novel, new aromatic sf5 derivatives · many examples of agents bearing cf3 ... many of the solids...
TRANSCRIPT
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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GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
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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GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
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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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GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
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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
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
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
LLOYDGARRICK
LiquidCrystals
AnotherwideopenareaofresearchwithmuchgrowthpotentialtheSF5groupimpartsastrongcrystallinenaturetocompoundstheyalsotendtobelowermeltingandmorevolatilethanonewouldexpectfromthemolecularweightinadditiontheSF5substituentcanimpartaverystrongdipolemomenttoamoleculecriticalforliquidcrystals
References
Liquidcrystallinemediumandliquidcrystaldisplay
LiquidCrystalsBasedonHypervalentSulfurFluoridesPentafluorosulfuranylasPolarTerminalGroup
LLOYDGARRICK
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
LLOYDGARRICK
These5areexamplesofSF5analogsofcurrentbio-activecompoundsallofwhicharebetterthantheoriginals
LLOYDGARRICK
Anewanti-malarialdrug(DSM265)verypromisingsofarandcurrentlyinclinicaltrialscontainsap-SF5-anilinosubstituentasshown
LLOYDGARRICK
Thesynthesis[seeDSM265linksjustbelow]involvesreplacementofchlorineonthetriazolopyrimidineringwithpara-aminophenylpentafluorosulfanateacompoundImadein50grlots(newprocess)
butwhichisnowonlyavailableingramquantitiesandprohibitiveprice(oldcurrentprocedures)
Thisisaperfectexampleofhowanewandverypromisingdrugwill(would)beprohibitivelyexpensiveifitemploystheSF5functionnowbutwiththenewSF5processeswillbemuchcheaperandmoreavailableAlsoSF5buildingblockswillbecheaperandmorereadilyavailable
thusenablingmoreresearchintonovelpharmaceutical(andagricultural)candidates
Morelinksconcerningbio-activecompoundsCF3vsSF5DopamineReceptorResearchpatentDirectComparisonCF3andSF5PentafluorosulfanylcompoundsmanufactureanduseaspharmaceuticalagentsStructuresofnewAnti-MalarialCandidatesDSM265Structure-guidedleadoptimizationDSM265chemistry
TheNewPreparationMethods
InordertocontributetoandimproveSF5chemistryaboveUBEhasstartedtodeliveraseriesofaromaticpentafluorosulfanylcompoundspreparedbynewinnovativeprocessesincludingourKFCl2methodwhichwasdevelopedbyIMampTResearchInc
LLOYDGARRICK
LLOYDGARRICK
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
LLOYDGARRICK
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
LLOYDGARRICK
IncorporationofSF5intoExplosivesandHighEnergyCompoundsandMolecules
LLOYDGARRICK
References
SheppardWAJAmChemSoc19623064YeCGardGLWinterRWSyvretRGTwamleyBShreeveJnMOrgLett200793841GargSShreeveJMJMaterChem2011214787AgrawalJPProgEnergyCombustSci1998241SitzmannMEGilliganWHOrnellasDLThrasherJSJEnergeticMat19908352SitzmannMEJFluorineChem1991195GaoHYeCWinterRWGardGLSitzmannMEShreeveJMEurJInorgChem20063221OrnellasDLPropellantsExplosivesPyrotechnics198914122
ChemistrySF5inexplosivecompounds
PentafluorosulfanylpolynitroaliphaticureamonocarbamateanddicarbamateexplosivecompoundsPolynitroaliphaticexplosivescontainingthepentafluorosulfanyl(SF5)groupTheselectionandstudyofamodelcompoundRecentTrendsinNewEnergeticMaterials134-Oxadiazolescontainingthepentafluorothio(SF5)GroupPentafluorosulfanylnitramideSaltsPentafluorosulfanylPolynitroaliphaticUreaExplosiveCompoundsPentafluorosulfanylMonocarbamateandDicarbamateExplosiveCompoundsPentafluorosulfanylCarbamateExplosivesHighEnergyPentafluorosulfanylPolynitroaliphaticUreaMonocarbamateandDicarbamateCompoundsPentafluorosulfanyl-substituted-poly-123-triazole-compounds
Ithasbeensaidthatthereareveryfew(inter)personal[and(inter)national]problemsthatcannotbesolvedthroughasuitableapplicationofhighexplosivesWellthenherearesomenewideastoponder
LLOYDGARRICK
[III]istheSF5analogofTETRYLwhichhasaNO2insteadTETRYLisaverypowerfulsecondaryexplosiveonceinwidespreadusebutnolongerasitistoounstableandsensitive
SinceSF5isknowntostabilizethesetypesofcompounds[III]isreasonablyexpectedtobeaverypowerfultertiaryexplosivestableenoughforuseitsmainadvantagehereistheeaseofsynthesis
[I]ismadefromthereadilyavailable[0]bythenewprocess(es)thenreactedwithdimethylaminetoproduce[II]SubstitutionoffluorinesontheseSF5compoundsbynucleophilesgenerallyprocedeswell-Ihavedonecountlesssuchreactions
ThentheactivatinganddirectingeffectsoftheamineandSF5enablenitrationtoprocedeunderrelativelymildconditions(similartotheTETRYLreactionfromdimethylaniline)toyieldtheproduct[III]
NextGenerationExplosivesthatareEASYtoSynthesize
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Ihaveproceededtothebifunctionalcompound[V]ingoodyielditisaclearoilpleasantodorThedinitrationshouldbestraightforwardIjusthaventdoneityet-Ineedalab
Compound[VII]analogoustotheknownandcurrentlyusedTATBwouldbeevenmorestableandverylikelymorepowerful
AndlookiehowEASYitistomake
NextGenExplosivesEasytoMake
LLOYDGARRICK
LLOYDGARRICK
Compound[I]iscommerciallyavailablenitrationto[II]shouldbeeasyfacilitatedbythefluorinesFormationof[III]willbeeasyIhavedonemanysuchreactionsDeprotectionreactionto[IV]would
normallyusecatalytic(5mol)AlCl3howeverthenitrogroupsmaycoordinatealsothusstoichiometricquantitymaybeneededalternativelythisdeprotectioncanalsobedonewithTFAorHF
ThenewprocessescanthenformtheSF5compoundfromthethiol
AlthoughnitrationcaneasilybedoneorthotoSF5(Ihavedoneit)theconverseissometimesdifficultStericeffectscaninterferewiththeformationoftheintermediateSF4ClDontknowhere-Ineedalabtofindout
Compound[VI]shouldbeverydenseduetotheSF5groupsandthesymmetrysinceexplosivepowerisproportionaltothesquareofthedensitythiscompoundshouldbeanextremelypowerfulexplosive-perhapsthebestyet(nonnuclear)
Italsohasanexcessofoxidantthusitcouldbeformulatedwithaluminumtitaniummagnesiumetcfurtherincreasingthepower
LLOYDGARRICK
Anotherwaytodoit
HexachlorobenzeneiscommerciallyavailableandcheaphexafluorobenzenewouldactuallyworkbetterbutitismoreexpensiveHexabromobenzenewouldpreventthe3rdstep(formationofSF5)duetosterichindrance
Proceedingtocompound[III]wouldbeuneventfulndashthisreactionworksquitewellandIhavedoneitcountlesstimesThenewUBEUmemotoprocess(ormynewprocess)wouldthenmakethetrichlorotri(pentafluorosulfanyl)compound[IV]
ReactionwithNH3possiblyaidedbyNaHshouldform[V]ThisreactionworkswellwiththeanalogousnitrocompoundasSF5issimilartoNO2inelectronegativityIexpectitalsotoworkhere
Oxidationofaminestonitroiseffectedbytheldquopersulfuricacidrdquomixthisdrasticreactionconditionshouldnotaffecttherock-stableSF5AlternativelythemuchmilderfluorineacetonitrilewateroxidizerisknowntoeffectthisconversionwellIjusthavenrsquottriedityetndashIneedalab
LLOYDGARRICK
Compound[I]iscommerciallyavailablealsoIhavemademulti-dozengramlotsof[IV]LikemostofthesecompoundsitisaclearfragrantoilThefluorinesareactivatinganddirectorthoandtherearethreeforadditiveeffectSF5isdeactivatinganddirectsmetaalleffectspointtotheopenpositionsthusthisdinitrationshould
alsobestraightforwardagain-Ijustneedalab
Iexpect[V]tobeadenseexplosivesolidverystablealsoperhapsdifficulttodetonateeven
Itislikelythatinthiscompound[V]aswellastheoneimmediatelyaboveit[VI]thefluorinesareverylabileandcouldeasilybesubstitutedwithappropriatenucleophilesgivingevenbettercompoundsSomepossiblesarephenylortriazinewithringnitros
