Problem

The exact mass of a compound determined by

HRMS is 212.0833. What is the molecular
formula of the compound?
H 1 00783 C 12 0 O 15 9949 N 14 0031 H 1.00783, C 12.0, O 15.9949, N 14.0031
Nitrogen rule? N yes or No?
Rule of 13 ? Subtract heteroatom equivalents
C
16
H
20
?
C
15
H
16
O ?
C
14
H
12
O
2
?
Index of H deficiency? = 14 12/2 + 1 = 9
212 (12%), 167 (4%), 105 (100%), 91 (45%), 77
(30%), 63 (10%), 51 (12%). Structure?
PhCOOCH2Ph
Fragmentation
Molecular ion = a radical cation
Homolytic cleavage or heterolytic cleavage
The probability of cleavage of a particular bond depends on The probability of cleavage of a particular bond depends on
1. Bond strength
2. Possibility of low energy transition y f gy
3. Stability of the fragments
Our knowledge of pyrolysis can be used
These are mostly unimolecular decompositions
Organic reactions are initiated by reagents, heat or light
Mass spectrometry is concerned with consequences Mass spectrometry is concerned with consequences
suffered by an organic molecule at a vapor pressure of
10
-6
mm Hg struck by an ionizing beam of electrons y
There are a number of rules to predict fragmentation
Fragmentation Rules (for EI only)
Remember, the rules are applicable to EI mass spectrometry only.
McLafferty Rearrangement
Rearrangement involving migration of a - hydrogen
atom to the heteroatom leading to elimination of alkene
low energy transitions and increased product stability
A molecule must possess a heteroatom, a double bond,
and an abstractable H atom to the C=O system and an abstractable H atom to the C=O system.
Prominent
characteristic characteristic
Peaks in MS
Simple Cleavage Rearrangement
Even numbered
molecular ion gives
Even numbered
molecular ion gives
odd numbered
fragment and
even numbered
fragment
vice a versa
Cleavage of a single Two cleavages at a g g
bond Nitrogen rule
g
time
The rearrangement of neo pentyl cation to ethyl cation The rearrangement of neo pentyl cation to ethyl cation
Involves much
complex mechanism p
Mass Spectra Mass Spectra
of
Some Chemical Classes
Hydrocarbons
Linear hydrocarbons always show M
+
peak
M
+
is of low intensity for long chain compounds
The fragmentation pattern is characterized by The fragmentation pattern is characterized by
clusters of peaks, with peaks of each cluster 14 mass
unit apart (CH
2
)
Largest peak in each cluster represents a C
n
H
2n
+1 Largest peak in each cluster represents a C
n
H
2n
1
peak and thus occur at m/z = 14n+1
This is accompanied by C
n
H
2n
and C
n
H
2n
-1 fragments.
The most abundant fragments are at C3 and C4 and The most abundant fragments are at C3 and C4, and
the abundance decrease in a smooth curve to [M-
C
2
H
5
]; [M-CH
3
] peak is almost missing or very weak.
This is typical of compounds with more than 8 C chain This is typical of compounds with more than 8 C chain
Characterization is based on M
+
peak.
For branched ones, the curve is not continuous
C H fragment is prominent C
n
H
2n
fragment is prominent
169
C
n
H
2n
[M15]
LossofH
Fragmentation of the Hexane Radical
C ti Cation
Mass Spectrum of n-Hexane Mass Spectrum of n-Hexane
Groupsofionscorrespondtolossofone,two,
three,andfourcarbonfragments.
Branched & cyclic hydrocarbons
Branched: More or less similar to linear ones but the smooth curve is
broken by preferred fragmentation at each branch.
E.g. in 5-methyl pentadecane, a M+ ion, a C12 fragment, absence of C11 g y p , , g ,
unit, peak at M-15, peaks for fragments on both sides of the branch
confirm the structure.
