This document outlines a graduate program on mass spectral analysis of alcohols, phenols, and ethers. It discusses the objectives to introduce mass spectroscopy, principles, functions, ionization techniques, and fragmentation patterns of various compounds. Specifically, it describes how primary, secondary, tertiary, and cyclic alcohols can be differentiated by their mass spectrometry peaks. It also examines the fragmentation of aromatic alcohols, phenols, and various types of ethers including aliphatic and aromatic ethers. The summary provides key differences in molecular ion peaks and fragmentation patterns between these compound classes.

1. University of Medical Science
and Technology
Faculty of Pharmacy
Graduate college
M.Sc. of Pharmaceutical Analysis And
Quality Control
Batch (9)
Program: Mass spectral analysis of Alcohols,
Phenols and Ethers
Prepared by:
Mohamed Hersi Farah
Under the supervision of:
Prof. Younis M.H. Younis

2. To obtain:
1. Alcohols:
1.1 Introduction of mass spectroscopy
1.2 Principle of mass spectroscopy
1.3 Essential functions of mass spectroscopy
1.4 Ionization
1.5 Fragmentation
1.6 Alcohols (Primary, Secondary, Tertiary and Cyclic)
1.7 Aromatic Alcohols
1.8 Phenols
2. Ethers:
2.1 Introduction
2.2 fragment ions
2.3 fragmentation of ethers
2.4 Aromatic Ethers
2.5 Summary
3. Reference

3. Objective:
1.1 Introduction of mass spectroscopy
1.2 Principle of mass spectroscopy
1.3 Essential functions of mass spectroscopy
1.4 Ionization
1.5 Fragmentation
1.6 Alcohols (Primary, Secondary, Tertiary and Cyclic)
1.7 Aromatic Alcohols
1.8 Phenols

5. 
 A beam of electrons will be bombarded in the analyte
compound and it will lead to removal of 1e from analyte.
 Due to removal of 1e, molecule will be positively charged
and know as molecular ion.
 Molecular ion will be fragmented
 Then fragment will accelerated
 And then goes mass analyzer
1.2 Principle:

6. 1.3 The mass spectrometer performs three essential
functions:
 It subjects molecules to bombardment by a stream of
high energy electrons, converting some of molecules
to ions, which are accelerated in an electric field .
 The accelerated ions are separated according to their
mass to- charge ratio in a magnetic or electric field.
 The ions that have a particular mass-to- charge Ratio
are accelerated by a device which can count the
number of ions striking it.

7. 1.4 IONIZATION
Ionization technique can be categorized into two:
1) Hard ionization technique (high energy, high
fragmentation.)
2) Soft ionization technique (low energy, low fragmentation.)
Ionization methods
Gas Phase ionization Desorption ionization Evaporation ionization
Electron Ionization(ei) Field Desorption Thermospary
Chemical
Ionization(CI)
Fast Atom
Bombardment (FAB)
Electrospray Ionization
Matrix Assisted Laser
Desorption Ionization
(MALDI)
Atmospheric Pressure
Chemical Ionization(apci)
Atmospheric Pressure Photo
Ionization(APPI)

8. In general, involves the loss of an
alkyl group ( alpha cleave) or a loss
of molecule of water (dehydration).
Most important fragmentation is the
loss of an alkyl group.
During the fragmentation process
the largest (or bulky) alkyl group is
the most readily lost.

9. FRAGMENTATION cont..
The largest alkyl group is usually lost; the mode of
cleavage typically is similar for all alcohols:
Primary
Secondary
Tertiary
For longer chain alcohols, a McLafferty type
rearrangement can produce water and
ethylene (M – 18 and M - 28)
OH
H2C
O H+
O H
+
OH O H+
OH
m/z
31
59
45
O
HR H O
H
R
H
+

10. 1) Molecular ion peak
2) Fragment ions peak
3) Rearrangement ions peak
4) Metastable ion peak
5) Multi-charged ions peak
6) Base peak
1.5.1Types of Peaks in Mass Spectroscopy

11.  Molecular ion peak: when a sample is
bombarded with electrons of 9 to 15ev energy, the
molecular ion is produced, by loss of single
electron.
 Fragment ion peak: when a energy is given
further more upto 70ev, fragment ion produced,
is have lower mass number.
 Rearrangement ion peak: recombination of
fragment ion is know as rearrangement peaks.
 Metastable ion peak: the ion resulting from the
decomposition between the source region and
magnetic analyzer are called metastable ions.
These appear as broad peaks called metastable
ion peaks.
 Multi-charged ions: ions may exist with 2 or 3
charges instead of usual single charge. The peaks
due to these charged ions are knows as multi-
charged ions peaks.

12.  Base peak: the longest peak in the mass
spectrum corresponding to the most abundant ion
or most intense peak in spectrum is called base
peak.

