Mass Spectrometry: Fragmentation Ethers & 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 possible Sulfides • M+ usually stronger than corresponding ether • cleavage pattern similar to ethers Mass Spectrometry: Fragmentation Ethers fragmentation patterns α-cleavage H R' R CH2 O R' R + O H inductive cleavage R CH2 O R' R CH2 + O R' rearrangement H H H CH CHR H + H2C=CHR H O 2 H O Mass Spectrometry: Fragmentation O Ethers MW = 88 ethyl propyl ether H H H H O O H m/z = 31 59 M-29 CH2CH2CH3 CH CH 3 2 m/z = 43 m/z = 29 H M (88) H O 73 M-15 Mass Spectrometry: Fragmentation O Ethers MW = 130 di-sec-butyl ether H H H3C O m/z = 45 m/z = 57 H H3C O 101 H M-29 H H CH3CH2 O CH CH O m/z = 59 3 2 115 M-15 M (130) Mass Spectrometry: Fragmentation O O Ethers 2-ethyl-2-methyl-1,3-dioxolane MW = 116 O O 87 M-29 O O 101 M-15 M+ absent Mass Spectrometry: Fragmentation OCH3 Aryl Ethers anisole MW = 108 M (108) H loss of C O H m/z = 78 O m/z = 65 93 M-15 Mass Spectrometry: Fragmentation Aryl Ethers fragmentation of aryl ethers O O CH3 - CH3 - CO m/z = 93 m/z = 65 O O - CH2O - H CH2 ≡ CH2 H H H H m/z = 78 m/z = 77 Mass Spectrometry: Fragmentation S Sulfides ethyl isopropyl sulfide MW = 104 M (104) mz = 61 89 M-15 75 M-29 Mass Spectrometry: Fragmentation Amines ! !!!! 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 mode largest group lost preferentially • McLafferty rearrangement / loss of NH3 (M-17) are not common Cyclic Amines • M+ usually strong • M-1 common • fragmentation complex, varies with ring size Aromatic Amines • M+ usually strong • M-1 common • loss of HCN is common in anilines Mass Spectrometry: Fragmentation Amines fragmentation patterns α-cleavage R' R' R + H N R N R" R" H loss of H radical R' R' R N R" R N + H R" H M-1 ring formation R NH NH2 R + 2 n = 1, m/z = 72 n = 2, m/z = 86 n n Mass Spectrometry: Fragmentation NH2 Amines MW = 45 ethylamine H H N H H mz = 30 H N M (45) H H 44 M-1 base peak Mass Spectrometry: Fragmentation N Amines H MW = 73 diethylamine N H H 58 H N M-15 H H α cleavage m/z = 30 M (73) 72 M-1 Mass Spectrometry: Fragmentation N Amines MW = 101 triethylamine 86 M-15 α cleavage H H N H H m/z = 30 M (101) 100 M-1 Mass Spectrometry: Fragmentation N H Amines MW = 87 N-ethylpropylamine 58 M-29 m/z = 30 α cleavage 72 M (87) M-15 Mass Spectrometry: Fragmentation Cyclic Amines N H piperidine MW = 85 N 84 H M-1 84 M-28 M (85) and N H Mass Spectrometry: Fragmentation NH2 Aromatic Amines MW = 93 aniline H H NH -HCN - H M-1 m/z = 66 m/z = 65 M (93) m/z = 65 92 M-1 Mass Spectrometry: Fragmentation Carbonyl Compounds ! !!! Common Fragmentation Modes α-cleavage (two possibilities) G = H, R', OH, OR', NR'2 O R C O + G R G O R + G C O R G β-cleavage O O R R + G G McLafferty rearrangement H R H R O O + G G Mass Spectrometry: Fragmentation Carbonyl 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: Fragmentation O Aliphatic Aldehydes H pentanal MW = 86 H O McLafferty H mz = 44 α cleavage β cleavage H C O mz = 29 CH CH CH 3 2 2 α cleavage mz = 43 C4H9 C O 85 M-1 M (86) Mass Spectrometry: Fragmentation O H Aldehydes 2-ethylbutanal MW = 100 H O H m/z = 72 H C O mz = 29 M (100) Mass Spectrometry: Fragmentation O H Aromatic Aldehydes MW = 106 benzaldehyde M (106) 105 M-1 mz = 77 Mass Spectrometry: Fragmentation O Aliphatic Ketones 2-hexanone MW = 100 43 O C CH α cleavage 3 M-57 H O McLafferty mz = 58 α cleavage O C 85 M-15 M (100) Mass Spectrometry: Fragmentation O Ketones acetophenone MW = 120 C O 105 M-15 mz = 77 M (120) Mass Spectrometry: Fragmentation O Cyclic Ketones cyclohexanone MW = 98 M (98) mz = 55 O mz = 42 O mz = 70 Mass Spectrometry: Fragmentation Cyclic Ketones cyclohexanone O O O O H H H + m/z = 55 O O H + m/z = 70 - CO m/z = 42 Mass Spectrometry: Fragmentation Carboxylic 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, respectively Amides • 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: Fragmentation O Aliphpatic