A pyridyl-triazole ligand for ruthenium and iridium catalyzed C=C and C=O hydrogenations in water/organic solvent biphasic systems

(1)

ContentslistsavailableatScienceDirect

Applied

Catalysis

A:

General

j o ur na l h o me p a 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

A

pyridyl-triazole

ligand

for

ruthenium

and

iridium

catalyzed

C

and

C O

hydrogenations

in

water/organic

solvent

biphasic

systems

Stefano

Paganelli

∗

,

Md.

Mahbubul

Alam,

Valentina

Beghetto,

Alberto

Scrivanti,

Emanuele

Amadio,

Matteo

Bertoldini,

Ugo

Matteoli

DepartmentofMolecularScienceandNanosystems,UniversitàCa’FoscariVenezia,viaTorino155,30170VeneziaMestre,Italy

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received1July2014

Receivedinrevisedform2October2014 Accepted10November2014

Availableonline21November2014

Keywords: Ruthenium Iridium Catalytichydrogenation Biphasiccatalysis Water

a

b

s

t

r

a

c

t

The water soluble pyridyl-triazole ligand sodium 2-(1-((pyridin-2-yl)methyl)-1H-1,2,3-triazol-4-yl) ethylsulfate(Na1)hasbeensuccessfullyemployedincombinationwithrutheniumandiridiumfor cat-alytichydrogenationofC CandC Odoublebondsinwater/toluenebiphasicsystems.Reactionofthe ligandwith[RuCl2(␩6-p-cymene)]2affordsthenewwatersolublecomplex[RuCl(␩6-p-cymene)(1)](2)

whichhasbeenfoundtobecatalyticallyactiveinthewater/organicsolventbiphasichydrogenation usingstyreneand2-cyclohexen-1-oneasmodelsubstrates.Veryconveniently,theiridiumbased cat-alyticsystemispreparedbysimplystirringinwater[Ir(␩4_-COD)Cl]

2withNa1(Ir:Na1molarratio=1:4),

theresultingsolutioniscatalyticallyactiveandappearsmoreefﬁcientthan2.WithboththeRu-and Ir-basedsystemsthecatalyticallyactiveaqueousphasescanbeusedatleastthreetimeswithoutlossof activity.

1. Introduction

Homogeneouscatalystsgenerallyprovideverygoodactivities andselectivities, but theirapplication inindustrial processes is hamperedby theirdifﬁcult separation from thereaction prod-ucts.Furthermore,recoveryofhomogeneouscatalystsappearsvery oftenachallengingandexpensivetask.Forallthesereasons,the developmentofwater soluble catalysts,whoseseparation from reagentsandproductscouldallowa promptrecycleofthe cat-alyticallyactivespecies, is highlydesirable [1–5].Thisprovides aninexpensiveanswertothechallengeofpreservingresources, makingtheprocessmoreenvironmentallyfriendly.

Nowadayswater-solublecatalystsareincreasingly employed eitherinwaterorinwater/organicsolventbiphasicmixtures.

The most commonly employed catalysts in water/organic phasebiphasicsystemsaremetalcomplexesmodiﬁedwithwater soluble phosphines, suchas TPPTS (triphenylphosphine-3,3,3 -trisulfonicacidtrisodiumsalt)which,forinstance,isemployedin therenownedOXEA(formerRuhrchemie/Rhône-Poulenc) hydro-formylationprocess[4–8].

In the last years new species bearing different hydrophilic groupssuchas COOH, NR3+, OH,etc.[1–4]andalsonatural

∗ Correspondingauthor.Tel.:+390412348592;fax:+390412348517. E-mailaddress:spag@unive.it(S.Paganelli).

compounds,suchasaminoacids,peptides,proteinsandsugarshave beenusedasligandsincombinationwithtransitionmetalspecies inordertoobtaincatalystsactiveinwater[9–18].

Forsometimenow,ourresearchgrouphasbeeninvolvedin thesynthesisoftriazolylligandstakingadvantageofthe copper-catalyzed azide-alkyne [3+2] cyclization (Scheme 1) [19–22]. Employing this efﬁcient strategy we have synthesized a small libraryofN NorN Sligandswhichweresuccessfullyemployed inpalladiumcatalyzedSuzuki–Miyaurareactions[23,24].Asapart ofthisongoingresearchwehaverecentlyreportedthesynthesisof thewatersolubleligandNa1(Scheme1)[25],whichwas success-fullyemployedinaqueousphasepalladiumcatalyzedS–Mcoupling reactions.

Inthepresent work,wewishtoreportthatNa1canbe suc-cessfullyemployedastheligandincombinationwithruthenium andiridiumtocatalyzecarbon–carbonandcarbon–oxygendouble bondhydrogenationinbiphasicwater/organicsolventmixtures.

2. Experimental

2.1. Materialsandinstrumentation

All reactions were carried out under inert atmosphere (argon)usingstandardSchlenktechniques.Commercialsolvents (Sigma–Aldrich) were puriﬁed as described in the literature [26]. Sodium 2-(1-((pyridin-2-yl)methyl)-1H-1,2,3-triazol-4-yl) http://dx.doi.org/10.1016/j.apcata.2014.11.013

(2)

Scheme1. Generalsyntheticschemeforbidentatepyridyl-triazolylligands.

ethyl sulfate (Na1) wasprepared as described in theliterature [25].[RuCl2(␩6-p-cymene)]2 [27] and[Ir(␩4-COD)Cl]2 [28]were preparedaccordingtoliteraturemethods.[Ir(␩4_-COD)Cl]

2isalso commerciallyavailable(AlfaAesar).

