novel, new aromatic sf5 derivatives · many examples of agents bearing cf3 ... many of the solids...

AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs

NovelNewAromaticSF5Derivatives

PreparedinHighYieldviaHighlyVersatileampCostCompetitiveMethods

AromaticSF5compoundsareexpectedtobeusefulasBUILDINGBLOCKSforpharmaceuticalagriculturalandotherbio-activeagentspesticidesliquidcrystalsnovelstructuralandconductivepolymersdyesorganicsemiconductorshighenergycompoundspropellantsandexplosivesandmanyotherhigherperformanceorganicmaterials

ManySF5containingintermediateshaverecentlybecomeavailablebutonlyinsmallquantitiespricedathundredstothousandsofdollarspergramcurrentlymadebyinefficientandexpensiveprocessesThenewrecentlydevelopedprocedures(describedbelow)whencommercializedpromisetomakethesecompoundsmorereadilyavailablemuchmoreaffordableandingreatervarietyforresearchandproductionofmanyusefulproducts

Anewerainchemistryhasbegunwiththeintroductionofthefirstnewfunctionalgroupinoveracentury

ILloydGarrickpreparedthecompoundsbelow[aswellasmanyothersnotlisted]in10-100gquantitiesaspartofmyResearchandProcessDevelopmentworkatUBEAmericaIncinDenverThefacilityhasbeencloseddownasofAugust2013ResearchDevelopmentandProductionofthesetypecompoundsisnolongerinprogressinthiscountrytoanysignificantextentasfarasIknowatthistime

Thecompoundsweremadeeitherdirectlybythenewprocess(es)fromtheappropriatethiolordisulfidestartingmaterialorinmanycasesbystandardderivatizationsofring-fluorinecontainingcompoundsOthercommonmanipulations(nitrationmetalationmethyloxidation)werealsousedSF5isinerttoallbutthemostdrasticreactionconditions

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Introduction

ConcurrentwithsignificantdevelopmentsinthesyntheticmethodologyforthepreparationofSF5containingcompoundsmanypotentialapplicationsderivedfromtheinterestinganduniquepropertiesoftheSF5functionhavebeenproposedparticularlyincertainadvancedspecialtychemicalfieldssuchaspharmaceuticalsagrochemicalsandelectronics

TheSF5functiononeofthemostelectron-withdrawinggroupsknownimpartsoutstandinglipophilicpropertiestocompoundswhichincorporateitaswellasaddedchemicalandthermalstabilityItisexpectedthatthehigherlipophilicityandotherpropertiesofSF5compoundswillshowinterestinganduniqueinfluencesonbiologicalactivitiesotherthanthoseobservedwithfluorineortrifluoromethyl-groups

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RegardingelectronicschemicalsitisreportedthattherehasbeenarapidincreaseinthenumberofpatentswhichlisttheSF5groupinliquidcrystalsduetothestrongdipolemomentwhichcanbeachievedbytheSF5group

PropertiesofAromaticSF5compounds

SF5groupiscalledSuper-trifluoromethylgroupandtheexpectedpropertiesofSF5-containingcompoundsaresimilartotheoneswhichareseeningeneralfluorinecompoundsalthoughmostofthemaresignificantlyenhancedbytheincrementofthenumberoffluorineatomsinSF5group

Electron-withdrawingEffect

SF5groupisrecognizedasastrongelectron-withdrawinggroupFigurebelowshowsthecomparativevaluesofpKainthesubstitutedbenzoicacidderivativeswhichhaveSF5CF3SCF3OCF3andFrespectivelyTheSF5derivativeisrankedasthesecondstrongestgroupafterthenitro-substitutedone

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Lipophilicity

Itiswellknownthatcompoundswhichincorporatefluorine(s)showgreaterlipophilicitySF5substitutedcompoundsareexpectedtoshowexcellentlipophilicitycomparedwithotherfluorine-containingcompoundsThelipophilicityindicesofseveralfunctionalgroupsareshownbelowThesevaluesarecalculatedbyformulafromtheXow-values(octanolwaterpartitioncoefficient)

Inparticularinagrochemistry[agriculturalchemistrycompoundssuchasherbicidesfungicidesinsecticidesplantgrowthregulatorsetc]thisqualityoflipophilicityisoftenexploitedasitisveryimportantManyexamplesofagentsbearingCF3OCF3andSCF3groupsareinuseorstillbeingdevelopedIllustrativeexamplesaredisplayedelsewhereonthispage

