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Mass Spectrometry Straight Chain Alkanes

When an alkane is ionized by EI, it will lose an electron to form a radical cation. This radical cation has the same mass as the parent compound (minus one electron) and is the molecular ion (M+). The type of radical formed follows the stability of radicals:
o o o

3 > 2 > 1 > methyl

The alkane molecular ion can further fragment to form a homologous series of cations of mass CnH2n+1. These cations arise from the loss of methyl radical (M - 15), ethyl radical (M - 29), etc. Scheme 3 shows a possible mechanism of fragmentation for pentane; the corresponding mass spectrum of pentane is given in Figure 3.

Scheme 3. Mechanism of fragmentation for pentane.

Notice the appearance of M - 15, M - 29, M - 43, and M - 57 ions in Figure 3. Table 5 shows the typical fragments lost by acyclic alkanes and their respective masses.

Table 5. Typical fragments lost from straight chain alkanes. Mass Lost Fragment Lost 1 H

2 15 29 43 57 71

2 H CH3 C2H5 C3H7 -or- C2H4 & CH3 C4H9 -or- C2H4 & C2H5 C5H11 -or- C3H6 & C2H5

The ions of m/z 57 and 43 result from the loss of methyl and ethyl radical, respectively. The ions of m/z 29 and 15 result from the subsequent loss of ethene from these two higher mass fragments. In general, once a radical is lost, the subsequent losses are of neutral molecules. This is called the even electron (EE) ion rule. That is, once an even electron ion is formed, it fragments by rearrangement to give other EE ions. For instance, in decane (see Figure 4): M [M 15] [M - 15 28] or [M - 15- 42] or [M - 15 56]. The same can be said for M - 29 [M - 29 28], etc. This is how that characteristic EE ion series: 29, 43, 57, 71, 85 arises in hydrocarbon MS.

Figure 3. Mass spectrum of pentane. The hydrocarbon ions are drawn as primary ions although by the time they reach the detector, they have rearranged to the more stable secondary and tertiary carbocations.

Ions observed in the mass spectra of straight chain alkanes will usually appear in groups of 14 mass unit intervals (corresponding to one CH2 group difference). The most abundant fragment ion is usually the 3 carbon fragment, with the abundances of higher mass ions decreasing with increasing mass. Often, the M - 15 ion (formed by loss of methyl + + + radical) will be absent. The series of fragments to look for in these spectra are of C nH2n+1 , CnH2n , and CnH2n-1 . The mass spectrum of n-hexadecane (Figure 4) illustrates these points.

Figure 4. Mass spectrum of n-hexadecane

Mass Spectrometry Branched Alkanes

Branched alkanes tend to fragment very easily owing to the presence of 2 , 3 , and 4 carbon atoms in the structure. When branched alkanes fragment, stable secondary and tertiary carbocations can form. For this reason, the molecular ion is much less abundant than for straight-chain alkanes. The most important mode of fragmentation in branched alkanes usually occurs at the branch point. Scheme 4 shows the mechanism of fragmentation for isobutane, and the mass spectrum for isobutane is contained in Figure 5. Notice the reduced intensity of the molecular ion ( m/z 58).

Scheme 4. Mechanism of fragmentation for isobutane.

Figure 5. Mass spectrum of isobutane.

Mass Spectrometry Cyclic Alkanes

The fragmentation patterns of cycloalkanes may show mass clusters in a homologous series, as for the alkanes. However, the most significant mode of cleavage of the cycloalkanes involves the loss of ethylene from the parent molecule or from intermediate radical-ions. Additionally, if the cycloalkane has a side chain, loss of that side chain is also a favorable mode of fragmentation. Scheme 5 provides the mechanism for the fragmentation for cyclohexane. The mass spectrum of cyclohexane (Figure 6) has an abundant ion of m/z 56 arising by the loss of ethylene.

Scheme 5. Mechanism of fragmentation for cyclohexane. The m/z 56 ion may initially be a distonic ion with charge on one terminus and the radical site on the other.

Cycloalkanes will also give ions akin to those arising from alkanes. For instance, the ion of m/z 69 is due to the loss of methyl radical. The ions of m/z 15, 29, and 43 are due to methyl, ethyl, and propyl cations, respectively.

