Post on 07-Feb-2018
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
inductive cleavage
rearrangement
R CH2 O R' OH
H
R'R +
R CH2 O R' +R CH2 O R'
O CH2
H
H CHRH
+ H2C=CHRO H
H
H
Mass Spectrometry: Fragmentation
Ethers
ethyl propyl ether
M (88)
73 M-15
59 M-29
O
MW = 88
O
H
H
O
H
H
CH3CH2m/z = 29
CH2CH2CH3m/z = 43
O
H
H H
m/z = 31
Mass Spectrometry: Fragmentation
Ethers
di-sec-butyl ether
O
MW = 130
M (130)
115 M-15
101 M-29
O
H
CH3CH2
O
H
H3C
m/z = 59
m/z = 45
O HH
H3C
O HH
CH3CH2
m/z = 57
Mass Spectrometry: Fragmentation
Ethers
2-ethyl-2-methyl-1,3-dioxolane
O O
MW = 116
101 M-15
87 M-29
M+ absent
O O
O O
Mass Spectrometry: Fragmentation
Aryl Ethers
anisole
93 M-15
m/z = 78
MW = 108
OCH3
m/z = 65
O
loss of C O
M (108)
HH
Mass Spectrometry: Fragmentation
Aryl Ethers
fragmentation of aryl ethers
O CH2
H
m/z = 78 m/z = 77
O CH2
HH
H
- CH2O - H≡
O CH3
m/z = 93 m/z = 65
- CH3O - CO
Mass Spectrometry: Fragmentation
Sulfides
ethyl isopropyl sulfide
S
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
ring formation
NH2R NH2R +
n n
R N R + NR"
H
HR'
R"
R'
n = 1, m/z = 72 n = 2, m/z = 86
loss of H radical
R N R N
R'
R"H
R'
R"+ H
M-1
Mass Spectrometry: Fragmentation
Amines
ethylamine
NH2
MW = 45
M (45)
mz = 30
44 M-1
NH
H
HH
base peak
NH
H
H
Mass Spectrometry: Fragmentation
Amines
diethylamine
NH
MW = 73
M (73) 72
M-1
58 M-15
m/z = 30
NH
H
HH
α cleavage
NH
Mass Spectrometry: Fragmentation
Amines
triethylamine
N
MW = 101
m/z = 30
NH
H
HH
M (101)
100 M-1
86 M-15
α cleavage
Mass Spectrometry: Fragmentation
Amines
N-ethylpropylamine
NH
MW = 87
M (87)
m/z = 30
72 M-15
58 M-29
α cleavage
Mass Spectrometry: Fragmentation
Cyclic Amines
piperidine
M (85)
84 M-1
MW = 85
NH
84 M-28
NH
and
NH
Mass Spectrometry: Fragmentation
Aromatic Amines
aniline
M (93)
92 M-1
NH2
MW = 93
NHHH
-HCN
M-1 m/z = 66 m/z = 65
- H
m/z = 65
Mass Spectrometry: Fragmentation
Carbonyl Compounds ! ! ! !
α-cleavage (two possibilities)
β-cleavage
McLafferty rearrangement
Common Fragmentation Modes
R G
OC OR + G
R G
OC OGR +
G
OR R +
G
O
G = H, R', OH, OR', NR'2
G
OR H
G
OHR+
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
Aliphatic Aldehydes
pentanal H
O
MW = 86
M (86)
mz = 29
85 M-1
mz = 43
mz = 44
McLafferty
α cleavage
H
OH
CH3CH2CH2
C OH
α cleavage
C OC4H9
β cleavage
Mass Spectrometry: Fragmentation
Aldehydes
2-ethylbutanal
M (100)
mz = 29
m/z = 72
C OH
H
O
MW = 100
H
OH
Mass Spectrometry: Fragmentation
Aromatic Aldehydes
benzaldehyde
M (106) 105 M-1
mz = 77
H
O
MW = 106
Mass Spectrometry: Fragmentation
Aliphatic Ketones
2-hexanone
O
MW = 100
M (100)
mz = 58
85 M-15
43 M-57
C O
OH
CH3CO
McLafferty
α cleavage
α cleavage
Mass Spectrometry: Fragmentation
Ketones
acetophenone
M (120)
mz = 77
105 M-15
O
MW = 120
C O
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 OH
OH
O
+H
OH
m/z = 55
O
+
m/z = 42
- CO
m/z = 70
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
Aliphpatic Carboxylic Acids
butyric acid
OH
O
MW = 88
M (88)
mz = 45
71 M-17
weak M+
mz = 60
C O
O
OH
H
OHCO
Mass Spectrometry: Fragmentation
Carboxylic Acids
2,4-dimethylbenzoic acid
O
OH
CH3H3C
MW = 150
M (150)
mz = 77
132 M-18
133 M-17
strong M+
O
OH C O
H
- H2O
Mass Spectrometry: Fragmentation
Esters
methyl butyrate OCH3
O
MW = 102
M (102)
71 M-31
59 M-43
74 M-28
15 M-87
OCH3
OHMcLafferty
CH3α cleavage
CH3CH2CH2
43 M-59
O
OCH3
loss of:
inductivecleavage
87 M-15
Mass Spectrometry: Fragmentation
Esters
butyl butyrate
M (144)
absent
101 M-43
89
O
O
MW = 144
McLafferty + 1
Pr O
O H
H
71 M-73
McLafferty
Pr O
O H
88
Mass Spectrometry: Fragmentation
Esters
fragmentation patterns
McLafferty rearrangement
McLafferty + 1
Pr O
O H
Pr O
