Interpretation of Mass Spectra Interpretation of Mass ... · PDF fileINTERPRETATION OF MASS...

INTERPRETATION OF MASS and TANDEMMASS SPECTRA FOR STRUCTURE

I. FRAGMENTATION OF GAS-PHASE IONSThere are two main classes of fragmentation of radical cations in EIMS:

(1) simple cleavage, and (2) rearrangement and elimination of neutralmolecules. Closed shell ions (in ESI, FAB, etc) fragment principally bycategory #2 to give closed-shell (EE) ions. Even-electron ion rule: “EEelectron ions fragment to give other EE ions.”

II. FRAGMENTATION BY SIMPLE CLEAVAGEThe following is organized around simple cleavage processes that

dominate the fragmentation of radical ions.

A. FRAGMENTATION OF ALKYL CHAINS (ALKANEPATTERN) & CLEAVAGE AT BRANCH POINTS:

Figure 1. Mass spectra of isomeric alkanes illustrating effects of branching.

Interpretation of Mass Spectra Interpretation of Mass Spectra

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Figure 2. EI Mass Spectrum of n-C20H42

Note the EE Ion Series: 29, 43, 57, 71, 85, . . . (alkyl carbocations)27, 41, 55, 69, 83, . . . (alkenyl carbocations)

∆Hf values: n-Butyl: 200 kcal/mol; i-butyl: 198 kcal/mols-butyl: 183 kcal/mol; t-butyl: 167 kcal/mol

Fragmentation Mechanisms:


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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 atm/z 27, 41, 55, 69, 83. . .

Mechanism for double-bond mobility:


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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 toidentify compound based on comparison of unknown and reference spectra.

Underlying mechanisms:


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E. SIMPLE AROMATIC COMPOUNDS:Without suitable substitution, the energy requirements for fragmentation arehigh (4-5 eV). One sees losses of substituents and seemingly implausableeliminations 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 thepresence of a facile cleavage allows distinctions in spectra.


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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

radical: n-C4H9Cl +. C4H9+ + Cl.

Called i for inductive as the electronegative halogen takes the unpr’d e-.

Figure 9. Mass spectra of an aliphatic and aromatic bromide.


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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 pairof electrons by resonance, it principally directs cleavage to an alpha site--sonitrogen-containing compounds undergo α−cleavage.

[CH3CH2NH-CH2CH3]+. CH3CH2NH=CH2+ + CH3

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.


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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 areintermediate between halogens and nitrogen. Both i- and α cleavages occur,and their competition depends on the stability of both the neutral and theionic products. The following spectra are examples of this competition.


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Mechanisms:


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Figure 13. EI mass spectra of thiols, alcohols, and ethers, illustratingcompetition between i and α−cleavages.

FRAGMENTATION DIRECTED BY CARBONYL ANDRELATED FUNCTIONS.

Recall that acylium ions are stable and the intermediates in Friedel-Craftsand other reactions in organic chemistry. Compounds containing carbonylgroups will fragment alpha to the heteroatom to give acylium ions:


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Figure 14. EI mass spectra of ketones and esters, illustratingcarbonyl-directed cleavages.

Competition for charge: Can be understood by employing the principlesof physical organic chemistry: ion stability and Hammett correlations (seeHarrison, 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+ fromfragmentation of CH3COC6H4X+., where X is the indicated substituent.


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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 ideaas 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. . . +COOH, +CH2COOH (COOCH3), +C2H5COOH). . . (acids, esters)

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)

39, 51, 77, 105 C3H3+, C4H3

+, C6H5+, C6H5CO+ (benzoyl-containing)

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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 LOSSOF SMALL MOLECULES (E.G., VIA CYCLOREVERSIONS):

A. GENERAL CONSIDERATIONSOE Ion EE Ion + Radical (Simple Cleavage)OE Ion OE Ion + Neutral Molecule (Rearrangement)EE Ion EE Ion + Neutral Molecule EE Ion OE Ion + Radical (violates “EE Ion Rule”)

Rearrangement ions can be easily picked out of mass spectra becausethey’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 EImass spectra: Note all significant OE ions. They usually point torearrangments 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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Figure 17. EI mass spectra of compds giving non specific losses.