Figure 6. Mass spectrum of cyclohexane.

Figure 7 contains the mass spectrum of methylcyclohexane. Note that the loss of the methyl side chain is perhaps the most important fragmentation event, and the M - 15 ion of m/z 83 gives the most intense signal in the spectrum. The next most abundant ion (m/z 55) may arise by the subsequent loss of ethylene from the m/z 83 fragment or by loss of a propyl group via rearrangement. For cycloalkanes to fragment, two carbon-carbon bonds must be broken. This process may require a significant amount of time (relative to the amount of time it takes an ion to reach the detector in a mass spectrometer); therefore, a significant amount of the molecular ion will reach the detector resulting in a large molecular ion (the molecular ion abundance of a cyclic compound is usually greater than that of an acyclic isomer).

Figure 7. Mass spectrum of methylcyclohexane.

Cycloalkanes tend to cleave in CnH2n , CnH2n-1 , and CnH2n-2 fragments. The larger number of even numbered mass fragments of cycloalkanes helps to distinguish this class of compounds from the acyclic alkanes.

Straight Chain Alkenes

The mass spectra of most alkenes show distinct molecular ions. This is probably due to the loss of a -bonding electron, leaving the carbon skeleton relatively undisturbed. The most important fragmentation events for alkenes involve cleavage of the allylic (favored) and vinylic (less favored) carbon-carbon bonds. For terminal alkenes, allylic fragmentation forms an allylic carbocation ofm/z 41. The fragmentation mechanism for 1-butene shown in Scheme 6 illustrates these points. The complete mass spectrum of 1-butene is given in Figure 8.

Scheme 6. Mechanism of fragmentation for 1-butene.

Figure 8. Mass spectrum of 1-butene.


+ + +

Alkenes usually form fragments corresponding to C nH2n+1 , CnH2n , and CnH2n-1 (the latter two fragment ion series are more abundant). It is very difficult to locate the position of the double bond in an alkene because of the easy migration of the double bond by hydride and hydrogen atom shifts. For this reason, the mass spectra of alkene isomers are nearly identical and almost impossible to distinguish, as is illustrated in Figure 9, which contains the mass spectra for 2- and 3-heptene, respectively.

Figure 9. Mass spectra of 2-heptene (top) and 3-heptene (bottom). Cyclic Alkenes

The mass spectra of cycloalkenes show distinct molecular ions. It may be impossible to locate the position of a double bond due to migration. The mechanism of fragmentation for cyclic alkenes is virtually the same as for straight chain alkenes. One noteworthy characteristic is the fragmentation of cyclohexenes to undergo a reverse Diels-Alder reaction as indicated in Scheme 7. This rearrangement is characteristic of many isoprenoid natural products and of tetralin derivatives, and is useful for assigning structure and distinguishing isomers. The complete mass spectrum of cyclohexene is given in Figure 10.

Scheme 7. Mechanism of fragmentation for cyclohexene.

Figure 10. Mass spectrum of cyclohexene.

Alkynes

The mass spectra of alkynes are virtually identical to those of alkenes. The molecular ion is usually more abundant, and fragmentation parallels that of the alkenes. Two differences are worth mentioning: terminal alkynes fragment to form propargyl ions (m/z 39), and can also lose the terminal (or an -) hydrogen, yielding a strong M - 1 ion. These two modes of fragmentation are outlined in Scheme 8 for 1-butyne, and the complete mass spectrum of 1-butyne is given in Figure 11.

Scheme 8. Mechanism of fragmentation for 1-butyne.

An alternative way to describe the loss of hydrogen radical from an alkyne would involve a 1,2-hydride shift (converting a vinylic radical cation to a more stable allylic radical cation) that subsequently loses hydrogen radical to give the M - 1 ion. This alternate mechanism is outlined in Scheme 9.

Scheme 9. Alternate mechanism of fragmentation for 1-butyne.

Either mechanism provides an explanation for the formation of the M - 1 ion. The mechanism in Scheme 9 does, however, provide a plausible explanation for the loss of hydrogen radical from internal alkynes (such as 2-butyne) the mass spectrum of which does indicate a relatively abundant M - 1 ion.