orazidesusinganaminehydrazineordiazobridgeHeck-simpleamineorhydrazineshouldworkniceEvenazideCompound[VI]mightstartlookingrealtreacherouswiththesesubstituentsbutremember-theSF5isstabilizingit
AndwithSF5youcangowherenomanhasgonebefore
LLOYDGARRICK
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
LLOYDGARRICK
ItsalongshotbutIdliketotryitanywayThecrazieritlooksthemorefunitistoplaywith
Wehavetrifluoromethyltransferagentshowaboutapentafluorosulfanyltransferreagent
Thetwofunctionssharemanyofthesamecharacteristicsandcopperlikesbondingtosulfur-itjustmightwork
[althoughIhaveneverusedthenewprocessesonmetal-sulfurbondedcompounds-noideawhattoexpect]butisntthat
whatresearchisallabout
thattoavoidlegalissues)5 Yougetafast-trackshort-cutone-uponthecompetitioninthecut-throatcompetitivearenaofdrugdevelopment6 IcoulddothismyselfbutasIsaidabove-Ineedalab
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Quiteanumberofcurrentlymarketeddrugs[andmorewillbecoming)containtheCF3functionsomeexamplesaredepictedbelowwiththeCF3replacedbySF5todemonstratehypotheticalconcepts
Nowhereisanideaforbolddaringentrepreneurialspiritedindividualsandorcompanies
1 Takeanycurrentlymarketeddrug[oragriculturalcompound]containingCF3maketheSF5analogandsubmititasanewcompound
2 ItisabetterthanevenbetthatitwillbeasignificantlybettercompoundenoughsothattheFDAwillacceptitassuchandnotjustanothercopycat
3 Sincealloftheresearchtimeexpenseandmanpowerhasalreadybeendoneontherestofthemoleculeyouwillbesparedthat
4 Anditisunlikelythattheoriginalpatent(s)wouldcoverthecarbon-sulfurbondatthatposition(butyouwillneedtoverify
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
LLOYDGARRICK
LiquidCrystals
AnotherwideopenareaofresearchwithmuchgrowthpotentialtheSF5groupimpartsastrongcrystallinenaturetocompoundstheyalsotendtobelowermeltingandmorevolatilethanonewouldexpectfromthemolecularweightinadditiontheSF5substituentcanimpartaverystrongdipolemomenttoamoleculecriticalforliquidcrystals
References
Liquidcrystallinemediumandliquidcrystaldisplay
LiquidCrystalsBasedonHypervalentSulfurFluoridesPentafluorosulfuranylasPolarTerminalGroup
LLOYDGARRICK
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
LLOYDGARRICK
These5areexamplesofSF5analogsofcurrentbio-activecompoundsallofwhicharebetterthantheoriginals
LLOYDGARRICK
Anewanti-malarialdrug(DSM265)verypromisingsofarandcurrentlyinclinicaltrialscontainsap-SF5-anilinosubstituentasshown
LLOYDGARRICK
Thesynthesis[seeDSM265linksjustbelow]involvesreplacementofchlorineonthetriazolopyrimidineringwithpara-aminophenylpentafluorosulfanateacompoundImadein50grlots(newprocess)
butwhichisnowonlyavailableingramquantitiesandprohibitiveprice(oldcurrentprocedures)
Thisisaperfectexampleofhowanewandverypromisingdrugwill(would)beprohibitivelyexpensiveifitemploystheSF5functionnowbutwiththenewSF5processeswillbemuchcheaperandmoreavailableAlsoSF5buildingblockswillbecheaperandmorereadilyavailable
thusenablingmoreresearchintonovelpharmaceutical(andagricultural)candidates
Morelinksconcerningbio-activecompoundsCF3vsSF5DopamineReceptorResearchpatentDirectComparisonCF3andSF5PentafluorosulfanylcompoundsmanufactureanduseaspharmaceuticalagentsStructuresofnewAnti-MalarialCandidatesDSM265Structure-guidedleadoptimizationDSM265chemistry
TheNewPreparationMethods
InordertocontributetoandimproveSF5chemistryaboveUBEhasstartedtodeliveraseriesofaromaticpentafluorosulfanylcompoundspreparedbynewinnovativeprocessesincludingourKFCl2methodwhichwasdevelopedbyIMampTResearchInc
LLOYDGARRICK
LLOYDGARRICK
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
LLOYDGARRICK
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
LLOYDGARRICK
IncorporationofSF5intoExplosivesandHighEnergyCompoundsandMolecules
LLOYDGARRICK
References
SheppardWAJAmChemSoc19623064YeCGardGLWinterRWSyvretRGTwamleyBShreeveJnMOrgLett200793841GargSShreeveJMJMaterChem2011214787AgrawalJPProgEnergyCombustSci1998241SitzmannMEGilliganWHOrnellasDLThrasherJSJEnergeticMat19908352SitzmannMEJFluorineChem1991195GaoHYeCWinterRWGardGLSitzmannMEShreeveJMEurJInorgChem20063221OrnellasDLPropellantsExplosivesPyrotechnics198914122
ChemistrySF5inexplosivecompounds
PentafluorosulfanylpolynitroaliphaticureamonocarbamateanddicarbamateexplosivecompoundsPolynitroaliphaticexplosivescontainingthepentafluorosulfanyl(SF5)groupTheselectionandstudyofamodelcompoundRecentTrendsinNewEnergeticMaterials134-Oxadiazolescontainingthepentafluorothio(SF5)GroupPentafluorosulfanylnitramideSaltsPentafluorosulfanylPolynitroaliphaticUreaExplosiveCompoundsPentafluorosulfanylMonocarbamateandDicarbamateExplosiveCompoundsPentafluorosulfanylCarbamateExplosivesHighEnergyPentafluorosulfanylPolynitroaliphaticUreaMonocarbamateandDicarbamateCompoundsPentafluorosulfanyl-substituted-poly-123-triazole-compounds
Ithasbeensaidthatthereareveryfew(inter)personal[and(inter)national]problemsthatcannotbesolvedthroughasuitableapplicationofhighexplosivesWellthenherearesomenewideastoponder
LLOYDGARRICK
[III]istheSF5analogofTETRYLwhichhasaNO2insteadTETRYLisaverypowerfulsecondaryexplosiveonceinwidespreadusebutnolongerasitistoounstableandsensitive
SinceSF5isknowntostabilizethesetypesofcompounds[III]isreasonablyexpectedtobeaverypowerfultertiaryexplosivestableenoughforuseitsmainadvantagehereistheeaseofsynthesis
[I]ismadefromthereadilyavailable[0]bythenewprocess(es)thenreactedwithdimethylaminetoproduce[II]SubstitutionoffluorinesontheseSF5compoundsbynucleophilesgenerallyprocedeswell-Ihavedonecountlesssuchreactions
ThentheactivatinganddirectingeffectsoftheamineandSF5enablenitrationtoprocedeunderrelativelymildconditions(similartotheTETRYLreactionfromdimethylaniline)toyieldtheproduct[III]
NextGenerationExplosivesthatareEASYtoSynthesize
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Ihaveproceededtothebifunctionalcompound[V]ingoodyielditisaclearoilpleasantodorThedinitrationshouldbestraightforwardIjusthaventdoneityet-Ineedalab
Compound[VII]analogoustotheknownandcurrentlyusedTATBwouldbeevenmorestableandverylikelymorepowerful
AndlookiehowEASYitistomake
NextGenExplosivesEasytoMake
LLOYDGARRICK
LLOYDGARRICK
Compound[I]iscommerciallyavailablenitrationto[II]shouldbeeasyfacilitatedbythefluorinesFormationof[III]willbeeasyIhavedonemanysuchreactionsDeprotectionreactionto[IV]would
normallyusecatalytic(5mol)AlCl3howeverthenitrogroupsmaycoordinatealsothusstoichiometricquantitymaybeneededalternativelythisdeprotectioncanalsobedonewithTFAorHF
ThenewprocessescanthenformtheSF5compoundfromthethiol
AlthoughnitrationcaneasilybedoneorthotoSF5(Ihavedoneit)theconverseissometimesdifficultStericeffectscaninterferewiththeformationoftheintermediateSF4ClDontknowhere-Ineedalabtofindout
Compound[VI]shouldbeverydenseduetotheSF5groupsandthesymmetrysinceexplosivepowerisproportionaltothesquareofthedensitythiscompoundshouldbeanextremelypowerfulexplosive-perhapsthebestyet(nonnuclear)
Italsohasanexcessofoxidantthusitcouldbeformulatedwithaluminumtitaniummagnesiumetcfurtherincreasingthepower
LLOYDGARRICK
Anotherwaytodoit
HexachlorobenzeneiscommerciallyavailableandcheaphexafluorobenzenewouldactuallyworkbetterbutitismoreexpensiveHexabromobenzenewouldpreventthe3rdstep(formationofSF5)duetosterichindrance
Proceedingtocompound[III]wouldbeuneventfulndashthisreactionworksquitewellandIhavedoneitcountlesstimesThenewUBEUmemotoprocess(ormynewprocess)wouldthenmakethetrichlorotri(pentafluorosulfanyl)compound[IV]
ReactionwithNH3possiblyaidedbyNaHshouldform[V]ThisreactionworkswellwiththeanalogousnitrocompoundasSF5issimilartoNO2inelectronegativityIexpectitalsotoworkhere
Oxidationofaminestonitroiseffectedbytheldquopersulfuricacidrdquomixthisdrasticreactionconditionshouldnotaffecttherock-stableSF5AlternativelythemuchmilderfluorineacetonitrilewateroxidizerisknowntoeffectthisconversionwellIjusthavenrsquottriedityetndashIneedalab
