotic drug.
THIOPHENE
-APARNASAKTHI V
INTRODUCTION
 THIOPHENE is Heterocyclic Aromatic Compound
with formula C4H4S

 Has two lone pairs of electron.

 Occurs in coal tar distillates.

 Structure analogous to Pyrrole.

 Due to the presence of 6 pi e- and a cloud around

sulphur, it follows Huckel’s rule and behave like
extremely reactive benzene derivatives.
 METHODS OF PREPARATION
1. THIOPHENE:
1. From Alkane: 2. From Acetylene:
 n-butane reacts with sulphur to form  Mixture of acetylene and H2S passed to a
thiophene and hydrogen sulphide. o
tube containing alumina at 400 C.
 Commercial method.
 Occurs at high temperature around 650oC.
3. By heating Sodium Succinate with Phosphorous Pentasulphide:
Sodium Succinate reacts with phosphorous penta sulphide and hydrogen peroxide gives thiophene.

4. By distillation of furoic acid with Barium sulphide:

Furoic acid is distillated in presence of BaS gives thiophene
2. SUBSTITUTED THIOPHENE:

1. Paal-Knorr synthesis:
 1,4 Dicarbonyl compound reacts with source of sulphur to give thiophene.
 Sources of sulphur used are Phosphorous sulphides or Lawesson's reagents.
 Lawesson's reagent - thionating reagent.

Lawesson's reagent
(C14H14O2P2S4)
2. Vohlhard-Erdmann Cyclization:

 Itaconic acid involves cyclization in the presence of Ranney nickel and phosphorous
o
sulphides at 80-100 C to form thiophene.

Itaconic acid
 PHYSICAL PROPERTIES
 Colourless, unpleasant odour and volatile.
 Insoluble in water, Soluble in organic solvents
 B.p : 84oC
 M.p : -38oC
 Density : 1.05 g/cm3.
 Like benzene, thiophene also forms Azeotrope (a mixture of two liquids which has
a constant boiling point and composition throughout distillation).
 The molecule is flat and planar.
 CHEMICAL PROPERTIES
1. Hydrogenation:
 Thiophene undergoes hydrogenation to form tetrahydrothiophene.
 Catalyst – Palladium(Pd).
 Catalytic poison – sulphur.
2. Oxidation:
 Oxidation occurs at both sulphur and 2,3-carbon double bond.
 At sulphur it forms thiophene s-oxide which is an intermediate further undergoes
Diels-Alder dimerisation gives sulphone and sulphoxide.
 At carbon double bond it gives thiophene 2,3-epoxide.
3. Reduction:
 Thiophene on reduction gives n-butane which on isomerization gives iso-butane and 2-
methyl 1-propene.
 Catalyst - Raney nickel.
4. Electrophilic Substitution:
 C2 attack gives more resonance contributing structures than C3.

 Extra stable contributing structures generate upon C2 attack.

a) Nitration:
Thiophene reacts with nitric acid and sulphuric acid gives 2 Nitro thiophene.

b) Sulphonation:
Thiophene undergoes sulphonation with H2SO4 gives thiophene 2 sulphonic acid.
c) Mercuration:
Thiophene undergoes mercuration HgCl2 and Sodium Acetate gives 2 chloromercurithiophene.

d) Halogenation:
*Chlorination:
o
Thiophene reacts with thionyl chloride at -30 C gives 2 chlorothiophene.
 *Iodination:
Thiophene reacts with Iodine in presence of HgO gives 2-Iodothiophene.

e) Chloromethylation:
Thiophene reacts with formaldehyde and HCl gives 2 chloromethylthiophene.
f) Friedel Crafts alkylation:
Thiophene reacts with acetic anhydride in presence of H3PO4 gives 2 acetyl
thiophene.
 APPLICATIONS OF THIOPHENE
 Inhibitors in corrosion of metals.
 Used in the fabrication of LED in Material Science.
 Has high therapeutic values as,
 Anti-microbial.
 Analgesic.
 Anti-hypertensive.
 Anti-tumor.
 Sitaxsentan – treatement of hypertension.
 Tiagabine - treatement of epilepsy. Medicinal Importance
 Articane - anesthetic agent.
FURAN
-LAKSHMINARAYANAN S
 INTRODUCTION

 FURAN is a Heterocyclic Organic Compound

consisting of a five-membered aromatic ring.

