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AFB QO I 2007/08 1
Química Orgânica I
Ciências Farmacêuticas
Bioquímica
Química
AFB QO I 2007/08 2
MS
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AFB QO I 2007/08 3
Adaptado de:
� Organic Chemistry, 6th Edition; L. G. Wade, Jr.
�� http://www.cem.msu.edu/~reusch/Vihttp://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/MassSpec/masspertualText/Spectrpy/MassSpec/masspec1.htm#ms1c1.htm#ms1
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Mass Spectrometry
� Molecular weight can be obtained from a very small sample.
� It does not involve the absorption or emission of light.
� A beam of high-energy electrons breaks the molecule apart.
� The masses of the fragments and their relative abundance reveal information about the structure of the molecule. =>
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From molecular ions to molecular mass
Chemical
Ionization
MH+
H+
H+
H+
H+
[M+H]+
Weighs one more than
MW
Dislodges an
electron
Electron Impact
M-e• -e•
-e•
-e•-e•
-e•
2e-•
M+•
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Electron Impact Ionization
A high-energy electron can dislodge an electron from a bond, creating a radical cation (a positive ion with an unpaired e-).
e- + H C
H
H
C
H
H
H
H C
H
H
C
H
H
H
H C
H
H
C
H
H
+ H
H C
H
H
C
H
H
H
+=>
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Mass Spectrometry- Ionization
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Separation of Ions
� Only the cations are deflected by the magnetic field.
� Amount of deflection depends on m/z.
� The detector signal is proportional to the number of ions hitting it.
� By varying the magnetic field, ions of all masses are collected and counted. =>
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Mass Spectrometer
=>
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The GC-MS
=>
A mixture of compounds is separated
by gas chromatography, then identified
by mass spectrometry.
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Simple spectra
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Base peak and molecular ion
=>
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High Resolution MS
� A molecule with mass of 44 could be C3H8, C2H4O, CO2, or CN2H4.
� If a more exact mass is 44.029, pick the correct structure from the table:
C3H8 C2H4O CO2 CN2H4
44.06260 44.02620 43.98983 44.03740
=>
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Molecules with Heteroatoms
� Isotopes: present in their usual abundance.
� Hydrocarbons contain 1.1% C-13, so there will be a small M+1 peak.
� If Br is present, M+2 is equal to M+.
� If Cl is present, M+2 is one-third of M+.
� If iodine is present, peak at 127, large gap.
� If N is present, M+ will be an odd number.
� If S is present, M+2 will be 4% of M+. =>
AFB QO I 2007/08 16
even-electron ionseven-number mass
odd-electron ionsodd-number mass
Ions having anodd # N atoms
even-electron ionsodd-number mass
odd-electron ionseven-number mass
Ions with no nitrogenor an even # N atoms
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Even-odd
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Isotopic Abundance
=>
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Mass Spectrum with Sulfur
=>
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Bromine
Bromine: 50.50% 79Br and 49.50% 81Br
e.g: Br-Br
79 + 79
79 + 81; 81 + 79
81 + 81
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Mass Spectrum with Bromine
=>
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vinyl chloride
Chlorine: 75.77% 35Cl and 24.23% 37Cl
(aprox. 3/4 : 1/4)
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Chloropropane
=>
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methylene chloride
� 2 x Cl
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Mass Spectra of Alkanes
More stable carbocations will be more abundant.
=>
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Fragmentation Patterns
hexyl (m/z = 85), pentyl (m/z = 71), butyl (m/z = 57), propyl (m/z = 43), ethyl (m/z = 29) and methyl (m/z = 15)
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Mass Spectra of Alkenes
Resonance-stabilized cations favored.
=>
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Mass Spectra of Alcohols
� Alcohols usually lose a water molecule.
� M+ may not be visible.
=>
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fragmentation patterns
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alkyl chain: m/z=57, 43, 41, 29 & 27
m/z=29 ion is probably composed of both ethyl and HCO cations
m/z=86 is more abundantLoss of carbonyl substituents by alpha-fragmentation include: - loss of methyl (M-15 at m/z=71) - loss of a propyl (M-43 at m/z=43)
Simetric moleculem/z=57 (loss of an ethyl) m/z=29 (an ethyl cation)
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Common Fragment Ions and Neutral Fragments
SH, CH2F33
CH3O31
CH2NH
230
C2H
5, CHO29
C2H
4, CO, H
2CN28
C2H
327
C2H
2, CN26
H3O, F19
H2O18
OH17
CH3
15 amu
compositionm/z
Common Small Ions
CH4O, S32
CH3O31
CH2O30
C2H
4, CO28
C2H
3, HCN27
HF20
F19
H2O18
OH17
CH3
15
H1 amu
compositionmass loss
Common Neutral Fragments
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/MassSpec/mspec.htm#ms1
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HI128
I127
C7H
791
HBr80(82)
Br79(81)
CH4CO
260
C4H
957
C4H
856
NO2
46
C2H
4O44
C3H
7, CH
3CO43
C3H
6, C
2H
2O, C
2H
4N42
C3H
5, C
2H
3N41
C3H
339
HCl36(38)
Cl35(37)
H2S34
SH, CH2F33
compositionm/z
Common Small Ions
HI128
I127
HBr80(82)
Br79(81)
SO2
64
C2H
4O
260
C2H
3O
259
C4H
957
C4H
755
C2H
5O45
CO2O, CONH
244
C3H
7, CH
3CO43
C3H
6, C
2H
2O, C
2H
4N42
HCl36(38)
Cl35(37)
H2S33
CH3
+ H2O, HS33
compositionmass loss
Common Neutral Fragments
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Some popular cleavages
Cleave β to a heteroatom
(capable of supporting
positive charge)
CH3 CH3
CH3CH3
CH3
C+
CH3
CH3.