Figure 11. Mass spectrum of 1-butyne.

Aromatic Compounds

The mass spectra of most aromatic compounds show distinct and abundant molecular ions. This is probably due to the loss of an electron from the system, leaving the carbon skeleton relatively undisturbed.

When an alkyl side-chain is attached to the ring, fragmentation usually occurs at the benzylic position, producing initially a benzyl ion, which often rearranges to the tropylium ion (m/z 91). However, fragmentation can also occur at the attachment point to the ring producing the phenyl cation ( m/z 77). If the side-chain is a propyl group or larger, then the McLafferty rearrangement is a possibility, producing a fragment of m/z 92. Formation of a substituted tropylium ion is typical for alkyl-substituted benzenes producing an ion of m/z 105. Each of these possible fragmentation events is described in Scheme 10.

Scheme 10. Mechanism of fragmentation for propylbenzene.

The phenyl cation will fragment further. One route involves the loss of acetylene yielding a fragment with formula + C4H3 (m/z 51). Another route involves the loss of presumably an allene diradical with formula C 3H2, forming probably + the simplest aromatic species of the formula C3H3 (m/z 39), namely the cyclopropenyl ion. A proposed mechanism for the formation of these fragments is given in Scheme 11. Note that this mechanism is complete conjecture, and only serves as one possible explanation.

Scheme 11. Proposed mechanism for phenyl cation fragmentation.

The complete mass spectrum of propylbenzene is given in Figure 12, which illustrates all of these points.

Figure 12. Mass spectrum of propylbenzene.

Aldehydes

The molecular ion is usually observable, although it can be of low relative abundance. The important - and cleavage patterns (as well as the McLafferty rearrangement) are illustrated in Scheme 12.

Scheme 12. Mechanism of fragmentation for hexanal.

The complete mass spectrum of hexanal, given in Figure 13, illustrates these points.

Figure 13. Mass spectrum of hexanal.

Ketones

The molecular ion is usually quite abundant. Fragmentation patterns mimic those of the aldehydes. It appears that the loss of the larger alkyl group is favored in ketones in the -cleavage process as shown in Scheme 13. This may not be strictly correct, however, because the abundance of a fragment ion is a balance of the rates of the reactions producing it and those causing it to decompose. For interpretation purposes, the rule that the larger alkyl group is lost is effective in interpretation.

Scheme 13. Mechanism of fragmentation for 2-pentanone.

The complete mass spectrum of 2-pentanone is given in Figure 14, which illustrates most of these points. The two ions formed by alpha cleavage (m/z 43 and 71) then lose CO (decarbonylate) to give carbocations (with masses of 15 and 43, respectively). When the alkyl chains are long, the resulting alkene will fragment by losses of alkenes and other neutrals (e.g., H2), in accord with EE ion rule.

Figure 14. Mass spectrum of 2-pentanone. For aromatic ketones, -cleavage usually involves cleavage of the alkyl group leaving behind an acylium ion. This is subsequently followed by a loss of carbon monoxide from the molecule as indicated in Scheme 14. If the aromatic ketone has a 3 carbon alkyl chain (or longer), then McLafferty rearrangements (as described above for 2-pentanone) are possible.

Scheme 14. Aromatic ketone fragmentation illustrated for acetophenone.

The phenyl cation (m/z 77, the product of decarbonylation) will subsequently lose acetylene, C 2H2, or an allene diradical, C3H2, to form fragment ions with m/z 51 and 39, respectively. This is very characteristic of the phenyl cation and the overall process is a signature for the benzoyl group, which is common in organic chemistry. Furthermore, the scheme is another example of the EE ion rule (see Figure 12 for an additional example of this cleavage). The complete mass spectrum of acetophenone is given in Figure 15, which illustrates these points.

Figure 15. Mass spectrum of acetophenone.

Esters

The molecular ion is usually of low abundance but generally observable for esters. As in all carbonyl compounds, cleavage is an important fragmentation process. In general, cleaving the C-O ester bond occurs most readily leading to the favorable loss of an alkoxy radical. Table 6 summarizes this cleavage process for the most common types of esters.