Carboxylic Acids OH MW = 88 butyric acid H O H O mz = 60 O C 71 M-17 O C OH mz = 45 M (88) weak M+ Mass Spectrometry: Fragmentation O OH Carboxylic Acids H3C CH3 2,4-dimethylbenzoic acid MW = 150 M (150) O - H O O H 2 C O H strong M+ 132 M-18 133 M-17 mz = 77 Mass Spectrometry: Fragmentation O Esters OCH3 methyl butyrate MW = 102 H loss of: O O McLafferty CH3CH2CH2 OCH3 OCH inductive 3 cleavage 43 74 M-59 M-28 CH3 15 α cleavage 71 M-87 M-31 59 87 M-43 M-15 M (102) Mass Spectrometry: Fragmentation O Esters O butyl butyrate MW = 144 71 M (144) M-73 absent H O H Pr O 89 H O McLafferty + 1 Pr O 88 McLafferty 101 M-43 H H O O Mass Spectrometry: Fragmentation + Bu Bu O O Esters m/z = 116 fragmentation patterns (not observed) McLafferty rearrangement H H O O + O Pr O m/z = 88 McLafferty + 1 H H H H O O O H O + H Pr O Pr O Pr O Pr O m/z = 89 Mass Spectrometry: Fragmentation O Esters O MW = 150 benzyl acetate OH α cleavage tropylium ion 108 M-42 91 M-59 O 43 M-108 M (150) Mass Spectrometry: Fragmentation Esters fragmentation patterns Benzyl ester rearrangement O O O H + O C CH2 H can fragment further Loss of alcohol O O R C + O O H R H X = CH2, O X X Mass Spectrometry: Fragmentation O Amides NH2 butyramide MW = 87 H O O C NH2 α cleavage McLafferty mz = 44 NH2 59 M-28 M (87) Mass Spectrometry: Fragmentation O Amides N H N-ethylpropionamide MW = 101 M (101) CH3CH2 mz = 29 H 57 72 N CH2 M-44 M-29 H mz = 30 O N H 86 M-15 Mass Spectrometry: Fragmentation O CH N 3 Aryl Amides H N-methylbenzamimde MW = 135 105 M-29 mz = 77 M (135) M-1 Mass Spectrometry: Fragmentation Nitriles Nitriles • 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: Fragmentation Nitriles fragmentation patterns Loss of α-hydrogen H H H + C C N R C N R M-1 Loss of HCN H R + HC N R C N M-27 McLafferty rearrangement R H N R + H2C C NH C m/z = 41 Mass Spectrometry: Fragmentation Nitriles C N hexanenitrile MW = 97 McLafferty H2C C NH mz = 41 H C C N C4H9 96 70 M-1 M-27 M (97) Mass Spectrometry: Fragmentation Nitro Compounds & Halides Nitro 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 patterns Halides • M+ often weak; stronger in aromatic halides • chloro and bromo compounds show strong M+2 peaks Cl – M : M+2 3 : 1 Br – M : M+2 1 : 1 • principle fragmentation is loss of halogen • Loss of HX also common • α-cleavage sometimes observed Mass Spectrometry: Fragmentation Nitro Compounds fragmentation patterns O O R N R + N O O m/z = 46 O + R N R O N O R O N O O m/z = 30 NO2 O + NO + C O m/z = 93 m/z = 65 NO2 + NO2 C4H3 + H H m/z = 77 m/z = 51 Mass Spectrometry: Fragmentation Nitro Compounds NO2 1-nitropropane MW = 89 M (89) CH3CH2CH2 absent 43 M-46 N O O N mz = 30 O mz = 46 Mass Spectrometry: Fragmentation NO2 Nitro Compounds nitrobenzene MW = 123 77 M-NO2 M (123) mz = 51 O N O 93 mz = 65 M-NO mz = 30 Mass Spectrometry: Fragmentation Organic Halides fragmentation patterns Loss of Halide R X R + X I > Br >> Cl > F Loss of HX H H R R C C X C CH2 + HX H H H HF > HCl > HBr > HI α-cleavage H H R C X R + C X H H Loss of δ Chain R X X R + Mass Spectrometry: Fragmentation Alkyl Halides Cl 1-chloropropane MW = 78 CH3CH2CH2 43 M-Cl α cleavage 42 H M-HCl C Cl H 80 mz = 49, 51 M (78) M+2 Mass Spectrometry: Fragmentation Cl Alkyl Halides MW = 78 2-chloropropane 43 M-Cl H C Cl CH3 m/z = 63, 65 M (78) 80 M+2 Mass Spectrometry: Fragmentation Cl Alkyl Halides 2-chloroheptane MW = 134 rearrngement 56 M-78 98 M - HCl Cl m/z = 105, 107 M (134) M+2 (136) H H Cl Cl Mass Spectrometry: Fragmentation Br Alkyl Halides 2-bromopropane MW = 123 CH3CHCH3 43 M-Br M (122) 124 M+2 Mass Spectrometry: Fragmentation Alkyl Halides Br MW = 165 1-bromohexane Br 85 M-Br mz = 135, 137 rearrngement mz = 57 166 M (164) M+2 Mass Spectrometry: Fragmentation Br Alkyl Halides bromobenzene MW = 157 mz = 77 M (156) 158 M+2 Mass Spectrometry: Fragmentation What Can the MS Tell You? ! Evaluation of UnknownCompounds by Mass Spectr 1.