Synthesis of C3-nitroalkylated-4-hydroxycoumarin and hydroxyiminodihydrofuroquinolinone derivatives

Tetrahedron67(2011)2870e2877

ContentslistsavailableatScienceDirect

Tetrahedron

journalhomepage:http://wendang.chazidian.com/lo

cate/tet

SynthesisofC3-nitroalkylated-4-hydroxycoumarinand

hydroxyiminodihydrofuroquinolinonederivativesviatheMichaeladditionofcyclic1,3-dicarbonylcompoundstob-nitrostyrenes

DeepakKumarBarange,VeerababuraoKavala,Chun-WeiKuo,Po-MinLei,Ching-FaYao*

DepartmentofChemistry,NationalTaiwanNormalUniversity,88,Sec.4,TingchowRoad,Taipei116,Taiwan,ROC

articleinfo

Articlehistory:

Received4November2010

Receivedinrevisedform28January2011Accepted22February2011

Availableonline26February2011

abstract

Herein,wedescribeapracticalandef?cientmethodfortheC3-alkylationof4-hydroxycoumarinbysonicationunder‘onwater’conditionsandmildtemperaturesusingvarioussubstitutedb-nitrostyrenes.Inaddition,wereportonthedevelopmentofaconvenientprocessfortheregioselectivesynthesisofangularhydroxyiminodihydrofuroquinolinonecatalyzedbybase.4-Hydroxycoumarinand4-hydroxy-1-methylquinolin-2(1H)-onereactedsmoothlywithvariousnitroole?nstofurnishC3-nitroalkylatedhydroxycoumarinderivatives(bysonicationand‘onwater’conditions)andhydroxyiminodihydrofur-oquinolinonederivatives(ambientcondition)asamixtureofZ(minor)andE(major)isomers,re-spectively.Themildreactionconditionsemployed,easeofisolationoftheproductsandexcellentyieldsconstituteimportantfeaturesofthemethodology.

Ó2011ElsevierLtd.Allrightsreserved.

1.Introduction

Ultrasoundirradiationiscommonlyusedinbothindustryandacademiaowingtothegreenvalueofharmlessacousticwaves.Sonochemistry1,2hasseveraladvantagesintermsofwastere-duction,http://wendang.chazidian.comanicreactionsinaqueousmediaor‘onwater’3,4haveattractedconsiderablerecentinterest,primarilybecauseofenvironmentalandsafetyissues.Theuseofwaterasasolventinsonochemistryisgoodcombinationfromthepointofviewofgreenchemistry.Therefore,todevelopagreenprotocolusing‘onwater’conditionsinconjunctionwithsonicationconditionwouldbehighlydesirable.

Coumarin5andfuroquinoline6scaffoldsarecommonlyfoundindiversenaturalproducts,biologicallyactivecompoundsandphar-maceuticals.Amongthevariouscoumarinderivatives,3-substituted-4-hydroxycoumarinhassigni?cantbiologicalproperties,whichin-cludeanti-HIV,anticancer,antibiotic,antiviralandanticoagulantsproperties.7Warfarin7f1andcoumatetralyl2areusedforpesticides,speci?callyasarodenticideandananticoagulant.

Warfarin1andC3-nitroalkylated4-hydroxycoumarin5havesomeresemblanceintermsoffunctionalgrouparrangement.OnexaminingthestructureofWarfarinandC3-nitroalkylated4-hydroxycoumarin5,itisclearthatbothpossessthesimilarbasic

*Correspondingauthor.Tel.:þ886229309092;fax:þ886229324249;e-mailaddress:cheyaocf@ntnu.edu.tw(C.-F.

Yao).

0040-4020/$eseefrontmatterÓ2011ElsevierLtd.Allrightsreserved.doi:10.1016/j.tet.2011.02.062

coreunitof4-hydroxycoumarin(Fig.2).Theonlydistinctionbe-tweenthesetwostructuresisthatthefunctionalitiesatC3aredifferent.Warfarinisananticoagulant,whichmaybeduetothepresenceofcoumarinandaketonegroup,whereasC3-nitro-alkylatedcoumarinalsocontainsacoumarinunitwithanaliphaticnitrogroupattheC3position,whichcouldbetransformedintoabiologicallyactivecompound.

