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Applied Catalysis A: General
j o ur na l h o me pa g e :w w w . e l s e v i e r . c o m / l o c a t e / a p c a t a
New insight on the mechanism of the catalytic hydrogenation of nitrobenzene to 4-aminophenol in CH
3CN–H
2O–CF
3COOH as a reusable solvent system. Hydrogenation of nitrobenzene catalyzed by precious metals supported on carbon
GiuseppeQuartarone,LucioRonchin∗,AliceTosetto,AndreaVavasori
DepartmentofMolecularSciencesandNanosystems,UniversityCa’FoscariofVenice,Dorsoduro2137,30123Venezia,Italy
a r t i c l e i n f o
Articlehistory:
Received14November2013
Receivedinrevisedform9January2014 Accepted13January2014
Availableonline22January2014
PaperdedicatedtoProf.LuigiToniolofor celebratinghislongresearchandteaching activityinthefieldofCatalysisand IndustrialChemistryafterhismandatory retirement.
Keywords:
Nitrobenzenehydrogenation 4-aminophenol
Trifluoroaceticacid Reusablesolvent Hydrogenationmechanism
a b s t r a c t
Thepreparationof4-aminophenolvia hydrogenationofnitrobenzeneinasingle liquidphase has beencarriedinthepresenceofdifferentpreciousmetalcatalysts. Theliquidphaseiscomposedof CH3CN–H2O–CF3COOH,whichcanbeeasilydistilledatlowtemperature,thusavoidingwork-upopera- tion.Theyieldof4-aminophenolisintherange45%andinthepresenceofsulfolaneaspromoterreaches almost50%.ThebestresulthasbeenobtainedinthepresenceofPt/Cashydrogenationcatalyst.Therole ofthesolventisstrictlyrelatedtotheselectivityto4-aminophenol,sinceCH3CNdecreasesthehydro- genationactivitycomparedtoothersolvent,CF3COOHpromotestheformationofthedesiredproduct bothviaBambergerrearrangementinsolutionaswellbyasurfacecatalyzedreaction,whileH2Ois responsiblefor4-aminophenolformationinbothreactions.Eventhough,nitrosobenzeneandphenylhy- droxylaminehavenotbeenobserved,theirreactivitysuggestacomplexpatternofreactionsoccurring eitheronthecatalystsurfaceorinthesolution.Indeed,formationof4-aminophenolmayoccurbothin solution,viaacidcatalyzedBambergerrearrangementandonthecatalystsurfacebytheformationofa surfacePt-nitreniumcomplex,whichundergoessurfacenucleophilicattackbyH2O.
©2014ElsevierB.V.Allrightsreserved.
1. Introduction
4-Aminophenolisanimportantrawmaterialforseveralprod- ucts in the field of dyes, polymer and pharmaceutics [1–3].
For instance,paracetamol(N-acetyl-4-aminophenol)is awidely employedanalgesicandantipyreticwhoseproductionisincon- tinuousgrowth,particularlyintheFarEastregion[4–9].Industrial synthesis of paracetamol is based on 4-aminophenol, which is obtainedthroughfourdifferentroutes:(i)nucleophilicsubstitu- tionofthechlorineofthe4-chloronitrobenzene,(ii)reductionof 4-nitro-phenol,(iii)selectivehydrogenationofnitrobenzene,(iv) Beckmannrearrangementof4-hydroxyacetophenoneoxime.
Tillnow,theselectivehydrogenationofnitrobenzeneislikely tobethemostconvenientfrombotheconomicalandenvironmen- talpointofview[1,2,4–9].Themajorconcernofthisprocessis, however,theuseofH2SO4,whichposescorrosion,safety,purifi- cationand environmentalproblems.The reactioniscarried out
∗ Correspondingauthor.
E-mailaddress:ronchin@unive.it(L.Ronchin).
incontinuousstirredtankreactorinwhichthebiphasicreaction medium is usedtoaccomplish simultaneouslythePtcatalyzed hydrogenationofnitrobenzeneandtheacidcatalyzedBamberger rearrangementoftheintermediateN-phenylhydroxylamine(see Scheme1) [4–6,8,9]. Theaqueous solutionof H2SO4 is thekey for obtaining high selectivity to the 4-aminophenol. The suc- cessisdue totheeasyprotonationofthephenylhydroxylamine (pka=1.9 [10]), which is extracted from the organic phase. In the acidsolution (H2SO4 concentration 0.6–1molL−1), the sul- fateof theN-phenylhydroxylamine is formed and itundergoes fastrearrangementtothecorresponding4-aminophenolsalt[11].
