Fragmentation in mass spectrometry involves the breakdown of molecular ions into smaller daughter ions. There are several types of fragmentation including homolytic cleavage, heterolytic cleavage, and rearrangement reactions. Homolytic cleavage involves equal transfer of electrons to both atoms, forming a radical and cation. Heterolytic cleavage involves both electrons being taken by one atom, forming an even electron cation and radical. Rearrangement reactions require changes to multiple bonds and can eliminate smaller molecules. Common rearrangements include McLafferty rearrangement and elimination reactions. Fragmentation patterns provide information about functional groups present in molecules.

1. FRAGMENTATION TECHNIQUES IN
MASS SPECTROSCOPY
Prepared by
MAHENDRA.G.S
1 M pharm
Department of Pharmaceutical chemistry
J S S College of Pharmacy
Mysuru

2. Definition:
It is a powerful analytical technique useful for
determination of molecular weight of compound.
Principle:
 Initially in mass spectroscopy the sample must be
converted into vapourised or gaseous form then it
undergo ionization to form a molecular ion with
the liberation of 1e-.
 This molecular ion normally undergoes
fragmentation to form several fragmented ions or
daughter ions.

3.  The process of breaking up of molecular ion into
smaller or daughter ions is known as
“fragmentation”.
 The molecular ion commonly decomposes to a pair
of fragments, which may be either a radical with an
ion or a small molecule & a radical cation.

4.  Bombardment of molecules by a electron beam
with energy between 10-15ev usually results in
the ionization of molecules by removal of one
electron (molecular ion formation).
 When the energy of electron beam is increased
between 50-7ev, these molecular ions acquire a
high excitation resulting in their break down
into various fragments.

5. Fragmentation of the molecular ion takes place in
following mods:
 Simple cleavage
1. Homolytic cleavage
2. Heterolytic cleavage
3. Semi heterolytic cleavage
 Rearrangement reactions
1. Elimination reactions
2. Ortho reaction
3. Mc-lafferty rearrangement

6.  In hemolytic cleavage the electrons are equally
transferred to both atoms & it forms radical and
cation.
R
H2C
CH
CH2
R
H2C
CH
CH2
R
+
CH
HC
CH2
IONISATION
HOMOLYTIC
CLEAVAGE

7.  Fragmentation by movement of two electrons:
 In this type of cleavage both the electrons of the
bond are taken over by one of the atoms; the
fragments are an even electron cation and a radical
with the positive charge residing on the alkyl
group.C4H9I
ionisation
CH3
CH2
+ I
C4H9I
HETEROLYTIC
CLEAVAGE

8.  In this one electron bond cleavage takes place
resulting in formation of radical & cation.
C
H
H H
H
C
H
H H
H
CH3
+
H
IONISATION CLEAVAGE

9.  It involves the cleavage of bonds and formation of
new bonds i.e., it requires changes to at least two
bonds.
 So the produced ions are not structural units of
precursors.
 Generally rearrangement leads to loss of smaller
molecules.

10.  In his fragmentation hydrogen is obstructed by
hydroxyl group or halogen or acetate functional groups
results in the elimination of water or neutral molecule.
R – CH2 – CH2 –CH2 R – CH2 – CH2 – CH2
+
OCOCH3
OCOCH3
CH3COOH + R – CH2 – CH
= CH2

11.  In the case of substituted aromatic compounds the
substitute & carbon come into proximity has help in
elimination of neutral molecule. This effect is called ortho
effect.
O
O
CH3
CH3
O
O
CH3
C
H2
C
O
CH2
+
OCH3
H
C
C
C
O
CH2
+ CH3OH
methyl 2-methylbenzoate
methyl 2-methylbenzoate ion
(6-methylenecyclohexa-2,4-
dienylidene)methanone
H

12.  The loss of an alkene fragment by cyclic
rearrangement of a carbonyl compounds ( like
aldehyde, ketones, acids, esters, amines),
unsaturated compounds with γ-hydrogens
undergo Mc-Lafferty rearrangement.
Or
 It involves the migration of γ-hydrogen atom
followed by cleavage of β-bond then
rearrangement leads to the elimination of neutral
molecule.

13. Fragmentation takes place only at γ-hydrogen
Then this hydrogen is obstructed by oxygen of
carbonyl group or unsaturated compound.
Carbonyl group is converted to hydroxyl group
Bond break down between α & β carbons resulting in
liberation of 2e-’s then rearrangement takes place to
form a simple alkene.

14. H
H2C
C
H2
CH2
C
HO
butyraldehyde
H
H2C
C
H2
CH2
C
HO
H2C
C
H
CH
C
HHO
CH2
CH2
+
OH
C
CH2
H
O
C
CH3
H
H
H2C
C
H2
CH2
C
HO
IONISATION
EXAMPLE: Aldehyde
If m/z value is 44(24+4+16) that indicates aldehyde is present and connected to
C3 chain.

15. H
H2C
C
H2
CH2
C
CH3O
H
H2C
C
H2
CH2
C
CH3O
H2C
C
H
CH2
CH
CH3HO
CH2
CH2
+
CH2
C
CH3HO
CH3
C
CH3O
H
H2C
C
H2
CH2
C
CH3
O
pentan-2-one
ionisation
If m/z value is 58 (36+16+6) that indicates the compound
containing ketone group attached to C3 chain
Ex:- ketone

16. H
H2C
C
H2
CH2
C
NH2O
H
H2C
C
H2
CH2
C
NH2O
H2C
C
H
CH2
CH
NH2HO
CH2
CH2
+
CH2
C
NH2HO
CH3
C
NH2O
butyramide
H
H2C
C
H2
CH2
C
NH2O
ionisation
Ex:-Amides
If m/z value is 59 (24+16+14+5) that indicates the compound
containing amide group attached to C3chain

17. REFERENCES:
 Instrumental methods of chemical analysis- B.K
Sharma,
 Instrumental methods of analysis By Chatwal,
 Principles of Instrumental analysis By Donglas
Skoog