Isomerization of a-pinene oxide over cerium and tin catalysts : selective synthesis of trans-carveol and trans-sobrerol.

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ContentslistsavailableatScienceDirect

Journal

of

Molecular

Catalysis

A:

Chemical

jo u rn al h om epa g e :w w w . e l s e v i e r . c o m / l o c a t e / m o l c a t a

Isomerization

of

␣-pinene

oxide

over

cerium

and

tin

catalysts:

Selective

synthesis

of

_{trans-carveol}

and

_{trans-sobrerol}

Vinícius

V. Costa

a

_,

_Kelly

_A.

_da

_Silva

_Rocha

b

_,

_Líniker

_F.

_de

_Sousa

b

_,

_Patricia

_A.

_{Robles-Dutenhefner}

b

_,

Elena

V. Gusevskaya

a,∗

a_Departamento_de_Química,_Universidade_Federal_de_Minas_Gerais,_31270-901,_Belo_Horizonte,_MG,_Brazil b_Departamento_de_Química,_Universidade_Federal_de_Ouro_Preto,_35400-000,_Ouro_Preto,_MG,_Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received3March2011

Receivedinrevisedform9May2011 Accepted22May2011

Available online 27 May 2011

Keywords: Isomerization ␣-Pineneoxide Solventeffect Tincatalysts Ceriumcatalysts

a

b

s

t

r

a

c

t

Aremarkableeffectofthesolventnatureontheacidcatalyzedtransformationof␣-pineneoxideallowed directionofthereactiontoeithertrans-carveolortrans-sobrerol.Eachofthesehighlyvaluable com-poundswasobtainedinnearly70%yieldusinganappropriatepolarsolvent,whosebasicityaffected stronglytheproductdistribution.Inacetone,aweaklybasicsolvent,thereactionoverheterogeneous sol–gelSn/SiO2orCe/SiO2catalystsgavemainlytrans-sobrerol.Noleachingofactivecomponentsoccurs

underthereactionconditionsandthecatalystscanberecoveredandreused.Ontheotherhand,inmore basicsolvent,i.e.,dimethylacetamide,thereactionwasessentiallydirectedtotrans-carveol.Duetothe leachingproblemswithSn/SiO2 andCe/SiO2materials,thesynthesisoftrans-carveolwasperformed

underhomogeneousconditionsusingCeCl3orSnCl2 ascatalystswithacatalystturnovernumberup

toca.1200.Themethodrepresentsoneofthefewexamplesofthesynthesisofisomersfrom␣-pinene oxide,otherthancampholenicaldehyde,withasufﬁcientforpracticalusageselectivity.

1. Introduction

Terpeniccompounds,ingeneral,areanimportantrenewable

feedstockfortheﬂavorandfragranceindustry.Theiroxygenated

derivativesusuallyshowinterestingorganolepticpropertiesand

formoneofthemostimportantgroupsoffragranceingredients

[1,2]. ␣-Pinene,a majorconstituent ofturpentine oils obtained

fromconiferoustrees,is aparticularlyvaluableraw materialin

theproduction of syntheticsubstitutes for natural aromas.The

epoxidationof␣-pineneprovides␣-pineneoxide,whichcanbe

convertedbyacid-catalyzedtransformationsinvariousexpensive

ingredientsfortheﬂavorindustry,suchascampholenicaldehyde,

trans-carveol,trans-sobrerolandtrans-pinocarveol.

␣-Pineneoxideishighlyreactiveinthepresenceofacidandcan

resultinagreatvarietyofproducts.Inoneofthepreviousworks,

over200compoundsformedfrom␣-pineneoxideattemperatures

above100◦Chavebeenfound[3].Therefore,thedevelopmentof

thereactionwhichisselectiveforoneparticularproductisavery

challengingtask.Mostofthestudieshavebeenfocusedonthe

syn-thesisofcampholenicaldehyde,whichisusedforthemanufacture

∗ Correspondingauthor.Tel.:+553134095741;fax:+553134095700. E-mailaddress:elena@ufmg.br(E.V.Gusevskaya).

ofsandalwood-likefragrances[4].Campholenicaldehydecanbe

obtainedfrom␣-pineneoxidewithasufﬁcientforpractical

appli-cationsselectivity[5–7],whereasallothercompoundsareusually

producedasminorproductswithlessthan25%selectivities.