Cyclic compounds give more intense M+, as frag. need two C-C
Fragmentation of cyclic compound is characterized by loss of two C
atoms as C
2
H
4
and C
2
H5
Also C-C cleavage is accompanied by loss of hydrogen to get C
n
H
2n
-1
Lossof
C
2
H
4
Fragmentation of Branched Alkanes Fragmentation of Branched Alkanes
The most stable carbocation fragments form in greater
amounts.
Mass Spectra of Alkanes Mass Spectra of Alkanes
Alkenes
M+ is usually distinct
Location of double bonds in acyclic olefins is difficult due to its
f il i ti facile migration
In cyclic olefins the double bond wont migrate much and there
is a strong tendency for allylic cleavage. Distinct M+ is seen.
l l Conjugation with carbonyl also fixes the position
Clusters of peaks at intervals of 14 units
C
n
H
2n-1
, C
n
H
2n
are more intense than C
n
H
2n-1 n 2n 1 n 2n n 2n 1
Limonene shows a
distinct mode of
l cleavage. 2 isoprenes.
Can you tell the name
reaction?
Its the Retro Diels-Alder reaction
Allylic cleavages
Double bond isomerization
(increased conjugation)
C H peaks n = 5
Bi-allylic bond
C
n
H
2n-1
peaks
41, 55, 69
n = 4
n = 3
n = 5
Mass Spectra of Alkenes Mass Spectra of Alkenes
Resonance-stabilized cations favored.
Aromatic compounds
Stable M+ so more intense peak
For alkyl substituted benzene rings most For alkyl substituted benzene rings, most
important peak is at m/z = 91 (tropylium ion)
peak at m/z = 92 is for -cleavage
Hydrogen migration-
alkene elimination alkene elimination
Rearrangements are
observed for
alkyl group y g p
larger than C2
-cleavage gives cluster of three characteristic peaks
at 77 (C
6
H
5
+
),78 (C
6
H
6
+
), 79 (C
6
H
7
+
)
Alcohols
Small M+ peak for pri./sec.; very weak for tert.
Alcohols.
Cleavage of C C bond next to oxygen is common Cleavage of C-C bond next to oxygen is common
(rule 8). Thus Pri. Alcohols show a prominent peak at
31 due to
+
CH
2
OH (diagnostic of primary alcohols if
more intense) more intense)
Sec. alcohols at
+
RCH-OH (45, 59, 73 etc.).
Tert. alcohols at
+
RRC-OH (59, 73, 87 etc.)
h l b ll d d l The largest substituent is expelled most readily
Occasionally C-H bond next to Oxygen is cleaved
Least preferred pathway give [M-1] peak Least preferred pathway give [M 1] peak
Occasionally [M-2] and [M-3] peaks are also seen
In addition to this, primary alcohols show pattern
lik lk ith k f h l i d i like alkenes with peaks of homologues in decreasing
intensity resulting from cleavage of C-C bond
Alcohols
Distinct peak at M-18 by loss of H
2
O.
Peak for M-(H
2
O + alkene) by thermal
decomposition at higher temperatures
M-33 for M-(H
2
O+CH
3
) in branched ones
C clic lc h ls sh c mpl x f m nt ti n Cyclic alcohols show complex fragmentation
Mass Spectra of Alcohols Mass Spectra of Alcohols
Benzyl Alcohols
Benzyl alcohols are unique in
showing prominent M+,
Moderate M-OH and weak M-2,
M-3 may be seen.
In Benzyl alcohol peaks at In Benzyl alcohol peaks at
107 (M-1), 79 (-CO), 77 (-H
2
)
Loss of H
2
O is common in ortho
substituted benzyl alcohols and substituted benzyl alcohols and
in phenols
Phen-ols
Distinct molecular ion peak
In phenol M+ is base peak (94). 77 (M-17, loss of OH), p p
M-18 (-H
2
O), M-28 (-CO) and M-29 (-CHO) are common.
In cresols M-1 (loss of benzylic H) > M+
I h l h l M CH i i M In o-ethylphenol M-CH
3
is intense > M+.