13. 1.6 Alcohols
General properties of alcohols in mass spectroscopy:
 The molecular ion is usually small and sometimes
undetectable especially in tertiary alcohols.
 In primary and secondary alcohols, the identification
of molecular ion is complicated by the prevalence of
a [M-1] peak caused by the loss of single hydrogen
from the alpha carbon.
 The compound can identified as an alcohol by the
presence of the [M-H], [M-OH] and m/z 31 that are
all characteristic of alcohol.

14. 1.6.1 Primary Alcohols
Can be identified as an alcohol because of the
characteristic at [M-H2O], M-18] and M/z 31.
The peak at m/z 31 can attributed to primary
alcohol because it is one of the larger peak in
the spectrum.
Primary alcohol show a peak resulting from
m/z 31.

15.  The largest alkyl group is most readily lost and form an
H2C=OH+ at peak 31m/e
 Loses an ethyl group to for the CH3CH=OH+ at peak 45m/e
 Loses a methyl group to form the (CH3)2C=OH+ at peak 59
m/e
Example: MS of primary alcohol: Butanol

16. 1.6.2 Secondary Alcohol
the small peak at m/z 31 indicate that this
alcohol is not a primary alcohol.
The presence of a [M-et] and [M-CH3] peak
indicates that is the secondary alcohol.
Secondary alcohol show a peak resulting from
{m/s 45,59,73 and etc}.

17. Example: MS of Secondary alcohol:
This figure below must contain an even
molecular ion since the major peaks (m/z 59 and
45 are both odd).The compound can be identified
as an alcohol by the presence of the [M – H], [M
– OH], and m/z 31 peaks that are all
characteristic of alcohols. The small peak at m/z
31 indicates that this alcohol is not a primary
alcohol. The presence of a [M – Et] and [M –
CH3] peak indicates that this four carbon alcohol
(determined from its molecular mass) is the
secondary alcohol 2-butanol.

18. 2-butanol

19. 1.6.3Tertiary Alcohols
Lacks of a molecular ion since there are
illogical fragments from either the m/z 59 or
60 peak.
Tertiary alcohols show a peak resulting from
{m/z 59,73,87 etc}.
Tertiary alcohols often do not show M+
(molecular ion) at all.

20. Example: MS of Tertiary alcohol:
2-methyl-2-pentanol
M+ 102
87
OH
OH
59

21. 1.6.4 Cyclic Alcohols
o Cyclic alcohols fragment similar to striaght
chain alcohols in that they give a [M-1] peak
from the loss of hydrogen and [M-18] peak
from the loss of water.
o They also create a peak at m/z 57 via a
complex ring cleavage.

22. Example: MS of Cyclic Alcohols
cyclopentanol
M+ 86
OHH OHH
+
57

23. 
Three types of alcohols in MS can be differentiated
by intensity of molecular ion.
M+
.
(molecular ion) of primary alcohols is very
weak.
M+
.
(molecular ion) of secondary alcohols is too
weak but detectable.
M+
.
(molecular ion) of tertiary alcohols is absent.
Summary of Alcohols

24. 
The other fragment ion peak appear in the
process dehydration which appear at m/e 56
but there intensity are different:-
In primary alcohols very strong (base peak)
In secondary alcohols very weak intensity.
In tertiary alcohols too weak intensity.
Cyclic alcohols fragment similar to straight
alcohols.
Secondary alcohols create a peak at m/e 57 via
a complex ring cleavage.
Summary of alcohols conti..

25. Differentiation of Alcohols
Primary Alcohols Secondary Alcohol
Tertiary Alcohols Cyclic Alcohols
OH
59
OHH OHH
+

26. 1.7 MASS SPECTRAL ANALYSIS OF
AROMATIC ALCOHOLS
Aromatic alcohols, unlike other alcohols, have a
prominent molecular ion peak due to the stability of
aromatic group.
Example benzyl alcohol:
 The molecular ion at M/z 108
 Loss of 17 (OH) gives peak at m/z 91
 Loss of 31 (-CH2OH) from the molecular ion gives m/z
77 corresponding to the phenyl cation.

28. 1.8 Mass spectral analysis of Phenols
Phenols usually give a weak peak at m/z 77 attributed to a
rearrangement and can be identified by to peaks at [M-CO] and [M-
COH]. Example MS: Phenols
Phenol
-CO 66
-HCO 65 M+ 94

29.  Aromatic alcohols gives a peak (M+1 or M+2), example the
small peaks at 109 and 110 in benzyl alcohol. Which
correspond to the presence of small amount of 13C in the
sample.
 Benzyl alcohol form a prominent parent peak. Following a cycle
cleavage at , an average abundance peak M-OH (M-17).
 Phenols: Phenols usually give a weak peak at m/z 77 attributed
to a rearrangement.
 Phenols are characterized by abundant molecular peak as ell as by the
M-CO (M-28) fragment.