 Found in heat-treated commercial foods.

 Produced through thermal degradation of natural

food constituents.

 Other name – Tetraphenol.

 Heat stable compound.

 METHODS OF PREPARATION
1. By Dry Distillation of Mucic Acid:
Mucic acid undergoes dry distillation gives furoic acid which upon heating in
o o
200 C - 300 C gives Furan.
2. By Oxidation of Furfural:
Furfural undergoes oxidation gives furoic acid which further undergoes decarboxylation gives
furan.

3. By Dehydration of Succinic Dialdehyde:

Succinic dialdehyde keto-enol tautomerism and reacts with P 2O5 gives furan and water.
4. Paal-Knorr Furan Synthesis:
 1,4 Diketone reacts with suitable acid to give Furan.
 It is a reversible reaction.

 A trace is acid is required usually TsOH. (p - MeC6H4SO3H).

5. Feist-Benery Synthesis:
 Reaction between α – halo ketone and β- Dicarbonyl compound to produce substituted furan
compound.
 Catalysed by Ammonia and Pyridine.

6. From Furfural:
 Decarbonylation(removal of carbonyl group) of furfural gives furan.
 Catalyst – Palladium(Pd).
 PHYSICAL PROPERTIES
 Colourless, highly volatile liquid.
 Density : 0.936 g/mL.
 M.p : −85.6 °C.
 B.p : 31.3 °C.
 Smells like Chloroform.
 Soluble in Organic solvents – Alcohol, ether, Acetone.

 Slightly soluble in H2O.

 CHEMICAL PROPERTIES
1. Reduction:
Reduction of furan leads to formation of Tetra Hydro furan (THF).
2. Diels-Aldor Reaction:
 Reaction between Furan and Malic Anhydride gives Bicyclic Diels-Aldor Adduct.
 ‘O’ atom is highly Electronegative, so the delocaliztion of lone pair electron(in aromatic
system of furan) is not overly effevtive.

3. Achmatowitz Reaction:
Substituted furan reacts with Bromine in the presence of methanol gives Dihydropyrine under
several rearrangements.
4. Electrophilic Substitution:
 C2 attack takes place.

 The attack on C1 also takes place but it is not common because of repulsions lone pairs of
Oxygen.
a) Nitration:
Furan reacts with nitric and sulphuric acid gives 2 nitro furan.

b) Sulphonation:
Furan undergoes sulphonation in presence of pyridine at 70°C gives Furan 2 sulphonic acid.
c) Bromination:
Furan undergoes bromination in presence of dioxane gives 2 bromofuran.

d) Friedal Crafts Acylation:

Furan reacts with acetic anhydride in presence of BF3 at 0°C gives 2 acetyl furan.
5. Reaction with n-butyl Lithium:
Furan reacts with n-butyl lithium in presence of ether gives 2 furan lithium and butane.

6. Mercuration:
Furan reacts with HgCl2 in presence Sodium acetate gives 2 chloromercurifuran
7. Ring Opening Reaction:
When treated with methanol and HCl, furan undergoes ring-opening forms diacetal of
succinndialdehyde.
 APPLICATIONS OF FURAN
 Used as Fungicide.
 Found in roasted coffee, instant coffee, and processed baby foods.
 Incorporation of furan nucleus is important in Drug discovery.
 Used in the production of,
• Resins.
• Agrochemicals.
• Pharmaceuticals.
 Responsible for Caramel like flavour and causing colour in flavouring food.
 Nitro furans – anti-protozoal agent. Medicinal
 Ranitidine – anti-histamic agent. Importance
FURFURAL
-KANISHKAA RITHAMI A R
 INTRODUCTION
o FURFURAL is a Heterocyclic Organic Compound with the formula C5H4O2.

o It has an aldehyde group attached to the 2-position of furan.

o First isolated in 1821 by the German Chemist Johann Wolfgang Döbereiner.

o IUPAC Name - Furan-2-Carbaldehyde.

