WIXLIB

Mass Spectrometry: FragmentationEthers & Sulfides!!!!!Ethers M usually stronger than corresponding alcohol; may be weak/absent α-cleavage of an alkyl radical Inductive cleavage Rearrangement with loss of CHR CHR’Aryl Ethers M strong C-O cleavage β to aromatic ring with subsequent loss of CO Cleavage adjacent to aryl ring also possibleSulfides M usually stronger than corresponding ether cleavage pattern similar to ethers

Mass Spectrometry: FragmentationEthersfragmentation patternsα-cleavageHR CH2 O R'R R'OHinductive cleavageR CH2R CH2 O R' O R'rearrangementHHOCH2HCHRHHOH H2C CHR

Mass Spectrometry: FragmentationOEthersMW 88ethyl propyl etherHHHOHm/z 31HO59M-29CH2CH2CH3CH3CH2m/z 29m/z 43HHO73M-15M (88)

Mass Spectrometry: FragmentationOEthersMW 130di-sec-butyl etherHH3COHm/z 45m/z 57HH3C101M-29HCH3CH2OOm/z 59HHCH3CH2O115M-15M (130)

Mass Spectrometry: FragmentationOEthersOMW M absent

Mass Spectrometry: FragmentationOCH3Aryl EthersMW 108anisoleM (108)loss of C OHHm/z 78Om/z 6593M-15

Mass Spectrometry: FragmentationAryl Ethersfragmentation of aryl ethersOOCH2H CH3- CH3OCH2HO- COm/z 93m/z 65- CH2O-HHHm/z 78m/z 77

Mass Spectrometry: FragmentationSSulfidesethyl isopropyl sulfideMW 104M (104)mz 6175M-2989M-15

Mass Spectrometry: FragmentationAmines!!!!!Aliphatic Amines M will be an odd number for monoamine; may be weak/absent M-1 common α-cleavage of an alkyl radical is predominate fragmentation modelargest group lost preferentially McLafferty rearrangement / loss of NH3 (M-17) are not commonCyclic Amines M usually strong M-1 common fragmentation complex, varies with ring sizeAromatic Amines M usually strong M-1 common loss of HCN is common in anilines

Mass Spectrometry: FragmentationAminesfragmentation patternsα-cleavageR'NRH RR'NR"R"Hloss of H radicalR'NRR"R'NRH R"HM-1ring formationRNH2nRNH2 nn 1, m/z 72n 2, m/z 86

Mass Spectrometry: FragmentationAminesNH2MW 45ethylamineHNHHHmz 30HNHbase peakHM (45)44M-1

Mass Spectrometry: FragmentationNHAminesMW 73diethylamineNHHNHH58M-15Hm/z 30α cleavageM (73)72M-1

Mass Spectrometry: FragmentationNAminesMW 101triethylamine86M-15α cleavageHNHHHm/z 30M (101)100M-1

Mass Spectrometry: FragmentationNHAminesMW 87N-ethylpropylamine58M-29m/z 30α cleavage72M-15M (87)

Mass Spectrometry: FragmentationCyclic AminesNHMW 85piperidineNH84M-184M-28M (85)andNH

Mass Spectrometry: FragmentationNH2Aromatic AminesMW 93anilineNHM-1H H-HCN-Hm/z 66m/z 65M (93)m/z 6592M-1

Mass Spectrometry: FragmentationCarbonyl Compounds!!!!Common Fragmentation ModesG H, R', OH, OR', NR'2α-cleavage (two possibilities)OR R C OGGORRG G C Oβ-cleavageOORR GGMcLafferty rearrangementRHROGH OG

Mass Spectrometry: FragmentationCarbonyl Compounds!!!!Aldehydes M usually observed; may be weak in aliphatic aldehydes M-1 common (α-cleavage) α-cleavage is predominant fragmentation mode; often diagnostic (m/z 29)especially in aromatic aldehydes (M-1; M-29) β-cleavage results in M-41 fragment; greater if α-substitution McLafferty rearrangement in appropriately substituted systems (m/z 44 or higher)Ketones M generally strong α-cleavage is the primary mode of fragmentation β-cleavage less common, but sometimes observed McLafferty rearrangement possible on both sides of carbonyl if chains sufficiently long Cyclic ketones show complex fragmentation patterns Aromatic ketones primarily lose R upon α-cleavage, followed by loss of CO

Mass Spectrometry: FragmentationOAliphatic AldehydesHpentanalMW 86HOMcLaffertyHmz 44α cleavageβ cleavageH C Omz 29CH3CH2CH2mz 43α cleavageC4H9 C O85M-1M (86)

Mass Spectrometry: FragmentationOHAldehydesMW 1002-ethylbutanalHOHm/z 72H C Omz 29M (100)