1_H_and13_C_NMR_spectra_were_recorded_in_deuterated_solvents (Sigma–Aldrich)onaBrukerAvance300spectrometeroperating at300.1and75.5MHz,respectively;thechemicalshiftvaluesare reportedin_ıunitswithreferencetotheresidualsolventsignal. The protonassignments were performed bystandard chemical shiftcorrelationsaswellasby1_H_2D_COSY_experiments._The13_C chemicalshiftvalueswereassigned throughDEPT-135and 2D-heteronuclearcorrelationexperiments(HMQCandHMBC).

ESI-MSanalyseswereperformedusingaFinniganLCQ-Duo ion-trapinstrument,operating inpositiveionmode(sheathgasN2, sourcevoltage 4.0kV,capillary voltage 21V, capillary tempera-ture200◦C).SamplesolutionswerepreparedbydissolvingtheRu complex(1mg)inmethanol(1mL)andthenfurtherdilutingwith methanol(1:30).SamplesolutionswereintroducedintotheESI sourcebya syringepumpat8␮L/minﬂow rate.Allmass spec-trawererecordedonfreshlypreparedsolutions.TheESI-MSdata, reportedbelow,havebeenconﬁrmedbyMS/MSexperimentsand isotopepatternanalysis.

The solutions resulting from the catalytic experiments were analyzed by GLC on a 6850 Agilent Technologies gas-chromatograph employing HP-1 capillary column (30m× 0.32mm×0.25␮m)orHP-5capillarycolumn(30m×0.32mm× 0.25␮m).GC–MSspectrawererecordedonaHP5890seriesII gas-chromatographinterfacedtoaHP5971quadrupolemassdetector employingaHP-5capillarycolumn(30m×0.25mm×0.25␮m). Thereactionproductswereidentiﬁedbycomparisonwith com-mercialsamples(Sigma–Aldrich).ICP-MSanalyseswereperformed byusinganAgilent7500a-Seriesinstrument.

2.2. Rutheniumcatalystsynthesis2

In a 50mL two-neck round-bottomed flask a mixture ofsodium2-(1-((pyridin-2-yl)methyl)-1H-1,2,3-triazol-4-yl)ethyl sulfate (Na1) (118mg, 0.39mmol) and [RuCl2(␩6-p-cymene)]2 (118mg, 0.20mmol) was stirred in methanol (20mL) at room temperaturefor3daysundernitrogen.Thenthemixturewas fil-teredandtakentodrynessinvacuo.Theresultingyellow-orange solidwasextractedwithboilingethanol andfiltered;on stand-ingovernight,orangemicrocrystals(155mg,72%yield)precipitate, mp234◦C(dec).1_H_NMR₍₃₀₀_MHz,_CD 3OD,298K)ı9.11(d,1H, J=5.8,H-1),8.33(s,1H,H-7),8.06(td,1H,J=7.7and1.3Hz, H-3),7.77(d,1H,J=7.2Hz,H-4),7.59(m,1H, J=5.8Hz, H-2),6.10 (d,1H, J=15.8Hz, H-6A), 6.08 (d,1H, J=6.1Hz,p-cym), 5.97(d, 1H,J=6.1Hz,p-cym),5.87(d,1H,J=6.1Hz,p-cym),5.81(d,1H, J=6.1Hz,p-cym),5.62(d,1H,J=15.8Hz,H-6B),4.28(m,2H,H-10), 3.11(m,2H,H-9),2.92(spt,1H,J=6.9Hz,ArCH),2.01(s,3H,ArCH3), 1.31(d,6H,J=6.9Hz,CHCH3).13_C_NMR_(75.5_MHz,_CD3OD,₂₉₈_K)_ı 159.5(C-1),154.7(C-5),149.7(C-7),141.8(C-3),130.1(C-4),127.4 (C-8orC-2),127.3(C-8orC-2),107.9(p-cym),102.6(p-cym),89.0 (p-cym),86.3(p-cym),85.6(p-cym),84.9(p-cym),67.1(C-10),55.4 (C-6),32.2(p-cymCH),27.2(C-9),22.6(CHCH3),22.3(CHCH3),18.3 (p-cymCH3).IR(KBr pellet)max:3591,3461,3127,3073,3022, 2947,1603,1468,1431,1254,1218,1005,896,773,742,581cm−1. Anal.Calc.forC20H25ClN4O4RuS(554.0):C,43.36;H,4.55;N10.11; Cl6.40%.Found:C,43.12;H,4.54,N9.88;Cl6.15%.

