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Session Objectives

By the end of this session, students will be able to:

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 Discuss the chemistry, reactivity, properties and method of synthesis of

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Indole

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Chemistry of Indole
• Indole was first prepared by Baeyer in 1866 by zinc dust
distillation of oxindole
• Found in coal tar and in essential oils (jasmine oil, orange oil)
of many plants

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• Also occurs in amino acids (tryptophan), plant growth

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hormone (indole-3-acetic acid), alkaloids (brucine, psilecene)

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and dye stuff (indigo)

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• Ring comprises of benzene ring fused to 2- and 3- positions of

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a pyrrole nucleus

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• IUPAC name is 1H-benzo[b]pyrrole

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• Positions 2- and 3- can be designated as α and β, 3a and 7a
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are bridgehead carbons
• Tautomeric forms of indole, known as indolenines

3
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Chemistry of indole
• Physical properties:
• Colorless crystalline solids with melting point 52 0C and boiling point 254
0C

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• Soluble in most organic solvents

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• Pure indole has a very pleasant smell and used as perfume base

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• Impure indole and skatole (2-methylindole) have unpleasant odor

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• Many indoles are quite stable in air

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• With exception of simple alkyl group at 2-position, oxidizes readily even

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when stored in a dark brown bottle

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• Responds to Ehrlich test and gives blue colour

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• Planar molecule with a conjugated system of 10π-electrons, two from
nitrogen and 8 from carbon atoms- π excessive molecule

4
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Chemistry of indole
• Synthetic methods:
• 1) Fischer-Indole synthesis:
• Most widely investigated method

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• Involves acid catalyzed rearrangement of a phenylhydrazone

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of an aldehyde or ketone with the elimination of molecule of

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ammonia

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• Conventional catalysts employed are zinc chloride,

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polyphosphoric acid

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• Madelung synthesis:

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• Involves cyclic dehydration of acyl o-toluidine in the presence
of strong base and at high temperature

5
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Chemistry of Indole
• 3) microwave irradiation: phenylhydrazine and acetone on treatment
with clay under microwave irradiation gives an excellent yield (86%) of
2-methylindole

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• Chemical properties:

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• 1) reaction with acids: indole is very weak base

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• In dilute acid, β-protonated 3H-indolium (1) cation is formed

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• In strong acid solutions, proton can be added to 1- and 2- positions

.b
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6
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Chemistry of Indole
• 2) electrophilic substitution: indole is a π-excessive molecule and
electron density on its carbon atoms is greater than in benzene
molecule
• Reacts easily with electrophile and attack takes place in heterocyclic

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ring

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• Highly regiospecific for position-3

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7
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Chemistry of Indole
• 3) halogenation: mild reagents are used for halogenation
• For chlorination, sulfuryl chloride, chlorine, N,N-

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dichlorocarbonate, phosphorus pentachloride and tert. Butyl
hypochloride have been used

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• For bromination, Br2/dioxane/0 0C or Br2/CH3COOH or NBS

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• If 3rd position is occupied by electron-withdrawing groups

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then attack occurs in benzene ring

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.b
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8
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