SyntheticCommunicationsReviews

STUDIESONQUINOLINEDIONE:SYNTHESIS,

REACTIONS,ANDAPPLICATIONS

WafaaS.Hamama,AlaaEl-DinE.Hassanien,and

HanafiH.Zoorob

ChemistryDepartment,FacultyofScience,MansouraUniversity,Mansoura,Egypt

GRAPHICALABSTRACT

AbstractInthisaccountwepresenttherapidlyexpandingbibliographyofpublishedresearchconcerningtheprogressintheareaofquioline-2,4-dionechemistry,includingsyntheticstrategies.

KeywordsQuinolone;reactionapplication;synthesis

INTRODUCTION

Quinolonederivativesconstituteanimportantclassofnitrogen-containing

heterocyclesthathavewithdiverseusefulbioactivities.Theyarewidelyusedas

keyintermediatesinthepreparationofsomenaturalproductsandrelatedstructures.

Abroadnumberoffascinatingpharmacologicalactivitieshavebeenassociatedwith

2-quinolinonederivatives.ThequinolinonealkaloidsisolatedfromtheRutaceae

familyofplants(Fig.1)havebeenshowntoexhibitavarietyofbiologicalproperties.

Thecorrespondingcompoundsexhibitsimilarproperties,suchasantibacterial,

antifungal,andantivirial.[1,2]

Onthebasisofthebiologicalevaluation,4-hydroxyquinolonesconstitutean

importantareaofresearchbecauseoftheiruseasanalgesics,dyestuffs,herbicides,

orallyactiveantagonists,andanti-inflammatory,antiallergenic,antitubercular,and

cardiovascularagents.[3–6]

ReceivedNovember12,2013.AddresscorrespondencetoWafaaS.Hamama,ChemistryDepartment,FacultyofScience,MansouraUniversity,El-GomhoriaStreet,ET-35516Mansoura,Egypt.E-mail:wshamama@yahoo.comSyntheticCommunications1,44:1833–1858,2014Copyright#Taylor&FrancisGroup,LLCISSN:0039-7911print=1532-2432onlineDOI:

10.1080/00397911.2013.867352

18334-Hydroxyquinolinesareimportantsynthonesandtheyareusedassynthetic

precursorsofmanynaturallyoccurringalkaloids,polycycliccondensedheterocycles,

multiazahetrocycles,isoxazoloquinolines,pyranoquinolines,piperazinylcarbomides,

pyrazoloquinolines,andoxazinoquinolines.Thesederivativesareusedaspotent

antiemetic,migraine-suppressing,antibacterial,fungicidal,antipyretic,anticoagulant,

CNS,andmemoryenhancingagentsandhaveshownanti-brain-tumoractivity

invivo.[3]

SYNTHESISOFQUINOLIN-2,4-DIONEDERIVATIVES

ReactionofAmineDerivativeswithAcidDerivatives

4-Hydroxy-2(1H)quinolinonederivatives1havebeensynthesizedfromthe

correspondingmethylN-(a-haloacyl)anthranilates(2)inthepresenceofsodium

telluride[7](Scheme1).

Biginellireactionofthederivativesof2-chlorobenzaldehyde,ethylaceto-

acetate,urea,orthioureaderivativesinthepresenceofboricacidafforded

ethyl-4-phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates(3)or

4-phenyl-6-methyl-2-thia-1,2,3,4-tetrahydropyrimidine-5-carboxylates(4).These

compoundsundergocyclizationwithammoniaunderpressuretogive5and6[8]

(Scheme

2).Figure1.Naturallyoccurringquinolonealkaloids.1834W.S.HAMAMA,A.E.-D.E.HASSANIEN,ANDH.H.ZOOROBOtherHeterocyclicCompounds

Condensationof1H-benzo[d][1,3]oxazine-2,4-dione(isatoicanhydridederiva-

tives)withmethylcyanoacetateinthepresenceofNaHafforded3-cyano-4-

hydroxylquinoline-2-one(7).[9]Condensationwithethylnitroacetateinthepresence

ofEt3Ngave4-hydroxyl-3-nitro-2-quinolonederivatives8.[10]Compound8can

besynthesizedfromisatoicanhydridederivativesviaringopeningbyanhydrous

MeOHinNaOHtogive9,whichisacetylatedbyaceticanhydridetoafford10.

Cyclizationofcompound10withpotassiumbis(trimethylsilyl)amide[KN(SiMe3)2]

inthepresenceofanhydroustetrahydrofuran(THF)gavecompound1,which

wasnitratedby70%HNO3tofurnishcompound8.[10]Condensationofisatoic

anhydridederivativeswithdiethylmalonateoritssodiumsaltunderbasic

conditionafforded1viatheCoppolamethod.[11]Treatmentofisatoicanhydride

derivativeswithethylacetoacetateinthepresenceofpostassiumt-butoxide

andt-butanolgave3-acetylquinolones11[12](Scheme

3).Scheme1.Synthesisof4-hydroxy-2(1H)quinolinonederivatives.

Scheme2.Synthesisofethyl-4-phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine.CHEMISTRYOFQUINOLINEDIONE1835Thereactionofbenzylaminewithcompound12[thatformedfromthereaction

ofisatinwithmethylacrylatederivativeinthepresenceof1,4-diazabicyclo[2.2.2]-

octane(DABCO)atroomtemperature]affordedtricyclic-2-benzyl-9b-hydroxyl-3,3a,

5,9b-tetrahydro-2H-pyrrolo[3,4-c]quinoline-1,4-diones(13)[13](Scheme4).

Hydrolysisof2,3-dioxo-1,2,3,4-tetrahydroquinolin-3-ylthiocyanate(14)afforded

4-hydroxy-2-quinolonederivative1[14](Scheme5).

Condensationofmethyl2-aminobenzoatederivativewith2-phenyl-

propanoicacidderivativesgavecompound15.Cyclizationof15bylithiumbis

(trimethylsilyl)amide(LiHMDS)affordedquinolone-2,4-dionederivatives16[15]

(Scheme

6).Scheme3.Reactionofisatoicanhydridederivativeswithdifferentreagents.1836W.S.HAMAMA,A.E.-D.E.HASSANIEN,ANDH.H.ZOOROB