Ontheotherhand,furoquinolinederivativesareanimportantclassofcompounds,becausetheybelongtotheknownfamilyoffuroquinolinealkaloids,whichpossessawidearrayofbiologicalproperties.8Amongthelinearandangularfuroquinolinones,an-gularfuroquinolinones8a,9(Fig.1,structure3and4)areofinterest,intermsoftheirsyntheticandbiologicalutilities.

TheMichaeladditionwithnitroalkenesisanimportantCeCbondformingreaction,whichprovideseasyaccesstosyntheticallyimportantnitroalkanes.Duringthelastdecade,ourgroupde-velopedseveralmethodologiesfortheMichaeladditionofnitro-alkenes10tovariousMichaelacceptors.Werecentlyreportedthatthereactionofnitroalkeneswithcyclic1,3-diketones6producedstereoisomerichydroxyiminodihydrobenzofurans7inthepresenceofsilicagelinmethanol11aundermicrowaveirradiationat60??Candtheuseof2-hydroxynaphthoquinone8resultedinthegenerationoftheMichaeladduct9under‘onwater’conditions(Scheme1).11bTheseresultsencouragedustoexaminethereactionofnitro-alkeneswithother1,3-diketones,suchas4-hydroxycoumarinand4-hydroxy-1-methylquinolin-2(1H)-one.ThereareseveralmethodsavailableforthesynthesisofC3-alkylated/substituted4-hydroxy-coumarin.12,13However,toourknowledge,thereisnodirectmethod

D.K.Barangeetal./Tetrahedron67(2011)2870e28772871

O O

1 2

O

Warfarin

Coumatetralyl

OH O Me 3 4

(+)-araliopsine

almeine

Fig.1.Biologicallyactivecoumarinandangularfuroquinolinonederivatives.

5

1

C3-nitroalkylated4-hydroxycoumarin

Warfarin

http://wendang.chazidian.comparisonbetweenwarfarin1andC3-nitroalkylated4-hydroxycoumarin5.

availablefortheC3-alkylationof4-hydroxycoumarinwithnitro-alkenes.Similarly,thesynthesisoflinearandangularfuro-quinolinonederivativescanbeachievedviaanumberofmethods.8a,9,14Saitoetal.reportedonthebasecatalyzedsynthesisofbenzofurans,buttheywerenotabletoisolatethecyclicoximein-termediate.15Ageneralmethodforthesynthesisofangularhydroxyiminodihydrofuroquinolinonehasnotbeenreportedtodate.Hence,inacontinuationofeffortstodevelopgreen,ef?cientandcatalyst-freemethodologies16usingnitroalkenes,wewishtoreporthereinonastudyofthereactionsofnitroalkeneswith4-hydroxycoumarinand4-hydroxy-1-methylquinolin-2(1H)-oneun-derdifferentconditions.

Scheme1.Ourprevioussyntheticapproachesusingnitroalkeneswithcyclic1,3-di-carbonylcompounds.

2.Resultsanddiscussion

Inordertoinitiallyassessthereactivityof1,3-dicarbonylcom-pounds,weexaminedthereactionof4-hydroxycoumarin10(1equiv)andnitrostyrene11a(1.2equiv)at30??CusingEt3Nasabasiccatalystinmethanol(Table1,entry1).Unfortunately,noproductswereobtained.Inthenextexperiment,weused‘onwater’conditionsat30??C,whichwasalsoresultedinnoproduct(entry2).Whenthereactiontemperaturewasincreasedto80??C,weweredelightedtoobtaintheMichaeladduct12ain40%yield(entry3).