Moreover,inaqueousphase,thecompetitivehydrogenationofthe phenylhydroxylamineisnegligible,beingthehydrogenationcata- lysthydrophobic.Infact,onlythefractionpresentintheorganic phaseishydrogenatedtoaniline[12].
Fromanenvironmentalpointofview,themajordrawbackof theprocessistheneutralizationoftheacidicphase,withthecon- sequentby-production ofsulfatesalts,whichareundesiredlow values productsand/orwastes.In addition,dilutedsulfuricacid causes huge corrosion concern, with theconsequent increased costs[1,2,4–6,8,9].
http://dx.doi.org/10.1016/j.apcata.2014.01.033 0926-860X/©2014ElsevierB.V.Allrightsreserved.
NO2
NHOH NH2
H2 Pt/C
aqueous H2SO4
H+
organic phase Pt/C
H2
NH2OH H+
NH3 HO
Scheme1. Hydrogenationofnitrobenzeneinbiphasicliquidsystem.
Therefore,removalofH2SO4useislikelytobethemostimpor- tanttargetfortheimprovementoftheprocess.Severalresearchers haverecentlyproposedtheuseofabiphasicliquidsystem(water- nitrobenzene)employingPtsupportedonsolidacidinthepresence ofsurfactantandpromoters,which,however,causeproblemsinthe recycleand/ordisposaloftheaqueousphase[13–15].
Besides,gasphasereactioncatalyzedbybifunctionalPt-zeolites catalystshasbeenproposed.Theyieldstothe4-aminophenolare interestingforpracticalpurposes,howeverextensivecatalystdeac- tivationlimitsitssyntheticutility[16].
Startingfromtheseconsiderations,asingleliquidphaseprocess couldbeacatwalktoamoresustainableprocessbyusingeasily reusablesolventsandcatalysts[17–20].Whenproductsaresolids orhighboilingpointliquidstheuseofamuchlowerboilingpoint solventcanbethekeytoimprovetheenvironmentalsustainability ofthewholeprocess,becauseofproductsseparation,catalystand solventsreuseismadeeasybyfiltrationandevaporation.Inthis way,thehighcostofCF3COOHiscounterbalancedbyitsrecycling, makingtheprocesssustainablealsofromaneconomicalpointof view.
ThebasesofthepresentresearcharetheresultsintheBeck- mannrearrangementofketoximestothecorrespondingamidesin CH3CN–CF3COOHassolventcatalyticsystem[17–20].Theanalogy between the Beckmann rearrangement with the process to 4- aminophenolvianitrobenzenehydrogenationoriginatesfromthe ideathattheN-phenylhydroxylamine(theintermediateofthepro- cess)(seeScheme1)mayundergoacidBambergerrearrangement veryeasilyinnon-aqueousCF3COOHsystem.
The rearrangement is well known from long time and the commonlyacceptedmechanismisvianitreniumionintermedi- atefollowedbynucleophilicattackofawatermolecule(Scheme2) [11,21,22].
Several solvents can be used for the hydrogenation reac- tion, but those to be considered in this research possess low nucleophilicityinordertoavoidsidereactionintheBamberger rearrangement[21,22].Inaddition,suitablesolvents(forinstance CH3CNand(CH3)2SO)havetolowerthehydrogenationactivityof
thepreciousmetalcatalystinordertodepressthereductionof N-phenylhydroxylaminetoaniline[23].
Here,we presentsomenewresultsonthehydrogenationof nitrobenzeneto4-aminophenolinasingleliquidphasecomposed ofsolvent-H2O–CF3COOHandin thepresencea preciousmetal hydrogenationcatalyst.Furthermore,weproposeareactionpath, whichallowsanexplanationfortheseveralfeaturesofthisreaction.
2. Experimental 2.1. Materials
Nitrobenzene,aniline,4-aminophenol,2-aminophenol,trifluo- roacetic acid, sulfolane were all Aldrich products, their purity werecheckedbytheusualmethods(meltingpoint,TLC,HPLC,GC andGC–MS)andemployedwithoutanypurification,acetonitrile HPLCgradientgradewassuppliedbyBDH,1,4-dioxane,methanol, nitromethane,dimethylformamideanddimethylsulfoxideareACS reagentsuppliedbyAldrich.
CatalystsusedwerecommercialmaterialssuppliedbyEngel- hard(nowBasfCatalysts):Pd/C5%:Escat10,Pt/C3%,Ru/C5%Escat 40andRh/C5%.