30. Obective:
2.1 Introduction
2.2 fragment ions
2.3 fragmentation of ethers
2.4 Aromatic Ethers
2.5 Summary
3. Reference

31. 2.1 Introduction of ethers
Ethers are a class of organic compounds that contain an
ether group, an oxygen atom connected to two alkyl or aryl
groups.
They have the general formula R-O-R’, where R and R’
represent the alkyl or aryl groups.
Ethers also can be classified into two varieties: if the
alkyl groups are the same on both sides the oxygen atom,
then it is a simple or symmetrical ether (diethyl ether
CH3CH2-O-CH2CH3), whereas if they are different, the
ethers are called mixed or unsymmetrical ethers (2-
ethoxyethanol HO-CH2CH2-O-CH2CH3).

32. 2.1 Introduction of ethers cont…
The molecular ion is usually of low abundance, but of
higher abundance than the molecular ions of alcohols.
Important fragments arise from cleavage of the carbon-
oxygen bond (ipso- cleavage), cleavage of the carbon-
carbon bond adjacent to the oxygen (α-cleavage), and
transfer of hydride from the β-carbon to the ether
oxygen (a rearrangement of the ion produced from
initial a-cleavage).

33. 2.2 Ethers– Fragment Ions
Slightly more intense M+ than for the corresponding
alcohols or alkanes.
The largest alkyl group is usually lost to a-cleavage; the
mode of cleavage typically is similar to alcohols:
Cleavage of the C-O bond to give carbocations is observed
where favorable
R
H2
C O R R H2C O R+
R
H
C O R R CH O R
RR
+

34. Rearrangement can occur of the following type, if a-carbon is branched:
Aromatic ethers, similar to phenols can generate the C6H5O+ ion by loss of the
alkyl group rather than H; this can expel CO as in the phenolic degradation
R C O C R C
HH
R
CH2
H
H
O
H
R
+
O
R
O
R + C O + C5H5
+
2.2 Ethers– Fragment Ions cont…

35. 
 Aliphatic ethers tend to exehibt molecular ion peaks
that are stronger than those of alcohols with same
molecular weight
 Principle modes of fragmentation include
 1-α-cleavage.
 2-formation of carbocation .
 3-loss of an alkoxy group.
2.3 Fragmentation of Ethers

36. Cleavage happens in two main ways:
1. Breakage of the C-C bond next to O (like
alcohols).The carbon –carbon bond to the α carbon may
be broken to yeild afragment ion that bears apositive
charge on the oxygen
2. C-O bond cleavage with the charge on the C fragment.
In this mode of fragmentation clavege of carbon-
oxygenbond of an ether yeild carbocation.

38. 2.3.1 Mechanism of fragmentation
dibutyl ether for example

39. MS of dibutyl ether

40. Example MS: ethers
butyl methyl ether
M+ 88
O
45

41. 
 Aromatic ethers have a slightly different of
fragmentation. They produce prominent molecular ion
due to the stability of benzene ring. The major
fragmentation occur at the  bond to the aromatic ring.
 Molecular ion is usually strong . MS is similar to phenols
–both form phenoxy cation and associated daughter.
 Primary cleavage occurs at the bond β to the ring. And the
first formed ion can decompose further
Ex.anesole
2.4 Aromatic Ethers

42. Example MS: ethers
Anisole
M+ 108
O
93
M-28 (-CH3, -CO)
65
O
77

43. Summary of ethers
The molecular peak is weak in aliphatic ethers.
Di-isopropyl ether

44. Summary of ethers cont..
Compared to alcohols, ethers do not support fragmentation
with water elimination.
Ether are characterized by fragmentation of the C-C bond
at  to oxygen.
The molecular peak is predominant in alkyl aryl ethers.
The bond at β to the cycle is the first to
break, followed by further breakdown of the resulting
fragment. Anisole with M+ by m/z 108
converts to m/z 93, m/z 65 and m/z 39 ions

45. Summary of ethers cont..
 Ethers are characterized by fragmentation of the C–C bond
at β to oxygen:
 For a possible H at β to O+, secondary fragmentation then
follows:
 Cleavage of the simple C–O bond, sometimes observed in
simple ethers, gives rise to branched ions:

46. 3. References
1. http://chemistrynotmystery.blogspot.com/2013/12/fra
gmentation-pattern-and-mass-spectra.html
2. http://people.whitman.edu/~dunnivfm/C_MS_Ebook/
CH6/6_10.html
3. Journal of American Chemical Society
4. SDBSWeb : http://riodb01.ibase.aist.go.jp/sdbs/
(National Institute of Advanced Industrial Science
and Technology, 11/28/09)
5. Pavia –lampman-kriz Introduction to spectroscopy
third addition

47. End