We have recentlystudiedtheapplicationof heteropoly acid

H3PW12O40(PW)fortheliquid-phaseisomerizationof␣-pinene

oxide in various solvents [8,9]. A remarkable effect of solvent

polarityandbasicityonthechemoselectivityofthisreactionwas

found,whichallowedaselectivesynthesisofvariousvaluable

fra-grancecompoundswithreasonableselectivities.Incyclohexane,

anon-polarsolvent,70%selectivitytocampholenicaldehydewas

obtainedonaheterogeneoussilica-supportedPWcatalyst,witha

combinedyieldforcampholenicaldehydeandtrans-carveolbeing

nearlyquantitative.Ontheotherhand,theuseofpolarsolvents

allowedswitchingthereactionpathwaytotheformationof

com-poundswithapara-menthenicskeleton,suchastrans-carveoland

trans-sobrerol.Polar basicsolvents, suchasdimethylacetamide,

favoredtheformationoftrans-carveol;whereaspolarweaklybasic

solvents,suchasacetone,promotedtheformationoftrans-sobrerol

[9].

Thehighest previously reportedyieldof trans-carveol(45%),

anexpensiveconstituentoftheValenciaorangeessenceoilused

in perfume bases and food ﬂavor compositions, was obtained

usingacidicmolecularlyimprintedpolymersasproticcatalystsin

equimolarto␣-pineneoxideamounts[10].trans-Sobrerol,a

well-knownmucolyticdrug,presentlyattractsincreasingattentionfor

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O 1 2 O OH OH OH 3 4

α-pineneoxide trans-carveol trans-sobrerol

5

+ + +

OH

trans-pinocarveol

campholenicaldehyde

Scheme1. Someproductsoftheacid-catalyzedtransformationsof␣-pinene-oxide.

itsotherimportantbiologicalactivities[11].Thehighestpreviously

reportedyieldoftrans-sobrerol(30%)wasobtainedinthereﬂux

dichloroethanesolutionsof␣-pineneoxideandcatalyticamounts

ofTiCl4[12].AlthoughwefoundthatthePWcatalystcouldpromote

theformationoftrans-carveolandtrans-sobrerolinhigherthan70%

yieldeachusinganappropriatepolarsolvent[9],thereactionswere

performedunderhomogeneousconditionsduetohighsolubilityof

PWinpolarsolvents.Nevertheless,theseresultsencouragedusto

workfurtherwiththeisomerizationof␣-pineneoxideinorderto

developheterogeneouscatalyticprocessesfortheselective

synthe-sisoftheproductsotherthancampholenicaldehyde,inparticular,

trans-carveolandtrans-sobrerol.

Withinourprogram aimedataddingvaluetonatural

ingre-dientsofrenewableessentialoils[13–16]wedecidedtoprepare

ceriumandtincontainingmolecularsievesandusedthemasacid

catalystsfortheisomerizationof␣-pineneoxideinpolarsolvents.

Thecatalystshavebeensynthesizedthroughadirecthydrothermal

sol–geltechniquewhichusuallyaffordsmorestabletoleaching

materialsthanconventionalimpregnationmethodsduetohigher

levelsofmetalincorporationinasilicaframework.

Inthepresentwork,wereportasimpleandefﬁcientsynthesis

ofseveralhighlyvaluablefragranceand/orpharmaceutical

com-poundsthroughtheliquid-phaseisomerizationof␣-pineneoxide

inthepresenceofceriumandtincatalysts.Aremarkableeffectof

solventbasicityonchemoselectivityalloweddirectionofthe

reac-tiontoeithertrans-carveolortrans-sobrerol,whichwereobtained

innearly70%yields.

2. Experimental

2.1. Catalystpreparationandcharacterization

The Sn/SiO2 and Ce/SiO2 catalysts were prepared by a

sol–gel method using tetraethoxysilane (14.90g, TEOS, 99%,

Sigma–Aldrich) and SnCl2×2H2O (0.90g, Sigma–Aldrich) or

CeCl3×7H2O(1.44g,Sigma–Aldrich),respectively,asprecursors.