2.3. Complex2aquation

5.5mg(0.01mmol) ofcomplex2weredissolvedin1.0mLof D2O.The following isthe descriptionofthe1HNMR spectrum registeredimmediatelyafterdissolution. 1_H _NMR_of _complex₂ (300MHz,D2O,298K)ı9.03(d,1H,J=5.8,H-1),8.33(s,1H, H-7),8.08(td,1H,J=7.8and1.3Hz,H-3),7.78(d,1H,J=7.2Hz,H-4), 7.59(m,1H,J=5.8Hz,H-2),6.08–6.00(m,3H,H-6Aand2Hof p-cym),5.90(d,1H,J=6.1Hz,p-cym),5.88(d,1H,J=6.1Hz,p-cym), 5.62(d,1H,J=15.8Hz,H-6B),4.31(m,2H,H-10),3.17(m,2H, H-9),2.81(spt,1H,J=6.9Hz,ArCH),2.07(s,3H,ArCH3),1.24(d,3H, J=6.9Hz,CHCH3),1.21(d,3H,J=6.9Hz,CHCH3).Onstandingthe signalsrelevanttocomplex3develop.Theequilibriumisreached after24h.The1_H_NMR_spectrum_displays_along _with_the_above reportedsignalsrelevanttocomplex2,newsignalsattributedto theaquospecies3,accordingtointegrationthe2:3molarratiois 0.45:0.55,respectively.1_H_NMR_of_complex₂₍₃₀₀_MHz,_D

2O,298K) ı8.99(d,1H,J=5.8,H-1),8.37(s,1H,H-7),8.15(td,1H,J=7.8and 1.3Hz,H-3),7.84(d,1H,J=7.2Hz,H-4),7.72(m,1H,J=5.8Hz, H-2),6.16–5.86(overlappingmultipletsattributedto6Aandp-cym of2and3),5.63(d,1H,J=15.8Hz,H-6B),4.31(m,2H,H-10),3.17 (m,2H,H-9),2.81(spt,1H,J=6.9Hz,ArCH),2.11(s,3H,ArCH3), 1.25–1.19(overlappingmultipletsattributedtoCHCH3of2and3). 2.4. Hydrogenationexperimentswithcatalyst2

As anexample the experimentaldetails relevant toEntry 3 inTable1arereported.In aSchlenktube,atoluene solutionof styrene(374mg,3.6mmolin2.0mL)wasaddedtoanaqueous solu-tionof2(4.0mg,0.0072mmolin2.0mLofwater)undernitrogen atmosphere.TheSchlenktubewasthentransferredintoa150mL stainlesssteelautoclaveundernitrogen.Thereactorwas pressur-izedatp(H2)=4.0MPaandthenheatedat80◦Cundermagnetic stirring.After6htheautoclavewascooledtoroomtemperature andtheresidualgasventedoff.

Theorganicphasewascarefullyseparated,driedonNa2SO4and, aftertheadditionof0.5mmolofmesitylene(astheinternalGC Table1

Biphasichydrogenationofstyreneinthepresenceoftherutheniumcatalyst2.a Entry p(H2)(MPa) t(h) %Conv.b(TOFc)

1stRun 2ndRun 3rdRun 1 4.0 1 25(125) 64(320) 60(300) 2 4.0 3 62(103) 96(160) 99(165) 3 4.0 6 100(83) 100(83) 100(83) 4 3.0 6 98(81) 99(82) 99(82) 5 2.0 6 78(65) 92(77) 88(73)

a_Reaction _conditions: _[RuCl(␩6_{-p-cymene)(1)]}₌_4.0_mg _(0.0072_mmol),

styrene=374mg(3.59mmol),T=80◦_C,_H₂_O₌_2.0_mL,_toluene₌_2.0_mL,_substrate:Ru

(molarratio)=500:1.

b_By_GLC.

(3)

standard),analyzedbyGCwhilethecatalyticaqueousphasewas recycledforfurtherexperiments.

2.5. Hydrogenationexperimentswiththeinsitupreparediridium catalyst

AsanexampletheexperimentaldetailsrelevanttoEntry3in Table4arereported.

InaSchlenktube,3.2mg(0.0048mmol)of[Ir(␩4_-COD)Cl]2_and 5.9mg(0.019mmol)ofligandNa1(metal/ligand=1/2molarratio) werestirredundernitrogenin2mLofdegassedwateruntil com-plete dissolution of the complex (about 30min). A solution of 461mg(4.8mmol)of2-cyclohexen-1-onein2mLoftoluenewas then added to the aqueous phase. The Schlenk tube was then transferredintoa150mLstainlesssteelautoclaveundernitrogen, pressurizedwithH2(0.5MPa)andmagneticallystirredfor6hat 40◦C.Thereactorwasthencooledtoroomtemperatureandthe residualgasventedoff.Theorganicphasewasseparated,driedon Na2SO4and,aftertheadditionof0.5mmolofmesitylene(asthe internalGCstandard),analyzedbyGCwhilethecatalyticaqueous phasewasrecycledforfurtherexperiments.

3. Resultsanddiscussion

3.1. Synthesisoftherutheniumcatalyst

Therutheniumcatalyst2waspreparedbystirring[RuCl2(␩6 -p-cymene)]2 with Na1 (Ru: Na1=1:1) in methanol at room temperature(seeScheme2).

Recrystallizationofthecrudeproductfromhotethanolaffords yellow-orange microcrystals which were found to be lamellar aggregatesunsuitableforX-raystructuredetermination.Therefore

2wasformulatedonthebasisoftheelementalanalysis, conduc-tivitymeasurements,ESI-MS,andNMRspectroscopydata.

