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. 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 determine possible formulas 3. 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 patterns of 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: Fragmentation

Commonly Lost Fragments

Pavia Appendix 11 Mass Spectrometry: Fragmentation

Common Fragment Peaks

Pavia Appendix 12 Mass Spectrometry: Fragmentation O Reporting Mass Spec Data OCH3 Low Resolution Mass Spec MW = 102 peak intensity 14.0 2.1 15.0 35.0 18.0 2.1 26.0 5.4 27.0 47.0 43 74 28.0 7.9 29.0 9.2 M-59 M-28 30.0 1.2 31.0 6.5 32.0 1.1 33.0 1.9 15 71 37.0 1.6 M-31 38.0 3.5 M-87 39.0 22.5 40.0 3.5 41.0 45.3 59 87 42.0 12.1 M-43 M-15 43.0 100.0 44.0 3.6 45.0 3.1 M (102) 55.0 10.4 59.0 22.2 69.0 1.5 71.0 49.9 72.0 2.3 74.0 64.2 75.0 2.2 87.0 16.4 Source Temperature: 240 °C 102.0 1.4 Sample Temperature: 180 °C RESERVOIR, 75 eV Mass Spectrometry O Reporting Mass Spec Data OCH3 Low Resolution Mass Spec MW = 102

ionization technique/method peak assignment

MS (EI, 75 eV): m/z 102 (M+, 1%), 87 (16), 74 (64), 71 (50), 59 (22), 43 (100) ....

mass height of peak relative to base peak Mass Spectrometry

Reporting Mass Spec Data !!!!! High Resolution Mass Spec

OH

O CO2Et Mass Spectrometry

Reporting Mass Spec Data

High Resolution Mass Spec

ionization method molecular ion observed

+ HRMS (ESI): calcd for C12H18O4Na ([M+Na] ) 249.1097; found 249.1094.

chemical formula of exact mass calculated mass found (quasi) molecular ion