O H
Pr O
O H H
Pr O
O H
H +
m/z = 89
O
O H
Pr O
O H+
m/z = 88
O
OH
O
OH+Bu Bu
m/z = 116(not observed)
Mass Spectrometry: Fragmentation
Esters
benzyl acetate
M (150)
108 M-42
91 M-59
O
O
MW = 150
OH
43 M-108
α cleavagetropylium ion
O
Mass Spectrometry: Fragmentation
Esters
fragmentation patterns
Loss of alcohol
Benzyl ester rearrangement
O
H
OO H + O C CH2
can fragment further
O
OR C O
X H X
+ H O RX = CH2, O
Mass Spectrometry: Fragmentation
Amides
butyramide NH2
O
MW = 87
M (87)
59 M-28
mz = 44
O C NH2NH2
OH
McLaffertyα cleavage
Mass Spectrometry: Fragmentation
Amides
N-ethylpropionamide
M (101)
72 M-29
57 M-44
NH
O
MW = 101
mz = 29
86 M-15
mz = 30
N CH2H
H
CH3CH2
NH
O
Mass Spectrometry: Fragmentation
Aryl Amides
N-methylbenzamimde
M (135)
105 M-29
mz = 77
N CH3
H
O
MW = 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
McLafferty rearrangement
Loss of α-hydrogen
R C
HH +
NC C
M-1R
HN
Loss of HCN
CR +N H2C C NH
HR
m/z = 41
R C
HR +
NHC N
M-27
Mass Spectrometry: Fragmentation
Nitriles
hexanenitrile
M (97) 70
M-27
mz = 41
96 M-1
C N
MW = 97
C CC4H9
HN
H2C C NHMcLafferty
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
R NO
OR + N
O
Om/z = 46
R NO
OR O N O R O N O
m/z = 30
+
NO2 O
+ NO C O+
m/z = 65m/z = 93
NO2
+ NO2 HHC4H3 +
m/z = 77 m/z = 51
Mass Spectrometry: Fragmentation
Nitro Compounds
1-nitropropane
43 M-46
MW = 89
NO2
M (89)
absent
mz = 30
mz = 46
N ONO
O
CH3CH2CH2
Mass Spectrometry: Fragmentation
Nitro Compounds
nitrobenzene
M (123)
NO2
MW = 123
mz = 30
N Omz = 65
mz = 51
77 M-NO2
O
93 M-NO
Mass Spectrometry: Fragmentation
Organic Halides
fragmentation patterns
Loss of Halide
Loss of δ Chain
α-cleavage
Loss of HX
R C XH
HC X
H
HR +
C C XRH
H H
HC CH2
R
H+ HX
HF > HCl > HBr > HI
XR XR +
R X R + X
I > Br >> Cl > F
Mass Spectrometry: Fragmentation
Alkyl Halides
1-chloropropane
M (78) mz = 49, 51 80
M+2
Cl
MW = 78
42 M-HCl
43 M-Cl
CH3CH2CH2
C ClH
H
α cleavage
Mass Spectrometry: Fragmentation
Alkyl Halides
2-chloropropane
m/z = 63, 65
43 M-Cl
Cl
MW = 78
M (78) 80 M+2
C ClH
CH3
Mass Spectrometry: Fragmentation
Alkyl Halides
2-chloroheptane
M (134) M+2 (136)
m/z = 105, 107
56 M-78
Cl
MW = 134
98 M - HCl
Cl
HCl
H Cl
rearrngement
Mass Spectrometry: Fragmentation
Alkyl Halides
2-bromopropane
Br
MW = 123
43 M-Br
M (122) 124 M+2
CH3CHCH3
Mass Spectrometry: Fragmentation
Alkyl Halides
1-bromohexane
85 M-Br
BrMW = 165
M (164) 166 M+2
mz = 135, 137
mz = 57
rearrngement
Br
Mass Spectrometry: Fragmentation
Alkyl Halides
bromobenzene
M (156)
158 M+2
mz = 77
Br
MW = 157
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
Reporting Mass Spec Data
Low Resolution Mass Spec OCH3
O
MW = 102
M (102)
71 M-31
59 M-43
74 M-28
15 M-87
43 M-59
Source Temperature: 240 °C Sample Temperature: 180 °C RESERVOIR, 75 eV
87 M-15
14.0 2.1 15.0 35.0 18.0 2.1 26.0 5.4 27.0 47.0 28.0 7.9 29.0 9.2 30.0 1.2 31.0 6.5 32.0 1.1 33.0 1.9 37.0 1.6 38.0 3.5 39.0 22.5 40.0 3.5 41.0 45.3 42.0 12.1 43.0 100.0 44.0 3.6 45.0 3.1 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 16.4 102.0 1.4
peak intensity
Mass Spectrometry
Reporting Mass Spec Data
Low Resolution Mass Spec OCH3
O
MW = 102
MS (EI, 75 eV): m/z 102 (M+, 1%), 87 (16), 74 (64), 71 (50), 59 (22), 43 (100) ....
ionization technique/method
mass
peak assignment
height of peak relative to base peak
Mass Spectrometry
Reporting Mass Spec Data ! ! ! ! ! High Resolution Mass Spec
O CO2Et
OH
Mass Spectrometry
Reporting Mass Spec Data
High Resolution Mass Spec
HRMS (ESI): calcd for C12H18O4Na ([M+Na]+) 249.1097; found 249.1094.
ionization method
exact mass calculated mass found
molecular ion observed
chemical formula of(quasi) molecular ion