2.2. Equipment
Products were identified by gas chromatography (GC), gas chromatography coupledmassspectrometry (GC–MS)and high performanceliquidchromatography(HPLC).GCandGC–MSanal- ysiswerecarriedoutwithaAgilent7890AequippedwithFIDor MSdetector(Agilent5975CandaHP5column(I.D.320m30m long),heliumwasemployedascarrierunderthefollowingcondi- tions:injector523K,detector543K,flow1mLmin−1,oven333K for3min523K15Kmin−1and523Kfor15min.Duetothether- malinstabilityoftheproducts,routineanalysiswerecarriedout byHPLC(PerkinElmer250pump,LC235diodearraydetectorand aC8,5m,4mmi.d.25cmlongcolumn)analysiswerecarried outwithCH3CN–H2Oasmobilephaseinisocratic70%ofCH3CN at1mLmin−1.Conversionyieldandselectivityarecalculatedby thecalibrationwithstandardsolutionsofthepureproducts.N2
physisorptionandCOchemisorptionhasbeencarriedoutwitha MicromeriticsASAP2010Cautomaticadsorptionanalyzer.
2.3. Catalystcharacterization
Chemisorptionofcarbonmonoxidewascarriedat308Kwith thedoubleisothermmethodand1minofequilibrationtime[24].
Thechemisorptionstoichiometrywasset1(1moleculeofCOfor 1 surface atomof metal) only for comparativepurpose. Before theanalysis,thecatalyst waspretreated in a flow ofhydrogen (20mLmin−1)at473Kfor3handfor5hundervacuumatthesame temperatureinordertoensuretotalreductionofthepreciousmetal particlesaveragediameterofcatalystparticles(40m)andappar- entdensity(0.54gmL−1)weregivenbythesupplierandarethe sameforallthecatalysts(seeTable1).
2.4. Hydrogenationofnitrobenzene
Somepreliminaryreactionshavebeencarriedoutinseveralsol- vents(1,4-dioxaneCH3NO2,(CH3)2NCHOand(CH3)2SOCH3OH).
Thekineticrunswerecarriedoutin awellstirredglassreactor thermostattedbycirculationbathintherange323–353K,using CH3CN–H2Oasasolvent,CF3COOHasanacidcatalystandapre- ciousmetalcatalyst(Pt,Pd,Rh,Ru)supportedoncarbon.Hydrogen wasfedcontinuouslyatconstantpressure(c.a.0.12MPa)byagum balloon(see supplementaryinformation).Blankreactionsinthe absenceofnitrobenzenehavebeencarriedoutinordertoverify
NHOH2 NH NH2
OH H2O
-H+ H+
-H2O NHOH NH
Scheme2. Bambergerrearrangementofphenylhydroxylamine.
Table1
Propertiesofpreciousmetalcatalystssupportedoncarbonblack:metaldispersion, totalsurfacearea.
Catalyst Metal dispersion(%)
COuptake (mLgcat−1)
BETsurface area(m2gcat−1)
Pt/C3% 65 2.5 920
Pd/C5% 27 3.2 880
Rh/C5% 24 2.9 890
Ru/C5% 23 2.8 910
thestabilityofthesolvent.Allthesolventsemployeddidnotshow anyproductsofreductionatGCanalysis.
Inatypicalexperiment2.5mLofacetonitrile,withsuspended thePd/Ccatalyst(typically50mg),wasintroducedintothereac- tor.Afterthatthereactorwasclosed,purgedbeforewithnitrogen andthenwithhydrogen,pressurizedat121kPa,finallyheatedat 353Kunderstirringfor2hinordertoactivatethecatalyst.The temperatureofreaction(range 323–363K)wasleft tostabilize, thanthepreheatedsolutionof acetonitrilewatertrifluoroacetic acidandnitrobenzene(c.a.22.5mL,concentrationnitrobenzene 0.075molL−1, CF3COOH 0.2–0.8molL−1) was added toreactor.
Afterthe addition of this solution,the computing of the reac- tion time starts and the liquid phase is periodically sampled and analyzed byGC, GC–MSand HPLC,during reaction course.
Nitrobenzeneataconcentrationof0.075molL−1iscompletelysol- ubleintheH2O–CH3CN–TFAtill5gofwaterin25mLofsolution.
3. Resultsanddiscussion
3.1. Influenceofthesolventsystemontheactivityandselectivity
Thetypeofsolventandtheacidityofthesystemareparame- tersofparamountimportanceforactivity,selectivityandresistance todeactivationofthepreciousmetalphase inacatalyzedreac- tion. This is especially true in the nitrobenzene conversion to 4-aminophenol,sincebothreactionsoftheprocess(consecutive hydrogenationandBambergerrearrangement)aresensitivetothe natureofthesolvent[23,25].Forthisreasonascreeningofvarious solventsisimportantinordertoselectthebestoneforthereaction.