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ThermalandChemicalStability

AromaticSF5compoundspossessexcellentthermalandchemicalstabilityForexampleitwasdemonstratedthatthethermaldecompositionrateofPhSF5(PSF)waslessthan20afteritwasheatedinasealedtubeat400Cfor7hoursItwasalsodemonstratedthataromaticSF5compoundsaremoretolerantthanaromaticCF3compoundsunderstrongconditionsofBronstedacidsandbasesandcanbewidelyappliedforcommonsynthetictransformationsinhighyieldExamplesofreactionsforAromaticSF5compoundsareshownbelow

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Toxicity

RegardingtheassessmentoftoxicityofAromaticSF5compoundsthearomaticSF5compoundsshownbelowwereassayedforbothAmesandAcuteOralToxicityTablebelowshowsbothresultsincludingtheempiricaldataobtainedfromtheAcuteOralToxicitytest4MPSFshowedweaktoxicitywithrange50-300mgKgandrankedasCategory3inUNGHSThisandotherdatasofarhaveshownthatSF5haslittle(ifany)intrinsictoxicityanditisntmetabolizedThusitshouldbeasignificantimprovementinbioactivecompoundswhereitcanreplacetoxicgroupslikeNO2BrandCN

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ALLoftheChloropentafluorosulfanatecompounds[Ar-SF4Cl]eventhecrystallinesolidsareextremelynoxiousTheyhavestrongpenetratingpersistantirritatingmustardlikeodorsIfWhenyousucceedinmakinganyyouwillknowitSkincontactwillproduceirritationandblisteringTheyarenotalkylatingagentsintheclassicalsensebutrathersulfonatingagentsasdepictedintheequationsjustbelowElectronwithdrawinggroupsontheringtendtomakethecompoundsmorestableandlessreactiveelectrondonatinggroupshavetheoppositeeffectofcourse

IncontrastthePentafluorosulfanate[SF5]compoundsarequitepleasantTheinertSF5substituentgivesitsmoleculescrystallinityvolatilitystabilityandahostofotherpleasantattributesincludingodorPhSF5isadense(155)liquidwithanodorbetweentolueneandlemonjuiceManyofthesolidsandpolyfunctionalSF5compoundsresemblecamphormintcloveetc

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HydrolyticStabilityandPhysicalCharacteristics

ArSF5canbeheldfor4hoursat100Cin1NNaOHwithoutmeasurablehydrolysiswhereasArCF3iswellknowntobesucceptibletoalkalinehydrolysisespeciallyiforthoorparatoaringhydroxylIna20NNaOHsolutionatroomtemperature4-CF3-anilinereadilyhydrolyzedwhereas4-SF5-anilinewasrecoveredinhighyield(91)ArCF3inconcH2SO4at90CiscompletelyhydrolyzedwithinminutesUndersimilarconditions[suchasmynitrationreactionsonPhSF5]nosignificanthydrolysisoccuredmono-nitrationproduct(s)alwaysrecoveredin~quantitativeyieldAlthoughSF5appearstobestabletoevenstrongalkalinecondiditonsveryvigorousacidconditionswillhydrolyzeitforexampleArSF5in90HNO330Oleumat80Cfor4-7days[myreactionfordi-nitrationofPhSF5]gaveabout60hydrolysistothesulfonateandproduct(s)recoveredwereabout40

ThevolumeofSF5islargerthanCF3andslightlysmallerthantert-butylLentzampSeppeltInChemistryofHypervalentCompoundsKAkiba(Ed)Wiley-VCHNewYork1998295TheSF5groupismoreelectronegativethanCF3SaeligthreBerrahBozekBoslashrveCarrollKukkGardWinterampThomasJAmChemSoc200112310729WipfHenningerampGeibJOrgChem1998636088UnlikeCF3theSF5groupisverystableunderstrongacidandbasicconditionsBowdenCominaGreenhallKariukiLovedayampPhilpTetrahedron2000563399TheutilityofSF5derivativesindrugdiscoverywasrecentlyshowcasedbyWipfandcoworkersinthedesignofimprovedMefloquineWipfMoGeibCaridhaDowGerenaRoncalampMilnerOrgBiomolChem200974163