Methanol or water solutions of 2 are nonconducting (M<1−1_cm2_mol−1 _for_a_1.0_×₁₀−3_M_solution)_in_agreement withitszwitterionicnature[29,30].

In the ESI-MS spectrum of 2 the most intense peaks have m/z1685(M3+Na)+_,₁₁₃₁ _(M2+Na)+_,_and ₅₇₇_(M+Na)+_,_the rel-ativeintensitybeing100, 40and 28,respectively.MS/MSscans showedthatfromthepeakatm/z=577(M+Na)+_arise_peaks_having m/z=519(M−Cl)+_,₄₉₇_(M_−SO3+Na),_and₄₃₉_(M_−SO3−Cl)+_.

NMRspectroscopyindicatesthatin2thepyridyl-triazolylligand chelatesrutheniumthroughtheN-pyridyl atomandthecentral Natomofthetriazolering(seeScheme2fortherelevant num-beringscheme).Infact,inthe1_H_NMR_spectrum_(CD

3OD,298K) of2boththeH(1)doubletandtheH(7)singletarefound signif-icantlydownﬁeld withrespecttothefreeligand(ı=0.57 and 0.33ppm,respectively)asfoundforotherpyridyl-triazoleligands whenchelatingtoametalcentre[23,31,32].Deﬁnitiveevidence forchelationof1atrutheniumcomesfromtheABspinpattern foundforthe methylene bridgeprotons. Thispattern isdue to

Scheme3.Catalytichydrogenationofstyrene.

thelackofanyelementofsymmetryin thesix-memberedring whichformsuponligandchelation.Hence,theaxialandthe equa-torialprotonsofthemethylenemoietybecomenon-equivalentand givetwoseparateresonanceswithageminalcouplingconstantof 15.8Hz.Owingtothelackofsymmetry,thearomaticprotonsof thecoordinatedp-cymenegivefourseparateresonances(twoAB spinsystems)inthe6.1–5.8ppmrange,about1ppmupﬁeldwith respecttothefreeligand.Thechemicalshiftsoftheisopropyland themethylmoietiesarealmostunchangedwithrespecttothe start-ingrutheniumcomplex;inthisconnectionitisworthnothingthat thetwomethylsofisopropylmoietywhichareaccidentally equiv-alentinthe1_H_NMR_spectrum_give_two_separate_signals_in_the13_C NMRspectrum.

Ligandchelationisalsoindicatedbythe13_C_NMR_spectrum_in whichbothC(1)andC(7)resonateatlowerﬁeldswithrespectto freeligandNa1,theısbeing3.9and3.5ppm,respectively.Itis worthremarkingthatboththe1_H_and_the13_C_NMR_spectra_are_in goodagreementwiththosereportedbyKˇosmrljandco-workers forthestrictlyrelatedspecies[RuCl(␩6_{-p-cymene)(1b)]Cl}_(for_the chemical structure ofligand1b seeScheme1)thestructure of whichhasbeendeterminedbyX-raycrystallography[32,33]. 3.2. Catalysiswithrutheniumcomplex2

In order to test the applicability of Na1 in biphasic hydro-genation, a ﬁrst setof experiments wascarried out employing therutheniumcomplex2.Styrenewaschosenastheexploratory modelsubstrate(seeScheme3),therelevantresultsaregathered inTable1.

Thereactionswerecarriedout ina water/toluenesystemat 80◦C.Aﬁrstexperimentcarriedoutatp(H2)=4.0MPashowedthat

2hasamoderatelygoodcatalyticactivityas25%ofthesubstrateis hydrogenatedtoethylbenzenein1h(Entry1).Mostimportantly, arecycleexperimentnotonlyshowsthattherecoveredaqueous phaseremainscatalyticallyactive,butalsothatitsactivityincreases affording67%ofsubstrateconversionunderthesameconditions (column5inEntry1);furthermore,thisenhancedcatalyticactivity ismaintainedinasecondrecycleexperiment.

Inasecondsetofexperimentsthereactiontimewasincreased to3h;thisallowedtoobtainasubstrateconversionof62%inthe firstrunandalmostcompleteconversioninthetwofollowing recy-cleexperiments,confirmingthatthecatalystbecomesmoreactive afterthefirstcatalyticrun.Whenthereactiontimeisextendedto 6h,styreneconversioniscompleteinthepresenceofbothfresh andrecycledcatalyst(Entry3).

(4)

Scheme4.Complex2aquation.

Owingtothegoodactivitydisplayedbythecatalyticsystem, anexperimentwascarriedoutbyloweringthehydrogenpressure to3.0MPa.Again,apracticallycompleteolefinhydrogenationis obtainedafter6h,andtherecoveredcatalystmaintainsits activ-ityunchangedintwoconsecutiverecycleexperiments(Entry4).A furtherdecreaseofp(H2)to2.0MPabringstoamoderatedecrease ofthesubstrateconversion(78%)inthefirstrun,butthecatalyst, whenrecycled,showsaremarkableincreaseofefficiencyaffording ethylbenzeneinabout90%yield(Entry5).