LLOYDGARRICK
Compound[I]iscommerciallyavailablealsoIhavemademulti-dozengramlotsof[IV]LikemostofthesecompoundsitisaclearfragrantoilThefluorinesareactivatinganddirectorthoandtherearethreeforadditiveeffectSF5isdeactivatinganddirectsmetaalleffectspointtotheopenpositionsthusthisdinitrationshould
alsobestraightforwardagain-Ijustneedalab
Iexpect[V]tobeadenseexplosivesolidverystablealsoperhapsdifficulttodetonateeven
Itislikelythatinthiscompound[V]aswellastheoneimmediatelyaboveit[VI]thefluorinesareverylabileandcouldeasilybesubstitutedwithappropriatenucleophilesgivingevenbettercompoundsSomepossiblesarephenylortriazinewithringnitros
orazidesusinganaminehydrazineordiazobridgeHeck-simpleamineorhydrazineshouldworkniceEvenazideCompound[VI]mightstartlookingrealtreacherouswiththesesubstituentsbutremember-theSF5isstabilizingit
AndwithSF5youcangowherenomanhasgonebefore
LLOYDGARRICK
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
LLOYDGARRICK
ItsalongshotbutIdliketotryitanywayThecrazieritlooksthemorefunitistoplaywith
Wehavetrifluoromethyltransferagentshowaboutapentafluorosulfanyltransferreagent
Thetwofunctionssharemanyofthesamecharacteristicsandcopperlikesbondingtosulfur-itjustmightwork
[althoughIhaveneverusedthenewprocessesonmetal-sulfurbondedcompounds-noideawhattoexpect]butisntthat
whatresearchisallabout
thattoavoidlegalissues)5 Yougetafast-trackshort-cutone-uponthecompetitioninthecut-throatcompetitivearenaofdrugdevelopment6 IcoulddothismyselfbutasIsaidabove-Ineedalab
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Quiteanumberofcurrentlymarketeddrugs[andmorewillbecoming)containtheCF3functionsomeexamplesaredepictedbelowwiththeCF3replacedbySF5todemonstratehypotheticalconcepts
Nowhereisanideaforbolddaringentrepreneurialspiritedindividualsandorcompanies
1 Takeanycurrentlymarketeddrug[oragriculturalcompound]containingCF3maketheSF5analogandsubmititasanewcompound
2 ItisabetterthanevenbetthatitwillbeasignificantlybettercompoundenoughsothattheFDAwillacceptitassuchandnotjustanothercopycat
3 Sincealloftheresearchtimeexpenseandmanpowerhasalreadybeendoneontherestofthemoleculeyouwillbesparedthat
4 Anditisunlikelythattheoriginalpatent(s)wouldcoverthecarbon-sulfurbondatthatposition(butyouwillneedtoverify
LLOYDGARRICK
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[SF5]-Flibanserin
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Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
CurrentlytheintroductionoffluorineintoorganicmoleculeshasbecomeverycommonmethodologyinbiomedicalfieldsandnumerousfluorinecontainingmoleculeshavebeendevelopedandmanyhaveshownsignificantpromiseandadvantagesinthisfieldInparticularthepentafluorosulfanyl(SF5)groupwhichisahighlyfluorinatedfunctionalgrouphasshownremarkableactivityinbiochemicalmoleculesTheintroductionoftheSF5groupbringsnotonlythenovelpropertieswhichoriginatefromFluorineelement(Strongelectronegativityhighlipophilicityandhighchemicalstability)tothemoleculebutalsoalargerstericeffectthantheCF3groupwhichisalsorecognizedasahighlyfluorinatedfunctionalgroupTherelativestericdemandoftheSF5groupisslightlylessthanthatofatert-butylgroupandconsiderablylargerthanthatofaCF3groupExamplesofbiologicalactivitiescomparingtheCF3substitutedagentvstheSF5analogareshownbelow
Mefloquineisusedforbothtreatmentandprophylaxisofmalaria8-SF5-Mefloquineshowedalongerhalf-life(68h)thanMefloquine(23h)afteradministrationtomiceFipronilisabroadspectruminsecticideTheSF5analogueofFipronilwasnotonlymoreactivethanFipronilbutshowednolossofpotencytowardstheresistantstrainofhouseflyincontrasttotheFipronil
LLOYDGARRICK
These5areexamplesofSF5analogsofcurrentbio-activecompoundsallofwhicharebetterthantheoriginals
LLOYDGARRICK
Anewanti-malarialdrug(DSM265)verypromisingsofarandcurrentlyinclinicaltrialscontainsap-SF5-anilinosubstituentasshown
LLOYDGARRICK
Thesynthesis[seeDSM265linksjustbelow]involvesreplacementofchlorineonthetriazolopyrimidineringwithpara-aminophenylpentafluorosulfanateacompoundImadein50grlots(newprocess)
butwhichisnowonlyavailableingramquantitiesandprohibitiveprice(oldcurrentprocedures)
Thisisaperfectexampleofhowanewandverypromisingdrugwill(would)beprohibitivelyexpensiveifitemploystheSF5functionnowbutwiththenewSF5processeswillbemuchcheaperandmoreavailableAlsoSF5buildingblockswillbecheaperandmorereadilyavailable
thusenablingmoreresearchintonovelpharmaceutical(andagricultural)candidates
Morelinksconcerningbio-activecompoundsCF3vsSF5DopamineReceptorResearchpatentDirectComparisonCF3andSF5PentafluorosulfanylcompoundsmanufactureanduseaspharmaceuticalagentsStructuresofnewAnti-MalarialCandidatesDSM265Structure-guidedleadoptimizationDSM265chemistry
TheNewPreparationMethods
InordertocontributetoandimproveSF5chemistryaboveUBEhasstartedtodeliveraseriesofaromaticpentafluorosulfanylcompoundspreparedbynewinnovativeprocessesincludingourKFCl2methodwhichwasdevelopedbyIMampTResearchInc
LLOYDGARRICK
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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
LLOYDGARRICK
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
LLOYDGARRICK
IncorporationofSF5intoExplosivesandHighEnergyCompoundsandMolecules
LLOYDGARRICK
References
SheppardWAJAmChemSoc19623064YeCGardGLWinterRWSyvretRGTwamleyBShreeveJnMOrgLett200793841GargSShreeveJMJMaterChem2011214787AgrawalJPProgEnergyCombustSci1998241SitzmannMEGilliganWHOrnellasDLThrasherJSJEnergeticMat19908352SitzmannMEJFluorineChem1991195GaoHYeCWinterRWGardGLSitzmannMEShreeveJMEurJInorgChem20063221OrnellasDLPropellantsExplosivesPyrotechnics198914122
ChemistrySF5inexplosivecompounds
PentafluorosulfanylpolynitroaliphaticureamonocarbamateanddicarbamateexplosivecompoundsPolynitroaliphaticexplosivescontainingthepentafluorosulfanyl(SF5)groupTheselectionandstudyofamodelcompoundRecentTrendsinNewEnergeticMaterials134-Oxadiazolescontainingthepentafluorothio(SF5)GroupPentafluorosulfanylnitramideSaltsPentafluorosulfanylPolynitroaliphaticUreaExplosiveCompoundsPentafluorosulfanylMonocarbamateandDicarbamateExplosiveCompoundsPentafluorosulfanylCarbamateExplosivesHighEnergyPentafluorosulfanylPolynitroaliphaticUreaMonocarbamateandDicarbamateCompoundsPentafluorosulfanyl-substituted-poly-123-triazole-compounds
Ithasbeensaidthatthereareveryfew(inter)personal[and(inter)national]problemsthatcannotbesolvedthroughasuitableapplicationofhighexplosivesWellthenherearesomenewideastoponder
LLOYDGARRICK
[III]istheSF5analogofTETRYLwhichhasaNO2insteadTETRYLisaverypowerfulsecondaryexplosiveonceinwidespreadusebutnolongerasitistoounstableandsensitive
SinceSF5isknowntostabilizethesetypesofcompounds[III]isreasonablyexpectedtobeaverypowerfultertiaryexplosivestableenoughforuseitsmainadvantagehereistheeaseofsynthesis
[I]ismadefromthereadilyavailable[0]bythenewprocess(es)thenreactedwithdimethylaminetoproduce[II]SubstitutionoffluorinesontheseSF5compoundsbynucleophilesgenerallyprocedeswell-Ihavedonecountlesssuchreactions
ThentheactivatinganddirectingeffectsoftheamineandSF5enablenitrationtoprocedeunderrelativelymildconditions(similartotheTETRYLreactionfromdimethylaniline)toyieldtheproduct[III]
NextGenerationExplosivesthatareEASYtoSynthesize
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Ihaveproceededtothebifunctionalcompound[V]ingoodyielditisaclearoilpleasantodorThedinitrationshouldbestraightforwardIjusthaventdoneityet-Ineedalab
Compound[VII]analogoustotheknownandcurrentlyusedTATBwouldbeevenmorestableandverylikelymorepowerful
AndlookiehowEASYitistomake
NextGenExplosivesEasytoMake
LLOYDGARRICK
LLOYDGARRICK
Compound[I]iscommerciallyavailablenitrationto[II]shouldbeeasyfacilitatedbythefluorinesFormationof[III]willbeeasyIhavedonemanysuchreactionsDeprotectionreactionto[IV]would
