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 CH2 O R'
R
+
R'
O
H
inductive cleavage
R CH2
R CH2 O R'
+
O R'
rearrangement
H
H
O
CH2
H
CHR
H
H
O
H
+
H2C=CHR
Mass Spectrometry: Fragmentation
O
Ethers
MW = 88
ethyl propyl ether
H
H
H
O
H
m/z = 31
H
O
59
M-29
CH2CH2CH3
CH3CH2
m/z = 29
m/z = 43
H
H
O
73
M-15
M (88)
Mass Spectrometry: Fragmentation
O
Ethers
MW = 130
di-sec-butyl ether
H
H3C
O
H
m/z = 45
m/z = 57
H
H3C
101
M-29
H
CH3CH2
O
O
m/z = 59
H
H
CH3CH2
O
115
M-15
M (130)
Mass Spectrometry: Fragmentation
O
Ethers
O
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
MW = 108
anisole
M (108)
loss of C O
H
H
m/z = 78
O
m/z = 65
93
M-15
Mass Spectrometry: Fragmentation
Aryl Ethers
fragmentation of aryl ethers
O
O
CH2
H
≡
CH3
- CH3
O
CH2
H
O
- CO
m/z = 93
m/z = 65
- CH2O
-H
H
H
m/z = 78
m/z = 77
Mass Spectrometry: Fragmentation
S
Sulfides
ethyl isopropyl sulfide
MW = 104
M (104)
mz = 61
75
M-29
89
M-15
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'
N
R
H
+
R
R'
N
R"
R"
H
loss of H radical
R'
N
R
R"
R'
N
R
H
+
R"
H
M-1
ring formation
R
NH2
n
R
NH2
+
n
n = 1, m/z = 72
n = 2, m/z = 86
Mass Spectrometry: Fragmentation
Amines
NH2
MW = 45
ethylamine
H
N
H
H
H
mz = 30
H
N
H
base peak
H
M (45)
44
M-1
Mass Spectrometry: Fragmentation
N
H
Amines
MW = 73
diethylamine
N
H
H
N
H
H
58
M-15
H
m/z = 30
α cleavage
M (73)
72
M-1
Mass Spectrometry: Fragmentation
N
Amines
MW = 101
triethylamine
86
M-15
α cleavage
H
N
H
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-15
M (87)
Mass Spectrometry: Fragmentation
Cyclic Amines
N
H
MW = 85
piperidine
N
H
84
M-1
84
M-28
M (85)
and
N
H
Mass Spectrometry: Fragmentation
NH2
Aromatic Amines
MW = 93
aniline
NH
M-1
H H
-HCN
-H
m/z = 66
m/z = 65
M (93)
m/z = 65
92
M-1
Mass Spectrometry: Fragmentation
Carbonyl Compounds
!
!
!
!
Common Fragmentation Modes
G = H, R', OH, OR', NR'2
α-cleavage (two possibilities)
O
R
+
R C O
G
G
O
R
R
G
+
G C O
β-cleavage
O
O
R
R
+
G
G
McLafferty rearrangement
R
H
R
O
G
H
+
O
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
mz = 43
α cleavage
C4H9 C O
85
M-1
M (86)
Mass Spectrometry: Fragmentation
O
H
Aldehydes
MW = 100
2-ethylbutanal
H
O
H
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
O C CH3
43
M-57
α cleavage
H
O
McLafferty
mz = 58
α cleavage
C
85
M-15
O
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
H
O
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
OH
Aliphpatic Carboxylic Acids
MW = 88
butyric acid
H
O
O
H
mz = 60
C
O
71
M-17
O C OH
mz = 45
M (88)
weak M+
O
Mass Spectrometry: Fragmentation
OH
Carboxylic Acids
H3C
2,4-dimethylbenzoic acid
CH3
MW = 150
M (150)
O
O
H
H
- H2O
C
O
strong M+
132
M-18
mz = 77
133
M-17
Mass Spectrometry: Fragmentation
O
Esters
OCH3
methyl butyrate
MW = 102
CH3CH2CH2
inductive
cleavage
43
M-59
H
loss of:
O
15
M-87
α cleavage
59
M-43
McLafferty
OCH3
OCH3
CH3
O
74
M-28
71
M-31
87
M-15
M (102)
Mass Spectrometry: Fragmentation
O
Esters
O
MW = 144
butyl butyrate
