proelectrophile-nucleophile adduct formation and permanganate oxidation of alkenes

238 Pages·2014·1.75 MB·English

PROELECTROPHILE-NUCLEOPHILEADDUCTFORMATIONAND
PERMANGANATEOXIDATIONOFALKENES:
USEOFMODELCOMPOUNDSTOPROBECOMPLEXREACTION
PATHWAYS
By
PhillipM.Flanders
AdissertationsubmittedtoJohnsHopkinsUniversityinconformity
withtherequirementsforthedegreeofDoctorofPhilosophy
Baltimore,Maryland
February,2014
©2014PhillipFlanders
AllRightsReserved
Abstract
Laboratorystudiesofreactionsbetweenmodelcompoundsyieldvaluableinsightsinto
complex reaction chemistries that would be difficult if not impossible to observe directly
in environmental media. We used model compounds to investigate two types of reaction
pathways: adductformationandpermanganateoxidation.
First, we mimicked covalent bond forming reactions between nucleophilic contaminants
and electrophilic sites within natural organic matter (NOM) or naturally occurring elec-
trophilictoxicants. InitialstudiesmodeledadductformationatelectrophilicNOMsitesby
reactingthemodelelectrophilesp-benzoquinoneandpatulinwithasuiteofmodelnucle-
ophiles. Furtherstudies usedMnO (s, pyrolusite)-oxidizedhydroquinone proelectrophiles
2
tosimulatethehighlyelectrophilicmoietiesthatcanbegeneratedwhenNOMreactswith
oxidants in a sediment or soil. Overall, our model compound studies demonstrated that
addednucleophilescompetewithH O/OH– toformmonoadducts,whichcanthenundergo
2
further oxidization and addition to form di- and triadducts. Mass spectra consistent with
monoadductsfromreactionsbetweenninenucleophilesandMnO -oxidizedgentisicacid
2
wereacquiredbyLC/MS.Separateexperimentsmonitoringboththeconsumptionofamodel
proelectrophileandanucleophile(acetylhydroquinoneand4-ethylaniline,respectively)and
the generation of MnII from reduction of MnO provided indirect evidence for multiple
2
oxidation-additionsteps.
ii
Second,weusedmodelcompoundstostudypermanganateoxidationofalkenes. Compe-
titionbetweenhydrolysis andoxidationofa commonintermediateleadsto adistributionof
products. TocollectdirectevidenceoftheinfluenceofpHandoxidantdoseonthisproduct
distribution, we selected cis-stilbenedicarboxylic acid as a model compound because it
yields permanganate oxidation products amenable to LC/MSanalysis. High permanganate
dosefavorshighlyoxidizedproducts,whilealkalinepHfavorsproductsfromhydrolysis.
Thisdissertationdemonstrateshowstrategicselectionofmodelcompoundscanelucidate
complexenvironmentalcontaminantremovalpathwaysbyprovidinganinternallyconsistent
systemforthestudyofmultiplereactionconditionsandcompetitivereactions.
Advisor: AlanT.Stone
Readers: A.LynnRobertsandStevenRokita
iii
Acknowledgments
I owe thanks and gratitude to many people who’ve helped me and been there for me
duringgraduateschool.
FirstIthankmyparents,JeffandKarenFlanders,fortheirloveandsupportthroughout
these many years of education. They have always offered inspiration, guidance, and
assistancewheneverIneededit–whetherIknewIneededitornot.
I’d like to thank my roommates who’ve lived with me during graduate school: John
Sivey,UmutAypar,AndrewClayborneandJenniferRonald. Theyputupwithmyquirks
overtheyearsandwereunderstandingfrontlinestotheday-to-daystressofgraduateschool.
I thank my advisor, Prof. Alan Stone, for all of his guidance, patience, and detailed
feedback. He hasbeenaninvaluableresourceandimaginativethinkerthroughoutthisentire
process.
I thank other professors at Johns Hopkins who have influenced me over the past few
years: Lynn Roberts, Bill Ball, Ed Bouwer, Kai Loon Chen, and Dimitri Sverjensky. I
thankmy DQEcommittee: AlanStone,LynnRoberts,Ed Bouwer, and KaiLoonChen. I
thank my GBO committee: Alan Stone, Lynn Roberts, Gerry Meyer, Caren Meyers, and
GaryPosner. Lastly,Ithankmydefensecommittee: AlanStone,LynnRoberts,andSteven
Rokita.
iv
I thank Penney Miller, my research advisor during my undergraduate years at Rose-
HulmanInstituteofTechnology. Shepiquedmyinterestinenvironmentalchemistry. Her
mentorship provided me with a set of skills that have been invaluable in my doctoral
research. ShegavemerealappreciationforHPLCandLC/MS.Shebuiltthefoundationof
myscientificwriting,presentation,andexperimentalplanningskills.
IthankChrisHigginsforteachingmehowtooperatetheLC/MS,whichIusedexten-
sivelyinmyresearch. Healsohasbeenacontinuingsourceofhelpandinspiration.