The sol was obtainedfrom a TEOS/ethanol/water mixture in a

1/3/10molarratiowiththeadditionofHClandHF(uptopH2.0)

ascatalysts.Thesamplesweredriedat110◦Cfor24hand

ther-mallytreatedfor2hat500◦Cinair.ApureSiO2 tobetestedin

blankreactionswaspreparedbythesameprocedurewithoutthe

additionofceriumortinchlorides.Thedeterminationoftotaltin

andceriumcontentswasperformedbyinductivelycoupledplasma

atomicemissionspectrometry(ICP-AES) onaSpectroCirosCCD

instrument.

Thetexturalcharacteristicsofthecatalystsweredetermined

from nitrogen adsorption isotherms (Autosorb-Quantachrome

NOVA-1200 instrument, nitrogen, −196◦_C). _Samples _were

out-gassed for 2h at 300◦C before analysis. Speciﬁc surface

areas were determined by the Brunauer–Emmett–Teller (BET)

equation. Average pore diameters were determined by the

Barrett–Joyner–Halenda(BJH)method.

2.2. Catalyticexperiments

The reactions were carried out in a glass reactor equipped

withamagneticstirrerat5–140◦C.Inatypicalrun,amixtureof

␣-pineneoxide(0.122–0.365g,0.8–2.4mmol),dodecane(110_␮L,

0.5mmol,internalstandard)andthesolidcatalyst(0.03–0.12gof

Ce/SiO2,Sn/SiO2orSiO2)orsolublemetalchloride(5–20␮molof

CeCl3×7H2OorSnCl2×2H2O) inaspeciﬁedsolvent(5mL) was

intensivelystirredunderairataspeciﬁedtemperature.The

reac-tionprogresswasfollowedbygaschromatography(GC)usinga

Shimadzu17 instrument ﬁttedwitha Carbowax20Mcapillary

columnandaﬂameionizationdetector.Atappropriatetime

inter-vals,aliquotsweretakenandanalyzedbyGC.TheGCmassbalance,

productselectivitiesandyieldswerecalculatedbasedonthe

sub-stratechargedusingdodecaneasinternalstandard.Thedifference

wasattributedtotheformationofoligomers,whichwerenotGC

determinable.

Catalystrecyclingexperimentswereperformedasfollows:after

thereaction,thecatalystwascentrifuged,washedwithacetonitrile

andthen withcyclohexane andreused.Tocontrolmetal

leach-ing,thecatalystwasremovedatthereactiontemperatureandthe

solutionwasallowedtoreactfurther.

The structures of products 2–5 were conﬁrmed by GC/MS

(ShimadzuQP2010-PLUSinstrument,70eV)bycomparisonwith

authenticsamples.Majorproductswereisolatedbycolumn

chro-matography(silica)andidentiﬁedby1_H_and13_C_NMR_spectroscopy

(BrukerDRX-400,tetramethylsilane,CDCl3,COSY,HMQC,DEPTand

NOESYexperiments).

Spectroscopicdataforcampholenicaldehyde(2)andtrans-carveol

(3)havebeenreportedinourpreviouswork[8].

Spectroscopicdata fortrans-pinocarveol (4): MS(m/z/rel.int.):

134/27[M+_−H

2O],119/53,109/33,105/20,95/20,93/32,92/100,

91/80,83/78,81/38,79/32,77/20,70/92,69/50,67/22,55/90,53/20.

Spectroscopicdatafortrans-sobrerol(5)havebeenreported

pre-viously[9].

3. Resultsanddiscussion

The results of the elemental analysis of the prepared solid

materials,theirBETsurfaceareas,averageporesizes,andpore

vol-umesarepresentedinTable1.BothCe/SiO2andSn/SiO2samples

exhibited theisotherms characteristic of mesoporous materials

andrelativelyhigherspeciﬁcsurfaceareas(297and366m2_g−1_,

respectively). Thematerials were tested as heterogeneous acid

catalystsintheliquid-phaseisomerizationof␣-pineneoxidein

various solvents. Transformations of ␣-pinene oxide (1) under

acidicconditions canresultincampholenic aldehyde(2),

trans-carveol(3),trans-pinocarveol(4)andtrans-sobrerol(5)shownin

Scheme1,aswellasinnumerousotherproducts.Inthepresent

work,oureffortsweredirectedtoachievehighselectivitytoany

otherthancampholenicaldehydeproductandtoperformthe

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Table1

ElementalanalysisdataandtexturalpropertiesoftheCe/SiO2andSn/SiO2catalysts.

