MS Interpretation II. Fragmentation

MS Interpretation II Fragmentation

Ionization E Electron Ionization (EI): Even-electron neutrals yield odd-electron radical cations. M(EE) EI - 1e - M (E) Electron can come from anywhere. EI EI even electron - 1e - (n) - 1e - (π) odd electron EI even electron odd electron even electron - 1e - (σ) odd electron

Ionization E Electron can (and does) come from anywhere. - 1e - (n) EI EI - 1e - (π) EI - 1e - (σ)

Ionization E Electron can (and does) come from anywhere. - 1e - (n) EI EI - 1e - (π) EI - 1e - (σ) Likelihood of each of these depends on energy levels in molecular orbitals: vacuum level σ* π* n π σ IE n most likely IE π IE σ least likely

Ionization E Electron can (and does) come from anywhere. - 1e - (n) EI EI - 1e - (π) EI - 1e - (σ) Naturally, cannot distinguish these in mass spectrometer (all have m/z = 100). But fragmentation patterns will be different.

Ionization EE CI, MALDI and ESI: Even-electron neutrals yield even-electron cations. M(EE) H MH (EE) Like EI, ionization may occur at multiple places. H H Again, instrument cannot distinguish.

Fragmentation Mechanisms: EE EE ions don't fragment to form E Fragmentations more familiar and spectra generally less complex than E More frequent and varied rearrangements can make interpretation more difficult Spectra can be more sensitive than EI to small structural changes Sensitivity to experimental conditions incompatible with reference libraries

Fragmentation Mechanisms: EE

Fragmentation Mechanisms: EE Bond cleavage with charge migration

Fragmentation Mechanisms: EE Bond cleavage with charge migration R-H2 R H2

Fragmentation Mechanisms: EE Bond cleavage with charge migration R-H2 R H2 Cleavage with cyclization and migration

Fragmentation Mechanisms: EE Bond cleavage with charge migration R-H2 R H2 Cleavage with cyclization and migration HN H N CR 2 HN CR 2 HN

Fragmentation Mechanisms: EE Bond cleavage with charge migration R-H2 R H2 Cleavage with cyclization and migration HN H N CR 2 HN CR 2 HN Two-bond cleavage with charge retention

Fragmentation Mechanisms: EE Bond cleavage with charge migration R-H2 R H2 Cleavage with cyclization and migration HN H N CR 2 HN CR 2 HN Two-bond cleavage with charge retention H H -H 2

Fragmentation Mechanisms: EE Bond cleavage with charge migration R-H2 R H2 Cleavage with cyclization and migration HN H N CR 2 HN CR 2 HN Two-bond cleavage with charge retention H H -H 2 ther fragmentations require MS/MS

Fragmentation Mechanisms in MS: E Electron Ionization: Fragmentation is always unimolecular. Two possible categories of fragmentation: parents daughters M (E) A (EE) B (E) charge migration (radical and charge part ways) M (E) A (E) B(EE) charge retention (neutral molecule is ejected)

Fragmentation Mechanisms: E

Fragmentation Mechanisms: E Direct dissociation

Fragmentation Mechanisms: E Direct dissociation R-R' R R'

Fragmentation Mechanisms: E Direct dissociation R-R' R R' Cleavage adjacent to a heteroatom

Fragmentation Mechanisms: E Direct dissociation R-R' R R' Cleavage adjacent to a heteroatom R-CH2-Y-R' R-CH2 Y-R'

Fragmentation Mechanisms: E Direct dissociation R-R' R R' Cleavage adjacent to a heteroatom R-CH2-Y-R' R-CH2 Y-R' R-CH2-Y-R' R-CH2 Y-R'

Fragmentation Mechanisms: E Direct dissociation R-R' R R' Cleavage adjacent to a heteroatom R-CH2-Y-R' R-CH2 Y-R' R-CH2-Y-R' R-CH2 Y-R' α-cleavage

Fragmentation Mechanisms: E Direct dissociation R-R' R R' Cleavage adjacent to a heteroatom R-CH2-Y-R' R-CH2 Y-R' R-CH2-Y-R' R-CH2 Y-R' α-cleavage R-CH2-Y-R' R CH2=Y-R'

Fragmentation Mechanisms: E Direct dissociation R-R' R R' Cleavage adjacent to a heteroatom R-CH2-Y-R' R-CH2 Y-R' R-CH2-Y-R' R-CH2 Y-R' α-cleavage R-CH2-Y-R' R CH2=Y-R' R-CH2-Y-R' R CH2-Y-R'

Fragmentation Mechanisms: E Direct dissociation R-R' R R' Cleavage adjacent to a heteroatom R-CH2-Y-R' R-CH2 Y-R' R-CH2-Y-R' R-CH2 Y-R' α-cleavage R-CH2-Y-R' R CH2=Y-R' R-CH2-Y-R' R CH2-Y-R' Two-bond cleavage