 METHODS OF PREPARATION
1. By acid catalysed dehydration:
o Furfural may be obtained by acid catalysed dehydration of 5 carbon sugars pentose
(or sometimes xylose).
o These sugars may be obtained from hemicellulose present in Lignocellulosic
biomass (plant dry matter).
 PHYSICAL PROPERTIES
oMolecular weight : 96.08 g/mol.
oBoiling point : 161.7 °C
oFreezing point : -36.5 °C
oIt is colourless oil with pleasant odour.
oDissolves readily in most polar organic solvents, but it is only slightly soluble in water.
oFurfural is easily oxidized by air, and the colour changing from the shade of yellow-brown to
black.
oThe oxidation can be prevented by storing Furfural in the absence of oxygen.
oThis can also be prevented by adding anti-oxidants like HYDROQUINONE.
 CHEMICAL PROPERTIES
1. Electrophilic Substitution:
a. Nitration:
Furfural can be nitrated to 5-nitrofurfural by cold nitric acid in the presence of acetic
anhydride.
b. Bromination:
When furfural is reacted with bromine and dicloromethane it gives rise to 5-bromo furfural.

CH2Cl2
Br2

c. Reaction with hydroxylamine:

Furfural forms oxime when condensed with hydroxylamine

NH2OH
2. Oxidation:
When furfural is oxidized with strong oxidizing agent like sodium chlorate it undergoes ring
opening forming Fumaric acid.

3. Reduction:
 Furfural is reduced to furfural alcohol in the presence of hydrogen and platinum.
 And on further reduction it gives rise to tetrahydrofurfural and tetrahydrofuran.
4. Claisen Schmidt reaction :
Reaction with acetone

Furfural reacts with acetone to give furfurylidene acetone.

5. Cannizaro reaction :
Furfural gives furoic acid and furfuryl alcohol in presence of strong alkali.
6. Grignard Addition:
Furfural reacts with Grignard reagent gives a secondary alcohol as a product.

7. Sodium Bisulphate Addition:

Sodium bisulphate adds to the carbonyl group of furfural to form a bisulphate addition product.
8. Reaction with Ethanolic Potassium Cyanide:
Furfural undergoes benzoin type condensation with ethanolic potassium cyanide
to form furoin.
 APPLICATIONS OF FURFURAL
o Used as a solvent for refining lubricating oils.
o Used as a Fungicide and Weed killer.
o Used in the production of Tetrahydrofuran.
o It can be converted into various,
 Solvents.
 Polymers.
 Fuels and other useful chemicals by catalytic reduction.
o Used as paint remover.
o Used in poultry to kill lice.
o It acts as a solvent for cellular esters.
TETRAHYDROFURA
N
-ANIZ P
INTRODUCTION
 TETRAHYDROFURAN(THF) is an Heterocyclic Organic Compound with the chemical formula(CH2)4O.

 Other name: Oxolane.

 Doesn't occur in nature.

 Cyclic ether.

 Produced from renewable sources.

 METHODS OF PREPARATION
1. From Butanediol:
 1,4-butanediol reacts with sulphuric acid in the absence of water gives
Tetrahydrofuran.
 Irreversible process.
2. From Hydrogenation Of Succinic Acid:
Hydrogenation of succinic acid over rhenium catalyst supported by H 2SO4 gives THF.