Ethers
Small M
+
peak larger ethers show M+1
Acetals show
Small M peak, larger ethers show M+1
Strong peaks at 31, 45, 59, 73
for RO
+
& ROCH
2
+
fragments 2 ways
Cl f C C b d O
c ta s show
weak M
+
,
Prominent M-R &/or M-OR
& weak M-H
Cleavage of C-C bond next to O
Cleavage of C-O bond; charge remaining on Carbon
All facile, mediated by O
Aromatic Ethers
Prominent M
+
peak Prominent M peak
Primary cleavage at bond to ring
For larger alkyl groups the C-C cleavage
d b H is accompanied by H migration
Diphenyl ether shows M-H, M-CO, M-CHO
by complex Rearrangements y p g
Ketones
Distinct M+
Cleavage of one of the R group (, C-C bond)
For Alkyl chain longer than C
3
, hydrogen migration
McLafferty Rearrangement is seen McLafferty Rearrangement is seen
Cyclic ketones
Prominent M+, cleavage of a C-C followed by H
migration to form resonance stabilized fragment 55
Aromatic ketones
Prominent M+,
In Aryl alkyl ketones ArCOR cleavage of a C-C bond
to ring to form stabilized -to ring to form stabilized
then loss of CO to Ar+
If R is longer than C3, the McLafferty R
n
is seen f s ong r than , th McLaff rty s s n
Diaryl ketone Diaryl ketone
P-chlorobenzophenone
M+2 is isotopic
(34% = Cl) (34% = Cl)
Aldehydes
ll bl Usually visible M+
Cleavage of C-H and C-C bond next to Oxygen results
in M-H and M-R (m/z 29, CHO
+
or C
2
H
5
+
), M-18 (H
2
O) (m 9,
2 5
), (
2
)
For Alkyl chain longer than C
3
, hydrogen migration
McLafferty Rearrangement is seen stabilized ion
Aromatic aldehydes show characteristic large M+ ion Aromatic aldehydes show characteristic large M+ ion
and M-1 peak which could be even larger.
further fragments to give Ar+ (77 for phenyl) which
eliminates acetylene to give C H
+
ion eliminates acetylene to give C
4
H
3
+
ion
Acids
Usually visible M+
Major (base) peak at m/z 60 comes
from McLafferty Rearrangement from McLafferty Rearrangement
Apart from this, a series of cluster
at the interval of 14 is seen
h d b I h l t hydrocarbon. In each cluster a
major peak is of C
n
H
2n-1
O
2
.
Aromatic acids Aromatic acids
Loss of OH (-17), COOH (-45) Loss of OH ( 17), COOH ( 45)
H
2
O (-18) is major if ortho gr. Contg. H
Ortho Effect six memb. TS, eliminate
neutral molecules H
2
O, ROH, NH
3
neutral molecules H
2
O, ROH, NH
3
Esters
Distinct M+ peak
Major (base) peak at m/z 74
( th l t f C6 t C26) (methyl esters from C6 to C26)
comes from McLafferty
Rearrangement Rearrangement
Apart from this, a series of
cluster at the interval of 14.
Cleavage of on both sides of
CO.
Aromatic esters
Loss of neutral ketene
Lactones Lactones
Distinct M+ but weaker if C4 subst. [M-alkyl] Distinct M but weaker if C4 subst. [M alkyl]
Amines
M+ of aliphatic monoamine is an odd number and gives
a weak peak
Base peak results from , cleavage (rule 8)
m/z = 30 (CH
2
NH
2
) for pri. and sec/tert without -
substituent substituent.
If no -substituent [M-1] is frequent.
Loss of largest alkyl group is preferred Loss of largest alkyl group is preferred
a series of cluster at the interval of 14 (30,44,58,72).
Amines
During fragmentation of long chain amines, cyclic
fragments occur 6 or 5 member rings formed
For amide esters cleavage of [ COOR] is preferred For amide esters, cleavage of [-COOR] is preferred
For cyclic amines M+ peak is strong, y p g
Cleavage next to N leads to loss of -H to give M-1 or
cleavage of ring followed by elimination of ethylene
Aromatic Amines (Anilines)
M+ of aromatic monoamine is an odd number and gives
an intense peak
Loss of one of the amino -H give M-1
Loss of neutral HCN followed by H give strong peaks
at 66 and 65 at 66 and 65
In alkyl aryl amines, the cleavage is controlled by N
Leading to cleavage of alpha C-C bond g g p
Amides
M+ of amide is usually seen
In long chain amines a base peak at 59 for g p
.