normallyusecatalytic(5mol)AlCl3howeverthenitrogroupsmaycoordinatealsothusstoichiometricquantitymaybeneededalternativelythisdeprotectioncanalsobedonewithTFAorHF
ThenewprocessescanthenformtheSF5compoundfromthethiol
AlthoughnitrationcaneasilybedoneorthotoSF5(Ihavedoneit)theconverseissometimesdifficultStericeffectscaninterferewiththeformationoftheintermediateSF4ClDontknowhere-Ineedalabtofindout
Compound[VI]shouldbeverydenseduetotheSF5groupsandthesymmetrysinceexplosivepowerisproportionaltothesquareofthedensitythiscompoundshouldbeanextremelypowerfulexplosive-perhapsthebestyet(nonnuclear)
Italsohasanexcessofoxidantthusitcouldbeformulatedwithaluminumtitaniummagnesiumetcfurtherincreasingthepower
LLOYDGARRICK
Anotherwaytodoit
HexachlorobenzeneiscommerciallyavailableandcheaphexafluorobenzenewouldactuallyworkbetterbutitismoreexpensiveHexabromobenzenewouldpreventthe3rdstep(formationofSF5)duetosterichindrance
Proceedingtocompound[III]wouldbeuneventfulndashthisreactionworksquitewellandIhavedoneitcountlesstimesThenewUBEUmemotoprocess(ormynewprocess)wouldthenmakethetrichlorotri(pentafluorosulfanyl)compound[IV]
ReactionwithNH3possiblyaidedbyNaHshouldform[V]ThisreactionworkswellwiththeanalogousnitrocompoundasSF5issimilartoNO2inelectronegativityIexpectitalsotoworkhere
Oxidationofaminestonitroiseffectedbytheldquopersulfuricacidrdquomixthisdrasticreactionconditionshouldnotaffecttherock-stableSF5AlternativelythemuchmilderfluorineacetonitrilewateroxidizerisknowntoeffectthisconversionwellIjusthavenrsquottriedityetndashIneedalab
LLOYDGARRICK
Compound[I]iscommerciallyavailablealsoIhavemademulti-dozengramlotsof[IV]LikemostofthesecompoundsitisaclearfragrantoilThefluorinesareactivatinganddirectorthoandtherearethreeforadditiveeffectSF5isdeactivatinganddirectsmetaalleffectspointtotheopenpositionsthusthisdinitrationshould
alsobestraightforwardagain-Ijustneedalab
Iexpect[V]tobeadenseexplosivesolidverystablealsoperhapsdifficulttodetonateeven
Itislikelythatinthiscompound[V]aswellastheoneimmediatelyaboveit[VI]thefluorinesareverylabileandcouldeasilybesubstitutedwithappropriatenucleophilesgivingevenbettercompoundsSomepossiblesarephenylortriazinewithringnitros
orazidesusinganaminehydrazineordiazobridgeHeck-simpleamineorhydrazineshouldworkniceEvenazideCompound[VI]mightstartlookingrealtreacherouswiththesesubstituentsbutremember-theSF5isstabilizingit
AndwithSF5youcangowherenomanhasgonebefore
LLOYDGARRICK
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
LLOYDGARRICK
ItsalongshotbutIdliketotryitanywayThecrazieritlooksthemorefunitistoplaywith
Wehavetrifluoromethyltransferagentshowaboutapentafluorosulfanyltransferreagent
Thetwofunctionssharemanyofthesamecharacteristicsandcopperlikesbondingtosulfur-itjustmightwork
[althoughIhaveneverusedthenewprocessesonmetal-sulfurbondedcompounds-noideawhattoexpect]butisntthat
whatresearchisallabout
thattoavoidlegalissues)5 Yougetafast-trackshort-cutone-uponthecompetitioninthecut-throatcompetitivearenaofdrugdevelopment6 IcoulddothismyselfbutasIsaidabove-Ineedalab
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Quiteanumberofcurrentlymarketeddrugs[andmorewillbecoming)containtheCF3functionsomeexamplesaredepictedbelowwiththeCF3replacedbySF5todemonstratehypotheticalconcepts
Nowhereisanideaforbolddaringentrepreneurialspiritedindividualsandorcompanies
1 Takeanycurrentlymarketeddrug[oragriculturalcompound]containingCF3maketheSF5analogandsubmititasanewcompound
2 ItisabetterthanevenbetthatitwillbeasignificantlybettercompoundenoughsothattheFDAwillacceptitassuchandnotjustanothercopycat
3 Sincealloftheresearchtimeexpenseandmanpowerhasalreadybeendoneontherestofthemoleculeyouwillbesparedthat
4 Anditisunlikelythattheoriginalpatent(s)wouldcoverthecarbon-sulfurbondatthatposition(butyouwillneedtoverify
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
Morelinksconcerningbio-activecompoundsCF3vsSF5DopamineReceptorResearchpatentDirectComparisonCF3andSF5PentafluorosulfanylcompoundsmanufactureanduseaspharmaceuticalagentsStructuresofnewAnti-MalarialCandidatesDSM265Structure-guidedleadoptimizationDSM265chemistry
TheNewPreparationMethods
InordertocontributetoandimproveSF5chemistryaboveUBEhasstartedtodeliveraseriesofaromaticpentafluorosulfanylcompoundspreparedbynewinnovativeprocessesincludingourKFCl2methodwhichwasdevelopedbyIMampTResearchInc
LLOYDGARRICK
LLOYDGARRICK
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
LLOYDGARRICK
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
LLOYDGARRICK
IncorporationofSF5intoExplosivesandHighEnergyCompoundsandMolecules
LLOYDGARRICK
References
SheppardWAJAmChemSoc19623064YeCGardGLWinterRWSyvretRGTwamleyBShreeveJnMOrgLett200793841GargSShreeveJMJMaterChem2011214787AgrawalJPProgEnergyCombustSci1998241SitzmannMEGilliganWHOrnellasDLThrasherJSJEnergeticMat19908352SitzmannMEJFluorineChem1991195GaoHYeCWinterRWGardGLSitzmannMEShreeveJMEurJInorgChem20063221OrnellasDLPropellantsExplosivesPyrotechnics198914122
ChemistrySF5inexplosivecompounds
PentafluorosulfanylpolynitroaliphaticureamonocarbamateanddicarbamateexplosivecompoundsPolynitroaliphaticexplosivescontainingthepentafluorosulfanyl(SF5)groupTheselectionandstudyofamodelcompoundRecentTrendsinNewEnergeticMaterials134-Oxadiazolescontainingthepentafluorothio(SF5)GroupPentafluorosulfanylnitramideSaltsPentafluorosulfanylPolynitroaliphaticUreaExplosiveCompoundsPentafluorosulfanylMonocarbamateandDicarbamateExplosiveCompoundsPentafluorosulfanylCarbamateExplosivesHighEnergyPentafluorosulfanylPolynitroaliphaticUreaMonocarbamateandDicarbamateCompoundsPentafluorosulfanyl-substituted-poly-123-triazole-compounds
Ithasbeensaidthatthereareveryfew(inter)personal[and(inter)national]problemsthatcannotbesolvedthroughasuitableapplicationofhighexplosivesWellthenherearesomenewideastoponder
LLOYDGARRICK
[III]istheSF5analogofTETRYLwhichhasaNO2insteadTETRYLisaverypowerfulsecondaryexplosiveonceinwidespreadusebutnolongerasitistoounstableandsensitive
SinceSF5isknowntostabilizethesetypesofcompounds[III]isreasonablyexpectedtobeaverypowerfultertiaryexplosivestableenoughforuseitsmainadvantagehereistheeaseofsynthesis
[I]ismadefromthereadilyavailable[0]bythenewprocess(es)thenreactedwithdimethylaminetoproduce[II]SubstitutionoffluorinesontheseSF5compoundsbynucleophilesgenerallyprocedeswell-Ihavedonecountlesssuchreactions
ThentheactivatinganddirectingeffectsoftheamineandSF5enablenitrationtoprocedeunderrelativelymildconditions(similartotheTETRYLreactionfromdimethylaniline)toyieldtheproduct[III]
NextGenerationExplosivesthatareEASYtoSynthesize
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Ihaveproceededtothebifunctionalcompound[V]ingoodyielditisaclearoilpleasantodorThedinitrationshouldbestraightforwardIjusthaventdoneityet-Ineedalab
Compound[VII]analogoustotheknownandcurrentlyusedTATBwouldbeevenmorestableandverylikelymorepowerful
AndlookiehowEASYitistomake
NextGenExplosivesEasytoMake
LLOYDGARRICK
LLOYDGARRICK
Compound[I]iscommerciallyavailablenitrationto[II]shouldbeeasyfacilitatedbythefluorinesFormationof[III]willbeeasyIhavedonemanysuchreactionsDeprotectionreactionto[IV]would
normallyusecatalytic(5mol)AlCl3howeverthenitrogroupsmaycoordinatealsothusstoichiometricquantitymaybeneededalternativelythisdeprotectioncanalsobedonewithTFAorHF
ThenewprocessescanthenformtheSF5compoundfromthethiol
AlthoughnitrationcaneasilybedoneorthotoSF5(Ihavedoneit)theconverseissometimesdifficultStericeffectscaninterferewiththeformationoftheintermediateSF4ClDontknowhere-Ineedalabtofindout
Compound[VI]shouldbeverydenseduetotheSF5groupsandthesymmetrysinceexplosivepowerisproportionaltothesquareofthedensitythiscompoundshouldbeanextremelypowerfulexplosive-perhapsthebestyet(nonnuclear)