Obs. in Mass Spec
+
neutral
+
RORO
RO
:
:Obs. in Mass Spec
Resonance stabilized
neutral
+
+
AFB QO I 2007/08 34
Some examples
Primary alcohols, m/z=31 CH2=OH+
Primary amines, m/z=30 CH2=NH2+
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Commonly encountered Electron-Impact fragments
N
CH2+
92
+ +91
H
H
H
H
H
+
77
CH2+
43 H
O
+29
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McLafferty Rearrangements
Radical cations localized on keto-type oxygen give β cleavage
The mechanism limits this to EI fragmentation
Needs a H atom on a γ sp3 carbon
Ketones, esters, carboxylic acids all give McLafferty products
O+
HR2
R1
• O+
H
•
OH
R1 R2
•••
+ Loss of
neutral
alkene
The new radical
cation is
stabilized by
resonance
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Important example of McLafferty
OH
OH
m/z = 60
+
•
Seen for primary carboxylic acids
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Cleavage αααα to C=O groups
O O
O
: .
+
++:
+: :Obs. in mass spec.
Acylium ions are
resonance-stabilized
neutral
CH3C=O+
m/z=43
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Example
O
O+
M+• -43; also
tropylium ion
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Rearangement Mechanisms in Fragmentation (McLafferty)
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Complexpaterns
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Cleave α to Heteroatoms like O, N
O
R
: .
+•
Heterolytic cleavage
R
O:: .
neutral
+
Observed in Mass Spec provided that a
good stabilized carbocation can form
+
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Rearrangements and fragmentations to give good Carbocations
CH2+
CH
+ CH2
H C
CH2
+
Benzylic
cation
(stabilized
including
“tropylium”
ion m/z=91
Good cleavage β to
aromatic rings
CH+
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Example
Bromine
pattern
Tropylium
ion
Br
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Carboxylic acids
γH present?; can give McLafferty rearrangement to
alkene plus CH2=C(OH)(OH)•+ at m/z=60
Loss of water, especially in CI
Loss of 44 is loss of CO2
m/z=45 suggests O≡C–OH+
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Amines
N•+ N+
-R•
R
Cyclic amines will lose adjacent H•, form iminium ion
In CI, ≡NH+ can eliminate adjacent alkene, reprotonate
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Silyl Ethers
SiO+
•Loss of CH3• from Si
Loss of R• in β cleavage
Loss of •CR3 then CH3• to (CH3)2Si=OH+ m/z=75
Total loss of carbinol to (CH3)3Si+ m/z=73
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H transfer in heterosubstitutedAnisoles
OCH3
ORLoss of CH2O
Extra H
transfer
mediated by
adjacent
heteroatom
H
O+
R
H
H
+•
AFB QO I 2007/08 50
Nitroaromatics
N
+
O•
OO
+
Loss of
•N=O
Loss of
C≡O
m/z= 93
(this can
form
from lots
of
different
origins)
CH+Aromatic!
m/z=65
Good test for aryloxy
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Sulfur Compounds
Fortunately there is an [M+2]+ of 4% for the natural
abundance of 34S. This is diagnostic for S vs 2x16O
Aliphatic thiols can split out H2S, [M-34]
Alpha cleavage at carbon bearing the sulfur in thiols,
thioethers, similar to ethers, etc.
S+
S+R
•
-R•
AFB QO I 2007/08 52
The “retro Diels-Alder”Cleavage
+
+•
+•
+
+•
Observed!
Observed!
Typically you see both.
More stable cation will predominate
Also works for hetero-substituted (e.g. make
enol)
Both EI (shown) and in Chemical Ionization.
(protonated molecular ion, cleave, then
reprotonation
Cyclohexenes, with favorable 6-membered transition state. Can include heteroatoms
(N,O, driven by keto-enol like stability.
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An Example from TerpenoidChemistry
+
•
+
•
+
∆12-Oleanenem/z 204