3. Catalytic Hydrogenation:
Furan can be conventionally converted into THF by M-TiO 2 (mesoporous titanium dioxide).
4. Catalytic Dehydration:
Ethyne in the presence of formaldehyde condensed to form
2,butyne-1,4diol which on further dehydration gives THF.

5. From Chlorobutanol:
 SN2 reaction takes place when 4-chlorobutanol reacts with water.
 Ring closure reaction.
 PHYSICAL PROPERTIES
 Colourless liquid.
 Smells like ether.
 Water miscible organic liquid with low viscosity.
 B.p : 66oC.
 M.p : -108.4oC.
 It is an Aprotic Solvent with dielectric constant 7.6 F/m.
 Highly inflammable.
 Stable compound with low boiling liquid with excellent solvency.
 CHEMICAL PROPERTIES
1. Oxidation:
Thermally treated iron containing clay is used as greener catayst for the conversion of
THF to BTL (butyrolactone).
2. Bromination:

THF is treated with excess of HBr at 373K to form 1,4 dibromobutane.

3. Reaction with Ammonia:

Tetrahydropyrrole (pyrolidine) is produced when ammonia is added with THF.

4. Hydrolysis:
THF undergoes hydrolysis in the presence of dilute H 2SO4 gives 1,4-butanediol.

5. Reaction with Hydrogen Sulphide:

THF reacts with H2S in presence of Al2O3 at 300oC gives tetrahydrothiophene.
6. Reaction with Hydrochloric acid:
THF reacts with,
* HCl gives 4-chlorobutanol.
* HCl and ZnCl2 gives 1,4 dichlorobutane.
 APPLICATIONS OF TETRAHYDROFURAN
 Versatile solvent.
 Used as a chemical intermediate.
 Processing aid in the production of Petroleum.
 Primary ingredient in PVC adhesives.
 THF can dissolve polymers.
 Acts as a lewis base(reducing agent).
 Used in Cellophane and PVC top coatings.
 Exposure to 25,000 ppm will cause Anaesthesia.
 THF can irritate the nose, throat and lungs.
 Used as a catalyst in Oxymercuration - Demercuration and Hydroboration Oxidation.
 Conversion of THF into Nylon 6,6
1. THF on reaction with HCl in the presence of Zinc chloride produces 1,4 dichlorobutane.

ZnCl2
+ HCl

KCN
o
2. Adiponitrile is formed when 1,4 dichlorobutane
DMSO reacts with KCN at (100 – 140) C.
3. Here Adiponitrile is divided into two parts one reduced to hexa methylene diamine and other
forming Adipic acid on hydrolysis of Adiponitrile.
H2 catalyst

H2O
H+

4. The formed two products of Adiponitrile gives Nylon-6,6

INDOLE
-MADHIARASU S
INTRODUCTION

 INDOLE is an aromatic Heterocyclic Organic Compound with

formula C8H7N.

 Bicyclic structure, consisting of a six-membered benzene ring

fused to a five-membered pyrrole ring.

 Widely distributed in the natural environment and can be

produced by a variety of bacteria.

 It occurs in coal tar.

 Produce red color with pine splint moisten with HCl.

 METHODS OF PREPARATION
1. Leimgruber–Batcho Indole Synthesis:
• Production of Indole from o-Nitro toluene.
• Formation of an enamine 2 using N,N-dimethylformamide dimethyl acetal
and Pyrrolidine.
• Futher reductive cyclisation leads to production of indole.
2. Fischer Synthesis:
• Treatment of phenyl hydrazine with pyruvic acid gives phenyl hydrazone .
• Further treatment with anhydrous zinc chloride gives indole-2-carboxylic acid.
• Further decarboxylation of indole-2-carboxylic acid gives Indole.
3. Reissert Synthesis:
• Condensation of o-Nitro toluene with diethyl oxalate to give ethyl o-Nitro phenyl pyruvate.
• Reductive cyclisation of ethyl o-Nitro phenyl pyruvate with zinc in acetic acid gives Indole-2-
Carboxylic acid.
• Indole-2-Carboxylic acid which on decarboxylation gives Indole.
4. Baeyer-Emmerling Indole Synthesis:

When o-Nitro Cinamic acid is treated with iron powder in strong basic solution gives Indole
5. Lipp Synthesis:
O-amino chlorostyrene is heated with sodium ethoxide at 160-170°C gives indole.