Table1

OptimizationofreactionconditionforC3-alkylationof4-hydroxycoumarin

NO2+

2

Ph

OTemp,Time

O

10

11a

12a

Entry

SolventTemp(C)Time(h)Yield(%)1cMethanol3012n.d.2Water3012n.d.3Water8012404d

Water

30

4

95

n.d.¼notdetected.a

Allthereactionswerecarriedoutusing10(1.0equiv)and11a(1.2equiv)on1.0mmolscale.b

Yieldsweredeterminedfromcrude1HNMRspectrumusingtolueneasaninternalstandard.c

Et3Nusedasabase(5mol%).d

Sonication

condition.

However,thebestyieldwasobtained,whenthereactionwasperformedunder‘onwater’conditionsusingsonicationandtheseconditionswerechosenforfurtherstudy(entry4).Thestructureof12awascon?rmedby1H,13CNMRanditsMassspectrum,andwasfurthersupportedbyX-raycrystallographicanalysis(Fig.3).

Fig.3.X-raycrystalstructureof12a(ORTEPdiagram).18

Toexplorethescopeandlimitationsofthismethodology,weexaminedthereactionof4-hydroxycoumarin10withvariousnitroalkenes11aenundertheoptimizedreactionconditionsandtheresultsaresummarizedinTable2.

Asindicated,theMichaeladditionofb-nitrostyreneswith4-hydroxycoumarinswasef?cientinallthecasesaffordingthecorrespondingC3-nitroalkylated-4-hydroxycoumarinderivatives12aeninexcellentyields(83e94%).Substituents,suchasmethyl(entry2),methoxy(entries3e5),chloro,?uoro,tri?uoromethylandnitrogroups(entries6e11)onthebenzeneringofnitroalkeneswerewelltoleratedunderthepresentreactionconditions.TheC-alkylationof4-hydroxycoumarinwasdirectedbyelectronicfac-torsassociatedwiththeb-nitrostyrenes.Thereactiontimevariedaccordingtothenatureofthesubstituentontheb-nitrostyrene.Forexample,theconjugateadditionof4-hydroxycoumarintoab-ni-trostyrenecontainingelectron-donatinggroups(OCH3andCH3)requiredalongerperiodoftimeforcompletionofthereaction(entries2e5).Whileelectron-withdrawinggroups(Cl,F,CF3,NO2)requiredrelativelyshortreactiontime(entries6e11).4-Substitutednitroalkenesaffordedgoodyieldsandrequiredlesstimecomparedto2-substitutednitroalkenes.Furthermoreacidsensitivesub-stituents,suchasfuranandthiophenegroupssurvivedunderthepresentreactionconditions,affordingexcellentyields(entries12and13).Interestingly,thesereactionconditionswereequallyef?-cientforthestericallyhindered(E)-2-(2-nitrovinyl)naphthalene

2872

D.K.Barangeetal./Tetrahedron67(2011)2870e2877

Table2

Synthesisof3-substituted4-hydroxycoumarinderivatives

NO+

2

O

ArNO2

30oC,Time

OO10

11a-n

))),12a-n

EntryArProductTime(h)Yield

(%)112a690

212b1092

3

12c

14

83

412d1287

512e1194

6

12f

10

84

712g

985

812h8

94912i891

1012j994

11

12k

10

96

12

12l14851312m1488

14

12n

16

85

a

Allreactionswerecarriedoutusing10(1.0equiv)and11(1.2equiv)ona2.0mmolscaleundersonication‘onwater’conditions.b

Isolated

yields.

derivative,affordingthecorrespondingMichaeladductingoodyield(entry14).Alloftheproductsobtainedwerecharacterizedby1

HNMR,13CNMR,MassandIRspectroscopictechniques.