CH
2
(=OH)NH
2
results from McLafferty Re
n
Primary amide gives a strong peak at 44 from
cleavage of R CONH bond [O C NH
+
] cleavage of R-CONH
2
bond [O=C-NH
2
+
]
A moderate peak at 86 results from gamma-delta C-C
bond cleavage accompanied by cyclization. g p y y
A i id M d h l f NH2 i Aromatic amides M+ and then loss of NH2 to give
PhCO+ and then loss of C=O to give Ph+.
Example
Nitriles
M+ of aliphatic nitriles is very weak (except
acetonitrile and propionitrile), M-1 is seen p p ),
A Strong peak at 41 (CH
2
=C=N
+
-H) due to McLafferty
but lacks diagnostic value as C
3
H
5
(41) is common in
hydrocarbons hydrocarbons
Intense peak at 97 is characteristic for C8 and more
series of peaks at the interval of 14 due to loss of
CH
2
.
Nitro compounds
M+ of aliphatic nitro compounds (odd
number) is very weak or absent (except number) is very weak or absent (except
lower homologs)
M i k i f k t th Main peaks are a series of peaks at the
interval of 14 upto M-NO
2
.
Presence of NO
2
group is indicated by
appreciable peak at m/z = 30 (NO+) and
a smaller peak at 46 (NO
2
+)
Aromatic Nitro compounds
M+ of aliphatic nitro compounds (odd number)
is intense is intense
Presence of NO
2
group is indicated by
prominent peak at M-46 (NO
2
radical) (base prominent peak at M 46 (NO
2
radical) (base
peak in nitrobenzene) and a peak at M-30 i.e.
loss of neutral NO molecule with
rearrangement to form phenoxy cation
Loss of acetylene from M-46 gives M-72
(strong)
Loss of CO from M-30 gives M-58
Diagnostic peak at m/z 30 for NO+ ion
Nitro-anilinines
O,m,p-nitroanilines strong M+ peak (even
numbered)
Two sequences
one loss of NO
2
(M-46) = m/z 92 which loses HCN
to produce m/z 65 to produce m/z 65
Second, loss of NO (M-30) = m/z 108 which loses
CO to give 80 CO to give 80
M and p comps. give a small peak at 122 by loss of
O whereas ortho compound loses OH to give 121 p g
Mass Spectrum with Sulfur Mass Spectrum with Sulfur
Sulfur has three isotopes:
32
S (95%),
33
S (0.8%),
and
34
S (4 2%) and
34
S (4.2%).
The M
+
peak of ethyl methyl sulfide has an M+2
peak that is larger than usual (about 4% of M
+
). p g ( )
If more than oneThe number of sulfur atoms can
be found from the intensity of M+2.
Sulfur compounds
Thiols show M+ & M+2,
Cleavage of C-C next to Sulfur gives Cleavage of C-C next to Sulfur gives
CH
2
=SH+ (47), cleavage of beta gamma
C-C bond give a peak at 61 which is 50% C-C bond give a peak at 61 which is 50%
in intensity as to 47, cleavege of ,
bond gives even smaller fragment at 75 bond gives even smaller fragment at 75
and cleavage of , bond gives a mpeak
which is more intense than 75 which is more intense than 75
presumably due to cyclization
Sulfides
Cleavage modes resemble ethers. Cleavage of larger
subst. favored
A strong peak at 61 in straight chain sulfides is due to
Cleavage of C-S bonds leaves a
h S lf charge on Sulfur
leading to cyclization
Molecules with Halogens Molecules with Halogens
Isotopes are present in their usual p p
abundance.
Carbon has a
13
C isotope present in 1.1% p p
abundance. The spectrum will show the
normal M
+
and small M+1 peak.