BiologicalActivities

OrganopentafluorosulfanylChemistry

Thepentafluorosulfanyl(SF5)groupisoneofonlyaveryfewtrulynewfunctionalgroupstobeintroducedtothearmentariumofthesyntheticorganicchemistinthelast100yearsThepseudooctahedralsymmetryoftheSF5grouppresentingasquarepyramidofelectrondensityasdefinedbythefluorineligandsisnototherwiseknowntothemedicinalorpharmaceuticalchemistHoweveronlywiththerecentavailabilityofthenecessaryreagentsandbuildingblockshasthisfunctionalgroupfoundapplicationsasanaromaticsubstituentinagrochemicalspharmaceuticalsandliquidcrystalsInaliphaticchemistrypentafluorosulfanylatedmaterialsareevenmorerarelyencounteredwithapplicationslargelylimitedtopolymeroroligomerpreparationsTheSF5groupisprofoundlyelectronwithdrawingbutwiththehighlypolarizablecarbon-sulfurbondmaydirectlyinfluencereactivityinamannerdifferentfromthatassociatedwiththetrifluoromethylgroup

TreflanAnalogs

Thesynthesisof26-dinitro-4-pentafluorosulfanyl-NN-dipropylaniline2wasachievedinastraightforwardmannerfromcommerciallyavailable1-nitro-4-pentafluorosulfanylbenzeneInpost-emergencescreening2wasfoundtobeapproximatelytwiceaspotentastrifluralinwiththesamegeneralspectrumofactivityIncontrastinpre-emergencetests2wasnearly5foldmorepotentagainstquackgrassandcrabgrass

References

SynthesisandHerbicidalActivityofaPentafluorosulfanylAnalogofTrifluralinDSLimJ-SChoiCSPakandJTWelchJPesticideScience2007inpresspentafluorosulfanylanalogoftrifluralinref1pentafluorosulfanylanalogoftrifluralinref2

SerotoninAnalogs

ThetrifluoromethylgroupoffluoxetineandfenfluramineandnorfenfluraminewassubstitutedbythepentafluorosulfanylgroupOnexaminationoftheefficacyofthepentafluorosulfanylcontainingcompoundsasinhibitorsof5-hydroxytryptaminereceptorsitwasfoundthatsubstitutioncouldleadtoenhancedselectivityandinthecaseofthepentafluorosulfanylanalogoffenfluramineledtosignificantlyenhancedpotencyagainstthe5-HT2b5-HT2cand5-HT6receptors

References

ThesynthesisandbiologicalactivityofpentafluorosulfanylanalogsoffluoxetinefenfluramineandnorfenfluramineJTWelchDSLimBioorgMedChem2007156659

AntineoplasticAgents

MuchpotentialforSF5existsinthefieldofchemotherapyanditislargelyunresearched(iewideopen)rightnowItiswellknownthattheinternalenvironmentsofneoplasms(tumorcellsetc)areparticularlylipophilicthustheSF5functionasitconfersstronglipophiliccharactertomoleculesincorporatingitshouldofferconsiderableimprovementinthesetherapeuticsparticularlythosethattargetneoplasmsinlipophilictissuesandenvironmentssuchasbrainandCNS

References

Bis(pentafluorosulfanyl)phenylazideasanexpeditioustoolforclickchemistrytowardantitumorpharmaceuticals1Bis(pentafluorosulfanyl)phenylazideasanexpeditioustoolforclickchemistrytowardantitumorpharmaceuticals2

CannabinoidReceptorLigands

Anarrayofcannabinoidligandsbearingmeta-andpara-substitutedpentafluorosulfanyl(SF5)anilinegroupsinposition3ofthepyrazoleringwasefficientlysynthesisedandcomparedwiththeexacttrifluoromethylandtert-butylanalogues

IngeneraltheSF5substitutedligandsshowedhigherlipophilicity(ielogPvalues)thantheCF3counterpartsandlowerlipophilicitythanthetert-butylonesIntermsofpharmacologicalactivitySF5pyrazolesgenerallyshowedslightlyhigherorequivalentCB1receptoraffinity(Ki)alwaysinthenanomolarrangeandselectivitytowardstheCB2relativetobothCF3andtert-butylanaloguesFunctionalszlig-arrestinrecruitmentassayswereusedtodetermineequilibriumdissociationconstants(Kb)andshowedthatallofthetestedSF5andCF3compoundsareCB1neutralantagonists

TheseresultsconfirmthepossibilityofsuccessfullyusinganaromaticSF5groupasastablesyntheticallyaccessibleandeffectivebioisostericanalogueoftheelectron-withdrawingCF3groupandpossiblyalsoofbulkyaliphaticgroupsfordrugdiscoveryanddevelopmentapplications

