MASS SPECTRA FOR STRUCTURE. I. FRAGMENTATION OF GAS-PHASE
IONS. There are two main classes of fragmentation of radical cations in EIMS:.
Interpretation of Mass Spectra
Interpretation of Mass Spectra
INTERPRETATION OF MASS and TANDEM MASS SPECTRA FOR STRUCTURE I. FRAGMENTATION OF GAS-PHASE IONS There are two main classes of fragmentation of radical cations in EIMS: (1) simple cleavage, and (2) rearrangement and elimination of neutral molecules. Closed shell ions (in ESI, FAB, etc) fragment principally by category #2 to give closed-shell (EE) ions. Even-electron ion rule: “EE electron ions fragment to give other EE ions.”
II. FRAGMENTATION BY SIMPLE CLEAVAGE The following is organized around simple cleavage processes that dominate the fragmentation of radical ions.
A. FRAGMENTATION OF ALKYL CHAINS (ALKANE PATTERN) & CLEAVAGE AT BRANCH POINTS:
Figure 1. Mass spectra of isomeric alkanes illustrating effects of branching. 1
Interpretation of Mass Spectra
Interpretation of Mass Spectra
Figure 2. EI Mass Spectrum of n-C20H42 Note the EE Ion Series:
∆Hf values:
29, 43, 57, 71, 85, . . . (alkyl carbocations) 27, 41, 55, 69, 83, . . . (alkenyl carbocations)
n-Butyl: 200 kcal/mol; s-butyl: 183 kcal/mol;
Fragmentation Mechanisms:
2
i-butyl: 198 kcal/mol t-butyl: 167 kcal/mol
Interpretation of Mass Spectra
Interpretation of Mass Spectra
C. ALLYLIC CLEAVAGE: One expects that cleavage at an allylic site to a C=C bond would be favored. Double bond migrations compete favorably with fragmentation, however.
Figure 3. EI mass spectra of isomeric octenes. Note the EE ion series at m/z 27, 41, 55, 69, 83. . . Mechanism for double-bond mobility:
3
Interpretation of Mass Spectra
Interpretation of Mass Spectra
D. BENZYLIC CLEAVAGE: Cleavage at a benzylic site is favored because one forms a benzylic carbocation, which can isomerize to tropylium.
Figure 4. EI mass spectra of isomeric ethylbenzenes compared to that of -propylbenzene. Note: Ortho, meta, and para isomerism is difficult to ascertain by EI MS, except when there is an “ortho effect” (discussed later). One may be able to identify compound based on comparison of unknown and reference spectra. Underlying mechanisms:
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Interpretation of Mass Spectra
Interpretation of Mass Spectra
E. SIMPLE AROMATIC COMPOUNDS: Without suitable substitution, the energy requirements for fragmentation are high (4-5 eV). One sees losses of substituents and seemingly implausable eliminations of portions of the ring (e.g., C2H2, HCN, even CH3, etc.).
Figure 5. EI mass spectrum of typical small aromatic compounds.
Figure 6. EI mass spectra of two isomeric polycyclic aromatic compounds, C14H10. Note the difficulty in distinguishing PAH isomers by EIMS.
Figure 7. EI mass spectra of isomeric C8H9Cl aromatic compounds. Note the presence of a facile cleavage allows distinctions in spectra. 5
Interpretation of Mass Spectra
Interpretation of Mass Spectra
Fragmentation Mechanisms:
Figure 8. Identify the compound that gives this EI mass spectrum.
F. FRAGMENTATION TRIGGERED BY HALOGENS: 1. Most alkyl halides fragment by i-cleavage to lose the halogen +. C4H9+ + Cl. radical: n-C4H9Cl Called i for inductive as the electronegative halogen takes the unpr’d e-.
Figure 9. Mass spectra of an aliphatic and aromatic bromide. 6
Interpretation of Mass Spectra
Interpretation of Mass Spectra
2. Some primary halides undergo δ-cleavage to give halonium ions
Figure 10. Mass Spectra of primary alkylhalides, showing δ-cleavage. Structures of halonium ions:
G. FRAGMENTATION TRIGGERED BY NITROGEN: Because nitrogen is not electronegative and has the ability to donate a pair of electrons by resonance, it principally directs cleavage to an alpha site--so nitrogen-containing compounds undergo α−cleavage. CH3CH2NH=CH2+ + CH3 [CH3CH2NH-CH2CH3]+. Note that these EE ions with one N will be of even mass (here m/z 58).
Figure 11. EI mass spectra of isomeric amines. 7
Interpretation of Mass Spectra
Interpretation of Mass Spectra
Figure 11 (cont’d). EI mass spectra of 4-carbon amines Note the strong ability of N to direct fragm. in large, aliphatic amines!
Figure 12. EI mass spectra of large, aliphatic amines
H. FRAGMENTATION DIRECTED BY O, S. Oxygen and sulfur have properties in directing fragmentation that are intermediate between halogens and nitrogen. Both i- and α cleavages occur, and their competition depends on the stability of both the neutral and the ionic products. The following spectra are examples of this competition.
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Interpretation of Mass Spectra
Interpretation of Mass Spectra
Mechanisms:
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Interpretation of Mass Spectra
Interpretation of Mass Spectra
Figure 13. EI mass spectra of thiols, alcohols, and ethers, illustrating competition between i and α−cleavages.
FRAGMENTATION DIRECTED BY CARBONYL AND RELATED FUNCTIONS. Recall that acylium ions are stable and the intermediates in Friedel-Crafts and other reactions in organic chemistry. Compounds containing carbonyl groups will fragment alpha to the heteroatom to give acylium ions:
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Interpretation of Mass Spectra
Interpretation of Mass Spectra
Figure 14. EI mass spectra of ketones and esters, illustrating carbonyl-directed cleavages.