71
M-73
M (144)
absent
O
Pr
H
O
H
89
O
Pr
H
McLafferty + 1
O
88
McLafferty
101
M-43
H
Mass Spectrometry: Fragmentation
H
O
O
+
Bu
O
Esters
McLafferty rearrangement
O
H
O
H
+
Pr
O
O
m/z = 88
McLafferty + 1
Pr
H
O
Bu
m/z = 116
(not observed)
fragmentation patterns
O
O
O
Pr
H
O
O
Pr
H
O
H
O
Pr
H
O
H
m/z = 89
+
Mass Spectrometry: Fragmentation
O
O
Esters
MW = 150
benzyl acetate
OH
α cleavage
O
43
M-108
tropylium ion
108
M-42
91
M-59
M (150)
Mass Spectrometry: Fragmentation
Esters
fragmentation patterns
Benzyl ester rearrangement
O
O H
O
+
O C CH2
H
can fragment further
Loss of alcohol
O
X
O
H
R
C
X = CH2, O
X
O
+
H
O
R
Mass Spectrometry: Fragmentation
O
Amides
NH2
butyramide
MW = 87
α cleavage
O C NH2
mz = 44
H
O
NH2
McLafferty
59
M-28
M (87)
Mass Spectrometry: Fragmentation
O
Amides
N
H
MW = 101
N-ethylpropionamide
M (101)
CH3CH2
mz = 29
H
N CH2
H
57
M-44
72
M-29
mz = 30
O
N
H
86
M-15
Mass Spectrometry: Fragmentation
O
N
H
Aryl Amides
N-methylbenzamimde
CH3
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
R
H
C N
H
+
C C N
R
M-1
Loss of HCN
H
R
R
C N
+
HC N
M-27
McLafferty rearrangement
R
H
C
N
R
+
H2C C NH
m/z = 41
Mass Spectrometry: Fragmentation
Nitriles
C N
hexanenitrile
MW = 97
H2C C NH
McLafferty
mz = 41
H
C C N
C4H9
70
M-27
96
M-1
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
O
R
+
N
O
m/z = 46
O
R N
O
NO2
R O
R O N O
+
N O
m/z = 30
O
+
NO
m/z = 93
+
C O
m/z = 65
NO2
+
m/z = 77
NO2
C4H3
m/z = 51
+
H
H
Mass Spectrometry: Fragmentation
NO2
Nitro Compounds
1-nitropropane
MW = 89
CH3CH2CH2
43
M-46
N O
mz = 30
O
N
O
mz = 46
M (89)
absent
Mass Spectrometry: Fragmentation
NO2
Nitro Compounds
MW = 123
nitrobenzene
77
M-NO2
M (123)
mz = 51
O
N O
mz = 30
mz = 65
93
M-NO
Mass Spectrometry: Fragmentation
Organic Halides
fragmentation patterns
Loss of Halide
R X
R
+
X
I > Br >> Cl > F
Loss of HX
H H
R C C X
H H
R
C CH2
H
+
HF > HCl > HBr > HI
α-cleavage
H
R C X
H
H
R
+
C X
H
Loss of δ Chain
R
X
R
+
X
HX
Mass Spectrometry: Fragmentation
Alkyl Halides
Cl
1-chloropropane
MW = 78
CH3CH2CH2
43
M-Cl
α cleavage
42
M-HCl
H
C Cl
H
mz = 49, 51
M (78)
80
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
H
Cl
H Cl
M (134)
M+2 (136)
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
M (164)
166
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
peak
intensity
14.0
15.0
18.0
26.0
27.0
28.0
29.0
30.0
31.0
32.0
33.0
37.0
38.0
39.0
40.0
41.0
42.0
43.0
44.0
45.0
55.0
59.0
69.0
71.0
72.0
74.0
75.0
87.0
102.0
2.1
35.0
2.1
5.4
47.0
7.9
9.2
1.2
6.5
1.1
1.9
1.6
3.5
22.5
3.5
45.3
12.1
100.0
3.6
3.1
10.4
22.2
1.5
49.9
2.3
64.2
2.2
16.4
1.4
MW = 102
43
M-59
74
M-28
71
M-31
15
M-87
59
M-43
87
M-15
M (102)
Source Temperature: 240 °C
Sample Temperature: 180 °C
RESERVOIR, 75 eV
Mass Spectrometry
O
Reporting Mass Spec Data
OCH3
Low Resolution Mass Spec
ionization technique/method
MW = 102
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
(quasi) molecular ion
exact mass calculated
mass found