References

Thepentafluorosulfanylgroupincannabinoidreceptorligandssynthesisandcomparisonwithtrifluoromethylandtert-butylanalogues

AgriculturalCompounds

TheSF5moietyshouldfindconsiderableutilityintheagricultural(herbicidepesticideinsecticidefungicideetc)sectorperhapsmoresoandsoonerthaninpharmaceuticalsasSF5willconfermanydesiredpropertiestothesebio-activemoleculesandtheydonotrequirethelengthy(andexpensive)trialsmandatedwithcompoundsforhumanuse

References[IllbeaddingmoreasIfindthem]

Herbicide

TherearemanyexamplesofagriculturalcompoundsnowinuseorbeingdevelopedwhichemploytheCF3functionorClBretcwherealargeelectronegativelipophilicgroupisneededItisavirtuallycertainbetthatreplacementofthesegroup(s)withSF5wouldyieldamuchbetterandmorepotentcompoundAgriculturalcompoundsarealsousuallysimplerthanhumanpharmaceuticalsthechemistryisthusmoredirectandsimpleSomecontemporaryexamplesareshownjustbelowalsotheFipronilexamplealittlefurtherdown

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LiquidCrystals

AnotherwideopenareaofresearchwithmuchgrowthpotentialtheSF5groupimpartsastrongcrystallinenaturetocompoundstheyalsotendtobelowermeltingandmorevolatilethanonewouldexpectfromthemolecularweightinadditiontheSF5substituentcanimpartaverystrongdipolemomenttoamoleculecriticalforliquidcrystals

References

Liquidcrystallinemediumandliquidcrystaldisplay

LiquidCrystalsBasedonHypervalentSulfurFluoridesPentafluorosulfuranylasPolarTerminalGroup

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HighTechandSpecialtyPolymersotherChemistryuses

SomeresearchhasbeendonemuchmoreisneededasthisareaoffersmuchpromiseforthermallyandchemicallystablepolymerstheSF5groupduetoitstendencytoimpartstrengthandcrystallinitytoitscompoundsmayalsohavevalueinhighstrengthpolymers

References

SF5incorporatedintopolymers

35-Bis(pentafluorosulfanyl)phenylboronicacidAneworganocatalystforConia-enecarbocyclizationof13-dicarbonylcompoundshavingterminalalkynes

SF5andconductingpolymers

EnvironmentalConsiderations

SinceSF5doesnotoccurinnatureitisrationallyexpectedthattherearenoenzymesystemstohandleitnoranygeneralbio-metabolicmechanismstodealwithitThisalongwithitsextremechemicalinertnessmightsuggestthatSF5wouldbuildupintheenvironmentandaccumulate

HoweversomeresearchhasalreadybeendoneandmorewillbeinthefutureWhathasbecomeknownatthistimeisthatSF5doesindeedbreakdownintheopenenvironmentparticularlyundertheinfluenceofsunlight

Theproductsformedarethecorrespondingsulfonate(ArSO3H)compounds(generallyinnocuous)andHF(instantlybufferedtofluoridewhichisubiquitousinnatureanyway)

References

EnvironmentalpropertiesofpentafluorosulfanylcompoundsphysicalpropertiesandphotodegradationEnvironmentalToxicologyandChemistry-WileyOnlineLibrary

CurrentlytheintroductionoffluorineintoorganicmoleculeshasbecomeverycommonmethodologyinbiomedicalfieldsandnumerousfluorinecontainingmoleculeshavebeendevelopedandmanyhaveshownsignificantpromiseandadvantagesinthisfieldInparticularthepentafluorosulfanyl(SF5)groupwhichisahighlyfluorinatedfunctionalgrouphasshownremarkableactivityinbiochemicalmoleculesTheintroductionoftheSF5groupbringsnotonlythenovelpropertieswhichoriginatefromFluorineelement(Strongelectronegativityhighlipophilicityandhighchemicalstability)tothemoleculebutalsoalargerstericeffectthantheCF3groupwhichisalsorecognizedasahighlyfluorinatedfunctionalgroupTherelativestericdemandoftheSF5groupisslightlylessthanthatofatert-butylgroupandconsiderablylargerthanthatofaCF3groupExamplesofbiologicalactivitiescomparingtheCF3substitutedagentvstheSF5analogareshownbelow

Mefloquineisusedforbothtreatmentandprophylaxisofmalaria8-SF5-Mefloquineshowedalongerhalf-life(68h)thanMefloquine(23h)afteradministrationtomiceFipronilisabroadspectruminsecticideTheSF5analogueofFipronilwasnotonlymoreactivethanFipronilbutshowednolossofpotencytowardstheresistantstrainofhouseflyincontrasttotheFipronil