Fragmentation Mechanisms in MS: Direct Cleavage EI (electron can come from any bond) Fragmentation (one-electron bond can break either way)

Fragmentation Mechanisms in MS: Direct Cleavage EI (electron can come from any bond) Fragmentation (one-electron bond can break either way) 15 43 57 71 71 43 29 15

Fragmentation Mechanisms in MS Relative Abundance m/z 15 43 57 71 71 43 29 15

Fragmentation Mechanisms in MS What governs which ions are predominant? 15 43 57 71 71 43 29 15

Fragmentation Mechanisms in MS What governs which ions are predominant? 1. Most ionizeable type of electrons. Here, all electron sources are σ bonds. 15 43 57 71 71 43 29 15

Fragmentation Mechanisms in MS What governs which ions are predominant? 1. Most ionizeable type of electrons. Here, all electron sources are σ bonds. 2. Combination of most stable cation and radical. (Actually, this addresses most ionizeable bond within type.) Here, secondary cation/radical combination favored over primary. 15 43 57 71 71 43 29 15

Fragmentation Mechanisms in MS Relative Abundance m/z 15 43 57 71 71 43 29 15

Fragmentation Mechanisms in MS: Direct Cleavage

Fragmentation Mechanisms in MS: Direct Cleavage 57 71

Fragmentation Mechanisms in MS: Direct Cleavage 57 71 43 Further fragmentation is common.

Fragmentation Mechanisms in MS: α-cleavage 56 41

Heteroatoms: Induced vs. Alpha Cleavage t-butyl ethyl ether 102

Heteroatoms: Induced vs. Alpha Cleavage t-butyl ethyl ether i 57 57 102

Heteroatoms: Induced vs. Alpha Cleavage t-butyl ethyl ether i 59 α H 87 57 CH 3 57 87 H 59 102

2-butyl ethyl ether 102

2-butyl ethyl ether i 57 57 102

2-butyl ethyl ether 45 i 57 α H 73 H 73 45 57 102

2-butyl ethyl ether 45 i 57 α H 73 H 73 45 57 59 87 102

Competition: i vs α Cleavage

Competition: i vs α Cleavage Induced cleavage is favored for larger heteroatoms

Competition: i vs α Cleavage Induced cleavage is favored for larger heteroatoms α-cleavage is favored for electron donating substituents

Competition: i vs α Cleavage Induced cleavage is favored for larger heteroatoms α-cleavage is favored for electron donating substituents Br,Cl < R,π bond,s, < N

butanethiol SH 41 90

butanethiol SH SH SH 47 41 47 90

butanethiol SH SH SH 57 SH 47 SH 41 57 47 90

butanethiol SH SH SH 57 SH 47 SH 41 57 90 Both α- and i- cleavage are observed here 47

butylamine NH 2 73

butylamine NH 2 NH 2 NH 2 30 30 73

butylamine NH 2 NH 2 NH 2 30 30 α-cleavage dominates spectrum here 73

E Fragments

E Fragments dd electron fragments are less common, especially at low mass

E Fragments dd electron fragments are less common, especially at low mass Even mass ions at low mass likely contain N

E Fragments dd electron fragments are less common, especially at low mass Even mass ions at low mass likely contain N These fragments arise from two-bond cleavages, or rearrangements

E Fragments dd electron fragments are less common, especially at low mass Even mass ions at low mass likely contain N These fragments arise from two-bond cleavages, or rearrangements Even mass E fragments are important ions, as they can be highly sensitive to structural changes

2-hexanone 71 85 100

2-hexanone 43 43 71 85 100

2-hexanone 43 H H H 43 H 58 58 71 85 100

2-hexanone 43 H H H 43 H 58 71 85 100 58 E Product is from McLafferty rearrangement

2-methyl 3-pentanone 43 29 100 85

2-methyl 3-pentanone 71 43 57 57 29 71 100 85

2-methyl 3-pentanone 71 43 57 57 29 McLafferty rearrangement is precluded here 71 100 No major E 85

158

104 104 158

104 104 Charge stays with styrene fragment in this case 158

143 158

130 158 130 143

130 158 130 143 Charge stays with phenylbutadiene

177 135 149 159 192 93 121 136 Match the spectrum to the structure 109 192 177

- 136 93 121 136 Retro Diels-Alder reaction is observed 109 192 177

Retro Diels-Alder reaction is not observed X 164 - CH 3 177 135 149 159 192 177 Aromatization via substitution dominates the spectrum

105 Match the Structure to the Spectrum Et Me Me 77 122 150 119 119 91 118 150 91 150

Et 77 105 H 122

Me 119 91

Me 91 119 118