OMass Spectrometry: FragmentationHAromatic AldehydesMW 106benzaldehydeM (106)105M-1mz 77

Mass Spectrometry: FragmentationOAliphatic KetonesMW 1002-hexanoneO C CH343M-57α cleavageHOMcLaffertymz 58α cleavageC85M-15OM (100)

Mass Spectrometry: FragmentationOKetonesacetophenoneMW 120C O105M-15mz 77M (120)

Mass Spectrometry: FragmentationOCyclic KetonesMW 98cyclohexanoneM (98)mz 55Omz 42Omz 70

Mass Spectrometry: FragmentationCyclic KetonescyclohexanoneOOOHOHH m/z 55OOH m/z 70- COm/z 42

Mass Spectrometry: FragmentationCarboxylic Acids, Esters & Amides!!!Carboxylic Acids M weak in aliphatic acids; stronger in aromatic acids Most important α-cleavage involves loss of OH radical (M-17) α-cleavage with loss of alkyl radical less common; somewhat diagnostic (m/z 45) McLafferty rearrangement in appropriately substituted systems (m/z 60 or higher) Dehydration can occur in o-alkyl benzoic acids (M-18)Esters M weak in most cases; aromatic esters give a stronger parent ion Loss of alkoxy radical more important of the α-cleavage reactions Loss of an alkyl radical by α-cleavage occurs mostly in methyl esters (m/z 59) McLafferty rearrangements are possible on both alkyl and alkoxy sides Benzyloxy esters and o-alkyl benzoates fragment to lose ketene and alcohol, respectivelyAmides M usually observed; Follow the Nitrogen Rule (odd # of N, odd MW) α-cleavage affords a specific ion for primary amides (m/z 44? McLafferty rearrangement observed when γ-hydrogens are present

Mass Spectrometry: FragmentationOOHAliphpatic Carboxylic AcidsMW 88butyric acidHOOHmz 60CO71M-17O C OHmz 45M (88)weak M

OMass Spectrometry: FragmentationOHCarboxylic AcidsH3C2,4-dimethylbenzoic acidCH3MW 150M (150)OOHH- H2OCOstrong M 132M-18mz 77133M-17

Mass Spectrometry: FragmentationOEstersOCH3methyl butyrateMW 102CH3CH2CH2inductivecleavage43M-59Hloss of:O15M-87α M-15M (102)

Mass Spectrometry: FragmentationOEstersOMW 144butyl butyrate71M-73M (144)absentOPrHOH89OPrHMcLafferty 1O88McLafferty101M-43

HMass Spectrometry: FragmentationHOO BuOEstersMcLafferty rearrangementOHOH PrOOm/z 88McLafferty 1PrHOBum/z 116(not observed)fragmentation patternsOOOPrHOOPrHOHOPrHOHm/z 89

Mass Spectrometry: FragmentationOOEstersMW 150benzyl acetateOHα cleavageO43M-108tropylium ion108M-4291M-59M (150)

Mass Spectrometry: FragmentationEstersfragmentation patternsBenzyl ester rearrangementOO HO O C CH2Hcan fragment furtherLoss of alcoholOXOHRCX CH2, OXO HOR

Mass Spectrometry: FragmentationOAmidesNH2butyramideMW 87α cleavageO C NH2mz 44HONH2McLafferty59M-28M (87)

Mass Spectrometry: FragmentationOAmidesNHMW 101N-ethylpropionamideM (101)CH3CH2mz 29HN CH2H57M-4472M-29mz 30ONH86M-15

Mass Spectrometry: FragmentationONHAryl AmidesN-methylbenzamimdeCH3MW 135105M-29mz 77M (135)M-1

Mass Spectrometry: FragmentationNitrilesNitriles M may be weak/absent; strong M in aromatic nitriles; follow nitrogen rule Fragment readily to give M-1 Loss of HC N fequently obsterved (M-27); aromatic nitriles also show loss of CN (M-26) McLafferty rearrangement in nitriles of appropriate length (m/z 41)

Mass Spectrometry: FragmentationNitrilesfragmentation patternsLoss of α-hydrogenHRHC NH C C NRM-1Loss of HCNHRRC N HC NM-27McLafferty rearrangementRHCNR H2C C NHm/z 41

Mass Spectrometry: FragmentationNitrilesC NhexanenitrileMW 97H2C C NHMcLaffertymz 41HC C NC4H970M-2796M-1M (97)

Mass Spectrometry: FragmentationNitro Compounds & HalidesNitro Compounds M almost never observed unless aromatic; follow nitrogen rule Principle degradation is loss of NO (m/z 30) and loss of NO2 (m/z 46) Aromatic nitro compounds show additional fragmentation patternsHalides M often weak; stronger in aromatic halides chloro and bromo compounds show strong M 2 peaksCl – M : M 23:1Br – M : M 21:1 principle fragmentation is loss of halogen Loss of HX also common α-cleavage sometimes observed