WeassumedthattheMichaeladditionofnitrostyreneswith4-hydroxycoumarinwouldproceedviathesamemechanisticpathwayaswasdescribedforthereactionof2-hydroxynaph-thoquinonewithnitroalkenes.11bInordertocon?rmthemecha-nismweexaminedtheMichaeladditionof4-hydroxycoumarin10withtheb-nitrostyrene11binD2Oundersonicationusingtheoptimizedconditions.Thisreactionaffordeda94%yieldof12b*asadeuteratedproduct.Acomparisonofthe1Hand13CNMRspectraofthedeuteratedandnondeuteratedcompounds,onedoubletofdoubletin1HNMRspectrumat5.14(indppm)appear,whichisduetothepresenceofadeuteriumatomatthe2-position.Whereas,inthecaseofthenondeuteratedcompoundonedoubletandonetripletappearedat5.40and5.22(indppm),respectively.Inthe13Cspectrumofthedeuteratedcompoundonetripletwasobservedat76.3(indppm)while,inthecaseofthenondeuteratedcompound,onlyonesingletwasobserved.Acomparisonof1HNMRand13CNMRspectraofdeuteratedproduct12b*andnormalproduct12bcanbeseeninScheme2,whichindicatesthattheoriginoftheprotonisfromwater.

Scheme2.Reactionof4-hydroxycoumarinand(E)-1-methyl-4-(2-nitrovinyl)benzeneinD2O/H2Oundersonicationat30??C.

TheD2Oexperimentsupportstheconclusionthatthisreactionfollowsthemechanismconsistentwiththatproposedinourpre-viouslyreportedstudy.11b

Encouragedbythepresentresults,wereplacedthe4-hydroxycoumarinunitwithanN-methyl-4-hydroxyquinolinonemoiety,inordertoevaluatethereactivityofother1,3-dicarbonylcompounds.Weinitiallycarriedoutthereactionof4-hydroxy-1-methylquinolin-2(1H)-one13with(E)-(2-nitrovinyl)benzene11aundersonication‘onwater’conditions.Asexpected,wewereun-abletoisolatetheMichaeladductfromthisreaction.TheMichaeladductunderwentcyclizationundersonication‘onwater’condi-tionstoaffordtheZ:Eisomerofhydroxyiminodihydrofur-oquinolinoneinaratioof1:1with40%ofyield(Table3,entry1).Wefurtherproceededtooptimizethereactiontoattainsuitableconditionsusingthereactionof(E)-(2-nitrovinyl)benzene11aand4-hydroxy-N-methylquinolinone13asamodel.

Table3

Optimizationofreactionconditionsforthesynthesisofhydroxyiminodihy-droquinolinonederivatives

NOH

O

NO2Catalyst(acidorbase)

Ph

NO

+

Ph

NOCH3Time

CH13

11a

315a

EntrySolventsAcid/BaseTemp(C)Time(h)Yields,(%)Selectivity(Z:E)1bWaterd3012301:12Waterd8012101:13dMeOHEt3N301801:94dMeOHK2CO3302781:95fMeOHDIPEA301921:406dMeOHDABCO301801:47dMeOHSilicagel30251:18dMeOHTFA3012n.d.n.d.9dMeOHPTSA

3012n.d.n.d.10d

MeOH

NH2SO3H

30

12

n.d.

n.d.

n.d.¼notdetected.a

Allthereactionwerecarriedoutbyusing13(1.0equiv)and11a(1.2equiv)on1.0mmolscale.b

Sonicationcondition.c

Calculatedbasedoncrude1HNMR.d

20mol%ofacidorbaseused.e

Basedoncrude1HNMRyieldusingtolueneasaninternalstandard.f

10mol%ofDIPEAused.

Whenthereactionwasperformedinwaterat80??C,only10%oftheproductwasobtainedin12h(Table3,Entry2)witha1:1se-lectivityofZ:Eisomers.Whenwenextchangedthesolventfromwatertomethanolandthereactionwasperformedat30??Cusing

D.K.Barangeetal./Tetrahedron67(2011)2870e28772873

Et3N/K2CO3,asubstantialimprovementintheyieldandselectivity(1:9)ofZ:Eisomers(entries3and4)wasobserved.Theproductyieldwasdrasticallyincreasedto92%,whenDIPEA(N,N-diisopro-pylethylamine,Hunig’sBase)wasused,withexcellentselectivity(1:40)ofZ:Eisomers(entry5).Nosigni?http://wendang.chazidian.comingsilicagelonly5%ofproductwasobtainedwithpoorselectivityofZ:Eisomers(1:1).Otheracidcatalyst,suchasTFA,PTSAandNH2SO3Hwereineffectiveforthisconversion.