6. From o-Toluidine:
O-toluidine reacts with formic acid to form
N-formyl-o-toluidine which on dehydration
with potassium-t-butoxide gives Indole.
7. From o-Nitrophenylacetaldehyde:
It involves the reduction of o-Nitrophenylacetaldehyde with iron powder and
sodium bisulphate to give o-amino phenyl acetaldehyde, which cyclizes
spontaneously gives indole.
8. From Trans-indigo:
 Oxidation of trans-indigo with potassium permanganate gives isatin which on reduction with
zinc and glacial acetic acid gives dioxindole and finally oxindole.
 This is next distilled with zinc dust to give indole.
 PHYSICAL PROPERTIES
 Colourless volatile solid.
 M.p : 52oC.
 B.p : 253oC.
 Soluble in hot water.
 Sparingly soluble in cold water.
 It occurs naturally in Human faecal matter.
 Has flowery smell at low concentration.
 Used in the manufacturing of many perfumes.
 CHEMICAL PROPERTIES
1. Electrophilic Substitution:
In Indole C3 attack takes palce and 3-substitution product is formed.
a) Nitration:
Indole reacts with ethylnitrate in presence of Sodium ethoxide at low temperature
(5oC) gives 3-Nitro Indole.

b) Bromination:
Indole reacts with Bromine in presence of dioxan at 0 oC gives 3-bromoindole.
c) Sulphonation:

Indole reacts with SO3 in presence of pyridine at 110oC gives Indole-3-Sulfonic acid.

2. Vilsmeier-Haack formylation:

Indole reacts with POCl3 and DMF(Dimethylformamide) in presence of Toluene gives

Indole-3-Carboxaldehyde.
3. Mannich Reaction:

When indole reacts with dimethylamine and formaldehyde in presence of ethanol gives Gramine.

4. Reimer-Tiemann Reaction:

When indole reacts with Chloroform in presence of strong base gives Indole-3-aldehyde.

NaOH
+ CHCl3
5. Friedel-Crafts Acylation:

When indole reacts with CH3COCl in presence of SnCl4 gives 3-acetyl indole.

SnCl4
+ CH3COCl

6. Diazo Coupling:

If indole reacts with Benzene diazonium chloride give 3 phenyl azo indole

+
7. Reduction:
When indole undergoes,
*Partial reduction gives Indoline .
*Complete reduction gives Octahydroindole.

8. Oxidation:
Indole undergoes oxidation in presence of formamide gives 2 formaminobenzaldehyde
 APPLICATIONS OF INDOLE
 Indole regulates various aspects of bacterial physiology including,
*Spore formation *Plasmid stability *Resistance to drugs *Virulence
 A number of indole derivatives have important cellular functions including neurotransmitters
such as Serotonin.
 Indole-3-Carbinol – found in many vegetables such as,
*Broccoli *Cabbage *Cauliflower *Turnips *Mustard greens etc.
 Used for prevention of,
*Breast cancer *Colon cancer *Lung cancer *Cervical cancer
*Prostate cancer
 Helps to reduce the inflammation in body – Anti inflammatory substance.
 Helps the body to get rid of Toxins and cleans the system.
 Helps in maintaining Oestrogen balance.
PYRIDINE
-VASANTH KANNA
 INTRODUCTION
 PYRIDINE is a basic Heterocyclic Organic Compound with the chemical formula C5H5N.

 It is structurally related to benzene, with one methine group (=CH−) replaced by a nitrogen atom.

 It is also known as Azabenzene Azine.

 It was produced from coal tar.

