Subject Chemistry

Paper No and Title Paper 12: Organic Spectroscopy

Module No and Title 26: General Fragmentation Rules

Module Tag CHE_P12_M26_etext

CHEMISTRY PAPER No. 12: Organic Spectroscopy

MODULE No. 26: General fragmentation rules
 TABLE OF CONTENTS
1. Learning Outcomes
2. Introduction
3. Types of fragmentation
4. Fragmentation pattern in few compounds
5. Summary

CHEMISTRY PAPER No. 12: Organic Spectroscopy

MODULE No. 26: General fragmentation rules
 1. Learning Outcomes
After studying this module, you shall be able to
 Know what is a molecular ion
 Learn about the fragmentation pattern and the factors affecting it
 Identify how fragments are generated
 Evaluate mass spectra

2. Introduction
The ionization of the sample molecule forms an entity known as a molecular ion that not only
carries a net positive charge but also has an unpaired electron. This molecular ion entity then is
actually a radical-cation and it contains which are odd in number. In a case where a molecular ion
has a lifetime less than a few microseconds, it is not possible to observe it, as the timespan of its
survival is too short. It is difficult to interpret a mass spectrum without a molecular ion peak as a
reference. Although, it is fortunate that most organic compounds generally give a mass spectrum
that includes a molecular ion peak. The organic compounds not giving a molecular ion peak in
their mass spectrum respond successfully to the use of milder ionization conditions. Aromatic
rings, other conjugated pi-electron systems and cycloalkanes are amongst some of the simple
organic compounds which are able to form the most stable molecular ions. Highly branched
alkanes like alcohols, ethers and highly branched alkanes usually tend to show the greatest
tendency toward fragmentation.
The molecular ion undergoes fragmentation in a mass instrument called the mass
spectrophotometer. The fragments obtained from the mass instruments upon fragmentation and
their nature give immense information about the molecular structure of the compound. For most
of the compounds and their classes, the fragmentation is characteristic. Most compounds and their
various classes have a characteristic fragmentation pattern.

Important Factors for Fragmentation:

a) Energy of the molecular ion and the fragments formed from it
b) Stability of the bonds in the ions
c) For rearrangements: steric factors, It is easier to move a H atom than a whole group
d) Stability of the formed ions or neutral particles resonance stabilization such as in an acylium
ion.

Stevenson’s rule
When fragment ions form in the mass spectrometer, they almost always do so by means of
unimolecular processes. These processes that are energetically most favourable give rise to the
most fragment ions. The important postulate of the Stevenson’s rule is that the most probable
fragmentation is the one that leaves positive charge on the fragment with the lowest ionization
energy. In other words, fragmentation processes that lead to the formation of more stable ions are
favoured over processes that lead to less stable ions.

CHEMISTRY PAPER No. 12: Organic Spectroscopy

MODULE No. 26: General fragmentation rules
 3. Types of Fragmentation
The extra energy during the collision with incident electrons places the molecular ion in a highly
excited vibrational state. The vibrationally excited molecular ion maybe unstable, and it may lose
some of its extra energy by breaking apart into fragments. If the lifetime of the molecular ion is
greater than 10-5 seconds, a peak corresponding to the molecular ion will appear in the mass
spectrum. However, molecular ions with lifetimes less than 10-5 seconds break apart into
fragments before they are accelerated within the ionization chamber and enter the mass analyser.
In such cases, peaks corresponding to the m/z ratio for these fragments appear in the mass
spectrum.
For a given compound, not all of the molecular ions formed by ionization have precisely the same
lifetime; some also have relatively shorter lifetimes than the others. As a result, in a typical EI
mass spectrum one observes peaks corresponding to both the fragments as well the molecular
ions.
Often fragmentation processes involve the loss of a fragment which is electrically neutral. The
fragment is absent in the mass spectrum but its presence can be easily deduced by the difference
in the masses of the obtained fragment ion and the original molecular ion. An OE+. can fragment
in two ways: cleavage of a bond to create an EE+ and a radical (R.) or cleavage of bonds to create
another OE+. and a closed-shell neutral molecule (N). An EE+, on the other hand, can only
fragment in one way-cleavage of bonds to create another EE+ and a closed shell neutral molecule
(N). This is the so called even electron rule. The most common mode of fragmentation involves
the cleavage of one bond. In the process, the OE+. yields a radical (R.) and an EE+ fragment ion.
Cleavage that lead to the formation of more stable carbocations are more favored. When the loss
of more than one possible radical is possible, a corollary to Stevenson’s rule is that largest alkyl
radical is lost preferentially.