Afterhavingestablishedtheoptimizedreactionconditionsfortheformationofhydroxyiminodihydrofuroquinolinones,weexploredthegeneralityandscopeofthiscyclizationprocess.Thus,4-hydroxy-N-methylquinolinone13wasreactedwithavarietyofnitroalkenes14undertheoptimizedconditionsandtheresultsaresummarizedinTable4.AscanbeseenfromTable4excellentyields(82e92%)ofthedesiredhydroxyiminodihydrofuroquinolinone15wereobtained.

Table4

Synthesisofangularhydroxyiminodihydrofuroquinolinonederivatives

OHH

O

Ar

+

Ar

NO2O

14a-g

MethanolO

CH3rt,Time

CH313

15a-g

EntryArProductTime

(h)Yield(%)Z:ESelectivity(%)

115a1891:40

215b1881:40315c2

831:40

4

15d

2

87

1:40

5

c

15e0.5821:9

6c

15f2841:9

7c

15g3851:9

a

Allreactionswerecarriedoutbyusing13(1.0equiv)and14(1.2equiv)on1.0mmolscale.b

Isolatedyields.c

Twoisomerswereinseparable.d

Z/Eselectivitywasestimatedbycrude1HNMRdetermination.

AsindictedinTable4,allofthenitroalkenestestedreactedsmoothlywith4-hydroxy-N-methylquinolinoneunderthepresentreactionconditions,affordingthecorrespondingproductinexcellentyields.Electroniceffectsplayasigni?cantroleinreactionsofaro-maticnitroalkenes.Thereactiontimedependsonthenatureofthesubstituentsonthebenzeneringofb-nitrostyrenes.Forexample,thereactioninvolvingelectronrichnitrostyrenederivatives(4-CH3,4-OCH3,3,4-OCH3)requiredalongerperiodoftimeforcompletionofthereactionandaffordedZandEisomersinaratioof(1:40).Whilethereactionofnitrostyrenesbearingelectron-withdrawinggroups(2,6-Cl)proceededsmoothlywithinashortreactiontimetogeneratethecorrespondinghydroxyiminodihydrofuroquinolinonede-rivativesingoodyields,withZ:Eratioof1:9.Stericallyhinderednitroalkenes,suchas(E)-2-(2-nitrovinyl)naphthalenerequiredmoretimeforcompletionofthereaction(entry7)toaffordthe

correspondingoximeproducts.ItisnoteworthythatweobtainedaninseparablemixtureofE:Zisomers.TheZisomercouldnotbeisolatedinpureform,frommixtureofEandZisomers(entries5e7)sincethesolubilityofthemixtureswasverypoor.However,itshouldbenoted,thatthemixtureunderwentaslowisomerizationofEisomertoZisomeruponheating.

Theproductassignmentwascarriedoutbasedona1HNMRspectrumofthecrudemixtureofZandEisomers.TheC3-methineprotonsignalin1HNMRpermitstheEandZisomerstobeiden-ti?ed.TheC3proton1HNMRsignalfor(Z)isomersappearedinanup?eldregioncomparedtothe(E)isomer,whichappearedmoredown?eld.Similarly,chemicalshiftsfortheC]NeOH(oxime)protonalsoprovidearoutetodistinguishbetweentheZandEisomers.TheC]NeOH(oxime)protoninthe1HNMRforthe(Z)isomerwasdown?eldcomparedtotheanalogousprotonforthe(E)isomer,whichappearedatanun?eldregionindppm.Thisisingoodagreementwithliteraturereports.17The1HNMRchemicalshiftsfortheC]NeOH(oxime)andC3-methine(CH)protonfortheZandEisomersareshowninTable5.