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These5areexamplesofSF5analogsofcurrentbio-activecompoundsallofwhicharebetterthantheoriginals

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Anewanti-malarialdrug(DSM265)verypromisingsofarandcurrentlyinclinicaltrialscontainsap-SF5-anilinosubstituentasshown

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Thesynthesis[seeDSM265linksjustbelow]involvesreplacementofchlorineonthetriazolopyrimidineringwithpara-aminophenylpentafluorosulfanateacompoundImadein50grlots(newprocess)

butwhichisnowonlyavailableingramquantitiesandprohibitiveprice(oldcurrentprocedures)

Thisisaperfectexampleofhowanewandverypromisingdrugwill(would)beprohibitivelyexpensiveifitemploystheSF5functionnowbutwiththenewSF5processeswillbemuchcheaperandmoreavailableAlsoSF5buildingblockswillbecheaperandmorereadilyavailable

thusenablingmoreresearchintonovelpharmaceutical(andagricultural)candidates

Morelinksconcerningbio-activecompoundsCF3vsSF5DopamineReceptorResearchpatentDirectComparisonCF3andSF5PentafluorosulfanylcompoundsmanufactureanduseaspharmaceuticalagentsStructuresofnewAnti-MalarialCandidatesDSM265Structure-guidedleadoptimizationDSM265chemistry

TheNewPreparationMethods

InordertocontributetoandimproveSF5chemistryaboveUBEhasstartedtodeliveraseriesofaromaticpentafluorosulfanylcompoundspreparedbynewinnovativeprocessesincludingourKFCl2methodwhichwasdevelopedbyIMampTResearchInc

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OurpatentedKFCl2methodiswidelyapplicabletovariousaromaticdisulfidecompoundswhicharedirectstartingmaterialsforthecorrespondingaromaticSF5compoundsThishasenabledustointroducetheSF5groupintovariousaromaticringsviaatwostepprocessfromthecorrespondingaryl-disulfideascomparedtothedirectfluorinationprocessutilizingelementalfluorinewhichislimitedbytheuseofonlynitro-arylcompoundsasstartingmaterials

WiththeKFCl2processaryl-disulfideisconvertedtothecorrespondingaryltetrafluorosulfanyl-chlorideThisprocessisequallyapplicabletoaromaticthiophenolcompoundsTheobtainedAryl-SF4ClfromtheKFCl2processcanthenbeconvertedtothecorrespondingaryl-pentafluoro-sulfanylcompoundwithzincdifluorideoranhydrousHFAryl-SF4Clpreparationproceedswithhighyieldaround80-90atroomtemperatureandthestartingmaterialsprovidedforthisreactionaryl-disulfideKFandCl2arecommoditymaterialswhichcanbeobtainedconvenientlyandatrelativelylowpricesforindustrialscaleproductionTheconversiontoAryl-SF5fromthecorrespondingAryl-SF4Clproceedswithhighyield(around70-80)withzincdifluorideat100CanditalsohasbeendemonstratedthatthisreactionproceedswithaHFinhighyield(70-75)below20CCertainothermetalfluoridesandmixturesthereofhavebeenfoundtoworkaswell

Thefollowinglinkswilltakeyoutothedetaileddescriptionsofthenewprocedure(s)

Theoriginalpaperdetailingtheprocessescanbeaccessedhere

ThisUBEpatentdetailstheprocedure(s)forthepoly-functionalSF5compoundsImustpointoutherethatIdidallofthehands-onlabworkanddevelopmentnotmostofitallofit100DuetoUBEpoliciesandlegaltechnicalitiesmynameisnotlistedonlytheauthoroftheoriginalconceptiscreditedAndthesamedealwiththisone[Yesthatsucksbutitistherealworld]

InadditionIhavesomenewresearchideaswhichwouldnotonlyimproveeventheexistingnewprocesssignificantlybutwouldalsoskirttheexistingpatents-allIneedisalabtodevelopthenewprocess[AndasInolongerworkforUBEIcanthusworkforyou]

FetchtheAcrobatPDFFileoftheoriginalBeilSteinarticle

DownloadthisentirewebpageasMS-WORDfile

Asapartofcontinuingresearchforenergeticmaterialsthatcombinehighperformancewithlowvulnerabilitytowardaccidentaldetonationtheeffectofintroductionofthepentafluorosulfanyl(SF5)grouponthepropertiesofexplosivenitrocompoundshasbeenreportedThisisbasedonthefactthatmoreenergyisreleasedduetotheformationofHFinthedetonationofSF5explosives

