Major Chemistry B.Sc.III ( Semester V) Spectral analysis Mass spectroscopy Part-I



Major Chemistry B.Sc.III ( Semester V)

Name of paper- Spectral analysis

CHE/DSC/T/301 

Mass Spectroscopy Part-I

Introduction, Basic Principle, Nature of mass spectrum, Importance of molecular ion peak, base peak.

Introduction:

Mass spectroscopy (MS), more accurately called mass spectrometry, is one of the most powerful analytical techniques used to identify, characterize, and quantify chemical compounds. It measures the mass-to-charge ratio (m/z) of ionized atoms or molecules, providing detailed information about their molecular weight, elemental composition, and structural characteristics. Due to its high sensitivity, accuracy, and rapid analysis, mass spectrometry has become an indispensable tool in chemistry, biochemistry, pharmaceutical sciences, environmental science, forensic science, and clinical diagnostics.

The basic principle of mass spectrometry involves converting neutral molecules into charged ions, separating these ions according to their mass-to-charge ratio using electric and magnetic fields, and detecting them to produce a mass spectrum. A mass spectrum is a graphical representation of ion intensity versus mass-to-charge ratio, where each peak corresponds to a specific ion. The molecular ion peak provides the molecular mass of the compound, while fragment ion peaks offer valuable information about the compound's structural features.

Basic Principle:

Mass spectrometry is the most accurate method for determining the molecular mass of the compound and its elemental composition. In this technique, the compound under investigation is bombarded with a beam of energetic electrons. The molecules are ionised and dissociate into several fragments, some of which are positive ions. Each kind of ion has a particular ratio of mass to charge, i.e., m/e ratio. Since multiple charged ions are produced only rarely relative to singly charged ions, the charge can normally be taken as one. Thus, for most ions, m/e ratio is simply the molecular mass of the ion. Hence, for neopentane, m/e ratio is 72.

Mass spectroscopy figure
Mass spectroscopy figure

The molecular ion (here C₅H₁₂) is called parent ion and is designated as M⁺. The set of ions (daughter ions or fragment ions) are analysed in such a way that a signal is obtained for each value of m/e. The intensity of each signal represents the relative abundance of the ion producing the signal. The largest, most intense peak in the structure is called the base peak and its intensity is arbitrarily assigned a value of 100%. The intensities of other peaks are represented relative to the base peak. The parent peak may not be confused with the base peak.

A mass spectrum is a presentation of the masses of positively charged fragments (including the parent ion) versus their relative concentrations. Mass spectrum is produced as a result of a series of competing and consecutive unimolecular reactions. A graphic presentation or a plot of the spectrum may be used which represents the intensities of the signals at various m/e values. A single mass spectrum is equivalent to dozens of physical properties of that compound for identifying the structure. No two compounds can have exactly similar mass spectra. Mass spectrometry is not a true spectroscopic technique because absorption of electromagnetic energy is not involved in any way. However, since it complements information provided to the chemist by IR, UV and NMR, it is conveniently considered alongside them.

The important advantages of mass spectrometry are its high sensitivity, reproducibility, accuracy, and the small amount of sample required for mass spectral analysis. Materials present in concentrations less than 1 ppm can be easily detected by this technique. In addition to elucidation of molecular structure Mass spectra are useful for determining molecular weight, investigating reaction mechanisms, identifying a functional group, and in tracer technique.

Nature of mass spectrum:

A mass spectrum will usually be presented as a vertical bar graph, in which each bar represents an ion having a specific mass-to-charge ratio (m/z) and the length of the bar indicates the relative abundance of the ion. The most intense ion is assigned an abundance of 100, and it is referred to as the base peak. Most of the ions formed in a mass spectrometer have a single charge, so the m/z value is equivalent to mass itself. Modern mass spectrometers easily distinguish (resolve) ions differing by only a single atomic mass unit (amu), and thus provide completely accurate values for the molecular mass of a compound.