Asfarastheobservedcatalystactivationisconcerned,itisto recall thatin organoruthenium arene complexessuchas 2,the Ru Clbondisquitereactiveand,inparticular,canbeeasilycleaved bywatertogivethecorrespondingaquocomplex(seeScheme4). Forinstance,theaquationreactionisthoughttoplayanimportant roleinsettingtheanticanceractivitydisplayedbysomeruthenium arenecomplexes[34].Aquationofcomplex2canbeinferredby1_H NMRspectroscopyandconductivitymeasurements.Infact,the1_H NMRspectrumof2inD2O,whichimmediatelyafterdissolution isalmostidenticaltotheoneregisteredinCD3OD,slowlychanges onstanding.After24h,the1_H_NMR_spectrum_is_the superimposi-tionofthesignalsrelevanttocomplex2andtheaquocomplex3in 0.45/0.55molarratio,respectively.Inthisconnectionitistopoint outthat[RuCl(␩6_{-p-cymene)(1b)]Cl}_displays_the_same_behaviour [33].InkeepingwithpartialbreakingoftheRu Clbondand for-mationofthechargedaquocomplex3,theMvalueofa10−3M water solutionof 2 upon standing increasesfrom about0.9 to 40−1_cm2_mol−1_,_value_which_agrees_with_a_partial_formation_of a1:1electrolyte[35].

Inordertosubstantiatetheinvolvementoftheaquospecies3

inthecatalystactivation,wecarriedoutahydrogenation exper-iment employing a sample of catalyst which was previously “pre-activated”bystirringinwaterunderH2 (p(H2)=4.0MPa)at 80◦C for1h.Employingsuch“pre-activated” catalyst,astyrene conversionof34%wasobtained(resultnotreportedinTable1). Accordingly,itappearsthataquationalonecannotaccountforthe catalystactivationobserved.

When employing ruthenium catalysts in homogeneous or biphasic hydrogenation, the reaction rate can be improved by introducingabasewhichactsaspromoterbyscavengingtheacid whichformsuponheterolytichydrogenactivation[36].Thus,some experimentswerecarriedoutinthepresenceofinorganicbases. Whenwetriedtocarryoutthereactionin0.1MofaqueousKOH,we observedimmediatedecompositionofthecatalysttoruthenium black.Thus,attributingcatalystdecompositiontothestrongbasic medium,weresolvedtouseK2CO3asbasicpromoterina1:1molar ratiowiththecatalyst.Inthiscasewedidnotobserveimmediate metalprecipitation,andtheaqueousphasecouldbeemployedin styrenehydrogenation.Assurmised,thepresenceofthebaseledto asigniﬁcantlyhigherreactionrateaffordingethylbenzenein80% yield.However,attheendofthereaction,extensiveformationof rutheniumblackinthewaterphasewasnoticed.Accordingtothese observations,wearebroughttobelievethatalsothesubstrateplays

Scheme5. Hydrogenationof2-cyclohex-1-one(I).

Table2

Biphasichydrogenationof2-cyclohexen-1-one(I)inthepresenceoftheruthenium catalyst2.a

Entry t(h) Run %Conv.b_(TOFc₎ _%Selectivityd

II IV 1 6 1st 17(14) 94 6 2 24 1st 100(21) 96 4 3 24 2nd 100(21) 95 5 4 24 3rd 100(21) 95 5 5 24 1st 36(7.5) 98 2

a_Reaction _conditions: _[RuCl(␩6_{-p-cymene)(1)]}₌_4.0_mg _(0.0072_mmol),

2-cyclohexen-1-one=345mg (3.59mmol), T=80◦C, p(H2)=2.0MPa, H2O=2.0mL,

toluene=2.0mL,substrate:Ru(molarratio)=500:1.

b_By_GLC.

c _Moles_of_hydrogenated_products/mol_of_catalyst_per_hour. d_Formation_of_III_was_never_observed.

aroleinactivatingthecatalyst,howeverwewereunabletoﬁnd evidencessupportingthishypothesisandtheactualmechanismof catalystactivationremainsuncertain.

Itisworthnotingthatinalltheexperimentscarriedoutusing complex2,nocatalystleachingwasobserved.Asamatteroffact, theorganicphase recovered aftertheﬁrst hydrogenation reac-tion(Entry1,Table1)wasusedascatalystinthehomogeneous hydrogenationof undec-1-eneintoluene, after6hat80◦C and 2.0MPaofH2 undecanewasnotformedatall.Furthermore,the toluenephasesrecoveredfromafewdifferentexperimentswere analyzedbyInductivelyCoupledPlasma-MassSpectrometry (ICP-MS)inordertodeterminethecontentofruthenium:innocasethe rutheniumcontentwasfoundtobegreaterthan1ppm.

Inordertotestthechemoselectivityofthecatalystwestudied thehydrogenationof2-cyclohexen-1-one(I,seeScheme5), the relevantdataarecollectedinTable2.

Ina ﬁrstexperimentcarriedoutat80◦Candp(H2)=2.0MPa the catalyst activity appeared modest as only 17% of the sub-stratewashydrogenatedis6h(Entry1).Ontheotherhand,the experiment showed that the catalyst is endowed witha good

(5)

chemoselectivity.Infact,onlysmallamountsofcyclohexanol(IV) areformedinadditiontocyclohexanone(II)whichisbyfarthe mostabundant product, while 2-cyclohexen-1-ol(III) does not formatall.