Sample CeorSn

content(wt%)

BETsurface

area(m2_g−1₎ Total_volumepore_(cm3_g−1₎ BJH_diameteraverage_(nm)pore

SiO2 – 272 0.91 10.2

Ce/SiO2 4.1 297 0.82 5.2

Sn/SiO2 4.6 366 0.56 6.7

ofactive componentsfromthesolid. Asthebest resultsinthe synthesisoftrans-carveolandtrans-sobrerolfrom␣-pineneoxide werepreviouslyobtainedindimethylacetamide(DMA)and ace-tonesolutions,respectively[9],we initiatedourstudywiththe

Ce/SiO2andSn/SiO2catalystsusingthesecompoundsassolvents.

␣-PineneoxidewasrelativelystableinDMAat140◦C.Inablank

reaction,onlya5%conversionwasobservedfor20h(Table2,run

1).Tooursurprise,puresilica,whichwaspreparedbythesame

procedureasCe/SiO2andSn/SiO2,promotedtheisomerizationof

␣-pineneoxideatareasonableratewithhighselectivityfor

trans-carveol.In thepresenceofonly2wt%ofSiO2 in DMA,a nearly

completeconversionof␣-pineneoxidewasattainedfor10h

result-ingintrans-carveolin70%selectivity(Table2,run2).Itisimportant

thatonlytwominorproductshavebeenobservedindetectable

amounts,i.e.,campholenicaldehydeandtrans-pinocarveol,which

arealsovaluable compounds.Acombinedselectivityfor

camp-holenicaldehyde,trans-carveolandtrans-pinocarveolwasashigh

as97%.

Thesol–gelsilica-includedceriumcatalyst,Ce/SiO2,promoted

muchfasterreactionthanpuresilicagivingasimilarproduct

distri-bution(Table2,run3andrun2).Inrun4,trans-carveolwasformed

innearly70%yield.However,inafurtherstudyithasbeenshown

thatthereactionisnottrulyheterogeneousandthecatalystloses

theactivityduetoleachingofactivecomponents.TheCe/SiO2

cat-alystrecoveredfromthereactionmixtureafterrun3byﬁltration

andreusedinrun5showedmuchloweractivity(52%vs.98%

con-versionin3h)thanduringtheﬁrstuse(Table2).Althoughinthe

thirdreactioncycle(Table2,run6)theactivityofthecatalystdid

notdecreasefurther,therateofthereactionwiththespentcatalyst

wasnearlythesameasthatwithpuresilica.Whereasthefresh

cat-alystresultedinavirtuallycompleteconversionfor3h(Table2,run

3),inrecyclingexperimentsaswellaswithpuresilica,onlyca.60%

ofthesubstratewasconvertedforthesamereactiontime(Table2,

runs2,5and6).Moreover,whenthecatalystwasﬁlteredoffatthe

reactiontemperature,theﬁltratecontinuedtoconvert␣-pinene

oxide.Thus,theCe/SiO2catalystreleasesactivecomponentstothe

DMAsolutionandtheprocessisnottrulyheterogeneous.

Thesol–gelsilica-includedtincatalyst,Sn/SiO2,alsopromoted

theisomerizationof␣-pineneoxide,withthereactionbeingeven

fasterthanthatoverCe/SiO2(Table2,cf.runs3and7).Themain

reactionproductwasalsotrans-carveolobtainedina70%yield.

Thecombinedyieldfortrans-carveolandcampholenicaldehyde

reached90%inthisreaction.However,leachingexperimentswith

thetincatalystalsoshoweddisappointingresults.Inrun8(Table2),

which wasperformedunder thesame conditionsas run7, the

catalystwasremovedbyﬁltrationafter0.5hatthereaction

tem-peratureandtheﬁltratewasallowedtoreactfurther.Asitcanbe

seen,thereactionkeepsgoingintheabsenceofthesolid,albeitat

alowerrate.Thus,boththeCe/SiO2andSn/SiO2materialsarenot

stableinDMAsolutionsunderthereactionconditionsandrelease

activecomponentstothesolution.