 Occurs in many important compounds, including Agrochemicals, Pharmaceuticals and Vitamins. .

 METHODS OF PREPARATION
1. Dehydrogenation of Piperidine:
By dehydrogenation of piperidine with concentrated sulphuric acid at 300 degree
Celsius gives pyridine.

H2SO4
300oC
2. Reaction with Dichloromethane:
By heating pyrrole with dicloromethane in the presence of Sodium ethoxide gives pyridine.

+ CH2Cl2 + CH3CH2ONa

3. From Acetylene and Hydroden cyanide:

Pyridine is obtained by passing a mixture of acetylene and hydrogen cyanide

2. + HCN
4. Oxidation of β – picoline:
ß-picoline undergoes oxidation with potassium dichromate and sulphuric acid gives nicotinic acid
which on decarboxylation with calcium oxide gives pyridine.

5. Heating Glutaconic aldehyde:

When Glutaconic aldehyde heated with ammonia gives pyridine
 COMMERCIAL METHOD OF PREPARATION
o By heating tetrahydrofurfuryl alcohol with NH3 in the presence of aluminium oxide at
500 degrees Celsius gives pyridine.

Al(OC2H5)3
+ NH3

o Reacting acetylene with ammonia and formaldehyde dimethylacetal in the presence of

aluminium oxide at 500 degree Celsius pyridine is obtained.

CH3OCH2OCH3 + NH3 +
 PHYSICAL PROPERTIES
 Pyridine is a colourless liquid.

 B.p : 115oC.

 M.p : -42oC.

 Density is very close to that of Water, at 0.982 g/cm3 (water's density is 1).

 It is able to mix easily with water and most other organic solvents.

 Pyridine is conventionally detected by the Gas chromatography and Mass spectrometry

methods.
 CHEMICAL PROPERTIES
1. Electrophilic Substitution:
 Pyridine is considerably less reactive than benzene towards electrophilic
substitution.
 Electrophilic substitution of pyridine takes place in the presence of Lewis acid.
Pyridine undergoes Electrophilic Aromatic Substitution at C3 position
a) Nitration:
Pyridine reacts with nitric acid in the presence of sulphuric acid at 300 degree Celsius gives
3- nitropyridine.

b) Sulphonation:
Pyridine reacts with fuming sulphuric acid in presence of mercuric sulphate at 230 oC to give
pyridine 3-sulphonic acid.
c) Bromination:
Pyridine undergoes bromination in presence of charcoal at 300oC gives 3
bromopyridine and 2,5 dibromo pyridine.
2. Nucleophilic Substitution:
 Pyridine undergoes nucleophilic substitution.
 The electronegativity of pyridine makes it highly reactive towards nucleophilic substitution.
 The substitution happens at C2 and at C4.
a) Reaction with Sodium Hydroxide:
Pyridine reacts with sodium hydroxide in presence of air or oxygen at 300 oC to yield an
equilibrium mixture of 2-hyroxypyridine and 2-pyridone.

b) Reaction with n-Butyl Lithium:

Pyridine reacts with n-butyl lithium at 100oC to give 2-n-butylpyridine.

100oC
+
3. Oxidation:
 Pyridine undergoes oxidation with per-acetic acid to give Pyridine-n-oxide.

4. Reduction:
 Pyridine on reduction with Na and NH3 gives 1,5-dihydropyridine(Birch Reduction).
 Reduction with LiAlH4 or H2 ion and H2O gives 2,4-dihydropyridine.
 APPLICATIONS OF PYRIDINE
 The main use of pyridine is as a precursor to the many herbicides.

 Used as Anti-septic in dental care Products

 Used for Anti-freeze mixture.

 Used as Sulphonating and Reducing agent.

 Used as disinfectant.

 Used as solvent which is suitable for Dehalogenation.

 Used for the treatment of Hypertension.

 Used in dyes and paints.