Itisalsowell-establishedthatsubstitutionofHbyFinhydrocarbonsleadstoasignificantincreaseindensityItimpliesthatSF5groupwouldprovidenitroexplosiveswithhigherdensityorinotherwordsimprovedperformanceasexplosivepowerisproportionaltothesquareofthecompounddensityToillustratePhSF5hasfullytwicethedensityoftheanalogousPhCH3(toluene)

BasedontheseassumptionssomepolynitroSF5explosiveshavebeendesignedandtheirperformancepredictedwhichisinagreementwiththeiractualperformanceTheinitialexperimentsofSitzmannetalsupportthehypothesisthattheSF5groupmayprovideexplosiveswithimprovedpropertiesincreaseddensityincreasedinsensitivityandincreasedenergycoupledwithbetterthermalstabilityndashauniquecombinationofpropertiesSomeexamplesofdensethermallystableimpactinsensitivepolynitroaliphaticexplosiveswithSF5groupsare

SF5CH2CO2CH2C(NO2)2Fdensity186gcm-3SF5CF2CF2CF2SF5density204gcm-3(SF5)2NCF2CH2SF5density213gcm-3

Correspondingworkwitharomaticcompoundsalthoughlimitedatthistimehasgivensimilarresultsthisisawide-openareaforresearchnowandthenewproductionprocessesforaromaticSF5compoundswillbeapplicable

References

BementLJ(1970)ApplicationoftemperatureresistantexplosivestoNASAmissionsProcSymponThermallyStableExplosivesNavalOrdnanceLaboratoryWhiteoakMd1970UrbanskiT(1984)ChemistryandTechnologyofExplosivesvol4PergamonPressOxfordUKp206DavenasA(2001)SolidPropellantsforFutureSpaceApplicationsEuropeanSpaceAgencySpecialPublicationndash484(SP-484)pp105ndash110

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RecentlytherehasbeenincreasedinterestregardingtheincorporationoftheSF5groupintoenergeticmaterialsItisknownthattheinclusionofSF5generallyincreasesthethermalandchemicalstabilityoforganicmoleculesandinadditiontothisithasbeendemonstratedthatthepresenceofSF5alsowillincreasethedensityandthustheperformanceoftheenergeticmaterialassuchperformanceisafunctionofthesquareofthedensity

ThepossibilityofahigherdensitylargerenergyreleaseandbetterthermalandchemicalstabilitywithoutincreasingthesensitivitymaketheSF5groupattractiveinthesynthesisofhighenergymaterials(explosives)

Thehighfluorinecontentalongwiththepresenceofhydrogenleadstotheformationofhydrogenfluoride(HF)upondetonationgeneratingalargeamountofenergyTheS-FBondDissociationEnergy(BDE)is79kcalmolwhiletheBDEofH-Fis136kcalmolMuchenergyisalsoreleasedintheformationofC-FbondsaswellasAl-Fifaluminum(orothermetal)isincludedintheformulation

TheformationofC-FH-ForAl-Fbondswhichhaveahigherbonddissociationenergy(BDE)thantheS-FbondinthepentafluorosulfanylgroupallowsthereleaseoflargeamountsofenergyupondetonationThiscombinedwiththepossibilityofhigherdensityhigherthermalandchemicalstabilityandlowsensitivitymakesthepentafluorosulfanylgroupveryattractiveforthesynthesisofhighperformanceenergeticmaterials(explosives)

AlargenumberofSF5-containingenergeticmaterialshavebeensynthesizedwherethepredictedperformanceisclosetothoseforHMXRDXandTNTbutwiththebenefitoflesserornoimpactsensitivity

Mostofthesearebuiltupfromtriazolesfurazansandotherhigh-nitrogenoxygenheterocycleswhichifthecorrespondingthiolisavailablewouldbeeasilyaccessiblebythesenewmethodsthusacceleratingresearchefforts

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IncorporationofSF5intoExplosivesandHighEnergyCompoundsandMolecules

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References

SheppardWAJAmChemSoc19623064YeCGardGLWinterRWSyvretRGTwamleyBShreeveJnMOrgLett200793841GargSShreeveJMJMaterChem2011214787AgrawalJPProgEnergyCombustSci1998241SitzmannMEGilliganWHOrnellasDLThrasherJSJEnergeticMat19908352SitzmannMEJFluorineChem1991195GaoHYeCWinterRWGardGLSitzmannMEShreeveJMEurJInorgChem20063221OrnellasDLPropellantsExplosivesPyrotechnics198914122