In a furtherstudy, we decided to usecerium and tin

chlo-ridesassoluble homogeneouscatalystsfor theisomerizationof

␣-pineneoxideinDMA.Thesecompoundscouldrepresentcheaper

alternativesforthehomogeneousPWcatalystforthesynthesisof

trans-carveolfrom␣-pineneoxidedevelopedinourpreviouswork

Table2

Isomerizationof␣-pineneoxide(1)indimethylacetamide(DMA)solutionsat140◦C.a

Run Catalyst CeorSn(␮mol) Substrate(mmol) Time(h) Conversion(%) Productselectivity(%) TONb _TOFb_(h−1₎

2 3 4 1 – – 0.8 20 5 2 SiO2(0.12g) – 0.8 3 58 10 95 16 70 11 3 Ce/SiO2 40 0.8 3 98 19 72 5 4 Ce/SiO2 40 2.4 8 98 18 73 5 5c _Ce/SiO 2 40 0.8 3 52 19 69 7 6d _Ce/SiO 2 40 0.8 3 58 20 70 6 7 Sn/SiO2 40 0.8 0.5 48 1.5 100 20 70 5 8e _Sn/SiO 2 40 0.8 0.5 52 3 92 20 71 6 9 CeCl3 20 0.8 2 100 17 42 36 40 20 10f _CeCl 3 20 0.8 4 100 16 41 38 40 10 11 SnCl2 20 0.8 0.5 100 16 70 10 40 80 12f _SnCl 2 20 0.8 1 100 15 68 12 40 40 13 SnCl2 20 1.6 1 100 19 62 15 80 80 14 SnCl2 5 1.6 1.5 100 17 65 15 320 213 15g _SnCl 2 5 1.6 1.5 98 17 62 17 634 210 1.6 2.5 95 19 64 15 938 122 1.6 4 90 18 60 19 1226 72

a_DMA₅_mL,_solid_catalyst_ca._2.0–2.5_wt%._Conversion_and_selectivity_were_determined_by_GC. b_TON_–_moles_of_the_substrate_{converted/moles}_of_Ce_or_Sn._TOF_–_the_average_turnover_frequency. c _The_catalyst_was_re-used_after_run_3.

d _The_catalyst_was_re-used_after_run_5.

e_The_catalyst_was_removed_by_ﬁltration_after_0.5_h_at_the_reaction_temperature_and_the_ﬁltrate_was_allowed_to_react_further. f ₁₂₀◦_C.

g_After_run_14,_three_fresh_portions_of_the_substrate_(1.6_mmol_each)_were_added_{consequently,}_each_one_after_the_nearly_complete_conversion_of_the_previous_portion._Total

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Table3

Isomerizationof␣-pineneoxide(1)inacetonesolutions.a

Run Catalyst CeorSn(␮mol) Substrate(mmol) T(◦C) Time(min) Conversion(%) Productselectivity(%)

2 3 5 1 – – 0.8 25 300 5 2 SiO2(0.12g) – 0.8 25 180 84 19 10 69 3 SiO2(0.12g) – 0.8 40 180 97 16 13 70 4 Ce/SiO2 40 0.8 25 30 96 14 12 72 5 Ce/SiO2 40 0.8 40 30 100 21 11 65 6 Ce/SiO2 40 0.8 5 90 100 18 10 70 7b _Ce/SiO₂ ₂₀ _0.8 ₂₅ ₁₈₀ ₉₈ ₁₆ ₁₀ ₇₂ 8 Sn/SiO2 20 0.8 25 15 100 17 11 70 9 Sn/SiO2 10 0.8 25 15 100 16 10 72 10 Sn/SiO2 10 1.6 25 60 95 17 11 72 11b _Sn/SiO 2 10 0.8 25 30 43 180 80 20 14 63

a_Conditions:_acetone₅_mL,_solid_catalyst_0.5–3.0_wt%._Conversion_and_selectivity_were_determined_by_GC. b _Water_was_added₍₁_vol%).

[9].RepresentativeresultsareshowninTable2.Inthepresenceof

CeCl3(0.025eq),thereactionoccurredsmoothlyresultingina

com-pleteconversionfor2–4hdependingonthereactiontemperature

(Table2,runs9and10).However,theproductdistributionwas

dif-ferentfromthatobservedintheheterogeneoussystem,inwhich

trans-pinocarveolwasdetectedonlyasaminorproduct(ca.5%).