Italsohasanexcessofoxidantthusitcouldbeformulatedwithaluminumtitaniummagnesiumetcfurtherincreasingthepower
LLOYDGARRICK
Anotherwaytodoit
HexachlorobenzeneiscommerciallyavailableandcheaphexafluorobenzenewouldactuallyworkbetterbutitismoreexpensiveHexabromobenzenewouldpreventthe3rdstep(formationofSF5)duetosterichindrance
Proceedingtocompound[III]wouldbeuneventfulndashthisreactionworksquitewellandIhavedoneitcountlesstimesThenewUBEUmemotoprocess(ormynewprocess)wouldthenmakethetrichlorotri(pentafluorosulfanyl)compound[IV]
ReactionwithNH3possiblyaidedbyNaHshouldform[V]ThisreactionworkswellwiththeanalogousnitrocompoundasSF5issimilartoNO2inelectronegativityIexpectitalsotoworkhere
Oxidationofaminestonitroiseffectedbytheldquopersulfuricacidrdquomixthisdrasticreactionconditionshouldnotaffecttherock-stableSF5AlternativelythemuchmilderfluorineacetonitrilewateroxidizerisknowntoeffectthisconversionwellIjusthavenrsquottriedityetndashIneedalab
LLOYDGARRICK
Compound[I]iscommerciallyavailablealsoIhavemademulti-dozengramlotsof[IV]LikemostofthesecompoundsitisaclearfragrantoilThefluorinesareactivatinganddirectorthoandtherearethreeforadditiveeffectSF5isdeactivatinganddirectsmetaalleffectspointtotheopenpositionsthusthisdinitrationshould
alsobestraightforwardagain-Ijustneedalab
Iexpect[V]tobeadenseexplosivesolidverystablealsoperhapsdifficulttodetonateeven
Itislikelythatinthiscompound[V]aswellastheoneimmediatelyaboveit[VI]thefluorinesareverylabileandcouldeasilybesubstitutedwithappropriatenucleophilesgivingevenbettercompoundsSomepossiblesarephenylortriazinewithringnitros
orazidesusinganaminehydrazineordiazobridgeHeck-simpleamineorhydrazineshouldworkniceEvenazideCompound[VI]mightstartlookingrealtreacherouswiththesesubstituentsbutremember-theSF5isstabilizingit
AndwithSF5youcangowherenomanhasgonebefore
LLOYDGARRICK
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
LLOYDGARRICK
ItsalongshotbutIdliketotryitanywayThecrazieritlooksthemorefunitistoplaywith
Wehavetrifluoromethyltransferagentshowaboutapentafluorosulfanyltransferreagent
Thetwofunctionssharemanyofthesamecharacteristicsandcopperlikesbondingtosulfur-itjustmightwork
[althoughIhaveneverusedthenewprocessesonmetal-sulfurbondedcompounds-noideawhattoexpect]butisntthat
whatresearchisallabout
thattoavoidlegalissues)5 Yougetafast-trackshort-cutone-uponthecompetitioninthecut-throatcompetitivearenaofdrugdevelopment6 IcoulddothismyselfbutasIsaidabove-Ineedalab
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Quiteanumberofcurrentlymarketeddrugs[andmorewillbecoming)containtheCF3functionsomeexamplesaredepictedbelowwiththeCF3replacedbySF5todemonstratehypotheticalconcepts
Nowhereisanideaforbolddaringentrepreneurialspiritedindividualsandorcompanies
1 Takeanycurrentlymarketeddrug[oragriculturalcompound]containingCF3maketheSF5analogandsubmititasanewcompound
2 ItisabetterthanevenbetthatitwillbeasignificantlybettercompoundenoughsothattheFDAwillacceptitassuchandnotjustanothercopycat
3 Sincealloftheresearchtimeexpenseandmanpowerhasalreadybeendoneontherestofthemoleculeyouwillbesparedthat
4 Anditisunlikelythattheoriginalpatent(s)wouldcoverthecarbon-sulfurbondatthatposition(butyouwillneedtoverify
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
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
LLOYDGARRICK
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
LLOYDGARRICK
IncorporationofSF5intoExplosivesandHighEnergyCompoundsandMolecules
LLOYDGARRICK
References
SheppardWAJAmChemSoc19623064YeCGardGLWinterRWSyvretRGTwamleyBShreeveJnMOrgLett200793841GargSShreeveJMJMaterChem2011214787AgrawalJPProgEnergyCombustSci1998241SitzmannMEGilliganWHOrnellasDLThrasherJSJEnergeticMat19908352SitzmannMEJFluorineChem1991195GaoHYeCWinterRWGardGLSitzmannMEShreeveJMEurJInorgChem20063221OrnellasDLPropellantsExplosivesPyrotechnics198914122
ChemistrySF5inexplosivecompounds
PentafluorosulfanylpolynitroaliphaticureamonocarbamateanddicarbamateexplosivecompoundsPolynitroaliphaticexplosivescontainingthepentafluorosulfanyl(SF5)groupTheselectionandstudyofamodelcompoundRecentTrendsinNewEnergeticMaterials134-Oxadiazolescontainingthepentafluorothio(SF5)GroupPentafluorosulfanylnitramideSaltsPentafluorosulfanylPolynitroaliphaticUreaExplosiveCompoundsPentafluorosulfanylMonocarbamateandDicarbamateExplosiveCompoundsPentafluorosulfanylCarbamateExplosivesHighEnergyPentafluorosulfanylPolynitroaliphaticUreaMonocarbamateandDicarbamateCompoundsPentafluorosulfanyl-substituted-poly-123-triazole-compounds
Ithasbeensaidthatthereareveryfew(inter)personal[and(inter)national]problemsthatcannotbesolvedthroughasuitableapplicationofhighexplosivesWellthenherearesomenewideastoponder
LLOYDGARRICK
[III]istheSF5analogofTETRYLwhichhasaNO2insteadTETRYLisaverypowerfulsecondaryexplosiveonceinwidespreadusebutnolongerasitistoounstableandsensitive
SinceSF5isknowntostabilizethesetypesofcompounds[III]isreasonablyexpectedtobeaverypowerfultertiaryexplosivestableenoughforuseitsmainadvantagehereistheeaseofsynthesis
[I]ismadefromthereadilyavailable[0]bythenewprocess(es)thenreactedwithdimethylaminetoproduce[II]SubstitutionoffluorinesontheseSF5compoundsbynucleophilesgenerallyprocedeswell-Ihavedonecountlesssuchreactions
ThentheactivatinganddirectingeffectsoftheamineandSF5enablenitrationtoprocedeunderrelativelymildconditions(similartotheTETRYLreactionfromdimethylaniline)toyieldtheproduct[III]
NextGenerationExplosivesthatareEASYtoSynthesize
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Ihaveproceededtothebifunctionalcompound[V]ingoodyielditisaclearoilpleasantodorThedinitrationshouldbestraightforwardIjusthaventdoneityet-Ineedalab
Compound[VII]analogoustotheknownandcurrentlyusedTATBwouldbeevenmorestableandverylikelymorepowerful
AndlookiehowEASYitistomake
NextGenExplosivesEasytoMake
LLOYDGARRICK
LLOYDGARRICK
Compound[I]iscommerciallyavailablenitrationto[II]shouldbeeasyfacilitatedbythefluorinesFormationof[III]willbeeasyIhavedonemanysuchreactionsDeprotectionreactionto[IV]would
normallyusecatalytic(5mol)AlCl3howeverthenitrogroupsmaycoordinatealsothusstoichiometricquantitymaybeneededalternativelythisdeprotectioncanalsobedonewithTFAorHF
ThenewprocessescanthenformtheSF5compoundfromthethiol
AlthoughnitrationcaneasilybedoneorthotoSF5(Ihavedoneit)theconverseissometimesdifficultStericeffectscaninterferewiththeformationoftheintermediateSF4ClDontknowhere-Ineedalabtofindout
Compound[VI]shouldbeverydenseduetotheSF5groupsandthesymmetrysinceexplosivepowerisproportionaltothesquareofthedensitythiscompoundshouldbeanextremelypowerfulexplosive-perhapsthebestyet(nonnuclear)
Italsohasanexcessofoxidantthusitcouldbeformulatedwithaluminumtitaniummagnesiumetcfurtherincreasingthepower
LLOYDGARRICK
Anotherwaytodoit
HexachlorobenzeneiscommerciallyavailableandcheaphexafluorobenzenewouldactuallyworkbetterbutitismoreexpensiveHexabromobenzenewouldpreventthe3rdstep(formationofSF5)duetosterichindrance
Proceedingtocompound[III]wouldbeuneventfulndashthisreactionworksquitewellandIhavedoneitcountlesstimesThenewUBEUmemotoprocess(ormynewprocess)wouldthenmakethetrichlorotri(pentafluorosulfanyl)compound[IV]
ReactionwithNH3possiblyaidedbyNaHshouldform[V]ThisreactionworkswellwiththeanalogousnitrocompoundasSF5issimilartoNO2inelectronegativityIexpectitalsotoworkhere
Oxidationofaminestonitroiseffectedbytheldquopersulfuricacidrdquomixthisdrasticreactionconditionshouldnotaffecttherock-stableSF5AlternativelythemuchmilderfluorineacetonitrilewateroxidizerisknowntoeffectthisconversionwellIjusthavenrsquottriedityetndashIneedalab
LLOYDGARRICK
Compound[I]iscommerciallyavailablealsoIhavemademulti-dozengramlotsof[IV]LikemostofthesecompoundsitisaclearfragrantoilThefluorinesareactivatinganddirectorthoandtherearethreeforadditiveeffectSF5isdeactivatinganddirectsmetaalleffectspointtotheopenpositionsthusthisdinitrationshould