The highest-mass ion in a spectrum is normally considered to be the molecular ion, and lower-mass ions are fragments from the molecular ion, assuming the sample is a single pure compound. The following diagram displays the mass spectra of three simple gaseous compounds, carbon dioxide, propane and cyclopropane.

Mass spectroscopy figure
Mass spectroscopy figure

The molecules of these compounds are similar in size, CO2 and C3H8 both have a nominal mass of 44 amu, and C3H6 has a mass of 42 amu. The molecular ion is the strongest ion in the spectra of CO2 and C3H6, and it is moderately strong in propane. The unit mass resolution is readily apparent in these spectra (note the separation of ions having m/z=39, 40, 41 and 42 in the cyclopropane spectrum). Even though these compounds are very similar in size, it is a simple matter to identify them from their individual mass spectra.

Since a molecule of carbon dioxide is composed of only three atoms, its mass spectrum is very simple. The molecular ion is also the base peak, and the only fragment ions are CO (m/z=28) and O (m/z=16). The molecular ion of propane also has m/z=44, but it is not the most abundant ion in the spectrum. Cleavage of a carbon-carbon bond gives methyl and ethyl fragments, one of which is a carbocation and the other a radical. Both distributions are observed, but the larger ethyl cation (m/z=29) is the most abundant, possibly because its size affords greater charge dispersal. A similar bond cleavage in cyclopropane does not give two fragments, so the molecular ion is stronger than in propane, and is in fact responsible for the the base peak. Loss of a hydrogen atom, either before or after ring opening, produces the stable allyl cation (m/z=41). The third strongest ion in the spectrum has m/z=39 (C3H3 ). Its structure is uncertain, but two possibilities are shown in the diagram. The small m/z=39 ion in propane and the absence of a m/z=29 ion in cyclopropane are particularly significant in distinguishing these hydrocarbons.

Fragmentation Modes:

A. Simple Cleavage

This process involves homolytic or heterolytic cleavage of a single bond.

Homolytic Cleavage

The homolytic cleavage is initiated by a radical site. Odd-electron ions have an unpaired electron which is capable of new bond formation. When a bond is formed, energy is released. The energy released by bond formation can help offset the energy required for the cleavage of some other bond in the ion. These reactions may occur according to the following modes:

Mode I

This fragmentation mode operates in compounds in which a hetero atom is singly bonded to a carbon atom. The parent ion is formed by the removal of one electron from the heteroatom. A new bond is formed with the adjacent atom through the donation of the unpaired electron and transfer of an electron from the adjacent bond.

Where X = hetero atom.
Where X = hetero atom.

Where X = hetero atom.

Abundant peaks are formed by the cleavage of the C–C bond which is in the α-position to the heteroatom in the mass spectra of amines, alcohols and ethers.

(i) Amines

Mass spectroscopy figure
Mass spectroscopy figure

(ii) Alcohols

Mass spectroscopy figure
Mass spectroscopy figure

(iii) Ethers

Mass spectroscopy figure
Mass spectroscopy figure

The mass spectra of three isomeric butyl alcohols are different. Primary alcohols give a strong peak at m/e 31.

Mass spectroscopy figure
Mass spectroscopy figure

Secondary alcohols (e.g., 2-alkanols and 3-alkanols) give strong peaks at m/e 45 and m/e 59.

Mass spectroscopy figure
Mass spectroscopy figure

3-Alkanols also break to give ethylene and hence a strong peak at m/e 31 is obtained.

Mass spectroscopy figure
Mass spectroscopy figure

Tertiary alcohols give a peak at m/e 59 which is more intense than that of secondary alcohols.

Fragmentation of tertiary alcohols:

Mass spectroscopy figure
Mass spectroscopy figure

Mode II

When a hetero atom is attached to a carbon atom by a double bond, α-cleavage is the preferred fragmentation mode.