Competition for charge: Can be understood by employing the principles of physical organic chemistry: ion stability and Hammett correlations (see Harrison, Alex G. Linear free energy correlations in mass spectrometry. J. Mass Spectrom. (1999), 34(6), 577-589.
Figure 15. Correlation of the relative abundance of CH3CO+ from fragmentation of CH3COC6H4X+., where X is the indicated substituent. 11
J. COMPETITION FOR CLEAVAGE: How do N, O/S, X, phenyl compete with each other for alpha cleavage? [HO-CH2-CH2-NH2]+.
+
HO=CH2 (1) or CH2=NH2+ (20)
[HO-CH2-CH2-Cl]+.
+
HO=CH2 (15) or CH2=Cl+ (1)
[HO-CH2-CH2-Ph]+.
+
HO=CH2 (1) or CH2=Ph+ (15)
[Ph-CH2-CH2-NH2]+.
+
Ph=CH2 (1) or CH2=NH2+ (10)
[HO-CH(CH3)-CH2-NH2]+.
+
HO=CHCH3 (1) or CH2=NH2+ (10)
K. SERIES OF EE IONS: These series should be noted when interpreting spectra. They give an idea as to the type or class of the unknown compound. 27, 41, 55. . .
C2H3+, C3H5+(CH2=CHCH2+), C4H7+ . . . (alkenes, cyclics)
29, 43, 57. . .
C2H5+, C3H7+, C4H9+ . . . (carbocations--alkanes, aliphatics)
29, 43, 57. . .
CHO+, CH3CO+, CH3CH2CO+ . . . (aldehydes, ketones)
31, 45, 59. . .
CH2OH+, C2H5OH+, C3H7OH+ (CH2OC2H5)+. . . (alcohols, ethers)
45, 59, 73. . .
+
30, 44, 58. . .
CH2NH2+, C2H5NH2+, C3H7NH2+ (CH2=NHC2H5)+. . . (amines)
47, 61, 75. . .
CH2SH+, C2H5SH+, C3H7SH+ (CH2SC2H5)+. . . (sulfides)
49, 63, 77. . .
CH2Cl+, C2H5Cl+, C3H7Cl+ . . . (alkyl chlorides)
40, 54, 68. . .
CH2CN+, C2H5CN+, C3H7CN+ (nitriles)
39, 51, 77. . .
C3H3+, C4H3+, C6H5+ (phenyl-containing)
39, 65, 91 . . .
C3H3+, C5H5+, C7H7+ (benzyl-containing)
COOH, +CH2COOH (COOCH3), +C2H5COOH). . . (acids, esters)
39, 51, 77, 105 C3H3+, C4H3+, C6H5+, C6H5CO+ (benzoyl-containing) 12
Interpretation of Mass Spectra
Interpretation of Mass Spectra
II. FRAGMENTATION OF EE IONS A. AMINES:
B. CARBOCATIONS (ALKYL IONS):
C. ACYLIUM IONS
D. OXONIUM IONS
F. PROTONATED ALCOHOLS, AMINES, SULFIDES. . .
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III. FRAGMENTATION BY REARRANGEMENT OR BY LOSS OF SMALL MOLECULES (E.G., VIA CYCLOREVERSIONS): A. GENERAL CONSIDERATIONS OE Ion OE Ion EE Ion EE Ion
EE Ion + Radical (Simple Cleavage) OE Ion + Neutral Molecule (Rearrangement) EE Ion + Neutral Molecule OE Ion + Radical (violates “EE Ion Rule”)
Rearrangement ions can be easily picked out of mass spectra because they’re OE ions--that is, they have an even mass when nitrogen number is 0, 2, 4, . . . And an odd mass when the number of nitrogens is odd. EI mass spectra are dominated by EE ions. One rule for interpretation of EI mass spectra: Note all significant OE ions. They usually point to rearrangments that contain structural information.
Figure 16. Mass spectra showing the importance of OE fragment ions
B. NON-SPECIFIC LOSSES OF H2O, HOAC, HX CH3CH2CH2OH+. C3H6+. + H2O (12%) +. +. CH3CH2CH2CH2OH C4H8 + H2O (100%) +. +. CH3CH2CH2CH2CH2CH2OH C6H10 + H2O (13%)
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Interpretation of Mass Spectra
Interpretation of Mass Spectra
Figure 17. EI mass spectra of compds giving non specific losses. Note that when acetic acid cannot be lost--no beta hydrogens available for a 1,2-loss--then ketene (CH2=C=O) is expelled. 15
Interpretation of Mass Spectra
Interpretation of Mass Spectra
C. THE McLAFFERTY REARRANGEMENT This rearrangement is highly specific (unlike water loss), involving a gamma hydrogen atom. It has a photochemical analog in the Norrish Type II rearrangement, which is triggered by a n π* transition. The McLafferty rearrangement is, on the other hand, triggered by a radical-cation site (i.e., by complete removal of the electron). The mechanism:
The following are spectra that illustrate its utility in structure problems.
Figure 18. Mass spectra of isomer pairs showing McLafferty rearrangement. Note 2-pentanone-5-phenyl, a compound undergoing a McL rearrangement in which the expelled olefin carries the charge. This is an example of Stevenson’s Rule: “The preferred OE product ion is the one whose neutral has the lower IE: IE(PhCH=CH2) = 8.4; IE(CH3COCH3) = 9.7 eV. 16
Interpretation of Mass Spectra
Interpretation of Mass Spectra
The McLafferty rearrangement is highly specific (evidence from isotop labeling). The transfer of H is 1o