alsobestraightforwardagain-Ijustneedalab
Iexpect[V]tobeadenseexplosivesolidverystablealsoperhapsdifficulttodetonateeven
Itislikelythatinthiscompound[V]aswellastheoneimmediatelyaboveit[VI]thefluorinesareverylabileandcouldeasilybesubstitutedwithappropriatenucleophilesgivingevenbettercompoundsSomepossiblesarephenylortriazinewithringnitros
orazidesusinganaminehydrazineordiazobridgeHeck-simpleamineorhydrazineshouldworkniceEvenazideCompound[VI]mightstartlookingrealtreacherouswiththesesubstituentsbutremember-theSF5isstabilizingit
AndwithSF5youcangowherenomanhasgonebefore
LLOYDGARRICK
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
LLOYDGARRICK
ItsalongshotbutIdliketotryitanywayThecrazieritlooksthemorefunitistoplaywith
Wehavetrifluoromethyltransferagentshowaboutapentafluorosulfanyltransferreagent
Thetwofunctionssharemanyofthesamecharacteristicsandcopperlikesbondingtosulfur-itjustmightwork
[althoughIhaveneverusedthenewprocessesonmetal-sulfurbondedcompounds-noideawhattoexpect]butisntthat
whatresearchisallabout
thattoavoidlegalissues)5 Yougetafast-trackshort-cutone-uponthecompetitioninthecut-throatcompetitivearenaofdrugdevelopment6 IcoulddothismyselfbutasIsaidabove-Ineedalab
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Quiteanumberofcurrentlymarketeddrugs[andmorewillbecoming)containtheCF3functionsomeexamplesaredepictedbelowwiththeCF3replacedbySF5todemonstratehypotheticalconcepts
Nowhereisanideaforbolddaringentrepreneurialspiritedindividualsandorcompanies
1 Takeanycurrentlymarketeddrug[oragriculturalcompound]containingCF3maketheSF5analogandsubmititasanewcompound
2 ItisabetterthanevenbetthatitwillbeasignificantlybettercompoundenoughsothattheFDAwillacceptitassuchandnotjustanothercopycat
3 Sincealloftheresearchtimeexpenseandmanpowerhasalreadybeendoneontherestofthemoleculeyouwillbesparedthat
4 Anditisunlikelythattheoriginalpatent(s)wouldcoverthecarbon-sulfurbondatthatposition(butyouwillneedtoverify
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
LLOYDGARRICK
References
SheppardWAJAmChemSoc19623064YeCGardGLWinterRWSyvretRGTwamleyBShreeveJnMOrgLett200793841GargSShreeveJMJMaterChem2011214787AgrawalJPProgEnergyCombustSci1998241SitzmannMEGilliganWHOrnellasDLThrasherJSJEnergeticMat19908352SitzmannMEJFluorineChem1991195GaoHYeCWinterRWGardGLSitzmannMEShreeveJMEurJInorgChem20063221OrnellasDLPropellantsExplosivesPyrotechnics198914122
ChemistrySF5inexplosivecompounds
PentafluorosulfanylpolynitroaliphaticureamonocarbamateanddicarbamateexplosivecompoundsPolynitroaliphaticexplosivescontainingthepentafluorosulfanyl(SF5)groupTheselectionandstudyofamodelcompoundRecentTrendsinNewEnergeticMaterials134-Oxadiazolescontainingthepentafluorothio(SF5)GroupPentafluorosulfanylnitramideSaltsPentafluorosulfanylPolynitroaliphaticUreaExplosiveCompoundsPentafluorosulfanylMonocarbamateandDicarbamateExplosiveCompoundsPentafluorosulfanylCarbamateExplosivesHighEnergyPentafluorosulfanylPolynitroaliphaticUreaMonocarbamateandDicarbamateCompoundsPentafluorosulfanyl-substituted-poly-123-triazole-compounds
Ithasbeensaidthatthereareveryfew(inter)personal[and(inter)national]problemsthatcannotbesolvedthroughasuitableapplicationofhighexplosivesWellthenherearesomenewideastoponder
LLOYDGARRICK
[III]istheSF5analogofTETRYLwhichhasaNO2insteadTETRYLisaverypowerfulsecondaryexplosiveonceinwidespreadusebutnolongerasitistoounstableandsensitive
SinceSF5isknowntostabilizethesetypesofcompounds[III]isreasonablyexpectedtobeaverypowerfultertiaryexplosivestableenoughforuseitsmainadvantagehereistheeaseofsynthesis
[I]ismadefromthereadilyavailable[0]bythenewprocess(es)thenreactedwithdimethylaminetoproduce[II]SubstitutionoffluorinesontheseSF5compoundsbynucleophilesgenerallyprocedeswell-Ihavedonecountlesssuchreactions
ThentheactivatinganddirectingeffectsoftheamineandSF5enablenitrationtoprocedeunderrelativelymildconditions(similartotheTETRYLreactionfromdimethylaniline)toyieldtheproduct[III]
NextGenerationExplosivesthatareEASYtoSynthesize
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Ihaveproceededtothebifunctionalcompound[V]ingoodyielditisaclearoilpleasantodorThedinitrationshouldbestraightforwardIjusthaventdoneityet-Ineedalab
Compound[VII]analogoustotheknownandcurrentlyusedTATBwouldbeevenmorestableandverylikelymorepowerful
AndlookiehowEASYitistomake
NextGenExplosivesEasytoMake
LLOYDGARRICK
LLOYDGARRICK
Compound[I]iscommerciallyavailablenitrationto[II]shouldbeeasyfacilitatedbythefluorinesFormationof[III]willbeeasyIhavedonemanysuchreactionsDeprotectionreactionto[IV]would
normallyusecatalytic(5mol)AlCl3howeverthenitrogroupsmaycoordinatealsothusstoichiometricquantitymaybeneededalternativelythisdeprotectioncanalsobedonewithTFAorHF
ThenewprocessescanthenformtheSF5compoundfromthethiol
AlthoughnitrationcaneasilybedoneorthotoSF5(Ihavedoneit)theconverseissometimesdifficultStericeffectscaninterferewiththeformationoftheintermediateSF4ClDontknowhere-Ineedalabtofindout
Compound[VI]shouldbeverydenseduetotheSF5groupsandthesymmetrysinceexplosivepowerisproportionaltothesquareofthedensitythiscompoundshouldbeanextremelypowerfulexplosive-perhapsthebestyet(nonnuclear)
Italsohasanexcessofoxidantthusitcouldbeformulatedwithaluminumtitaniummagnesiumetcfurtherincreasingthepower
LLOYDGARRICK
Anotherwaytodoit
HexachlorobenzeneiscommerciallyavailableandcheaphexafluorobenzenewouldactuallyworkbetterbutitismoreexpensiveHexabromobenzenewouldpreventthe3rdstep(formationofSF5)duetosterichindrance
Proceedingtocompound[III]wouldbeuneventfulndashthisreactionworksquitewellandIhavedoneitcountlesstimesThenewUBEUmemotoprocess(ormynewprocess)wouldthenmakethetrichlorotri(pentafluorosulfanyl)compound[IV]
ReactionwithNH3possiblyaidedbyNaHshouldform[V]ThisreactionworkswellwiththeanalogousnitrocompoundasSF5issimilartoNO2inelectronegativityIexpectitalsotoworkhere
Oxidationofaminestonitroiseffectedbytheldquopersulfuricacidrdquomixthisdrasticreactionconditionshouldnotaffecttherock-stableSF5AlternativelythemuchmilderfluorineacetonitrilewateroxidizerisknowntoeffectthisconversionwellIjusthavenrsquottriedityetndashIneedalab
LLOYDGARRICK
Compound[I]iscommerciallyavailablealsoIhavemademulti-dozengramlotsof[IV]LikemostofthesecompoundsitisaclearfragrantoilThefluorinesareactivatinganddirectorthoandtherearethreeforadditiveeffectSF5isdeactivatinganddirectsmetaalleffectspointtotheopenpositionsthusthisdinitrationshould
alsobestraightforwardagain-Ijustneedalab
Iexpect[V]tobeadenseexplosivesolidverystablealsoperhapsdifficulttodetonateeven
Itislikelythatinthiscompound[V]aswellastheoneimmediatelyaboveit[VI]thefluorinesareverylabileandcouldeasilybesubstitutedwithappropriatenucleophilesgivingevenbettercompoundsSomepossiblesarephenylortriazinewithringnitros
orazidesusinganaminehydrazineordiazobridgeHeck-simpleamineorhydrazineshouldworkniceEvenazideCompound[VI]mightstartlookingrealtreacherouswiththesesubstituentsbutremember-theSF5isstabilizingit
AndwithSF5youcangowherenomanhasgonebefore
LLOYDGARRICK
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
LLOYDGARRICK
ItsalongshotbutIdliketotryitanywayThecrazieritlooksthemorefunitistoplaywith
Wehavetrifluoromethyltransferagentshowaboutapentafluorosulfanyltransferreagent
Thetwofunctionssharemanyofthesamecharacteristicsandcopperlikesbondingtosulfur-itjustmightwork
[althoughIhaveneverusedthenewprocessesonmetal-sulfurbondedcompounds-noideawhattoexpect]butisntthat
whatresearchisallabout
thattoavoidlegalissues)5 Yougetafast-trackshort-cutone-uponthecompetitioninthecut-throatcompetitivearenaofdrugdevelopment6 IcoulddothismyselfbutasIsaidabove-Ineedalab
