Fragmentation of the Molecular Ion

As mentioned earlier, fragmentation of the molecular ion results in the formation of a number of other radicals and cations. In some cases, fragmentation is so facile that essentially all the molecular ions react and no M peak appears in the spectrum. Let s see how the masses of these fragments can be used to help determine the structure of the compound. 

we need to discuss the structure of the molecular ion in more detail. It is a radical cation, resulting from the loss of one electron from the original molecule. What electron is lost It must be the highest-energy electron in the compound. If the compound has only sigma bonds, the location of the odd electron and the positive charge is uncertain and the radical cation is usually represented as shown in the following equation  

The radical cation from compounds that have nonbonding or pi electrons can also be represented in this manner. However, because the highest-energy electron is known in these cases, the structure of the radical cation can be drawn more specifically as illustrated in the following equations  

Show the molecular ions formed from these compounds  

There are two general types of fragmentation reactions. In one type the radical cation fragments to a neutral molecule and a new radical cation. This process is especially favorable when the neutral product is a small, stable molecule. For example, the loss of water from the molecular ion of alcohols is very facile. For this reason the M+ peak is very small for primary and secondary alcohols, and it is usually undetectable for 

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The 4-Hydroxy-thiazoles are characterized by infrared absorption near 1610 cm (KBr) (3) or 1620 to 16.S0cm (CCI4) (8), indicating a strongly polarized carbonyl group. H-5 resonates near 5.6 ppm in the NMR spectrum like similar protons in other mesoionic compounds (3). Two fragmentations of the molecular ion are observed in the mass spectra. The first involves rupture of the 1,2 and 3,4 bonds with loss of C2R 0S . In the second, the 1,5 and 3,4 bonds are cleaved with elimination of C2R 0. ... 

Simple fragmentation of the molecular ion of iodobenzene gives a fragment ion, CjH,. The difference in measured masses between the molecular and fragment ions gives the mass of the ejected neutral iodine atom. 

There is another oxygen-stabilized cation of mIz 87 capable of being formed by fragmentation of the molecular ion in the mass spectrum of sec-butyl ethyl ether. Suggest a reasonable structure for this ion. 

The mass spectral fragmentations of 9,10-dimethoxy-2,3,4,6,7,ll/)-hexa-hydro-l//-pyrimido[6,l-n]isoquinolin-2-ones 140 and -2,4-diones 141, under electron ionization (at 70 eV) were examined by metastable ion analysis, a collosion-induced dissociation technique and exact mass measurement (97RCM1879). Methyl substituent on N(3) in 140 (R = Me) had a larger effect on both the fragmentation and on the peak intensities, than a methyl substituent on C(6) (R = Me). The ionized molecules of 140 (R = H) were rather stable, whereas 4-phenyl substitution on C(4) of 140 (R = Ph) promoted the fragmentations of the molecular ions. The hexahydro-1//-pyrimido[6,l-n]isoquinoline-2,4-diones 141 were more stable, than the hexahydro-l//-pyrimido[6,l-n]isoquinolin-2-ones 140, and the molecular ions formed base peaks. 

The other fragmentation pathways are typical for diaryl sulfoxides1-4-6,1. A corresponding ortho effect was found in chlorodiphenyl ethers and sulfides but not in sulfones12 (12) were the sulfinate ester rearrangements1-4,6,11 and the consequent formation of the m/z 125 and m/z 159 ions suppress the other possible fragmentations of the molecular ions (equation 4). It is also noteworthy that the ratio [m/z 125] [m/z 159] increases with increasing distance between the chlorine and the sulfur (equation 4). 

In the mass spectra of ot-amyrine, a peak was observed at m/z 426, relating to the molecular ion, along with peaks at m/z 411 and 408, arising from the fragmentation of the molecular ion by the loss of a methyl radical and of a water molecule, respectively. The peak at m/z 393 is due to the loss of a methyl radical and a water molecule. 

An extremely useful approach was proposed by Budzikievicz and coworkers [14] and later developed by McLafferty and Turecek [26]. The concept is based on the postulate that reactions of fragmentation of the molecular ions of complex organic molecules are initiated by the charge or unpaired electron, localized at a certain moiety. Despite its limitations this approach is very convenient to remember the different reactions of various particles. 