Mass Spectrometry: FragmentationNitro Compoundsfragmentation patternsOOR NOR NOm/z 46OR NONO2R OR O N O N Om/z 30O NOm/z 93 C Om/z 65NO2 m/z 77NO2C4H3m/z 51 HH

Mass Spectrometry: FragmentationNO2Nitro Compounds1-nitropropaneMW 89CH3CH2CH243M-46N Omz 30ONOmz 46M (89)absent

Mass Spectrometry: FragmentationNO2Nitro CompoundsMW 123nitrobenzene77M-NO2M (123)mz 51ON Omz 30mz 6593M-NO

Mass Spectrometry: FragmentationOrganic Halidesfragmentation patternsLoss of HalideR XR XI Br Cl FLoss of HXH HR C C XH HRC CH2H HF HCl HBr HIα-cleavageHR C XHHR C XHLoss of δ ChainRXR XHX

Mass Spectrometry: FragmentationAlkyl HalidesCl1-chloropropaneMW 78CH3CH2CH243M-Clα cleavage42M-HClHC ClHmz 49, 51M (78)80M 2

Mass Spectrometry: FragmentationClAlkyl HalidesMW 782-chloropropane43M-ClHC ClCH3m/z 63, 65M (78)80M 2

Mass Spectrometry: FragmentationClAlkyl Halides2-chloroheptaneMW 134rearrngement56M-7898M - HClClm/z 105, 107HClH ClM (134)M 2 (136)

Mass Spectrometry: FragmentationBrAlkyl Halides2-bromopropaneMW 123CH3CHCH343M-BrM (122)124M 2

Mass Spectrometry: FragmentationBrAlkyl HalidesMW 1651-bromohexaneBr85M-Brmz 135, 137rearrngementmz 57M (164)166M 2

Mass Spectrometry: FragmentationBrAlkyl HalidesbromobenzeneMW 157mz 77M (156)158M 2

Mass Spectrometry: FragmentationWhat Can the MS Tell You?!Evaluation of UnknownCompounds by Mass Spectr1. Get an overview of the spectrum. Is it simple? Complex? Are there groups of peaks?2. Identify and evaluate the molecular ion.- Is M strong or weak?- Are their significant peaks due to isotopes (e.g. M 1, M 2, etc.)?- Is the molecular ion an odd number (Apply the Nitrogen Rule)?- Is there an M-1 Peak?- If a molecular formular is not provided, check tables or on-line calculators to determinepossible formulas3. Evaluate the major fragments- What mass is lost from M to give these peaks?- What ions could give these peaks?- If available, use IR data to identify functionality, and consider known fragmentation patternsof these groups.- Consider the loss of small neutral molecules (e.g. H2O, HOR, H2C CH2, HC CH, HX, CO2, etc.)- Consider possible diagnostic peaks (e.g. m/z 29, 30, 31, 39, 41, 44, 91, 45, 59, etc.)4. Use fragmentation information to piece together possible structure

Mass Spectrometry: FragmentationCommonly Lost FragmentsPavia Appendix 11

Mass Spectrometry: FragmentationCommon Fragment PeaksPavia Appendix 12

Mass Spectrometry: FragmentationOReporting Mass Spec DataOCH3Low Resolution Mass 110.422.21.549.92.364.22.216.41.4MW 10243M-5974M-2871M-3115M-8759M-4387M-15M (102)Source Temperature: 240 CSample Temperature: 180 CRESERVOIR, 75 eV

Mass SpectrometryOReporting Mass Spec DataOCH3Low Resolution Mass Specionization technique/methodMW 102peak assignmentMS (EI, 75 eV): m/z 102 (M , 1%), 87 (16), 74 (64), 71 (50), 59 (22), 43 (100) .massheight of peak relative to base peak

Mass SpectrometryReporting Mass Spec Data!!!High Resolution Mass Spec!!OHOCO2Et

Mass SpectrometryReporting Mass Spec DataHigh Resolution Mass Specionization methodmolecular ion observedHRMS (ESI): calcd for C12H18O4Na ([M Na] ) 249.1097; found 249.1094.chemical formula of(quasi) molecular ionexact mass calculatedmass found

MW 100 M (100) mz 58 85 M-15 43 M-57 C O O H OCCH3 McLafferty α cleavage α cleavage. Mass Spectrometry: Fragmentation Ketones acetophenone M (120) mz 77 105 M-15 O MW 120 CO. Mass Spectrometry: Fragmentation Cyclic Ketones cyclohexanone O MW 98 M (98) mz 55 mz 70 mz 42 O O. Mass Spectrometry: Fragmentation Cyclic Ketones cyclohexanone O O H O H O