Intheceriumcatalyzedhomogeneousreaction,trans-carveoland

trans-pinocarveolwereformedincomparableamountsinca.40%

selectivityeach,withcampholenicaldehydebeingamainminor

product(ca.15%).Thesystemissyntheticallyusefulconsidering

ahighcombinedyieldforthreeexpensivefragrancecompounds

(95%),lowcatalysttosubstrateratioandpossibilitytore-usethe

catalystsolutioninDMAaftertheextractionoftheproductswith

hydrocarbonsolvent,e.g.,hexane.Inmostofthereportedsystems,

themain product ofthe ␣-pineneoxide isomerization(usually

campholenicaldehyde)wasobtainedalongwithnumerousside

products[3,7].

The conversion of ␣-pinene oxide in the solutions of SnCl2

(0.025eq) was very fast, much faster than with CeCl3. The tin

catalyzedreactionsshowedfour timeshigher averageturnover

frequencies(TOFs)thanthosecatalyzedbycerium(Table2,runs

11and12vs.runs9and10)andgaveca.95%combinedyieldfor

campholenicaldehyde,trans-carveolandtrans-pinocarveol,with

trans-carveolaccountingforca.70%ofthemassbalance.Aimingto

improvethecatalystefﬁciencyintermsofturnovernumber(TON)

weincreasedthesubstrateconcentrationandthendecreasedthe

catalystamounts(Table2,runs13and14).Inrun14,TONof320

permolofSnand65%selectivitytotrans-carveolwereobtained.

Afterrun14,threefreshportionsofthesubstrate(1.6mmoleach)

wereaddedconsequently,eachoneafterthenearlycomplete

con-versionofthepreviousportion.ThetotalTONof1226permolof

Snwasobtainedinthisreaction,whichgave campholenic

alde-hyde,trans-carveolandtrans-pinocarveolinanearlyquantitative

combinedyield(Table2,run15).

Thus,intheDMAsolutions,tinand ceriumcatalystsaswell

aspuresilicapromotetheisomerizationof␣-pineneoxidegiving

mainlytrans-carveol,withonlytwominorproducts:campholenic

aldehydeandtrans-pinocarveol.

Ina furtherstudy,wehave testedthepreparedCe/SiO2 and

Sn/SiO2materialsfortheisomerizationof␣-pineneoxidein

ace-tonesolutions.RepresentativedataarecollectedinTable3.Inthis

case,muchmorepromisingresultsintermsofcatalystleaching

wereobtained,whichallowedthedevelopmentoftruly

heteroge-neousprocessesforthesynthesisofhighlyvaluabletrans-sobrerol.

Ina blank reactionwithnocatalyst added,only 5%conversion

wasobservedfor6hatroomtemperature(Table3,run1).Inthe

presenceofpuresilica,␣-pineneoxideundergoesarelativelyfast

isomerizationevenatroomtemperature(Table3,run2).At40◦C

withpuresilica,anearlycompleteconversionwasachievedfor3h

givingtrans-sobrerolinca.70%yield(Table3,run3).

WiththeCe/SiO2catalyst,thereactionshowedasimilarproduct

distribution;however,itwasmuchfasterthanthatwithpuresilica

(Table3,runs2and3vs.runs4and5).Forthecomparisonpurpose,

thesamemassamountsofSiO2 andCe/SiO2 wereusedinthese

runs.Inanattempttochangethereactionselectivity,wedecreased

thereactiontemperature;however,itdidnotaffectsigniﬁcantly

thereactionpathways(Table3,run6).Then,wehaveaddedwater

(1vol%)tothesystemtryingtoincreasetheyieldofthemain

prod-uct,trans-sobrerol,whoseformationrequireswater(Table3,run

7).However,wedidnotsucceed:thebestobtainedyieldof

trans-sobrerol wasnearly 70%. It is importantto notethat only two

minorproductshavebeenobservedindetectableamountsalong

withtrans-sobrerol,i.e.,campholenicaldehydeandtrans-carveol,

withatotalyieldforallthreevaluablecompoundsbeingalmost

quantitative.