Table 6. Alkoxy Radicals formed from the most common esters. Ester Alkoxy Radical Formed methyl CH3O ethyl CH3CH2O propyl (and isopropyl) CH3CH2CH2O phenyl C6H5O (PhO) benzyl C6H5CH2O (BzO)

Ion to Observe M - 31 M - 45 M - 59 M - 93 M - 105

Since methyl esters are very common and their formation is used in the derivatization of fatty acids for GC/MS, the example below is presented to indicate the most common fragmentation patterns observed for a simple methyl ester, methyl butyrate. Loss of the alkoxy group is the most important of these fragmentations as shown in Scheme 15.

Scheme 15. Mechanism of fragmentation for methyl butyrate.

The complete mass spectrum of methyl butyrate is given in Figure 16, which illustrates most of these points. Ethyl, and particularly larger alkyl esters, do a double rearrangement - sometimes called a double McLafferty rearrangement - to make a protonated acid RCOOH2+. The mass spectrum of butyl benzoate, for example, gives the abundant ion of m/z 123 arising from this double rearrangement.

Figure 16. Mass spectrum of methyl butyrate.

Benzyl and phenyl esters undergo a rearrangement involving hydride transfer from the -carbon to the ester oxygen. The resulting fragments include a neutral ketene and a charged alcohol as described in Scheme 16 below.

Scheme 16. Most common fragmentation involving benzyl and phenyl esters.

The mass spectra for benzyl acetate and phenyl acetate are given in Figure 17, which illustrates the point.

Figure 17. Mass spectra of benzyl acetate (top) and phenyl acetate (bottom).
+

Benzoate esters tend to lose the alkoxy group (as a radical) to form an acylium ion (C6H5CO , m/z 105), which + subsequently loses carbon monoxide to form the phenyl cation (C 6H5 , m/z 77). This is reminiscent of the fragmentation often observed for aromatic ketones (see Scheme 11 and Figures 12 and 15). An important exception to this pattern involves benzoate esters bearing alkyl, amino, or hydroxy substituents at the ortho position. Proton transfer from the ortho substituent to the ester oxygen eliminates a neutral alcohol fragment. This fragmentation is an example of a proximity effect in organic mass spectra, specifically an ortho effect. The remaining aromatic radical cation is often the most abundant species detected. Illustrations of these two common pathways are given in Scheme 17 below. The mass spectra for both methyl benzoate and methyl 2-aminobenzoate, given in Figure 18, show that the ortho substituted benzoate ester undergoes a facile loss of methanol resulting in an abundant M - 32 (m/z 119) ion in the mass spectrum (Figure 18, bottom). Ortho effects offer one way of distinguishing ortho from meta and para isomers by mass spectrometry. When this process cannot occur, the mass spectra of ortho, meta, and para isomers are usually very similar and nearly indistinguishable (e.g., o-, m-, and p-ethyl toluene have nearly identical spectra).

Scheme 17. Most common fragmentation involving benzoate and ortho substituted benzoate esters.

Figure 18. Mass spectra of methyl benzoate (top) and methyl 2-aminobenzoate (bottom).

Mass Spectrometry Carboxylic Acids

The molecular ion is often of low abundance for carboxylic acids, but generally observable. As for all other carbonyl compounds, -cleavage, -cleavage, and McLafferty rearrangements rule the day. As is indicated in Scheme 18, the loss of hydroxyl radical (leading to an M - 17 ion) is indicative of the presence of the carboxylic acid functionality. All the important fragmentation events for carboxylic acids are illustrated in Scheme 18.

Scheme 18. Mechanism of fragmentation for butyric acid.

The complete mass spectrum of butyric acid is given in Figure 19, which illustrates most of these points. The presence of ions of m/z 60 and 45 are indicative of carboxylic acids.

Figure 19. Mass spectrum of butyric acid.

As was seen with esters, benzoic acids substituted with alkyl, amino, or hydroxy substituents at the ortho position readily dehydrate via proton transfer from the ortho substituent to the hydroxyl group (ortho effect). Water is lost, resulting in a major M - 18 ion in the mass spectrum. Scheme 19 outlines this process for o-toluic acid.