General fragmentation:

Mass spectroscopy figure
Mass spectroscopy figure

This type of fragmentation is shown by ketones, esters and amides, etc. In ketones, significant peaks are observed due to the cleavage of the C–C bond which is α to the carbonyl group. Unsymmetrical ketones show two types of peaks since either alkyl group can be lost. The elimination of the larger alkyl radical is preferred. In the same way, the fragmentation mode in aldehydes, esters and amides leads to the cleavage of the C–H, C–O and C–N bonds respectively. However, compounds containing C=N or C=S groups do not show this type of fragmentation. The presence of amino and hydroxyl groups, which are electron-donating in nature, reduces the relative abundance of the acylium ion (R−C≡O+). The presence of electron-withdrawing substituents such as nitro and cyano increases the relative abundance of the ion.

(c) Mode III

Benzylic cleavage is an energetically preferred fragmentation mode. It involves the cleavage of a C–C bond that is β to the aromatic ring.

General fragmentation:

Mass spectroscopy figure
Mass spectroscopy figure

The resulting ion is the tropylium ion. m/e = 91 Considerable stabilization of the tropylium cation is provided by the aromatic system. Thus, ethyl benzene exhibits a very intense (M − C₂H₅) ion at m/e 91.

2. Heterolytic Cleavage

The cleavage of the C–X bond (X = O, N, S, Cl) is more difficult than that of a C–C bond. In such a case, the positive charge is carried by the carbon atom and not by the hetero atom. This can be shown in the fragmentation of alkyl halides.

In the spectra of monohalogenated compounds, the hydrocarbon ions are formed in low abundance. As the size of the halogen atom increases, the C–X bond becomes weaker. Accordingly, C–X bond cleavage becomes easier and iodides are easily broken and tend to break by the process of α-cleavage.Alkyl fluorides and chlorides are less susceptible to fragmentation, but they have a tendency to eliminate HF and HCl, respectively.

Mass spectroscopy figure
Mass spectroscopy figure

Retro-Diels–Alder Reaction

This reaction is characteristic of cyclic olefins, which undergo multicentre fragmentation. Here, the cleavage of two bonds of a cyclic system occurs, resulting in the formation of two stable unsaturated fragments in which two new bonds are formed. The highly substituted or more conjugated fragment, which has a lower ionization potential, carries a positive charge. In simple systems, the charge is carried by a diene.

Mass spectroscopy figure
Mass spectroscopy figure

B. Rearrangement reaction:

1. Hydrogen Transfer Rearrangements

These involve intramolecular hydrogen rearrangements in aliphatic and aromatic hydrocarbons. In H-transfer rearrangements, generally a six-membered transition state is formed, although other transition states are also common.

Mass spectroscopy figure
Mass spectroscopy figure

2. Elimination Reactions

These reactions operate not only from the molecular ion but also from the fragment ion. The positive charge generally remains on the carbon-containing fragment. Alcohols usually eliminate a molecule of water from the molecular ion. n-Butyl and n-pentyl chlorides undergo hydrogen chloride elimination by the abstraction of an α-hydrogen atom through a 1,3-mechanism. The elimination of ketene (CH₂=C=O) is a characteristic fragmentation mode of n-alkyl amides and O-acetates of phenols.

Mass spectroscopy figure
Mass spectroscopy figure

Ortho-Elimination

In ortho-substituted aromatic compounds or in cis-olefins, the substituent and a hydrogen atom can come in close proximity so as to eliminate a neutral molecule.

Mass spectroscopy figure
Mass spectroscopy figure

Such an elimination of a neutral molecule distinguishes:

Between cis and trans isomers, and

Ortho-substituted compounds from meta and para substituted isomers.

4. McLafferty Rearrangement Ion

McLafferty rearrangement involves the cleavage of a β-bond followed by a γ-hydrogen transfer. The rearrangement leads to the elimination of neutral molecules from amines, aldehydes, ketones, unsaturated compounds, and substituted aromatics. The rearrangement proceeds through a sterically hindered six-membered transition state.Consider a ketonic compound.

Mass spectroscopy figure
Mass spectroscopy figure

Similarly, amines, alcohols, ketones, acids, and esters which contain a γ-hydrogen atom form a McLafferty rearrangement ion.