Note that when acetic acid cannot be lost--no beta hydrogens available for a1,2-loss--then ketene (CH2=C=O) is expelled.


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C. THE McLAFFERTY REARRANGEMENTThis rearrangement is highly specific (unlike water loss), involving a gammahydrogen atom. It has a photochemical analog in the Norrish Type IIrearrangement, which is triggered by a n π* transition. The McLaffertyrearrangement 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 inwhich the expelled olefin carries the charge. This is an example ofStevenson’s Rule: “The preferred OE product ion is the one whose neutralhas the lower IE: IE(PhCH=CH2) = 8.4; IE(CH3COCH3) = 9.7 eV.


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The McLafferty rearrangement is highly specific (evidence from isotoplabeling). The transfer of H is 1o<2o<3o.

D. DOUBLE McLAFFERTY REARRANGEMENT

Figure 18. EI mass spectra of isomers giving double McL rearrangements.

Mechanism:

F. McLAFFERTY PLUS ONE REARRANGEMENTThis rearrangement involves two H transfers to give an EE product ion. It ischaracteristic of ethyl and larger ions. The rearrangement in aliphatic acidsgives rise to an ion series of 61, 75, 89. . .

Figure 19. EI mass spectra of isomeric esters giving McL + 1 Rearr.


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Mechanism:

Figure 20. Methyl esters do not give McL + 1 rearr, but other acid esters do.

G. PHENETOLE REARRANGEMENTAromatic compounds give a similiar rearrangement as the McLafferty but thetransfer of H is via an “ion-neutral complex” (not a 6-membered ring).

Figure 21. EI mass spectra of compounds that undergo either a facile or aweak “phenetole rearrangement.”


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Mechanism:

H. ORTHO EFFECTSNormally, it is difficult to identify cis/trans and o, m, p-isomerism by massspectrometry. In favorable cases cis or ortho isomers undergo arearrangement due to proximity. Following spectra are examples.Mechanism:

Figure 22. EI mass spectra of aromatic compounds giving an “ortho effect.”


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IV. FRAGMENTATION OF CYCLIC MOLECULES

I. SMALL, STABLE MOLECULE LOSSES GIVE OE IONSStable (e.g., aromatic) molecules undergo losses of neutral molecules,usually by expulsion or cycloreversion reactions. These reactions are of highenergy, and they occur because there are no low-energy pathways.

Figure 23. EI mass spectra of simple, aromatic compounds for which loss ofa stable, neutral molecule is the most facile reaction.


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B. GENERAL CONSIDERATIONS FOR NON-AROMATICSCleave one bond: no change in m/zCleave second bond: produce OE ionRearrange hydrogen and cleave: EE ionCleave side chains: produce EE ionMol. Ions more stable; fragmentation gives both EE and OE ions

C. CYCLOALKANES

Figure 24. EI mass spectra of cycloalkanes. Note that both compounds losemethyl, but it’s more facile with methyl cyclohexane.

Mechanisms:

D. CYCLIC KETONES AND AMINESRing opening via simple cleavage will occur as directed by the substituent.

Figure 25. EI mass spectra of two isomeric cyclic ketones. Distinctionachieved by carbonyl-directed ring opening, rearr., and fragmentation.


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Mechanism:

E. CYCLIC ETHERS AND SULFIDESRing opening can be i or α, as controlled by the heteroatom. Ring openingcan lead to “distonic ions,” .CH2CH2CH2CH2CH2X+

Figure 26. EI mass spectra of analog cyclic ether and sulfide. Note thelarger number of sulfur-containing than oxygen-containing ions! Why?


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F. THE RETRO DIELS-ALDER REACTION GIVES OE ION

A characteristic reaction of cyclohexene-type compounds.Mechanism:

Figure 27. RDA Reaction distinguishes cyclohexene isomers.

Facile cleavage should not compete for the RDA to be important. Forexample, in cyclohexene-4-Me-1-isopropyl, the facility of the RDA isdecreased because the stability of the expelled olefin is not high and theready loss of 43 (C3H7) is more competitive than in the fragmentation of theother cyclohexene isomer

Figure 28. RDA Reaction also distinguishes tetralins.


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