Scheme 19. The ortho effect fragmentation of o-toluic acid.

The mass spectrum of o-toluic acid (given in Figure 20) indicates the facile nature of this dehydration event (the signal for the product ion is the base peak).

Figure 20. Mass spectrum of o-toluic acid.

Amides

The molecular ion is usually observable, and will be a good indication of the presence of an amide (invoke the nitrogen rule!). An important fragmentation pattern involves -cleavage (breaking either bond to the carbonyl carbon) as shown in Scheme 20.

Scheme 20. Mechanism of fragmentation for butyramide.

The complete mass spectrum of butyramide is given in Figure 21, which illustrates most of these points.

Figure 21. Mass spectrum of butyramide.

Anhydrides

Aliphatic acid anhydrides rarely afford a molecular ion in their mass spectra whereas aromatic anhydrides usually do. Understanding and interpreting the mass spectra for anhydrides is quite straight forward, as they fragment by following the general rules set forward for all carbonyl compounds: -cleavage on either side of the carbonyl carbon contributes to the major ions observed in the mass spectrum as shown in Scheme 21 for butyric anhydride.

Scheme 21. Mechanism of fragmentation for butyric anhydride.

The mass spectrum of butryic anhydride (Figure 22) indicates the major cleavage pattern outlined above.

Figure 22. Mass spectrum of butyric anhydride.

Aromatic anhydrides show evidence of the molecular ion and undergo a similar fragmentation as seen for butyric anhydride. However, an additional rearrangement where carbon monoxide is lost from the molecule is evident in nearly all mass spectra of aromatic anhydrides. The cleavage pattern for benzoic anhydride is given in Scheme 22.

Scheme 22. Mechanism of fragmentation for benzoic anhydride.

The mass spectrum of benzoic anhydride (Figure 23) indicates the major cleavage pattern outlined above.

Figure 23. Mass spectrum of benzoic anhydride. (Adapted from NIST Mass Spec Data Center, S.E. Stein, director, "Mass Spectra" in NIST Chemistry WebBook, NIST Standard Reference Database Number 69, Eds. P.J. Linstrom and W.G. Mallard, June 2005, National Institute of Standards and Technology, Gaithersburg MD, 20899 (http://webbook.nist.gov))

It is interesting to note that the ortho effect (as described above for ortho substituted esters and carboxylic acids) applies to aromatic anhydrides as well. The fragmentation for o-toluic anhydride (given in Scheme 23) is an example of this general effect.

Scheme 23. Mechanism of fragmentation for o-toluic anhydride.

The mass spectrum of o-toluic anhydride (Figure 24, top) indicates the major cleavage pattern outlined above. Note the presence of the ion due to the loss of o-toluic acid (m/z 118), and the corresponding absence of that ion in the spectrum for benzoic anhydride (Figure 23, the ion would be at m/z 104), and for p-toluic anhydride (Figure 24, bottom, the ion would be at m/z 118). Another interesting note is the absence of an M - 28 ion (corresponding to the loss of carbon monoxide, CO) in the spectrum for o-toluic anhydride, and the presence of that ion in the spectrum forp-toluic anhydride (at m/z 226). Apparently, the ortho effect provides for a more facile fragmentation event.

Figure 24. Mass spectra of o-toluic anhydride (top) and p-toluic anhydride (bottom).

Mass Spectrometry Acid Halides

Acid halides afford very low abundance, if not entirely absent, molecular ions in their mass spectra. This is true even for aromatic acid halides. Again, as with all carbonyl compounds, -cleavage is a very facile process with loss of a halogen radical perhaps the most common event. Acid chlorides can also lose HCl from the molecule; this is not a 35 37 probable event with acid bromides. Keep in mind that the two common isotopes for chlorine ( Cl and Cl in a 3:1 79 81 ratio) and bromine ( Br and Br in a 1:1 ratio) will lead to the production of M + 2 observed ions in the spectra. Since the molecular ion is not abundant, the M + 2 ions are typically very difficult to ascertain. Scheme 24 contains the common fragments formed for butyryl chloride.

Scheme 24. Mechanism of fragmentation for butyryl chloride.