Other examples of McLafferty rearrangement are:

Mass spectroscopy figure
Mass spectroscopy figure

Molecular ion peak:

The electron bombardment with energy 10–15 eV usually removes one electron from the molecule of the organic compound in the vapor phase. It results in the formation of the molecular ion (Table 2). The highest occupied orbital of aromatic system and non-bonding electron orbitals on oxygen and nitrogen atoms readily lose one electron. An electron from a double bond (2-Ï€ electrons) or triple bond (4-Ï€ electrons) is usually lost. In alkanes, the ionization of C—C sigma bonds is easier than that of C—H bonds. Some examples are:

Mass spectroscopy figure
Mass spectroscopy figure

The mass of the parent ion gives the molecular mass of the sample. It is important to locate the molecular ion at the high mass region of the spectrum. The stability of the parent ion decides its relative abundance. In some cases, parent ion peak is not formed, which means that the rate of decomposition of parent ion is too high for its detection. The rate of decomposition of the parent ion increases with the molecular size in the homologous series.

In general, the relative height of the parent peak decreases in the following order:

Aromatics > Conjugated olefins > Alicyclics > Unbranched hydrocarbons > Ketones > Amines > Esters > Ethers > Carboxylic acids > Branched hydrocarbons > Alcohols.

Important Features of the Parent Ion Peak

The molecular ion peak in aromatic compounds is relatively much intense due to the presence of π-electron system.

Unsaturated compounds give more intense peaks as compared to the saturated or the cyclic molecules.

The relative abundance of saturated hydrocarbons is greater than the corresponding branched-chain compounds with the same number of carbon atoms. For example, the molecular ion peak for n-pentane is more intense than that of neopentane.

Absence of the molecular ion peak in the mass spectrum means that the compound is highly branched or a tertiary alcohol.

Primary and secondary alcohols give very small molecular ion peaks.

Conjugated olefins show more intense molecular ion peaks as compared to the corresponding non-conjugated olefins. Conjugated olefins are more stable than the corresponding non-conjugated olefins.

Table 1: Some common losses from molecular ions

Mass spectroscopy figure
Mass spectroscopy figure

Substituent groups like –NH₂, –OH, –OR, etc., which lower the ionization potential, increase the relative abundance in aromatic compounds, whereas groups such as –NO₂ and –CN, which increase the ionization potential, decrease the relative abundance of aromatics.

In the case of chloro- or bromo-compounds, isotope peaks are also formed along with the molecular ion peak. For chlorine and bromine compounds, M⁺ and (M⁺ + 2) peaks are formed in the intensity ratio of 3 : 1 and 1 : 1, respectively.

A peak at m/z 19 always indicates fluorine, while m/z 30 is characteristic of primary amines. Peaks at m/z 31, 45, 59 indicate the presence of oxygen as an alcohol or ether; m/z 33 indicates a thiol; m/z 77 corresponds to the benzene ring; and m/z 91 indicates a monosubstituted carboxylic acid or the presence of a tolyl group.

The peak at m/z 29 may be due to C₂H₅⁺ or C₄H₁₀²⁺. Mass spectrometers cannot distinguish between singly charged ions of a given mass and doubly charged ions of twice the mass.

Peaks at m/z 59, 44, and 30 indicate the fragments C₃H₇O⁺, C₃H₇⁺, and C₂H₅⁺, respectively, in which either one hydrogen is replaced by the heavier isotope deuterium or ¹³C.

Nitrogen-containing compounds with an odd number of nitrogen atoms in the molecule must have an odd molecular mass. Molecules with an even number of nitrogen atoms (or no nitrogen atoms) have an even molecular mass.

General Rules for Predicting Prominent Peaks in a Spectrum

The relative height of the parent ion peak is usually greatest for straight-chain compounds and decreases as the degree of branching increases.

The relative height of the parent peak decreases with increasing molecular weight in a homologous series. Fatty esters appear to be an exception.

Cleavage is favoured at branched carbon atoms; the more branched the carbon atom, the more likely cleavage is. This results from the increased stability of a tertiary carbonium ion over a secondary carbonium ion, which is, in turn, more stable than a primary carbonium ion.

