Mass Spectrometry: Fragmentationchemistry.miamioh.edu/gung/CHM526/pdfs/Mass-fragmentation.pdfMass...

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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

Transcript of Mass Spectrometry: Fragmentationchemistry.miamioh.edu/gung/CHM526/pdfs/Mass-fragmentation.pdfMass...

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