Different types of fragmentation are:

1. Sigma electron ionisation
2. Radical site initiation
3. Charge site initiation
4. Rearrangement

1. Sigma electron ionisation

The fragmentation in molecular ion of alkane takes place as follows:

Exampe is homolytic dissociation in 2-butanone. The acylium ion formed by loss of the largest
alkyl radical is preferred.

CHEMISTRY PAPER No. 12: Organic Spectroscopy

MODULE No. 26: General fragmentation rules
 Figure 1: Fragmentation pattern in 2-butanone

2. Radical site initiation

In some molecular ions, fragmentation occur by donation of an electron to form new bond to an
adjacent atom concomitant with cleavage of other bond to that atom takes place in some
molecular ions. Radical-site-initiated fragmentation is one of the most common one-bond
cleavages and is more commonly called an α-cleavage. α-cleavages may occur at saturated or
unsaturated sites that may or may not involve a heteroatom.

Example is the formation of stable allylic carbocation in case of 4-methyl-1-hexene.

Figure 2: Formation of allylic carbocation in 4-methyl-1-hexene

CHEMISTRY PAPER No. 12: Organic Spectroscopy

MODULE No. 26: General fragmentation rules
 3. Charge site initiation
This charge-site initiated or inductive cleavage is often indicated in a fragmentation mechanism
by the symbol i. This involves the attraction of an electron pair by an electronegative heteroatom
that ends up as a radical or as a closed-shell neutral molecule. When α-cleavage is a
fragmentation of OE+ only, inductive cleavage can operate on either an OE+ or an EE+.

4. McLafferty Rearangements
This was first described by Fred Mc Lafferty in 1956 and is one of the most predictable
fragmentations, next to the simple α-cleavage. In this process, a hydrogen atom on a carbon 3
away from the radical cation of an alkene, arene, carbonyl, or imine (a so called γ-hydrogen) is
transferred to the charge site via a six membered transition state, with concurrent cleavage of a
sigma bond between what were the original β and γ carbons. For simplicity, the mechanism of the
McLafferty rearrangement is usually drawn as a concerted process.

Cleavages which forms the carbocation which is more stable are favored. Thus ease of
fragmentation to form ions increases in the order.

In branched radical cations, the largest group is preferentially lost.

One bond or two bond cleavages

Fragmentation may involve one bond or two bond cleavage. One of the most well-known modes
of fragmentation involves the cleavage of one bond. This process yields an odd electron neutral

CHEMISTRY PAPER No. 12: Organic Spectroscopy

MODULE No. 26: General fragmentation rules
 fragment and an even-electron fragment ion generated from odd electron molecular ion. The
neutral fragment that is lost is radical and the ionic fragment is the carbocation type.

Example of fragmentation via the cleavage of one of the bonds are:

The next most important type of fragmentation is the cleavage of two bonds. In this the odd-
electron molecular ion yields an odd-electron fragment ion and an even-electron neutral fragment,
usually a small molecule of some type. Example:

Apart from these processes, fragmentation processes involve rearrangements, migration of

groups and secondary fragmentation of fragments are also possible.

4. Fragmentation Pattern in Few Compounds

Section of the module discusses briefly the fragmentation pattern in some of the most commonly
occurring classes of organic compounds.

 Alkanes are characterized by strong molecular ion peaks. The fragmentation pattern
contains clusters of peaks 14 mass units apart (which represent loss of (CH2)nCH3). As
the carbon skeleton becomes more highly branched, the intensity of the molecular ion
peak decreases. Straight chain alkanes have fragments that are always primary
carbocations. Since these are unstable, thus fragmentation is not favoured. As seen in the
mass spectra of hexane (C6H14) with MW = 86.18 (figure 3).

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MODULE No. 26: General fragmentation rules
 Figure 3: Fragmentation in hexane

 A functional group having a heteroatom Y containing non-bonding valence electrons

(Y=N, O, S, X etc.) drastically affects the pattern of fragmentation of a compound.

 The intensity of the molecular ion peak in the mass spectrum of a primary or a secondary
alcohol is usually rather low, and the molecular ion peak is often entirely absent in the
mass spectrum of a tertiary alcohol. Cleavage of the C-C bond adjacent to the oxygen
usually occurs. A loss of H2O may occur as seen in the spectra of 3-pentanol (C5H12O)
with MW = 88.15 (figure 4).