The mass spectrum of butyryl chloride (Figure 25) indicates the major cleavage pattern outlined above.

Figure 25. Mass spectrum of butyryl chloride

Halogenated Compounds

The molecular ion for alkyl halides ranges from observable for alkyl iodides to barely detectable for alkyl fluorides. Because of the isotope ratios for chlorine and bromine, the M+ and M + 2 observed ions are quite clear and indicate the presence of these elements.

The most important fragmentation process for the heavier alkyl halides (bromine and iodine) involves simply losing the halogen to form an alkyl carbocation (ipso-cleavage). For this reason, the mass spectra for these halogenated compounds will be dominated by the fragmentation of an alkyl ion and, thus, mimic the mass spectra of simple alkanes. Competing with this loss (for sufficiently long chain primary halides) is a cleavage (e.g., the loss of an ethyl group in the fragmentation of 1-bromohexane (to give ions of m/z 135/137) and 1-chlorohexane (to give ions of m/z91/93)) - (see Scheme 31 and Figures 37 and 38). The product ions are 5-membered ring halonium ions.

Scheme 31. Mechanism of fragmentation for 1-bromohexane. The fragment with m/z 85, although drawn as a primary carbocation, will have rearranged to a more stable secondary carbocation.

For the lighter halogens (fluorine and chlorine) the loss of hydrogen halide is important particularly when a 1,3 or 1,4elimination is possible. In the cases of 1-chlorohexane and 1-fluorohexane, the product from loss of HCl (or HF) is the product ion of m/z 84 (see Scheme 32 and Figures 38 and 39).

Scheme 32. Mechanism of fragmentation for 1-chlorohexane. The fragment with m/z 85, although drawn as a primary carbocation, will have rearranged to a more stable secondary carbocation.

The complete mass spectra of 1-iodohexane, 1-bromohexane, 1-chlorohexane, and 1-fluorohexane are given in Figures 36-39, respectively.

Figure 36. Mass spectra of 1-iodohexane. (Adapted from NIST Mass Spec Data Center, S.E. Stein, director, "Mass Spectra" in NIST Chemistry WebBook, NIST Standard Reference Database Number 69, Eds. P.J. Linstrom and W.G. Mallard, June 2005, National Institute of Standards and Technology, Gaithersburg MD, 20899 (http://webbook.nist.gov))

Figure 37. Mass spectra of 1-bromohexane.

Figure 38. Mass spectra of 1-chlorohexane.

Figure 39. Mass spectra of 1-fluorohexane

Mass Spectrometry Amines

The molecular ion is of low abundance or not detectable. When observable, its odd mass (when an odd number of nitrogens is present) is a good indication of the presence of an amine (nitrogen rule). Important fragments arise from cleavage of the carbon-carbon or carbon-hydrogen bond adjacent to the nitrogen (-cleavage), and hydrogen transfer from the -hydrogen to the nitrogen. These processes are outlined in Scheme 29 for dipropyl amine. If two or more alkyl groups of different length are attached to the alpha carbons, then loss of the largest alkyl group is preferred.

Scheme 29. Mechanism of fragmentation for dipropyl amine.

The m/z 58 ion is formed by loss of H to give an iminium ion of m/z 100 in a manner similar to the formation of the m/z 72 ion. It then rearranges by H transfer to N to lose 42. Consistent is a similar rearrangement of the m/z 72 ion to lose 42 as well and give m/z 30 ion. Ethyl butyl amine will lose methyl and then 56 or lose propyl, and then ethene. Methyl pentyl amine will lose butyl and then stop because lose of methylene has too high an energy requirement. The complete mass spectrum of dipropyl amine is given in Figure 31, which illustrates most of these points.

Figure 31. Mass spectrum of dipropyl amine. For most amines, ipso-cleavage of the alkyl group is rarely observed. However, -cleavage of primary amines leads to + the production of an iminium ion (with formula H2C=NH2 ) of m/z 30. The presence of this ion is very indicative of a primary amine. Figure 32 contains the mass spectrum of propyl amine, where the base peak (at m/z 30) is due to this ion.

Figure 32. Mass spectrum of propyl amine.

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