ChemistrySF5inexplosivecompounds

PentafluorosulfanylpolynitroaliphaticureamonocarbamateanddicarbamateexplosivecompoundsPolynitroaliphaticexplosivescontainingthepentafluorosulfanyl(SF5)groupTheselectionandstudyofamodelcompoundRecentTrendsinNewEnergeticMaterials134-Oxadiazolescontainingthepentafluorothio(SF5)GroupPentafluorosulfanylnitramideSaltsPentafluorosulfanylPolynitroaliphaticUreaExplosiveCompoundsPentafluorosulfanylMonocarbamateandDicarbamateExplosiveCompoundsPentafluorosulfanylCarbamateExplosivesHighEnergyPentafluorosulfanylPolynitroaliphaticUreaMonocarbamateandDicarbamateCompoundsPentafluorosulfanyl-substituted-poly-123-triazole-compounds

Ithasbeensaidthatthereareveryfew(inter)personal[and(inter)national]problemsthatcannotbesolvedthroughasuitableapplicationofhighexplosivesWellthenherearesomenewideastoponder

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[III]istheSF5analogofTETRYLwhichhasaNO2insteadTETRYLisaverypowerfulsecondaryexplosiveonceinwidespreadusebutnolongerasitistoounstableandsensitive

SinceSF5isknowntostabilizethesetypesofcompounds[III]isreasonablyexpectedtobeaverypowerfultertiaryexplosivestableenoughforuseitsmainadvantagehereistheeaseofsynthesis

[I]ismadefromthereadilyavailable[0]bythenewprocess(es)thenreactedwithdimethylaminetoproduce[II]SubstitutionoffluorinesontheseSF5compoundsbynucleophilesgenerallyprocedeswell-Ihavedonecountlesssuchreactions

ThentheactivatinganddirectingeffectsoftheamineandSF5enablenitrationtoprocedeunderrelativelymildconditions(similartotheTETRYLreactionfromdimethylaniline)toyieldtheproduct[III]

NextGenerationExplosivesthatareEASYtoSynthesize

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Ihaveproceededtothebifunctionalcompound[V]ingoodyielditisaclearoilpleasantodorThedinitrationshouldbestraightforwardIjusthaventdoneityet-Ineedalab

Compound[VII]analogoustotheknownandcurrentlyusedTATBwouldbeevenmorestableandverylikelymorepowerful

AndlookiehowEASYitistomake

NextGenExplosivesEasytoMake

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Compound[I]iscommerciallyavailablenitrationto[II]shouldbeeasyfacilitatedbythefluorinesFormationof[III]willbeeasyIhavedonemanysuchreactionsDeprotectionreactionto[IV]would

normallyusecatalytic(5mol)AlCl3howeverthenitrogroupsmaycoordinatealsothusstoichiometricquantitymaybeneededalternativelythisdeprotectioncanalsobedonewithTFAorHF

ThenewprocessescanthenformtheSF5compoundfromthethiol

AlthoughnitrationcaneasilybedoneorthotoSF5(Ihavedoneit)theconverseissometimesdifficultStericeffectscaninterferewiththeformationoftheintermediateSF4ClDontknowhere-Ineedalabtofindout

Compound[VI]shouldbeverydenseduetotheSF5groupsandthesymmetrysinceexplosivepowerisproportionaltothesquareofthedensitythiscompoundshouldbeanextremelypowerfulexplosive-perhapsthebestyet(nonnuclear)

Italsohasanexcessofoxidantthusitcouldbeformulatedwithaluminumtitaniummagnesiumetcfurtherincreasingthepower

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Anotherwaytodoit

HexachlorobenzeneiscommerciallyavailableandcheaphexafluorobenzenewouldactuallyworkbetterbutitismoreexpensiveHexabromobenzenewouldpreventthe3rdstep(formationofSF5)duetosterichindrance

Proceedingtocompound[III]wouldbeuneventfulndashthisreactionworksquitewellandIhavedoneitcountlesstimesThenewUBEUmemotoprocess(ormynewprocess)wouldthenmakethetrichlorotri(pentafluorosulfanyl)compound[IV]

ReactionwithNH3possiblyaidedbyNaHshouldform[V]ThisreactionworkswellwiththeanalogousnitrocompoundasSF5issimilartoNO2inelectronegativityIexpectitalsotoworkhere