QUINOLINE
-MONICAA
K
 INTRODUCTION
 QUINOLINE is an Heterocyclic Aromatic Compound with chemical formula C9H7N.

 It is consists of a benzene ring fused to the α and β positions of a pyridine ring.

 It is obtained by heating the famous antimalarial alkaloid "QUININE" with alkali

 It occurs in coal tar, bone oil and in Angostura bark.

 It's other name is Benzo β Pyridine.

.
 METHODS OF PREPARATION
1. Skraup Synthesis:
• Commercial method, Exothermic and very violent reaction.
• A mixture of aniline and glycerol is heated in the presence of H 2SO4 and a
mild oxidizing agent, usually nitrobenzene or arsenic pentoxide.
Mechanism:

Step 1: Glycerol undergoes dehydration with H2SO4 to give Acrolein.

Step 2: Aniline adds to acrolein(1,4-addition) to give 3-phenylamine prop-1-en-1-ol.

Step 3: Ring closure.

Step 4: Oxidation of 1,2dihydroxyquinoline.

2. Friedlander Synthesis:
The condensation of o-Aminobenzaldehyde with acetaldehyde in the presence of an alkali gives
Quinoline.
 PHYSICAL PROPERTIES
 Colourless oily liquid.
 Hygroscopic and strong odour.
 B.p: 237oC.

 M.p: -15oC.
 Soluble in organic solvents.
 Slightly soluble in water.
 Smells like Pyridine.
 It turns Yellow on standing.
 Weak base.
 CHEMICAL PROPERTIES
1. Oxidation:
• Quinoline is oxidized by Per-acetic acid to give Quinoline-n-oxide.
• With KMnO4 gives Quinolinic acid.
2. Reduction:
 Mild reduction with Tin and HCl gives 1,2,3,4-tetrahydroquinoline.
 With hydrogen and platinum catalyst produces decahydroquinoline.

3. Reaction with Alkyl Halides:

 Quinoline give n-alkylquinolinium halide by reacting with alkyl halide.
4. Electrophilic Substitution:
 Quinoline undergoes Electrophilic Substitution reactions only under vigorous conditions.
 Substitution occurs at C8 and C5.
a) Nitration:
Quinoline reacts with fuming HNO3 and H2SO4 gives 5 nitroquinoline and 8 nitroquinoline.

b) Sulphonation:
o
Quinoline reacts with fuming H2SO4 at 220 C gives quinoline 8 sulphonic acid and
quinoline 5 sulphonic acid.
5. Nucleophilic Substitutions:
 Quinoline also undergoes Nucleophilic Substitution reactions.
 Occurs at C2 (or C4 if C2 is blocked).

a) Reaction with n-butyl Lithium:

Quinoline reacts with n-butyl Lithium to yield 2-n butlyquinoline
b) Reaction with KOH:
o
Quinoline reacts with KOH at 220 C gives 2 hydroxyquinoline.

c) Reaction with Sodamide:

o
Quinoline reacts NaNH2 and Liq.NH3 at about 100 C gives 2 aminoquinoline.
 APPLICATIONS OF QUINOLINE
 High boiling basic solvent in organic reactions.
 Used in the production of pharmaceuticals, dyes and insecticides.
 Used as feed stocks in the production of other specialty chemicals.
 Irritant of the eyes and respiratory tracts.
 Quinoline and its derivatives are used in the manufacturing of food colours, salt free dyes etc.

Medical Uses:
1. Anti-Malarial drug: 2. Antibiotic: Ciprofloxacin, Ofloxacin
Cinchona alkaloids: Quinine, Quinidine.
4-aminoquinolines : Chloroquine, Amodiaquine. 3. Antiseptics: 8-hydroxyquinoline.
8-aminoquinolines : Primaquine, Bulaquine.
ISOQUINOLINE
-RAGHUL T
INTRODUCTION
 ISOQUINOLINE is a Heterocyclic Aromatic Compound with
a pyridine ring fused with benzene ring.

 Isomer of Quinoline.

 Natural compound found in aromatic amino acid tyrosine.

 First obtained from coal tar.

 Isoquinoline was isolated from acid sulphate through

fractional distillation.

 Analog to pyridine.
METHODS OF PREPARATION
1. ISOQUINOLINE:

1. Pomeranz-Fritsch Synthesis:
• Acid promoted synthesis of isoquinoline from benzaldehyde and
2,2-dialkoxyethylamine.
• Lewis acid such as Trifluoroacetic anhydride and lanthanide tri-flates are used as a
proton donor.
2. From Cinnamaldehyde:
 Condensation of Cinnamaldehyde with hydroxyl amine gives isoquinoline.
 The oxime intermediate formed undergoes Beckmann’s rearrangement and
ring closure.
2. SUBSTITUTED ISOQUINOLINE:

1. Bischler-Napierlaski Synthesis:
 2-aryl-ethylamine reacts with acylchloride or anhydride to form amide which undergoes
cyclisation gives substituted isoquinoline.
 Cyclisation can be accomplished by POCl3 or PCl5.
2. Pictet-Spengler Synthesis:
 2-phenyl ethanamine reacts with aldehyde forms tetra hydro isoquinoline dehydrogenated by
Pd forms isoquinoline.
 Imine is formed as an intermediate.
 An electron donating substituent on the Carbo-aromatic ring is required.
 PHYSICAL PROPERTIES
 Colourless hygroscopic liquid at room temperature.

 M.p: 26oC.

 B.p: 243oC.

 Smells like Almond.

 Turns Yellow on normal storage.

 Soluble in organic solvents.

 Less soluble in water.

 Weak base forms adducts with Lewis acids.

 CHEMICAL PROPERTIES
1. Oxidation:
Isoquinoline is oxidised by alkaline potassium permanganate to give
pyridine-3,4 dicarboxylic acid (Cinchomeronic acid) and Pthalic acid.
2. Reduction:
Isoquinoline on reduction with,
* Diethyl aluminium hydride yields 1,2-dihydroisoquinoline.
* Sodium and ethanol gives 1,2,3,4-tetrahydroisoquinoline.
3. Electrophilic Substitution Reaction:

Like quinoline, it undergoes electrophilic substitution reaction at C 5 and C8.

a) Nitration:
o
Isoquinoline reacts with fuming HNO3 and conc.H2SO4 at 0 C gives
5 nitroisoquinoline and 8 nitroisoquinoline.
b) Sulphonation:
Isoquinoline reacts with H2SO4 gives isoquinoline 5 sulphonic acid.

c) Bromination:
o
Isoquinoline reacts with Bromine at 450 C gives a small amount of 1-bromo
isoquinoline.
o
450 C
+ Br2
4. Nucleophilic Substitution Reaction:
 Isoquinoline undergoes nucleophilic substitution at C 1 or C3.
 Reaction of isoquinoline with sodamide gives 1-aminoisoquinoline.
 Also called as Chichibabin reaction.
5. Electrophilic Addition Reaction:
Isoquinoline reacts with strong mineral acids to form salts.
 APPLICATIONS OF ISOQUINOLINE
 Isoquinoline are the family of synthesized Broad Spectrum Antibiotics.
 It is neither narcotic nor addictive.
 Mainly used for the treatment of Malaria and Schistosomiasis.
 It is of beneficial effect on Angina pectoris.
 Used in rubber accelerators.
 Used in the production of dyes, paints, fungicides and insecticides.
 Precursor to mptp - used in the treatment of Parkinson's disease.

Medical Uses:
 Neuromuscular blocking agent : Curare alkaloids, Atracurium.
 Anti-pasmodic agent : Papaverine(vasodilator)
 Antitussive agent (cough-suppressing agent) : Noscapine.
 Anesthetics : Dimethisoquin.
 Anti-retroviral agent : Saquinavir.
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