IthankKeithRitchieforallofhistimeandeffortmakingsurethattheinstrumentsand
toolsthatIusewerekeptinworkingorder. I’malsogratefulforhishelpwiththelabforthe
ExperimentalMethodscourse.
I thank the department’s front office staff for all of their help making this dissertation
happen: Joe,Joyce,Christine,Rob,Rok,Adena,Denise,andthestudentworkers.
I thank the other members of Prof. Stone’s research group during my time at Johns
Hopkins: Zhi Shi, Nathan Boland, Grace Stokes, and Xiaomeng Xia. I also thank the
otherdoctoralstudentswhoworkedalongwithmeinthelabs: JohnSivey,KevinBisceglia,
KatieOnesios, JessicaLawson, Amar Wadhawan, AndrewGraham, PavloBohutskyi,Jin
Yang, AnHuynh, PengYi, YaqiYou,Shao-YiuHsu, and StephanieLau. Thediscussions,
collaborations, and friendships I’ve had with all of you were an invaluable part of these
yearsofmylife.
Lastly,IneedtothankthefriendsIhavemadeinBaltimoreformakingsurethat–whenI
havesomefreetime–Ialwaysenjoyedmyself! Youguysarethebest! Iwouldalsoliketo
thanktheDissertationSupportGroupforyouradviceandinspiration.
Thankstoeveryonewhohasbeenapartofmylifethesepastsixyears!
v
Thisdissertationisdedicatedto
thearmyofpeoplewhobelievedinme
andmadeitpossible.
vi
Contents
Abstract ii
Acknowledgements iv
ListofTables xiii
ListofFigures xix
ListofSymbols xx
1 Introduction 1
1.1 Motivation 1
1.2 OxidationStatesofManganese 6
1.3 ResearchObjectivesandThesisOutline 8
2 Aqueous Addition Reactions of Patulin andp-Benzoquinone: Competition Be-
tweenAddedNucleophiles,Water,andBuffers 23
2.1 Introduction 23
2.2 MaterialsandMethods 28
2.2.1 Chemicals 29
2.2.2 ExperimentalDesign 29
vii
2.2.3 InstrumentationandAnalysis 30
2.3 ResultsandDiscussion 33
2.3.1 p-Benzoquinone 33
2.3.2 Patulin 35
2.3.3 ComparisonofElectrophilicity: p-BenzoquinoneandPatulin 35
2.3.4 Assessing Nucleophilicity: Aminopyralid, Chloramben, and Clo-
pyralid 37
2.4 Conclusions 38
2.5 SupportingInformation 54
2.5.1 PatulinMichaelAdditionMechanismProposedbyFliegeandMetzler 54
2.5.2 p-BenzoquinoneandReactionswithBufferCompounds 57
2.5.3 PatulinandReactionswithBufferCompounds 61
3 Highly Reactive p-Benzoquinone Electrophiles Generated by the Oxidation of
SubstitutedHydroquinonesUsingMnO (s,pyrolusite)asanOxidant 78
2
3.1 Introduction 78
3.2 MaterialsandMethods 87
3.2.1 Chemicals 87
3.2.2 ExperimentalDesign 88
3.2.3 InstrumentationandAnalysis 89
3.3 ResultsandDiscussion 91
3.3.1 Proelectrophile Experiments with Acetylhydroquinone, 4-Ethyl-
aniline,andMnO 91
2
3.3.2 InfluenceofProelectrophileandNucleophileStructure 96
3.3.3 LC/MSEvidenceofMonoadducts 99
viii
3.4 Conclusions 101
3.5 SupportingInformation 123
3.6 ApplicationoftheLangmuir-Hinshelwood-Hougan-Watsonkineticmodel 123
4 PermanganateOxidationofAlkenes: StudyingProductDistributionUsingcis-
StilbenedicarboxylicAcidasaConvenientModelCompound 144
4.1 Introduction 144
4.2 MaterialsandMethods 152
4.2.1 Chemicals 153
4.2.2 ReactionMediumandExperimentalDesign 154
4.2.3 TimeCourseExperimentsandKineticAnalysis 155
4.2.4 ReactionQuenchExperimentsandOxidizingEquivalents 157
4.2.5 InstrumentalAnalysis 161
4.3 Results 162
4.3.1 TimeCourseExperiments 162
4.3.2 ReactionQuenchExperimentsandOxidizingEquivalents 164
4.4 Discussion 166
4.5 Conclusions 170
4.6 SupportingInformation 190
4.6.1 RedoxReactionsforPermanganateOxidationofanAlkene 190
4.6.2 3-Cyclopentene-1-carboxylicacid 194
5 Conclusion 208
5.1 SummaryofFindings 208
5.1.1 NucleophilicAdditionReactions 208
5.1.2 PermanganateoxidationofAlkenes 211
ix
5.2 FutureResearch 212
5.2.1 NucleophilicAdditionandtheProelectrophilePathway 212
5.2.2 OxidationbyPermanganate 214
Vita 216
x