The largest substituent at a branch is eliminated most readily as a radical because a long-chain radical can acquire some stability by delocalisation of the lone electron.

Double bonds, cyclic structures, aromatic rings, and heteroaromatic rings stabilize the parent ion and thus increase the probability of its appearance.

Double bonds favor allylic cleavage and produce the resonance-stabilised allylic carbonium ion.

Mass spectroscopy figure
Mass spectroscopy figure

Saturated rings tend to lose side chains at the α-bond. The positive charge tends to remain with the ring fragment. Saturated rings also prefer to lose two ring atoms rather than one ring atom.

Mass spectroscopy figure
Mass spectroscopy figure

In alkyl-substituted aromatic compounds, cleavage is very probable at the β-bond to the ring, giving the resonance-stabilised benzyl ion or the tropylium ion directly.

Mass spectroscopy figure
Mass spectroscopy figure

9. Stronger the ring, more intense is the parent peak.

10. Compounds containing rings give peaks at mass numbers characteristic of the ring. Thus, in the case of benzene and naphthalene, the parent peaks at m/z 78 and m/z 128, respectively, are also the base peaks.

11. Carbonyl compounds undergo α-cleavage at the carbonyl group, with the positive charge remaining on the acyl fragment.

Mass spectroscopy figure
Mass spectroscopy figure

12. Cleavage is often associated with the elimination of small, stable neutral molecules such as H₂O, CO, NH₃, H₂S, HCN, olefins, ketones, alcohols, or mercaptans. These cleavages often occur with rearrangements.

13. An even-numbered peak derived from an even-numbered molecular ion results from two cleavages, which may involve a rearrangement.

Base peak:

The peak that has 100% intensity in the mass spectrum is called the base peak. All the other peaks are recorded relative to this peak. The ion that contributes to this base peak is the most stable fragment of the molecule.

Case 1-Base peak and molecular ion peak same:

In the mass spectrum of benzene which is given below, the molecular ion [M+ ion ] i.e., [C6H6]+ is the most stable fragment of benzene molecule and so is the base peak too. Therefore, the molecular ion peak (m/z = 78) has 100% relative abundance.

Mass spectroscopy figure
Mass spectroscopy figure

Figure1: Mass spectrum of benzene

Case 2 – Base peak larger than molecular ion peak:

Consider the mass spectrum of methylcyclohexane. Methylcyclohexane has a molecular weight of 98; therefore, the peak occurring at m/z = 98 represents the unfragmented, but positively charged molecule. The molecular ion peak at m/z = 98 is not the base peak unlike benzene molecule discussed above. The base peak at m/z = 83 is due to the stable fragment of the molecule which is due to the formation of cyclohexyl ion.

Mass spectroscopy figure
Mass spectroscopy figure

Figure2: Mass spectrum of methylcyclohexane

Mass spectroscopy figure
Mass spectroscopy figure

Fragmentation paths of methylcyclohexane

Case 3 - Base peak is present, molecular ion peak is absent:

In the mass spectrum of 2,2,4-trimethylpentane (isooctane) which is given below, the base peak is at m/z = 57 (100%) is while the M+ (molecular ion) peak m/z = 114 is absent in the spectrum.

Mass spectroscopy figure
Mass spectroscopy figure

Figure3: Mass spectrum of 2,2,4-trimethylpentane (isooctane)

Therefore, it can be understood that since isooctane is a highly branched alkane, the ionization leads to cleaving of the various branch points in the molecule. Thus, the molecular ion immediately fragments to a stable peak at m/z = 99 with a loss of CH3 group. Further, another cleavage at the C-C bond near the tertiary carbon results in tertiary butyl ion [(CH3)3C]+ which has a m/z of 57. Since this is the most stable fragment when compared to other cleavage points, the peak due to this [(CH3)3C]+ ion is the base peak for the molecule at m/z = 57.

Mass spectroscopy figure
Mass spectroscopy figure

Fragmentation pattern of 2,2,4-trimethylpentane

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