We were delighted to ﬁnd that when the reaction time is increasedto24h,completesubstratehydrogenationisobtained. Thisresultcanbeexplainedonlybyadmittingthatthecatalyst undergoesanactivationprocessduringthereaction.Oncethe cat-alysthasbeenactivateditmaintainsitsactivityforatleasttwo recycleexperiments(Entries3and4ofTable2).Inthis connec-tionitisworthnotingthatactivationprocessdoesnotchangethe chemoselectivityofthecatalyst.

Thehighselectivitytowardsformationofthesaturatedketone isnoteworthysincemostcommonlywithrutheniumcatalyststhe opposite selectivityis found, i.e.the unsaturated alcohol selec-tively forms. Nevertheless, exceptions are known [37], and, in particular,itistoremindthatJoó[38]demonstratedthatthepH ofthe aquous phase maystrongly inﬂuence thehydrogenation selectivity.

Sincewatersolutionsofcomplex2arealmostneutral(pH=6.2) andinbasicsolutionsthecatalystdecomposestorutheniumblack, wehavecarriedoutanexperimentunderacidicconditionsinorder toascertainifthepHcouldchangethehydrogenationselectivity. TheexperimentwascarriedoutatpH=3dissolvingthecatalystin a10−3MHClsolution,whilealltheotherreactionconditionswere unchanged(Entry5ofTable2).Notsurprisingly,underacidic condi-tionsthereactionrateisstronglydepressedandonly36%substrate conversionisobtainedby24h.Moreover,itappearsthatthepHhas noinﬂuenceontheselectivitysincenoformationofunsaturated alcoholisobserved.

Accordingtotheseresultsitmustbeconcludedthattheunusual selectivitycouldbeattributedtotheN,N-bidentatenatureofour ligand.

Summingup,complex2 appearsendowedwithan interest-ingcatalyticactivitywhichdoesnotappear tobefarfromthat of the most employed biphasic hydrogenation catalysts based onsulphonatedmono- anddiphosphines [38,39]andcompares favourablywiththatofwatersolublenitrogenligands[37b]. 3.3. Catalytichydrogenationswiththeinsitupreparedsystem [Ir(4_-COD)Cl]2/Na₁

Tofurtherexplorethescopeofourligandinaqueousbiphasic hydrogenation, we studied the catalytic activity of a system preparedby combiningin situ Na1with[Ir(␩4_-COD)Cl]

2 (COD: 1,5-cyclooctadiene)whichisacommerciallyavailableiridium pre-cursorwidelyusedinhydrogenationreactions[40,41].Forthesake ofcomparisontheefﬁciencyofthesystemwastestedwiththesame substratesemployedwithruthenium.

Plainstirring ofNa1 withthe iridiumprecursorin degassed wateratroomtemperatureaffordsinabout30mina clear cat-alyticallyactive solution. Preliminaryexperiments showed that thecatalyticactivitydependsontheligandtoiridiumratio,the bestresultsbeingobtainedusing4 molesof ligandfor moleof [Ir(␩4_-COD)Cl]

2 (Na1/Ir=2/1), therefore such ratio was used in allthehydrogenation experiments.Themostsigniﬁcantresults obtainedin styrenehydrogenation (Scheme 2) are reported in Table3.

Aﬁrstexperimentcarriedoutundermildconditionsaffordsa modestethylbenzeneyield(26%,Entry1),butwhenthe temper-atureisincreasedto60◦Candthehydrogenpressureto4.0MPa completesubstrateconversionisobtainedinonly1h.Most impor-tantly, therecovered aqueous phase can be reused four times (Entries2a–d).ICP-MSanalysesindicatesthattheorganicphases recoveredafterthehydrogenationreactioncontainsmallamounts of iridium(about 8ppm). Accordingto theseresults it maybe

Table3

Styrenehydrogenationinwater/tolueneusingtheiridium/Na1system.a

Entry(recycle) T(◦C) t(h) %Conv.b_(TOFc₎

1d ₄₀ ₃ ₂₆₍₄₃₎ 2 60 1 100(500) 2a(1st) 60 1 98(490) 2b(2nd) 60 1 96(480) 2c(3rd) 60 1 95(475) 2d(4th) 60 1 93(465)

a_Reaction_conditions:_[Ir(␩4_-COD)Cl]

2=3.2mg(0.0048mmol),p(H2)=4.0MPa,

styrene=500mg (4.8mmol), toluene=2.0mL, H2O=2.0mL, Na1=5.9mg

(0.019mmol),ligand:Ir(molarratio)=2:1,styrene:Ir(molarratio)=500:1.

b_By_GLC.

c _Mol_of_hydrogenated_product/mol_of_catalyst_per_hour. d _p(H

2)=1.0MPa.

Table4

2-Cyclohexen-1-onehydrogenationinwater/tolueneusingtheiridium/1system.