The final stage of mass spectrum processing involves development of a fragmentation scheme. The scheme should reflect the most characteristic pathways of fragmentation of the molecular ion, composition of the fragment ions (and if possible their structures), the relationship of the fragment ions with one another, and sometimes the relative abundances of their peaks (Schemes 5.23 and 5.24). 

The loss of isobaric neutral species from the molecular ions of isomeric nitroanisoles has been studied using deuterium labelling74. The mass analysis indicated that specific loss of CH2O occurs from the molecular ions of 2-nitroanisole, while a specific loss of NO takes place from 3-nitroanisole74. Although the peak due to [M —NO]+ is neglectible in the MS of 2-nitroanisole, it is apparently an important transient intermediate in the consecutive fragmentation of the molecular ions. 

Often but not necessarily, the peak at highest m/z results from the detection of the intact ionized molecule, the molecular ion, M. The molecular ion peak is usually accompanied by several peaks at lower m/z caused by fragmentation of the molecular ion to yield fragment ions. Consequently, the respective peaks in the mass spectrum may be referred to as fragment ion peaks. 

Fig. 6.53. El mass spectrum of pyridine. HCN loss represents the most important primary fragmentation of the molecular ion. Spectrum used by permission of NIST. NIST 2002.

With one exception, naphthalen-l,4-imines with a double bond between C-2 and C-3 are not known to dissociate thermally by either possible retro-Diels-Alder pathway (the reverse of reactions described in Section III, A, 1 and 2), and the enthalpy requirements for the formation of a benzyne or an acylic acetylene are doubtless unfavorable. However, the mass spectra of compounds 93-99 reveal one important fragmentation of the molecular ions to be loss of dimethyl acetylene-dicarboxylate, and another fragmentation pathway involves the formation of nitrilium ions MeC=NR and PhC=NR from 93-95 and 96-99, respectively. ... 

The energy of the electron responsible for the ionisation process can be varied. It must be sufficient to knock out an electron and this threshold, typically about 10-12 eV, is known as the appearance potential. In practice much higher energies ( 70 eV) are used and this large excess energy (1 eV = 95 kJ mok ) causes further fragmentation of the molecular ion. 

There are a number of other methods for ionising the sample in a mass spectrometer. The most important alternative ionisation method to electron impact is Chemical Ionisation (Cl). In Cl mass spectrometry, an intermediate substance (generally methane or ammonia) is introduced at a higher concentration than that of the substance being investigated. The carrier gas is ionised by electron impact and the substrate is then ionised by collisions with these ions. Cl is a milder ionisation method than El and leads to less fragmentation of the molecular ion. 

Another common method of ionisation is Electrospray Ionisation (ES). In this method, the sample is dissolved in a polar, volatile solvent and pumped through a fine metal nozzle, the tip of which is charged with a high voltage. This produces charged droplets from which the solvent rapidly evaporates to leave naked ions which pass into the mass spectrometer. ES is also a relatively mild form of ionisation and is very suitable for biological samples which are usually quite soluble in polar solvent but which are relatively difficult to vaporise in the solid state. Electrospray ionisation tends to lead to less fragmentation of the molecular ion than EL... 

Also in the mass spectrum of 3-hydrazino-5,6-diphenyl-l,2,4-triazine (82) the elimination of nitrogen from the molecular ion could not be detected. The dominant process in this case is the fragmentation of the molecular ion into a highly delocalized diphenylacetylene radical ion at 178 mass units (7lOMS(5)i085). 

A characteristic of the mass spectrum of isoflavanone (3-phenylchroman-4-one, 86) is its simplicity. Here again, fragmentation of the molecular ion occurs to give an [RDA]t ion as the base peak which decomposes by loss of CO. Hydrogen transfer occurs to give an ion corresponding to [RDA + H]+ (66BSF2892). 

Mass spectra are used to determine molecular weights and molecular composition (from the parent or molecular ion) and to obtain structural information from the fragmentation of the molecular ion into daughter ions. Electrospray ionization (ESI-MS) and matrix-assisted laser desorption ionization (MALDI-MS) mass spectroscopy can be used to obtain structural information about macromolecules, including proteins, polymers, and drug-DNA complexes. 

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