InthepresenceoftheSn/SiO2material,thereactionwasvery

fastastheanalysisoftheﬁrstaliquottakenafter15minshoweda

completeconversion(Table3,runs8and9).Further,theamount

ofthecatalystwasdecreased whereasthesubstrate

concentra-tionwasincreased(Table3,run10).Inthisrunwithonly0.5wt%

ofthecatalyst,trans-sobrerolwasobtainedinca.70%yield.

Con-sideringthatfortheformationoftrans-sobrerolwaterisneeded

wehaveadded 1vol%ofwater tothesystem(Table3,run11).

However,thepresenceofextraamountsofwaterresultedinno

changesintheproductdistribution,withthereactionratebeing

decreased signiﬁcantly(Table3,run 11 vs.run 9).Itshouldbe

mentionedthat,generally,water wasnot addedtothereaction

system.Theamountofhydrationwaterpresentinthesolid

cata-lystsandcommercial␣-pineneoxideandacetonewassufﬁcient

fortheformationofsobrerol.Inaddition,watercouldbepresent

inside SiO2 poresof the catalystswhich had a pore volume of

0.56–0.91cm3_g−1_.

TheleachingofactivecomponentsfromtheCe/SiO2andSn/SiO2

materialsunder the reaction conditions wasveriﬁed in special

experiments.Afterruns5and9(Table3),thecatalystswereﬁltered

offatthereactiontemperaturetoavoidre-adsorptionofleached

metalionsontothesolidsupport.Then,theﬁltrateswererecharged

withfreshsubstrateandallowedtoreactfurther.Noconversion

of␣-pineneoxidewasobservedaftercatalystremoving,

provid-ingstrongevidenceinsupportofheterogeneouscatalysis.Thus,

thereactionsolutionscontainednosigniﬁcantamountsofactive

speciesandtheactivityofbothsol–gelsilica-includedcatalysts,

Ce/SiO2andSn/SiO2,wasduetotheactivespeciesimmobilizedin

themesoporoussilicaframework.Thebehaviorofbothspent

cat-alystsrecoveredafterruns5and9(Table3)withfreshsubstrate

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2 A OH OH OH B O C 1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 8 9 10 7 7 2 9 5 1 10 3 4 6 8 3 5 routeC routeB +H2O O O O O 4 OH La La=Lewisacid 1 O La La -La La La -La -La -La routeA

Scheme2.SchematicrepresentationoftheLewisacid-catalyzedtransformationsof␣-pinene-oxide.

AschematicrepresentationoftheLewisacid-catalyzed

trans-formationsof1intoproducts2–5isgiven inScheme2.In this

scheme,“La”representsLewisacidactivesitesonthecatalyst

sur-face(cationicceriumandtinspecies)orinthesolution(Ce3+_and

Sn2+_ions)._The_activation_of_the_epoxide_moiety_by_the_acidic_sites

inducesepoxyringopeningandinitiallygivescarbeniumionA.The

lattercanundergoseveralcompetingprocesses.First,itcangive

directly,withoutanyisomerization,trans-pinocarveol4througha

hydrogenshiftfromtheC-10methylgrouptotheoxygenatom.

Thehydrogen abstractionand transfer couldbeassisted in our

systembythebasicsolvent,DMA.IntheCeCl3/DMAsystem,

trans-pinocarveolaccountsforca.40%ofthemassbalance.Inaddition,

carbeniumionAcanrearrangeintocarbeniumionsBorCthrough

themovementofthepairofelectronsfromthesamecarbon-carbon

␴-bondtoeitherC-7orC-6,respectively.CarbocationBgives

cam-pholenicaldehyde2throughtheC-1–C-2bondcleavage,whereas

carbocationCformstrans-carveol3throughtheprotonshiftfrom

theC-9methylgroup.Thelatterprocesscouldalsobeassistedby

thebasicsolvent(inDMA)and/orbytheoxygenatomsfromthe

SiO2supportactingasLewisbasicsites(inbothacetoneandDMA

solvents).