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Quiteanumberofcurrentlymarketeddrugs[andmorewillbecoming)containtheCF3functionsomeexamplesaredepictedbelowwiththeCF3replacedbySF5todemonstratehypotheticalconcepts
Nowhereisanideaforbolddaringentrepreneurialspiritedindividualsandorcompanies
1 Takeanycurrentlymarketeddrug[oragriculturalcompound]containingCF3maketheSF5analogandsubmititasanewcompound
2 ItisabetterthanevenbetthatitwillbeasignificantlybettercompoundenoughsothattheFDAwillacceptitassuchandnotjustanothercopycat
3 Sincealloftheresearchtimeexpenseandmanpowerhasalreadybeendoneontherestofthemoleculeyouwillbesparedthat
4 Anditisunlikelythattheoriginalpatent(s)wouldcoverthecarbon-sulfurbondatthatposition(butyouwillneedtoverify
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
LLOYDGARRICK
LLOYDGARRICK
Ihaveproceededtothebifunctionalcompound[V]ingoodyielditisaclearoilpleasantodorThedinitrationshouldbestraightforwardIjusthaventdoneityet-Ineedalab
Compound[VII]analogoustotheknownandcurrentlyusedTATBwouldbeevenmorestableandverylikelymorepowerful
AndlookiehowEASYitistomake
NextGenExplosivesEasytoMake
LLOYDGARRICK
LLOYDGARRICK
Compound[I]iscommerciallyavailablenitrationto[II]shouldbeeasyfacilitatedbythefluorinesFormationof[III]willbeeasyIhavedonemanysuchreactionsDeprotectionreactionto[IV]would
normallyusecatalytic(5mol)AlCl3howeverthenitrogroupsmaycoordinatealsothusstoichiometricquantitymaybeneededalternativelythisdeprotectioncanalsobedonewithTFAorHF
ThenewprocessescanthenformtheSF5compoundfromthethiol
AlthoughnitrationcaneasilybedoneorthotoSF5(Ihavedoneit)theconverseissometimesdifficultStericeffectscaninterferewiththeformationoftheintermediateSF4ClDontknowhere-Ineedalabtofindout
Compound[VI]shouldbeverydenseduetotheSF5groupsandthesymmetrysinceexplosivepowerisproportionaltothesquareofthedensitythiscompoundshouldbeanextremelypowerfulexplosive-perhapsthebestyet(nonnuclear)
Italsohasanexcessofoxidantthusitcouldbeformulatedwithaluminumtitaniummagnesiumetcfurtherincreasingthepower
LLOYDGARRICK
Anotherwaytodoit
HexachlorobenzeneiscommerciallyavailableandcheaphexafluorobenzenewouldactuallyworkbetterbutitismoreexpensiveHexabromobenzenewouldpreventthe3rdstep(formationofSF5)duetosterichindrance
Proceedingtocompound[III]wouldbeuneventfulndashthisreactionworksquitewellandIhavedoneitcountlesstimesThenewUBEUmemotoprocess(ormynewprocess)wouldthenmakethetrichlorotri(pentafluorosulfanyl)compound[IV]
ReactionwithNH3possiblyaidedbyNaHshouldform[V]ThisreactionworkswellwiththeanalogousnitrocompoundasSF5issimilartoNO2inelectronegativityIexpectitalsotoworkhere
Oxidationofaminestonitroiseffectedbytheldquopersulfuricacidrdquomixthisdrasticreactionconditionshouldnotaffecttherock-stableSF5AlternativelythemuchmilderfluorineacetonitrilewateroxidizerisknowntoeffectthisconversionwellIjusthavenrsquottriedityetndashIneedalab
LLOYDGARRICK
Compound[I]iscommerciallyavailablealsoIhavemademulti-dozengramlotsof[IV]LikemostofthesecompoundsitisaclearfragrantoilThefluorinesareactivatinganddirectorthoandtherearethreeforadditiveeffectSF5isdeactivatinganddirectsmetaalleffectspointtotheopenpositionsthusthisdinitrationshould
alsobestraightforwardagain-Ijustneedalab
Iexpect[V]tobeadenseexplosivesolidverystablealsoperhapsdifficulttodetonateeven
Itislikelythatinthiscompound[V]aswellastheoneimmediatelyaboveit[VI]thefluorinesareverylabileandcouldeasilybesubstitutedwithappropriatenucleophilesgivingevenbettercompoundsSomepossiblesarephenylortriazinewithringnitros
orazidesusinganaminehydrazineordiazobridgeHeck-simpleamineorhydrazineshouldworkniceEvenazideCompound[VI]mightstartlookingrealtreacherouswiththesesubstituentsbutremember-theSF5isstabilizingit
AndwithSF5youcangowherenomanhasgonebefore
LLOYDGARRICK
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
LLOYDGARRICK
ItsalongshotbutIdliketotryitanywayThecrazieritlooksthemorefunitistoplaywith
Wehavetrifluoromethyltransferagentshowaboutapentafluorosulfanyltransferreagent
Thetwofunctionssharemanyofthesamecharacteristicsandcopperlikesbondingtosulfur-itjustmightwork
[althoughIhaveneverusedthenewprocessesonmetal-sulfurbondedcompounds-noideawhattoexpect]butisntthat
whatresearchisallabout
thattoavoidlegalissues)5 Yougetafast-trackshort-cutone-uponthecompetitioninthecut-throatcompetitivearenaofdrugdevelopment6 IcoulddothismyselfbutasIsaidabove-Ineedalab
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Quiteanumberofcurrentlymarketeddrugs[andmorewillbecoming)containtheCF3functionsomeexamplesaredepictedbelowwiththeCF3replacedbySF5todemonstratehypotheticalconcepts
Nowhereisanideaforbolddaringentrepreneurialspiritedindividualsandorcompanies
1 Takeanycurrentlymarketeddrug[oragriculturalcompound]containingCF3maketheSF5analogandsubmititasanewcompound
2 ItisabetterthanevenbetthatitwillbeasignificantlybettercompoundenoughsothattheFDAwillacceptitassuchandnotjustanothercopycat
3 Sincealloftheresearchtimeexpenseandmanpowerhasalreadybeendoneontherestofthemoleculeyouwillbesparedthat
4 Anditisunlikelythattheoriginalpatent(s)wouldcoverthecarbon-sulfurbondatthatposition(butyouwillneedtoverify
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
NextGenExplosivesEasytoMake
LLOYDGARRICK
LLOYDGARRICK
Compound[I]iscommerciallyavailablenitrationto[II]shouldbeeasyfacilitatedbythefluorinesFormationof[III]willbeeasyIhavedonemanysuchreactionsDeprotectionreactionto[IV]would
normallyusecatalytic(5mol)AlCl3howeverthenitrogroupsmaycoordinatealsothusstoichiometricquantitymaybeneededalternativelythisdeprotectioncanalsobedonewithTFAorHF
ThenewprocessescanthenformtheSF5compoundfromthethiol
AlthoughnitrationcaneasilybedoneorthotoSF5(Ihavedoneit)theconverseissometimesdifficultStericeffectscaninterferewiththeformationoftheintermediateSF4ClDontknowhere-Ineedalabtofindout
Compound[VI]shouldbeverydenseduetotheSF5groupsandthesymmetrysinceexplosivepowerisproportionaltothesquareofthedensitythiscompoundshouldbeanextremelypowerfulexplosive-perhapsthebestyet(nonnuclear)
Italsohasanexcessofoxidantthusitcouldbeformulatedwithaluminumtitaniummagnesiumetcfurtherincreasingthepower
LLOYDGARRICK
Anotherwaytodoit
HexachlorobenzeneiscommerciallyavailableandcheaphexafluorobenzenewouldactuallyworkbetterbutitismoreexpensiveHexabromobenzenewouldpreventthe3rdstep(formationofSF5)duetosterichindrance
Proceedingtocompound[III]wouldbeuneventfulndashthisreactionworksquitewellandIhavedoneitcountlesstimesThenewUBEUmemotoprocess(ormynewprocess)wouldthenmakethetrichlorotri(pentafluorosulfanyl)compound[IV]
ReactionwithNH3possiblyaidedbyNaHshouldform[V]ThisreactionworkswellwiththeanalogousnitrocompoundasSF5issimilartoNO2inelectronegativityIexpectitalsotoworkhere
Oxidationofaminestonitroiseffectedbytheldquopersulfuricacidrdquomixthisdrasticreactionconditionshouldnotaffecttherock-stableSF5AlternativelythemuchmilderfluorineacetonitrilewateroxidizerisknowntoeffectthisconversionwellIjusthavenrsquottriedityetndashIneedalab
LLOYDGARRICK
Compound[I]iscommerciallyavailablealsoIhavemademulti-dozengramlotsof[IV]LikemostofthesecompoundsitisaclearfragrantoilThefluorinesareactivatinganddirectorthoandtherearethreeforadditiveeffectSF5isdeactivatinganddirectsmetaalleffectspointtotheopenpositionsthusthisdinitrationshould
alsobestraightforwardagain-Ijustneedalab
Iexpect[V]tobeadenseexplosivesolidverystablealsoperhapsdifficulttodetonateeven
Itislikelythatinthiscompound[V]aswellastheoneimmediatelyaboveit[VI]thefluorinesareverylabileandcouldeasilybesubstitutedwithappropriatenucleophilesgivingevenbettercompoundsSomepossiblesarephenylortriazinewithringnitros
orazidesusinganaminehydrazineordiazobridgeHeck-simpleamineorhydrazineshouldworkniceEvenazideCompound[VI]mightstartlookingrealtreacherouswiththesesubstituentsbutremember-theSF5isstabilizingit
AndwithSF5youcangowherenomanhasgonebefore
LLOYDGARRICK