Oxidationofaminestonitroiseffectedbytheldquopersulfuricacidrdquomixthisdrasticreactionconditionshouldnotaffecttherock-stableSF5AlternativelythemuchmilderfluorineacetonitrilewateroxidizerisknowntoeffectthisconversionwellIjusthavenrsquottriedityetndashIneedalab

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Compound[I]iscommerciallyavailablealsoIhavemademulti-dozengramlotsof[IV]LikemostofthesecompoundsitisaclearfragrantoilThefluorinesareactivatinganddirectorthoandtherearethreeforadditiveeffectSF5isdeactivatinganddirectsmetaalleffectspointtotheopenpositionsthusthisdinitrationshould

alsobestraightforwardagain-Ijustneedalab

Iexpect[V]tobeadenseexplosivesolidverystablealsoperhapsdifficulttodetonateeven

Itislikelythatinthiscompound[V]aswellastheoneimmediatelyaboveit[VI]thefluorinesareverylabileandcouldeasilybesubstitutedwithappropriatenucleophilesgivingevenbettercompoundsSomepossiblesarephenylortriazinewithringnitros

orazidesusinganaminehydrazineordiazobridgeHeck-simpleamineorhydrazineshouldworkniceEvenazideCompound[VI]mightstartlookingrealtreacherouswiththesesubstituentsbutremember-theSF5isstabilizingit

AndwithSF5youcangowherenomanhasgonebefore

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TetraPentafluorosulfanylTetrahedrane

[I]and[II]areknowncompoundsIhaventworkedwiththemyetTheyaremadefromClSF5Et3BLiOHadditioneliminationreactionsonunsaturatedcompoundsManyvariationsandmuchroomforimprovementyet

Idontknowhowtogetfrom[II]to[III]perhapstherightcobaltorpalladiumcomplexshoulddoititlookslikeasimple[2+2][III]isofcourseanti-aromaticthusunstableandpronetopolymerizationanddecompositionhowever

theelectronpulloftheSF5groupsmightstabilizeitsomewhatifIcangetitintothephotolysisapparatusquickenoughablastof254shouldcreate[IV]

Iexpect[IV]tobeadensehighlyexplosivesolidperhapstoounstableforpracticalusesitmaynotbepossibletoexistatallCurrentlyonlythetetra-t-butyl-tetrahedranehasbeenmadeDespiteconsiderableeffortthetetra-nitroandparentcompounds

haveeludedsynthesisTheelectronpulloftheSF5groupswouldfurtherweakenthealreadyhighlystrainedcageandmightmakethiscompoundimpossibleDontknow-Ineedalab

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ItsalongshotbutIdliketotryitanywayThecrazieritlooksthemorefunitistoplaywith

Wehavetrifluoromethyltransferagentshowaboutapentafluorosulfanyltransferreagent

Thetwofunctionssharemanyofthesamecharacteristicsandcopperlikesbondingtosulfur-itjustmightwork

[althoughIhaveneverusedthenewprocessesonmetal-sulfurbondedcompounds-noideawhattoexpect]butisntthat

whatresearchisallabout

thattoavoidlegalissues)5 Yougetafast-trackshort-cutone-uponthecompetitioninthecut-throatcompetitivearenaofdrugdevelopment6 IcoulddothismyselfbutasIsaidabove-Ineedalab

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Quiteanumberofcurrentlymarketeddrugs[andmorewillbecoming)containtheCF3functionsomeexamplesaredepictedbelowwiththeCF3replacedbySF5todemonstratehypotheticalconcepts

Nowhereisanideaforbolddaringentrepreneurialspiritedindividualsandorcompanies

1 Takeanycurrentlymarketeddrug[oragriculturalcompound]containingCF3maketheSF5analogandsubmititasanewcompound

2 ItisabetterthanevenbetthatitwillbeasignificantlybettercompoundenoughsothattheFDAwillacceptitassuchandnotjustanothercopycat

3 Sincealloftheresearchtimeexpenseandmanpowerhasalreadybeendoneontherestofthemoleculeyouwillbesparedthat

4 Anditisunlikelythattheoriginalpatent(s)wouldcoverthecarbon-sulfurbondatthatposition(butyouwillneedtoverify

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[SF5]-Flibanserin

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Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]

whichwedevelopedatUBEconcurrentlywiththenewSF5process

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Created in Fedora Linux by Lloyd Garrick 01012018

AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs