核磁化学位移――解析培训

Table1.1HNMRDataOrganicProcessResearch&DevelopmentArticleDOI:10.1021/acs.oprd.5b00417Org.ProcessRes.Dev.XXXX,XXX,XXX−XXXBandspectralsimilarity.Standardsolutionswerepreparedusingweighedamountsofthefollowingcompounds:o-xylene/iso-amylalcohol;m-xylene/iso-butylacetate;p-xylene/iso-propylacetate;p-cymene/n-butylacetate;toluene/n-butylalcohol;anisole/iso-butylalcohol;pyridine/methyliso-butylketone;ethylbenzene/aceticanhydride;formicacid/iso-amylacetate;Table1.continuedaDataforthesesolventsarefromrefs7and8.Greentriangles=Ratedas“recommended”inCHEM21solventselectionguides.Yellow,upsidedowntriangles=Ratedas“problematic”inCHEM21solventselectionguides(seerefs6and9).bChemicalshiftsnotdeterminedduetoreactivityindeuteratedsolvent.cChemicalshiftsinbracketscorrespondto−ODisotopomer.Seetextformoreinformation.dAsecondsetofresonanceswasobservedforanisoleinD2O:6.79,t(7.9);6.50−6.43,m;3.08,s.SeetextandSupportingInformationformoreinformation.e1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone.fOverlapping−OHand−ODisotopomerresonanceswereobserved.g1:1:1triplet,JH−D=0.8Hz.OrganicProcessResearch&DevelopmentArticleDOI:10.1021/acs.oprd.5b00417Org.ProcessRes.Dev.XXXX,XXX,XXX−XXXCTable2.13CNMRDataOrganicProcessResearch&DevelopmentArticleDOI:10.1021/acs.oprd.5b00417Org.ProcessRes.Dev.XXXX,XXX,XXX−XXXDTable2.continuedOrganicProcessResearch&DevelopmentArticleDOI:10.1021/acs.oprd.5b00417Org.ProcessRes.Dev.XXXX,XXX,XXX−XXXEDMPU/n-heptane;tetrahydrofuran/methylcyclohexane;ethyltert-butylether/methylacetate;glycoldiacetate/tert-amylmethylether;cyclopentylmethylether/benzylalcohol;L-ethyllactate/sulfolane;2-methyl-tetrahydrofuran/chloroben-zene.Whennecessary,assignmentswereconfirmedbygHSQCandHMBCexperimentsoranalyzedindividually.1HNMRsampleswerepreparedwith3μLofthestandardsolutionand600μLofdeuteratedsolventandwerereferencedtoTMS(0ppm).13C{1H}NMRsampleswerepreparedusing25μLofstocksolutionand600μLofdeuteratedsolventandreferencedtoTMS(0ppm).Intheoriginalpublication,1HNMRchemicalshiftsinD2Owerereportedrelativetosodium3-(trimethylsilyl)propanesulfonate.Tominimizespectralover-lapofthereferencestandardwithresonancesofinterest,thecommerciallyavailablesodiumsaltof3-(trimethylsilyl)-propionic-2,2,3,3-d4acid(TSP)wasinsteadusedasachemicalshiftreference(0ppm).The1HNMRsingletforthe-SiMe3groupsofTSPandsodium3-(trimethylsilyl)propanesulfonatewerewithin±0.02ppm.10For13CNMRspectrainD2O,5μLofmethanolwasaddedtoeachcorrespondingNMRsample,anditsmethylresonancewassetto49.50ppm.■RESULTSANDDISCUSSION1HNMRspectraldataforindustriallypreferredsolventsinsixcommonlyusedNMRsolvents(CDCl3,DMSO-d6,CD3CN,acetone-d6,CD3ODandD2O)areprovidedinTable1.SolventsinTable1wereclassifiedaseitherrecommended(greentriangles)orproblematic(yellow,upsidedowntriangles)intheinitialCHEM21survey.6Problematicsolventsposehazardsthatcantypicallybemanagedinaproductionenvironment.Solventsthatwereratedashazardouswereexcluded.Additionally,less-classicalsolvents(e.g.,p-cymene,L-ethyllactate)thatscoredbetterthana7inbothhealthandenvironmentalcategoriesfromthesecondcommunicationpublishedbyCHEM21wereincluded.9AlthoughNMRdatafor19ofthesesolventswereincludedineithertheoriginalreportorthe2010update,7,8dataforanadditional29solventswereobtained.Furthermore,dataforpreviouslyreportedsolventshavebeenmodifiedtoincludechemicalshiftrangesofmultiplets.Table2contains13C{1H}NMRdataforthesesamesolventimpurities.Atabulationofthe1Hand13CNMRdataforall48impuritiesinorderofchemicalshiftisincludedintheSupportingInformationtoaidintheassignmentofunknownpeaks.AllofthecompoundsinTable1wereobtainedassingleisomers.However,somesolventsusedinmanufacturingprocessesareoftenobtainedasmixturesofcomponentsthatareisolatedbydistillationoveraboilingpointrange.Forexample,xylenesisoftencomprisedofamixtureoftheortho,meta,andparaisomers,alongwithethylbenzene.NMRdataforeachindividualcomponentofxylenesareprovidedtoaidintheidentificationofallresidualsolventimpuritiesthatcouldbeencounteredwhenxylenesisused.Alcoholsarecommonlypreferredsolventsthatareoftenavailablefromrenewablesources.AnoftenoverlookedspectralfeatureofalcoholsisthatoccasionallyasecondsetofcertainresonancescanbeobservedduetoslowexchangebetweenROHandRODisotopomersontheNMRtimescale.11ThisisTable2.continuedaDataforthesesolventsarefromrefs7and8.Greentriangles=Ratedas“recommended”inCHEM21solventselectionguides.Yellow,upsidedowntriangles=Ratedas“problematic”inCHEM21solventselectionguides(seerefs6and9).bChemicalshiftsnotdeterminedduetoreactivityindeuteratedsolvent.cChemicalshiftsinbracketscorrespondto−ODisotopomer.Seetextformoreinformation.dSolventwasanalyzedindividually,notinpairs.e1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone.OrganicProcessResearch&DevelopmentArticleDOI:10.1021/acs.oprd.5b00417Org.ProcessRes.Dev.XXXX,XXX,XXX−XXXFConfidential1WuXiPharmaTechCo.,LtdSeptember29,2005核磁共振图谱解析培训手册药明康德核磁分析实验室Confidential2WuXiPharmaTechCo.,LtdSeptember29,2005常用的核磁共振（NMR）实验1H13C13C－DEPT135o(CHCH3,CH2)13C－DEPT90o(CH)1H－1HCOSY(化学键上相邻氢原子的识别)1H－1HTOCSY(结构片断的识别)1H－1HNOESY(空间上相近的氢原子的识别)1H－13C(HSQC,HMQC)(碳氢直接