Figure 4: Fragmentation in 3-pentanol

 The molecular ion peak of an aliphatic aldehyde is usually observable, but generally it is
weak. Principal modes of fragmentation include α-cleavage and β-cleavage. If the carbon
chain attached to the carbonyl group contains at least three carbons, McLafferty
rearrangement is also commonly observed. Aromatic aldehydes also exhibit intense
molecular ion peaks, and the loss of one hydrogen atom via α-cleavage is a favorable
process.

CHEMISTRY PAPER No. 12: Organic Spectroscopy

MODULE No. 26: General fragmentation rules
 In aldehydes cleavage of bonds next to the carbonyl group results in the loss of hydrogen
(molecular ion less 1) or the loss of CHO (molecular ion less 29). The mass spectra of 3-
Phenyl-2-propenal or cinnamaldehyde (C9H8O) with MW = 132.16 is shown (figure 5).

Figure 5: Fragmentation in cinnamaldehyde

 In case of aliphatic amines molecular ion peak maybe very weak or maybe totally absent.
α-cleavage dominates aliphatic amines. Fragmentaion pattern of n-Butylamine (C4H11N)
with MW = 73.13 is shown in figure 6.

Figure 6: Fragmentation in n-butylamine

 Aliphatic carboxylic acids generally show weak but observable, molecular peaks.
Aromatic carboxylic acids on the other hand show strong molecular ion peaks. In short
chain acids, peaks due to the loss of OH (molecular ion less 17) and COOH (molecular
ion less 45) are prominent due to cleavage of bonds next to C=O. The mass spectra of 2-
butenoic acid (C4H6O2) with MW = 86.09 is shown in figure 7.

Figure 7: Fragmentation in 2-butenoic acid

 Fragmentation is esters is especially facile, but it is usually possible to observe weak

molecular ion peaks in the mass spectra of methyl esters. The esters of higher alcohols
form much weaker molecular ion peaks, and esters of alcohols larger than four carbon

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MODULE No. 26: General fragmentation rules
 atoms may form molecular ion peaks that fragment too quickly to be observed. In esters
fragments appear due to bond cleavage next to C=O (alkoxy group loss, -OR) and
hydrogen rearrangements as can be seen in the mass spectra of ethyl acetate (C4H8O2)
with MW = 88.11 (figure 8).

Figure 8: Fragmentation in ethyl acetate

 The mass spectra of ketones show an intense molecular ion peak. In case of ketones
major fragmentation peaks result from cleavage of the C-C bonds adjacent to the
carbonyl. The pattern of fragmentation is similar to that of aldehydes as briefly described
above. Stevenson’s rule is to be kept in mid while considering the cleavage of alkyl
groups. Generally acylium ion is formed by α-cleavage in ketones and in aldehydes. In
case of 4-Heptanone (C7H14O) with MW = 114.19 fragments appear at m/z 71 and 43
(figure 9).

Figure 9: Fragmentation in 4-heptanone

McLafferty rearrangement is also possible when carbonyl group of ketones is attached to at least
one alkyl group that is three or more carbon atoms in length.
 These examples shall help in the better understanding of detailed Mass spectral studies of
various other functional groups discussed in further modules.

CHEMISTRY PAPER No. 12: Organic Spectroscopy

MODULE No. 26: General fragmentation rules
 5. Summary
 The ionization of the sample molecule forms a molecular ion that not only carries a
positive charge but also has an unpaired electron. The molecular ion then is actually a
radical-cation and it contains odd number of electrons.
 The molecular ion of a compound undergoes fragmentation in a mass spectrophotometer.
The nature of the fragments gives information about the structure of the molecule.
 The various types of fragmentation are Sigma electron ionisation, Radical site initiation,
Charge site initiation and Rearrangement
 Cleavages which lead to the formation of more stable carbocation are favoured.
 In branched radical cations, the largest group is preferentially lost.
 The molecular ion peaks present in alkanes are of low intensity. The pattern of
fragmentation shows a cluster of peaks 14 mass unita apart representing a loss of
[(CH2)nCH3].
 A functional group having a heteroatom Y containing non-bonding valence electrons
(Y=N, O, S, X etc.) drastically affects the pattern of fragmentation of a compound.

CHEMISTRY PAPER No. 12: Organic Spectroscopy

MODULE No. 26: General fragmentation rules