Entry(recycle) p(H2)(MPa) T(◦C) t(h) %Conv.b(TOFc) Selectivity

II IV 1 4.0 60 21 100(23) 4 96 2 4.0 60 1 100(500) 80 20 2a(1st) 4.0 60 1 100(500) 81 19 2b(2nd) 4.0 60 1 100(500) 83 17 3 0.5 40 6 100(83) 100 0 3a(1st) 0.5 40 6 100(83) 95 5 3b(2nd) 0.5 40 6 100(83) 97 3

a _Reaction _conditions: _[Ir(␩4_-COD)Cl]

2=3.2mg (0.0048mmol), H2O=2mL,

toluene=2mL, ligand=5.9mg (0.019mmol), 2-cyclohexen-1-one=461mg (4.8mmol),Ir/ligand(molarratio)=1/2,substrate/Ir(molarratio)=500/1.

b_By_GLC.

c _Moles_of_hydrogenated_products/mol_of_catalyst_per_hour.

concludedthattheiridium/Na1systemissigniﬁcantlymoreactive than the ruthenium catalyst 2, while this latter appears more robust.

Toshedsomelightontheligandrole,anhydrogenation experi-ment(notreportedinTable3)wascarriedoutundertheconditions ofEntry2intheabsenceofNa1.Intheabsenceoftheligand,the irid-iumprecursordissolvesintheorganicphasegivingapaleyellow solutionandalthoughstyreneiscompletelyhydrogenated, exten-sivedecompositionof[Ir(␩4_-COD)Cl]

2toiridiumblackoccurs.This ﬁndingdemonstratesthekeyroleplayedbytheligandwhichnot onlyimmobilizesthemetalinthewaterphase,butalsostabilizesit againstreductiontometal.Inthisconnectionitistopointoutthat noligandisdetectedby1_H_NMR_spectroscopy_in_the_organic_phase afterthecatalyticexperiments.

Theresultsof2-cyclohexen-1-onehydrogenation(Scheme5) arecollectedinTable4.

Under the same reaction conditions employed for styrene hydrogenation(60◦Candp(H2)=4.0MPa),completesubstrate con-versionisachievedby21hleadingtoamixtureofIVandIIin96/4 molarratio(Entry1).Accordingly,thereactiontimewasreduced to1hinorder tounderstandthroughwhich reactionsequence thefinalproductsform(i.e.ifthereactionpathisI→II→IV,or ifI→III→IV). Theexperiment showedthattheactualreaction sequenceistheformer,andthatthehydrogenationofthe endo-cyclicC C is much fasterthan C O hydrogenationresulting in amoderateselectivitytowardstheformation ofcyclohexanone. Theaqueousphaseremainscatalyticallyactiveandmaybereused twotimeswithoutlossofefficiency.Completechemoselectivity towardscyclohexanonewasfinallyobtainedbyfurtherdecreasing thetemperatureto40◦C andthep(H2)to0.5MPa.Underthese verymildconditions,completeC Cdoublebondhydrogenationis achievedby6h,cyclohexanonebeingtheonlyproductobserved; moreover,itispossibletorecycleatleasttwotimestheaqueous phasewithonlyanegligiblelossofchemoselectivity.

(6)

4. Conclusions

Summing up, the present work demonstrates the useful-ness ofthe pyridyl-triazoleNa1as ligandfor hydrogenation in water/organicsolventbiphasicsystems.Na1canbesuccessfully employedincombinationwithbothrutheniumandiridium. Reac-tionofNa1withrutheniumaffordsawelldeﬁnedspecies(complex

2) which displays a fairly good catalytic activity; the catalyst is robustand nometal leachingin theorganicphase hasbeen detected,sothattheaqueousphasecanbereusedatleastthree times withoutloss of activity. A peculiar feature of the ruthe-niumcatalystisrepresentedbyitsactivationoccurringduringthe ﬁrstcatalyticrun;studiesdevotedtorationalizethisfacetarein progress.ThepracticalusefulnessofNa1isevenmoreevidentwhen weconsiderthatthehighlyactiveiridiumsystemispromptly pre-paredbysimplystirringanaqueoussolutionof theligandwith thecommerciallyavailable[Ir(␩4_-COD)Cl]

2.Notwithstandingthe smallamountsofiridiumleachingintheorganicphase,thesystem retainsitsactivityalmostunchangedandthecatalyticallyactive aqueousphasecanbereusedatthreetimeswithoutdrawbacks.

References

[1]F.Joò,AqueousOrganometallicCatalysis,KluwerAcademicPublishers, Dor-drecht,2001.

[2]B.Cornils,W.A.Herrmann,Aqueous-PhaseOrganometallicCatalysis,second ed.,Wiley-VCH,Weinheim,2004.

[3]B. Cornils, W.A. Herrmann, I.T. Horváth, W. Leitner, S. Mecking, H. Olivier-Bourbigou,D.Vogt,MultiphaseHomogeneousCatalysis,Wiley-VCH, Weinheim,2005.

[4]D.J.Cole-Hamilton,R.P.Tooze,CatalystSeparation,RecoveryandRecycling, Springer,Dordrecht,2006.

[5]P.H.Dixneuf,V.Cadierno,Metal-CatalyzedReactionsinWater,Wiley-VCH, Weinheim,2013.

[6]E.G.Kuntz,Chem.Tech.17(1987)570–575.

[7]B.Cornils,E.G.Kuntz,J.Organomet.Chem.502(1995)177–186.

[8]B.Cornils,Org.ProcessRes.Dev.2(1998)121–127.

[9]N.Zhang,F.Li,Q.J.Fu,S.C.Tsang,React.Kinet.Catal.Lett.71(2000)393–404.

[10]E.Guibal,Prog.Polym.Sci.30(2005)71–109.