WetestedseveralsolventsinthepresenceofPt/C,however,CH3CN givesthebestresults(seeTable2andsupplementarymaterials).
Thereasonofthehigheryieldin4-aminophenolbyusingCH3CN asasolventislikelyduetoasimultaneousandsynergiceffectof CH3CNindeactivatingthestageofhydrogenationandinpromoting therearrangementoftheN-phenylhydroxylamine.Asamatterof fact,insinglephasereactionswhenCH3CNisnotthesolventmuch loweryieldin4-aminophenolisobtained.Forinstance,inthepres- enceof1,4-dioxane,methanolandnitromethanethereactionis selectivetoaniline,whileitshowsacomplexmixtureofproducts indimethylformamide.Onthecontrary,thereactionsarepracti- callyinhibitedbyusingdimethylsulfoxideorsulfolaneassolvents, sincetheyarebothdeactivatingsubstancesforhydrogenationpre- ciousmetalcatalysts[26].Moreover,thereactionhasbeentestedin thepresenceofHClandCH3SO3Hasacidsystems.Inthepresence ofHCl,asexpected,thereactionproceedtotheformationofaniline
andchloroanilines,whileinthepresenceCH3SO3Hweobserveani- lineandacomplexmixturesofnotidentifiedproducts.Inaddition, wefoundtheformationoftwoliquidphasesandprecipitationof saltsinbothreactions.
3.2. Influenceofthecatalysttypeonreactionrateandselectivity
Theresultsintheprevioussectionsuggestthat thebestsol- ventisCH3CN,coupledwithCF3COOHasacidcatalyst.Becauseof theseevidenceswewillexclusivelyshowresultsofexperiments carriedoutinthemixtureCF3COOH–CH3CN,whichisactuallya CF3COOH–H2O–CH3CNsystemsinceH2Oiscontainedeitherinthe solventorinthereagent.Inaddition,H2OisareagentintheBam- bergerrearrangementforthisreasonitsroleinthereactionpath willbestudied.
Thecomparisonofvariouspreciousmetalcatalystsisreported inTable2.Itisnoteworthythatthebestperformingone,interms ofbothcatalyticactivityandyieldto4-aminophenol,isPt/C.This givesthebestresultsalsowiththebiphasicsulfuricacidnitroben- zenesystem[1–6].BothPd/CandRh/Cshowhighhydrogenation activity,but4-aminophenolyields(inbothcases)islowerthan thatobservedinthepresenceofPt/C.Ru/Cshowsbothpoorhydro- genationactivityandnegligible4-aminophenolyield,becauseof itsintrinsiclowhydrogenationactivityobservedinthesereactions (Table3).
Fig.1showsthatthetrendsof4-aminophenol yieldvs.time are similar in the presence of different metal catalysts. These trendsshowthat theformation of 4-aminophenoldecreasesas thereactionproceedssuggestinganinfluenceoftheproductson the4-aminophenolyield.Asamatteroffact,aminesreducethe overallacidityofthesolution,thuslikely decreasingtherateof rearrangementoftheN-phenylhydroxylamineandtheoverallyield in4-aminophenol.Besides,itislikelythatthebetterperformance
0 200 400 600 800 1000 1200
0 10 20 30 40 50 60
yield (%)
time (minutes) Pt/C
Pd/C Rh/C Ru/C
Fig.1.Influenceofthecatalysttypeon4-aminophenolyield.Runconditions:T:
353K,kPa,PH2121kPa,nitrobenzene0.075molL−1,CF3COOH0.6molL−1,H2O2.2g, CH3CN22g,catalyst50mg.
Table2
Influenceofthesolventon4-aminophenolandanilineyieldafter20h.Runconditions:T:353K,PH2121kPa,nitrobenzene0.075molL−1,acidcatalyst0.6molL−1,H2O2.2g, solvent22g,catalystPt/C3%50mg.
Solvent-acid Conversion(%) Yield4-APa(%) YieldANb(%) Yieldothers(%) Notes
CH3CN–CF3COOH 65 42 13 10 Azoxy-azobenzene
CH3CN–HCl 20 traces 10 10 Azoxy-azobenzene,chloroanilines
CH3CN–CH3SO3H 20 traces 12 8 Azoxy-azobenzene
C4H4O2c–CF3COOH 98 5 90 3 trifluoroacetanilide
CH3NO2–CF3COOH 88 15 60 13 Azoxy-azobenzene,2-EtO-anilineand
anilides
(CH3)2NCHO–CF3COOH 92 10d 40 42 Unidentifiedproducts
(CH3)2SO–CF3COOH <1 – – Traces At378K1MPareactiondoesnot
proceed
(CH2)4SO2e–CF3COOH <1 Traces Traces Traces Practicallynoreaction
CH3OH–CF3COOH 96 5 60 31 Trifluoroacetanilides,2-EtO-aniline
andanilides,Azoxy-azobenzene
a4-AP=4-aminophenol.
b AN=aniline.
c 1,4-Dioxane.
d mainlyN-trifluoroacetyl-4-aminophenol.
eSulfolane.