Table51

HNMRchemicalshifts(indppm)fortheC]NeOH(oxime)andmethine(CH)protonsignalsforZandEisomers

HO

NNOHO

O

R

R

NO

NO

CH3

CH3

(Z)isomer(minor)

(E)isomer(major)

EntryR

C]NeOH,Methine(CH),C]NeOH,Methine(CH),(Zisomer)(Zisomer)(Eisomer)(Eisomer)1C6H5

dd10.325.4024-CH3eC6H4dd10.285.3434-OCH3eC6H4dd10.275.3443,4-OCH3eC6H3dd10.315.3552,6-CleC6H310.596.1410.316.1962-OCH3eC6H410.365.4010.015.487

2-Naphthyl

10.62

5.50

10.32

5.58

TheprotonsignalfortheZisomericoxime(C]NeOH)appearedinamoredown?eldregioncomparedtotheEisomericoximeproton,duetointramolecularhydrogenbondingbetweentheOHoftheoximegroupandtheoxygenofthefuranringofZ-hydroxy-iminodihydrofuroquinolinone.ThisalsodistinguishestheZisomerfromitscounterpartEisomerandwasinagreementwithobser-vationsreportedintheliterature(Fig.4).17b,c

NNOCH3

CH3

Zisomer

Eisomer

IntramolecularhydrogenbondingNohydrogenbonding

Fig.4.HydrogenbondingintheZisomerofhydroxyiminodihydrofuroquinolinone.

ThestructureoftheEisomerofhydroxyiminodihydrofuro-quinolinonewasunambiguouslycon?rmedbysinglecrystalX-rayanalysisof15ashowninFig.5.18

AplausiblemechanismfortheformationoftheproductisshowninScheme3.Initially,4-hydroxy-N-methylquinolinone13

2874D.K.Barangeetal./Tetrahedron67(2011)2870e2877

Fig.5.X-raycrystalstructureof15a(ORTEP

diagram).

Scheme3.RegioselectiveformationofAngularhydroxyiminodihydrofuroquinolinonederivatives.19

undergoesC-alkylationwithb-nitrostyrenestogiveintermediateII,whichwouldenolizetoformintermediatesIIIaandIIIbunderbasicconditions.Thisintermediatethenproceedsfurtherbasedonthereactivitypatternofthecarbonylgroup.Therearetwopossi-bilitiesforintramolecularcyclization.Theseintermediatescancy-clizewhentheC]NO2Hisplacedattherightpositionbyfreerotationofthesigmabond,andhencecontrolstheregioselectivityofthereaction.PathwayAcouldaffordthelinearhydroxy-iminodihydrofuroquinolinoneIV,whichwasnotobservedunderthepresentconditions.WhilepathwayBproceedsthroughanintramolecularcyclizationtoaffordintermediateV,whichisthenprotonated,undergoesdehydration,followedbynitroso-oximetautomerizationtofurnishtheangularhydroxyiminodihydrofuro-quinolinonederivatives.Thepossibilityofformingotherproducts,suchas15(i),15(ii)and15(iii)wasnotobservedunderthepresentprotocol.

3.Conclusion

Insummary,wereportonthedevelopmentofasimpleandef?cientmethodfortheC-alkylationof4-hydroxycoumarinde-rivativesundersonication‘onwater’conditionsusingvarioussubstituted(phenylandheteroaryl)b-nitrostyrenes.Angularhydroxyiminodihydrofuroquinolinonederivativeswerealsosyn-thesizedinaregioselectivemannerundermildconditionsatroomtemperature.Operationalsimplicity,inexpensivereagentsandgoodproductyieldsarethekeyadvantagesofthepresentprotocol.Furtherworkisinprogresstoextendthescopeofthismethodology

forthesynthesisofmorecomplexstructuresandstudiesofthebiologicalactivityofthesecompoundsareunderway.4.Experimental4.1.General