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
LLOYDGARRICK
ItsalongshotbutIdliketotryitanywayThecrazieritlooksthemorefunitistoplaywith
Wehavetrifluoromethyltransferagentshowaboutapentafluorosulfanyltransferreagent
Thetwofunctionssharemanyofthesamecharacteristicsandcopperlikesbondingtosulfur-itjustmightwork
[althoughIhaveneverusedthenewprocessesonmetal-sulfurbondedcompounds-noideawhattoexpect]butisntthat
whatresearchisallabout
thattoavoidlegalissues)5 Yougetafast-trackshort-cutone-uponthecompetitioninthecut-throatcompetitivearenaofdrugdevelopment6 IcoulddothismyselfbutasIsaidabove-Ineedalab
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Quiteanumberofcurrentlymarketeddrugs[andmorewillbecoming)containtheCF3functionsomeexamplesaredepictedbelowwiththeCF3replacedbySF5todemonstratehypotheticalconcepts
Nowhereisanideaforbolddaringentrepreneurialspiritedindividualsandorcompanies
1 Takeanycurrentlymarketeddrug[oragriculturalcompound]containingCF3maketheSF5analogandsubmititasanewcompound
2 ItisabetterthanevenbetthatitwillbeasignificantlybettercompoundenoughsothattheFDAwillacceptitassuchandnotjustanothercopycat
3 Sincealloftheresearchtimeexpenseandmanpowerhasalreadybeendoneontherestofthemoleculeyouwillbesparedthat
4 Anditisunlikelythattheoriginalpatent(s)wouldcoverthecarbon-sulfurbondatthatposition(butyouwillneedtoverify
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
Anotherwaytodoit
HexachlorobenzeneiscommerciallyavailableandcheaphexafluorobenzenewouldactuallyworkbetterbutitismoreexpensiveHexabromobenzenewouldpreventthe3rdstep(formationofSF5)duetosterichindrance
Proceedingtocompound[III]wouldbeuneventfulndashthisreactionworksquitewellandIhavedoneitcountlesstimesThenewUBEUmemotoprocess(ormynewprocess)wouldthenmakethetrichlorotri(pentafluorosulfanyl)compound[IV]
ReactionwithNH3possiblyaidedbyNaHshouldform[V]ThisreactionworkswellwiththeanalogousnitrocompoundasSF5issimilartoNO2inelectronegativityIexpectitalsotoworkhere
Oxidationofaminestonitroiseffectedbytheldquopersulfuricacidrdquomixthisdrasticreactionconditionshouldnotaffecttherock-stableSF5AlternativelythemuchmilderfluorineacetonitrilewateroxidizerisknowntoeffectthisconversionwellIjusthavenrsquottriedityetndashIneedalab
LLOYDGARRICK
Compound[I]iscommerciallyavailablealsoIhavemademulti-dozengramlotsof[IV]LikemostofthesecompoundsitisaclearfragrantoilThefluorinesareactivatinganddirectorthoandtherearethreeforadditiveeffectSF5isdeactivatinganddirectsmetaalleffectspointtotheopenpositionsthusthisdinitrationshould
alsobestraightforwardagain-Ijustneedalab
Iexpect[V]tobeadenseexplosivesolidverystablealsoperhapsdifficulttodetonateeven
Itislikelythatinthiscompound[V]aswellastheoneimmediatelyaboveit[VI]thefluorinesareverylabileandcouldeasilybesubstitutedwithappropriatenucleophilesgivingevenbettercompoundsSomepossiblesarephenylortriazinewithringnitros
orazidesusinganaminehydrazineordiazobridgeHeck-simpleamineorhydrazineshouldworkniceEvenazideCompound[VI]mightstartlookingrealtreacherouswiththesesubstituentsbutremember-theSF5isstabilizingit
AndwithSF5youcangowherenomanhasgonebefore
LLOYDGARRICK
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
LLOYDGARRICK
ItsalongshotbutIdliketotryitanywayThecrazieritlooksthemorefunitistoplaywith
Wehavetrifluoromethyltransferagentshowaboutapentafluorosulfanyltransferreagent
Thetwofunctionssharemanyofthesamecharacteristicsandcopperlikesbondingtosulfur-itjustmightwork
[althoughIhaveneverusedthenewprocessesonmetal-sulfurbondedcompounds-noideawhattoexpect]butisntthat
whatresearchisallabout
thattoavoidlegalissues)5 Yougetafast-trackshort-cutone-uponthecompetitioninthecut-throatcompetitivearenaofdrugdevelopment6 IcoulddothismyselfbutasIsaidabove-Ineedalab
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Quiteanumberofcurrentlymarketeddrugs[andmorewillbecoming)containtheCF3functionsomeexamplesaredepictedbelowwiththeCF3replacedbySF5todemonstratehypotheticalconcepts
Nowhereisanideaforbolddaringentrepreneurialspiritedindividualsandorcompanies
1 Takeanycurrentlymarketeddrug[oragriculturalcompound]containingCF3maketheSF5analogandsubmititasanewcompound
2 ItisabetterthanevenbetthatitwillbeasignificantlybettercompoundenoughsothattheFDAwillacceptitassuchandnotjustanothercopycat
3 Sincealloftheresearchtimeexpenseandmanpowerhasalreadybeendoneontherestofthemoleculeyouwillbesparedthat
4 Anditisunlikelythattheoriginalpatent(s)wouldcoverthecarbon-sulfurbondatthatposition(butyouwillneedtoverify
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
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
LLOYDGARRICK
ItsalongshotbutIdliketotryitanywayThecrazieritlooksthemorefunitistoplaywith
Wehavetrifluoromethyltransferagentshowaboutapentafluorosulfanyltransferreagent
Thetwofunctionssharemanyofthesamecharacteristicsandcopperlikesbondingtosulfur-itjustmightwork
[althoughIhaveneverusedthenewprocessesonmetal-sulfurbondedcompounds-noideawhattoexpect]butisntthat
whatresearchisallabout
thattoavoidlegalissues)5 Yougetafast-trackshort-cutone-uponthecompetitioninthecut-throatcompetitivearenaofdrugdevelopment6 IcoulddothismyselfbutasIsaidabove-Ineedalab
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Quiteanumberofcurrentlymarketeddrugs[andmorewillbecoming)containtheCF3functionsomeexamplesaredepictedbelowwiththeCF3replacedbySF5todemonstratehypotheticalconcepts
Nowhereisanideaforbolddaringentrepreneurialspiritedindividualsandorcompanies
1 Takeanycurrentlymarketeddrug[oragriculturalcompound]containingCF3maketheSF5analogandsubmititasanewcompound
2 ItisabetterthanevenbetthatitwillbeasignificantlybettercompoundenoughsothattheFDAwillacceptitassuchandnotjustanothercopycat
3 Sincealloftheresearchtimeexpenseandmanpowerhasalreadybeendoneontherestofthemoleculeyouwillbesparedthat
4 Anditisunlikelythattheoriginalpatent(s)wouldcoverthecarbon-sulfurbondatthatposition(butyouwillneedtoverify
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
thattoavoidlegalissues)5 Yougetafast-trackshort-cutone-uponthecompetitioninthecut-throatcompetitivearenaofdrugdevelopment6 IcoulddothismyselfbutasIsaidabove-Ineedalab
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
Quiteanumberofcurrentlymarketeddrugs[andmorewillbecoming)containtheCF3functionsomeexamplesaredepictedbelowwiththeCF3replacedbySF5todemonstratehypotheticalconcepts
Nowhereisanideaforbolddaringentrepreneurialspiritedindividualsandorcompanies
1 Takeanycurrentlymarketeddrug[oragriculturalcompound]containingCF3maketheSF5analogandsubmititasanewcompound
2 ItisabetterthanevenbetthatitwillbeasignificantlybettercompoundenoughsothattheFDAwillacceptitassuchandnotjustanothercopycat
3 Sincealloftheresearchtimeexpenseandmanpowerhasalreadybeendoneontherestofthemoleculeyouwillbesparedthat
4 Anditisunlikelythattheoriginalpatent(s)wouldcoverthecarbon-sulfurbondatthatposition(butyouwillneedtoverify
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
LLOYDGARRICK
LLOYDGARRICK
[SF5]-Flibanserin
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
LLOYDGARRICK
Compound[IX]hasgottohaveaveryinterestingpharmacological(CNS)profileTheinterestingbutscarcelyknownanduseddifluoro-methylene-dioxyfunctionisconvenientlymadeusingthenewFLUOLEADdeoxofluorinatingreagent[IF]
whichwedevelopedatUBEconcurrentlywiththenewSF5process
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
LLOYDGARRICK
GoBacktoMainPage
Created in Fedora Linux by Lloyd Garrick 01012018
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs
AromaticSF5PerfluorosulfanatePentafluorosulfanateSulfanylPentafluorideSulfurpentafluoridePerfluorosulfanylPentafluorosulfanylSF5LloydGarrickexplosivesexplosivepropellantrocketfuelhighenergyFLUOLEADagriculturalpharmaceuticalmedicinaldrugdrugs