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
CH2 CHR H + H2C=CHR
H O 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
CH3CH2
m/z = 43
m/z = 29
H

H O
M (88)

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
CH3CH2 O
m/z = 59
115
M-15
M (130)
Mass Spectrometry: Fragmentation
O O
Ethers
MW = 116
2-ethyl-2-methyl-1,3-dioxolane

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

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
H
≡ CH2
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 NH2
NH2 R + 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
MW = 85
piperidine

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
R H R H
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 CH3CH2CH2
α cleavage
mz = 43

C4H9 C O

85
M-1 M (86)
Mass Spectrometry: Fragmentation O

H
Aldehydes

2-ethylbutanal MW = 100

H
O

m/z = 72

H C O

mz = 29

M (100)
 O
Mass Spectrometry: Fragmentation
H
Aromatic Aldehydes
MW = 106
benzaldehyde

M (106)
105
M-1
mz = 77
Mass Spectrometry: Fragmentation
O
Aliphatic Ketones
MW = 100
2-hexanone

43 α cleavage
O C CH3
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
MW = 98
cyclohexanone

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

H
O
H
O

mz = 60

O
C

71
M-17
O C OH
mz = 45

M (88)

weak M+
 O
Mass Spectrometry: Fragmentation
OH
Carboxylic Acids H3C CH3

2,4-dimethylbenzoic acid MW = 150

M (150)
O
- H2O O
H C
O
H
strong M+
132
M-18

133
M-17
mz = 77
Mass Spectrometry: Fragmentation
O
Esters
OCH3
methyl butyrate MW = 102

loss of: H
O
O McLafferty
CH3CH2CH2
OCH3
OCH3
inductive
cleavage 43 74
M-59 M-28

CH3
α cleavage 71
15
M-31
M-87

59 87
M-43 M-15

M (102)
Mass Spectrometry: Fragmentation
O
Esters O
MW = 144
butyl butyrate

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
Mass Spectrometry: Fragmentation O
+
O
Bu Bu
O O
Esters
m/z = 116
(not observed)
fragmentation patterns

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

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 C NH2 O
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

N
H
86
M-15
Mass Spectrometry: Fragmentation O
CH3
N
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
MW = 123
nitrobenzene

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 (134)
m/z = 105, 107
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
Br
Alkyl Halides
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 71
37.0 1.6 15
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

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