Allreactionswereperformedinoven(130??C)driedglasswareunderaninertatmosphereofargonunlessotherwisespeci?ed.Solventsforextractionandchromatographyweredistilledbeforeuse.Allchemicalsusedinthisstudywereofcommercialgradeandweredistilledpriortouse.AnalyticalthinlayerchromatographywasperformedwithE.Mercksilicagel60F254aluminumplates.Allpuri?cationswerecarriedoutby?ashchromatographyusing230e400meshsilicagel.1Hand13CNMRwererecordedwithaBrukerAdvanceEX400FTNMRinstrument.Chemicalshiftsarereportedinpartspermillion(d)usingTMSastheinternalstandardandcouplingconstantsareexpressedinhertz.MassspectrawereobtainedonaJOELSX-102Aspectrometeratanionizationpotentialof70eVanddataarereportedasmass/charge(m/z)withthepercentrelativeabundance.High-resolutionmassspectra(HRMS)wereacquiredwithaFINNIGANMAT-95XLspectrometer.There-actionswerecarriedoutinathermostated(30Æ1??C)ultrasoniccleaningbath(BransonUltrasonics,UltrasonicbathModel3010R-DTH)at50kHzfrequency.Theultrasoniccleaningbathhadanoutputof100Wandapowersupplyof335W.4.2.GeneralprocedurefortheC-alkylationof4-hydroxycoumarin

Amixtureof4-hydroxycoumarin(10)(1mmol)andb-nitro-styrene(11)(1.2mmol)wassuspendedin5mLofwaterina20mLvial.Thevialwasplacedintotheultrasonicbath(BransonUltra-sonics,UltrasonicbathModel3010R-DTH,50kHzfrequency)at30??Cforthespeci?ctimementionedinTable2.TheprogressofthereactionwasmonitoredbyTLC.Aftercompletionofthereaction,theresultingsolidproductwas?lteredandwashedwithwater(2Â10mL)andn-hexane(5Â10mL).Thensolidwasdriedundervacuumtoobtaintheproduct(12aen)inalmostpureforminexellentyields(83e94%).

4.3.Generalprocedureforthesynthesisof

hydroxyiminodihydrofuroquinolinonederivatives

Amixtureof4-hydroxy-N-methylquinolin-2(1H)one(13)(1mmol)andb-nitrostyrene(14)(1.2mmol)dissolvedin3mLofmethanol.Tothissolution,10mol%ofDIPEAwasaddedandthereactionmixturewasstirredatroomtemperatureforthetimein-dicatedintheTable4.TheprogressofthereactionwasmonitoredbyTLC.Aftercompletionofthereaction,waterwasadded,theresultingsolidproductwas?lteredandwashedwithwater(2Â10mL)andn-hexane(5Â10mL).Thensolidwasdriedunderavacuumtogivetheproduct(15aeg)asamixtureofZandEiso-mersofangularhydroxyiminodihydrofuroquinolinoneinexellentyields(82e92%).4.4.Spectraldata

4.4.1.4-Hydroxy-3-(2-nitro-1-phenylethyl)-2H-chromen-2-one(12a).Whitesolid;mp:158e160??C.FT-IR(KBr)n/cmÀ13440,1701,1607,1550,1378.1HNMR(400MHz,DMSO-d6)d8.01(d,J¼8.0Hz,1H),7.63(t,J¼7.8Hz,1H),7.41e7.36(m,4H),7.31(t,J¼7.3Hz,2H),7.23(d,J¼7.0Hz,1H),5.46(dd,J¼14.2,8.2Hz,1H),5.43(dd,J¼8.2,6.8Hz,1H),5.28(dd,J¼14.2,6.8Hz,1H).13CNMR(100MHz,DMSO-d6)d162.0,161.9,152.2,138.9,132.4,128.4,127.5,127.0,124.0,123.6,116.3,115.8,104.1,76.5,38.5.MS(ESI)(m/z)(relativeintensity)

334