Theresultsobtainedinthepresentworkshowedthatasolvent

naturecanprofoundlyaffectthereactionpathwaysandproduct

composition.Thisobservationallowedustodevelopefﬁcient

syn-theses ofvarious compoundsfrom␣-pinene oxidethroughthe

choiceoftheappropriatesolvent.AsitcanbeseeninScheme2,

relativeamountsoftrans-pinocarveol4,theproductwithabicyclic

non-isomerizedpinaneskeleton,andmonocycliccompounds2,3

and5dependonthebalancebetweenthehydrogentransferin

cationA(routeA)anditsisomerizationincationsBandC(routes

BandC).Trans-pinocarveolwasformedinsigniﬁcantamountsin

DMAsolutionsbutnotinacetone.Both,DMAandacetonearehighly

polarsolvents;however,DMAhasmuchhigherbasicity(pKa≈−0.5

forDMAH+_vs._pK

a≈−7for(CH3)2COH+[17]).Therefore,itseems

reasonablethatcarbocationAismorepromptedtoundergoa

pro-tonshift(routeA)beforeitsisomerization(routesBandC)inDMA,

whichhasrelativelystrongprotonacceptorproperties,thaninless

basicacetone.

On theother hand,theratio betweenaldehyde 2and

para-menthenic compounds 3 and 5 is inﬂuenced by the balance

betweentwo differentrearrangements ofcarbeniun ion A:into

cyclopentaniccationB(routeB)andintopara-mentheniccation

C(routeC).TertiarycarbeniunionCismorethermodynamically

stablethansecondarycarbeniumionB;therefore,theformationof

aldehyde2shouldbekineticallycontrolled.CarbeniumionCcan

givetrans-carveol3orundergoanucleophilicattackbywaterto

formtrans-sobrerol5.

Inthepreviouswork[9],wehavefoundthattheincreasein

bothsolventbasicityandpolaritystronglyprejudicesrouteBto

aldehyde 2, whereasit favors routeC topara-menthenic

prod-ucts.Forexample,incyclohexane,anon-polarnon-basicsolvent,

themainreactionproductwascampholenicaldehyde 2.Ahigh

ion-solvatingabilityofpolarsolventscouldresultinstabilization

ofcation Afavoringitsrearrangementintomorestabletertiary

carbeniumionC.Ontheotherhand,thedistributionbetween

para-menthenicproducts3and5dependsonsolventbasicityratherthan

onitspolarity.InbasicandpolarDMA,wheretheprotontransfer

inCcanbeassistedbythesolvent,theformationoftrans-carveol

3occursfasterthantheformationoftrans-sobrerol5andbecomes

thepreferablereactionpathway.

Itshouldbementionedthattheresultsobtainedwith

(6)

betweenthereactionpathwaysleadingtodifferentproductsfrom

␣-pineneoxideismostlydeterminedbythenatureofthesolvent

ratherthanbythenatureofthecatalystorotherreactionvariables.

However,furtherstudiesshouldbetargetedtowardclarifyingthe

effectofsolventpolarityandbacisityontheacidityofthe

cata-lystsurface,which shouldalsobeconsideredforunderstanding

thereactionselectivity.

4. Conclusions

Chemoselectivityof theisomerizationof␣-pineneoxidecan

becontrolledthrough thechoiceof thesolvent,whosepolarity

andbasicitydeterminethereactionpathways.Theheterogeneous

process for the synthesis of highly valuable trans-sobrerolhas

been developed using weakly basic acetone as a solvent and

silica-includedtinandceriummaterialsaseasilyrecoverable

cat-alysts. Even pure silica alone can be used as a heterogeneous

catalyst in this reaction, albeit less effective in terms of

cat-alyticactivity.On theotherhand,indimethylacetamide, which

ismuchmorebasic,thereactionisessentiallydirectedto

trans-carveol,regardlessofthecatalyst.Thesol–gelSn/SiO2andCe/SiO2

materialsshowedhighactivityand selectivityfor trans-carveol;

however,theﬁltratesolutionspromotedtheisomerizationof

␣-pinene oxideafter the catalyst removal. Dueto these leaching

problems,thesynthesisoftrans-carveolwasperformedusing

dis-solvedCeCl3 orSnCl2 ashomogeneouscatalystsorpuresilicaas

aheterogeneouscatalyst.Thedevelopedmethodsareamongfew

examplesoftheselectivesynthesisofotherthancampholenic

alde-hydecompoundsfrom␣-pineneoxidethroughitsacid-catalyzed

isomerization.

Acknowledgments

FinancialsupportfromtheCNPq,CAPES,FAPEMIGand

INCT-Catálise(Brazil)isgratefullyacknowledged.

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