[11]J.Steinreiber,T.R.Ward,Coord.Chem.Rev.252(2008)751–766.

[12]M.Marchetti,F.Minello,S.Paganelli,O.Piccolo,Appl.Catal.A:Gen.373(2010) 76–80.

[13]H.Mao,X.Liao,B.Shi,Catal.Commun.16(2011)210–214.

[14]M.Marchetti,G.Mangano,S.Paganelli,C.Botteghi,TetrahedronLett.41(2000) 3717–3720.

[15]M.Marchetti,S.Paganelli,Chim.Ind.10(2005)44–46.

[16]C.Bertucci,C.Botteghi,D.Giunta,M.Marchetti,S.Paganelli,Adv.Synth.Catal. 344(2002)556–562.

[17]S.Paganelli,M.Marchetti,M.Bianchin,C.Bertucci,J.Mol.Catal.A:Chem.269 (2007)234–239.

[18]S.DiDio,M.Marchetti,S.Paganelli,O.Piccolo,Appl.Catal.A:Gen.399(2011) 205–210.

[19]C.W.Tornøe,C.Christensen,M.Meldal,J.Org.Chem.67(2002)3057–3064.

[20]V.V.Rostovtsev,L.G.Green,V.V.Fokin,K.B.Sharpless,Angew.Chem.Int.Ed.41 (2002)2596–2599.

[21]V.D.Bock,H.Hiemstra,J.H.vanMaarseveen,Eur.J.Org.Chem.(2006)51–68.

[22]M.Meldal,C.W.Tornøe,Chem.Rev.108(2008)2952–3015.

[23]E.Amadio,A.Scrivanti,G.Chessa,U.Matteoli,V.Beghetto,M.Bertoldini,M. Rancan,A.Dolmella,A.Venzo,R.Bertani,J.Organomet.Chem.716(2012) 193–200.

[24]E.Amadio,A.Scrivanti,M.Bortoluzzi,M.Bertoldini,V.Beghetto,U.Matteoli,G. Chessa,Inorg.Chim.Acta405(2013)188–195.

[25]E.Amadio,A.Scrivanti,V.Beghetto,M.Bertoldini,M.M.Alam,U.Matteoli,RSC Adv.3(2013)21636–21640.

[26]W.L.F.Armarego,D.D.Perrin,PuriﬁcationofLaboratoryChemicals,fourthed., Butterworth-Heinemann,Oxford,1996.

[27]M.A.Bennett,A.K.Smith,J.Chem.Soc.DaltonTrans.(1974)233–241.

[28]J.L.Herde,J.C.Lambert,C.V.Senoff,M.A.Cushing,Inorg.Synth.15(1974)18–20.

[29]R.R.Schrock,J.A.Osborn,Inorg.Chem.9(1970)2339–2343.

[30]H.J.Nolte, G. Gafner, L.M.Haines, J. Chem.Soc. Chem.Commun. (1969) 1406–1407.

[31]E.Amadio,M.Bertoldini,A.Scrivanti,G.Chessa,V.Beghetto,U.Matteoli,R. Bertani,A.Dolmella,Inorg.Chim.Acta370(2011)388–393.

[32]D.Urankar,B.Pinter,A.Pevec,F.DeProft,I.Turel,J.Kˇosmrlj,Inorg.Chem.49 (2010)4820–4829.

[33]I.Bratsos,D.Urankar,E.Zangrando,P.Genova-Kalou,J.Koˇsmrlj,E.Alessio,I. Turel,DaltonTrans.40(2011)5188–5199.

[34]F.Wang,H.Chen,S.Parsons,I.D.H.Oswald,J.E.Davidson,P.J.Sadler,Chem.Eur. J.9(2003)5810–5820.

[35]W.J.Geary,Coord.Chem.Rev.7(1971)81–122.

[36]Selectedreferences:

(a)G.S.Forman,T.Ohkuma,W.P.Hems,R.Noyori,TetrahedronLett.41(2000) 9471–9475;

(b) D. Jantke, M. Cokoja, M. Drees, F.E. Kühn, ChemCatChem 5 (2013) 3241–3248.

[37]Selectedreferences:

(a)A.Andriollo,J.Carrasquel,J.Mariﬁo,F.A.Lopez,D.E.Paez,I.Rojas,N.Valencia, J.Mol.Catal.A:Chem.116(1997)157;

(b)C.Stangel,G.Charalambidis,V.Varda,A.G.Coutsolelos,I.D.Kostas,Eur.J. Inorg.Chem.(2011)4709–4716;

(c)L.G.Melean,M.Rodriguez,A.González,B.González,M.Rosales,P.J.Baricelli, Catal.Lett.141(2011)709–716.

[38]F.Joó,J.Kovács,Cs.A.Bényei,Á.Kathó,Angew.Chem.Int.Ed.37(1998) 969–970.

[39]F.Joó,Acc.Chem.Res.35(2002)738–745.

[40]G.-H.Hou, J.-H. Xie,P.-C. Yan,Q.-L.Zhou,J. Am.Chem.Soc.131 (2009) 1366–1367.

[41]G.Hou,R.Tao,Y.Sun,X.Zhang,F.Gosselin,J.Am.Chem.Soc.132(2010) 2124–2125.