Table3
Influenceofthecatalysttypeonnitrobenzeneconversion,4-aminophenolyieldminutesandinitialreactionrateafter180min.Runconditions:T:353K,PH2121kPa, nitrobenzene0.075molL−1,CF3COOH0.6molL−1,H2O2.2g,CH3CN22g,catalyst50mg.
Catalyst Conversion(%) Yield4-APa(%) YieldAN(%) Yieldothers(%) r0(molL−1min−1gmet−1)
Pt/C3% 41 26 2 12 0.13
Pd/C5% 42 14 26 1 0.078
Rh/C5% 46 16 29 1 0.080
Ru/C5% 0.4 Traces 0.19 0.2 0.0007
aTheseproductsareamixtureof4-aminophenolandtrifluoroacetylatedcompoundsof4-aminophenol.
ofPt/Ccatalystis duetoa specificselectivityofthecatalystto 4-aminophenol.
3.3. Timevs.concentrationprofiles
In Fig. 2 reaction shows time vs. concentration profiles of the species observed in the hydrogenation of nitrobenzene in CH3CN–H2O–CF3COOH. The concentrationof 4-aminophenol increasessmoothlywiththetime,onthecontrary,theyieldto aniline hasa significantincrease only after a long time. Other productshavebeen identified,but not preciselyquantified and aresignedas“other”.Themainsideproducts(inagreementwith the Haber reduction scheme of nitrobenzene [27]) are azoxy- benzeneandazo-benzene,whicharehydrogenatedtoanilineafter alongertime.Besides,therearetracesofN-phenylhydroxylamine
0 200 400 600 800 1000 1200
0 1 2 3 4 5 6 7 8
102 concentration (mol L-1)
time (minutes)
nitrobenzene 4-aminophenol aniline other
Fig. 2.Time concentration profile of nitrobenzene hydrogenation to 4- aminophenol.Runconditions:T:353K,PH2121kPa,nitrobenzene0.75molL−1, CF3COOH0.6molL−1,H2O2.2g,CH3CN22g,catalystPt/C50mg.
andnitrosobenzene,buttheseproductsarepresentinverysmall amountandonlyafterfewminutesofreaction.Itisnoteworthythat theproducts“other”passthroughamaximumandtheirdecrease isaccompaniedwiththesteepestanilineincrease.Thisbehavioris consistentwiththeHaberreductionschemeofnitrobenzenewhere azobenzeneandazoxybenzeneareintermediatestoaniline[27].
3.4. Influenceofcatalystamountontheinitialreactionrate
Fig.3showstheinfluenceofthecatalystamountontheinitial reactionrateandontheyieldof4-aminophenol.Itappears(Fig.3a) thatexternalmasstransferpoorlyinfluencesthereactionkinetics becauseofthesmallvalueoftheintercept[28].However,acom- pleteevaluationoftheinfluenceofrateofdiffusionofreagentsand productsonthereactionkineticsisbeyondthescopeofthepresent work,inwhichinitialreactionratedataaregivenonlyforcom- parativepurpose.Theyieldof4-aminophenolseemstobefaintly influencedbythecatalystamount(Fig.3b),furthermore,catalyst deactivationaffectstheoverallreactionkinetics,beingreacheda plateau,inanycase.
3.5. Influenceoftemperatureonreactionrateandselectivity
TheArrheniusplotoftheinitialreactionrate(seesupplemen- tarymaterials)presentsanalmostlineartrend,withatemperature coefficient (orapparent activation energy) of 91kJmol−1. Even though,kineticdataarereferredtoinitialreactionrate,thevalue oftheapparentactivationenergytogetherwiththeresultsofthe previoussectionsuggestthekineticofreactionispoorlyinfluenced ofbyexternaldiffusionlimitation[28].Inadditions,theinspection ofWheeler–Weiszcriterionimplieslittleinfluenceoftheinternal diffusion,sincevaluesintherangeof0.05–0.11arecalculatedfor hydrogenandnitrobenzene,respectively[28].Theseresultsarein agreementwithotherhydrogenationreactioncarriedoutunder similarconditionsbyusingPd/Ccatalystswithsimilarporosityand granulometry[24].
