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JournalofChemicalandPharmaceuticalResearch
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J.Chem.Pharm.Res.,2011,3(5):519523
ISSNNo:09757384
CODEN(USA):JCPRC5

Indole:Themoleculeofdiversepharmacologicalactivities
RameshDhani*,A.Avinash,S.K.Salenaagina,M.V.SaicharanTeja,P.Masthanaiah,P.
RajaRathnamandV.Chandanasilpa.
NarayanaPharmacyCollege,ChinthaReddyPalem,Nellore
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ABSTRACT
Indoleisafusedaromaticheterocyclicring,consistingofasixmemberedbenzeneringfusedto
a fivemembered nitrogen containing pyrrole ring, Indole nucleus is present in compounds
involved in research aimed at evaluating new products that possess interesting biological
activities like antimicrobial, antiviral, antitubercular, antiinflammatory, anticancer,
antidiabetic,anticonvulsant,antimicrobial,antioxidant,antidepressantactivities.
Indole adalah cincin heterosiklik aromatik menyatu, yang terdiri dari cincin benzena
beranggota enam menyatu dengan nitrogen beranggota lima -mengandung cincin pirol, indol inti
hadir dalam senyawa yang terlibat dalam penelitian yang bertujuan untuk mengevaluasi produk
baru yang memiliki aktivitas biologis menarik seperti antimikroba, antivirus, antitubercular, antiinflamasi, antikanker, antidiabetes, antikonvulsan, antimikroba, antioksidan, kegiatan anti
depresan. Indole adalah komponen populer wewangian dan prekursor untuk obat-obatan banyak.
Key words: Indole, analgesic and antiinflammatory, anticancer, antifungal, antiviral,
antitubercular,antioxidant,antidiabetic.
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INTRODUCTION
ThesmallandsimpleIndolenucleusispresentincompoundsinvolvedinresearchaimedat
evaluatingnew products thatpossess interesting biologicalactivities likeantimicrobial,anti
viral,antitubercular,antiinflammatory,anticancer,antidiabetic,anticonvulsant,antimicrobial,
antioxidant, antidepresent, anticonvulsant activities. Indole is used primarily in industry and
research.Beinganaromaticfusedheterocycliccompoundconsistingofasixmemberedbenzene
ringfusedtoafivememberednitrogencontainingpyrrolering,indolefindsuseinresearchasa
startingmaterialforthesynthesisoflarger,usuallybioactivestructures[1].
ChemistryofIndole[1]:
MolecularformulaC8H7N,Molarmass117.15g/mol,Denisity1.1747g/cm3,solid,Meltingpoint
5254C, Appearance White solid, Boiling point 253 254C (526 K), Acidity (pKa) 16.2,
Bascityi(pKb)17.6.

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N
H
1H-indole
Fig.no.1Indole

Generalproperties[2]:
Indoleisasolidatroomtemperature.Itoccursnaturallyinhumanfecesandhasanintensefecal
odor.Atverylowconcentrations,however,ithasaflowerysmell,andisaconstituentofmany
flower scents (such as orange blossoms) and perfumes. It also occurs in coal tar. Indole
undergoes electrophilic substitution, mainly at position 3. substituted indoles are structural
elements of (and for some compounds the synthetic precursors for) the tryptophanderived
tryptaminealkaloidsliketheneurotransmitterserotonin,andmelation.Otherindoliccompounds
include the plant hormone Auxin (indole3acetic acid, IAA), the antiinflammatory drug
indomethacin, the betablocker pindolol, and the naturally occurring hallucinogen
dimethyltryptamine(N,NDMT).Thenameindoleisaportmanteauofthewordsindigodyeand
oleum,sinceindolewasfirstisolatedbytreatmentoftheindigodyewitholeum.
Basicity[4]:
Unlikemostamines,indoleisnotbasic,Thebondingsituationiscompletelyanalogoustothatin
pyrrole. Very strong acids such as hydrochloric acid are required to protonate indole. The
protonated form has an pka of 3.6. The sensitivity of many indolic compounds (e.g.
tryptamine)underacidicconditionsiscausedbythisprotonation
Methodology[5]:
ThemainindustrialroutesstartfromanilineIllustrativeofsuchlargescalesyntheses,indole
(andsubstitutedderivatives)formviavaporphasereactionofanilinewithethyleneglycolinthe
presenceofcatalysts

Ingeneral,reactionsareconductedbetween200and500 C.Yieldscanbeashighas60%.
Otherprecursorstoindoleincludeformyltoluidine,2ethylaniline,and2(2nitrophenyl)ethanol,
allofwhichundergocyclizations.Manyothermethodshavebeendevelopedthatareapplicable.
LeimgruberBatchoindolesynthesis[6]

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J.Chem.Pharm.Res.,2011,3(5):519523
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Itisanefficientmethodofsythesizingindoleandsubstitutedindoles.Originallydisclosedina
patentin1976,thismethodishighyieldingandcangeneratesubstitutedindoles.
FischerIndole Synthesis[7]: The most important synthesis of indole is the Fischerindole
Synthesiswhichhasbeeninvestigatedverywidely.TheFischerindolesynthesisiscarriedout
byheatingphenylhydrazoneorsubstitutedphenylhydrazoneofanaldehydeorketone.The
reactioniscatalyzedbyzincchloride,polyphosphoricacid,sulphuricacidorborontrifluoride
andproceedswitheliminationofamoleculeofammonia

Themostacceptablemechanismisgiveninfig.2.

Fig.2

Reactions[8]:
Electrophilic Substitution of Indole: The electron density of carbons in heterocyclic ring of
indole is higher due to contribution from nitrogen as in case of pyrrole. Therefore, the
heterocyclicringofindoleismorereactivetowardselectrophilescomparedtoitsbenzenering.
TheelectrophilicsubstitutioninindoletakesplaceatC3andnotatC2asinpyrrole.Thiscan
beexplainedfromthefollowingobservations.ElectrophilicattackatC2andC3givesdifferent
intermediatesasshownbelowfig.3

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Fig.3

ThecarbocationresultingfromelectrophilicattackatC2islessfavourablethanthecarbocation
resulting from electrophilic attack at C3 because though the former has more resonance
structures,inthelatterintermediate,thepositivechargeresidesonheterocyclicringcarbonor
thenitrogenatomwithoutaffectingthebenzenering[9].
PharmacologicalimportanceofIndole[10,11]:
Indolepossessthefollowingactivitiesthatisshowninfig.4

Fig.4

Applications:
Natural jasmine oil, used in the perfume industry, contains around 2.5% of indole. Since 1
kilogramofthenaturaloilrequiresprocessingseveralmillionjasmineblossomsandcostsaround
$10,000,indole(amongotherthings)isusedinthemanufactureofsyntheticjasmineoil(which
costsaround$10/kg).
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