Bromine has two isotopes:
79
Br (50.5%)
and
81
Br (49.5%). Since the abundances
l l h ill b M k are almost equal, there will be an M
+
peak
and and M+2 peak of equal height.
Mass Spectrum with Bromine Mass Spectrum with Bromine
Bromine is a mixture of 50 5%
79
Br and 49 5% Bromine is a mixture of 50.5% Br and 49.5%
81
Br. The molecular ion peak M
+
has
79
Br be as
tall as the M+2 peak that has
81
Br.
Mass Spectrum with Chlorine Mass Spectrum with Chlorine
Chlorine is a mixture of 75 5%
35
Cl and Chlorine is a mixture of 75.5% Cl and
24.5%
37
Cl. The molecular ion peak M
+
is 3
times higher than the M+2 peak.
53
g p
Isotope peaks in polyhalogens Isotope peaks in polyhalogens
Compounds containing two chlorines, or two Compounds containing two chlorines, or two
bromines or a chlorine and a bromine show
distinct M+4 peak in addition to M+2 due
t f t t f h i t to presence of two atoms of heavy isotope.
Thus three atoms give peaks at M+2, M+4
nd M+6 the rel tive bund nce c n be and M+6 the relative abundance can be
predicted
Useful for aromatic than aliphatic halo Useful for aromatic than aliphatic halo
compounds
Neither F nor I has isotopes Neither F nor I has isotopes
Beynon 1968
Isotopic Peak Pattern
Hetetroaromatic compounds Hetetroaromatic compounds
Intense M+
Cleavage of the bond beta to the ring
Localize the charge on the heteroatom

H Migrations H Migrations
Practice Problems Practice Problems
For example
CO N CH N &C H
HRMS
CO, N
2
, CH
2
N &C
2
H
4
M. Wt. = 28
The sum of formula
masses of the most
abundant isotope gives
HRMS
For CO
1 12 000 1 15 9949 1x12.000 + 1x15.9949 =
27.9959
For N
2
14.0031 x 2 = 28.0062
For CH
2
N
1x12.0 + 2x1.00783 +
1x14.0031 = 28.0187
For C H For C
2
H
4
2x12.0+4x1.00783 =
28.0312.
Atomic weight is however
th f ll th the average of all the
isotopes
Index of Hydrogen Deficiency/
Sit (D ) f U t ti Sites (Degrees) of Unsaturation
It is the no of pairs of hydrogen atoms that must be It is the no. of pairs of hydrogen atoms that must be
removed from the corresponding saturated formula to get
the compound of interest.
The index is the sum of the number of rings the number The index is, the sum of the number of rings, the number
of double bonds and twice the number of triple bonds.
(benzene =4, nitro = 1)
Index for C H X N O can be calculated from eqn Index for C
n
H
m
X
x
N
y
O
z
can be calculated from eqn.
Index = (n) (m/2) (x/2) + (y/2) + 1
Calculate for C
7
H
7
NO
7 3 5 0 5 1 5 7 3.5 + 0.5 + 1 = 5
The index give some idea about the structure of molecular
ion. Even-electron ions give an odd multiple of 0.5, while
dd l t f t i i i t l f th odd electron fragment ions give integer values of the
index.
Answers to problems Answers to problems
Try to solve the problems without Try to solve the problems without
looking at the answers first. After you
get the answer you can cross check it get the answer you can cross check it
with the model answer.
Enjoy problems solving!!! Enjoy problems solving!!!
Index of Hydrogen Deficiency/
Sit (D ) f U t ti Sites (Degrees) of Unsaturation
It is the no of pairs of hydrogen atoms that must be It is the no. of pairs of hydrogen atoms that must be
removed from the corresponding saturated formula to get
the compound of interest.
The index is the sum of the number of rings the number The index is, the sum of the number of rings, the number
of double bonds and twice the number of triple bonds.
(benzene =4, nitro = 1)
Index for C H X N O can be calculated from eqn Index for C
n
H
m
X
x
N
y
O
z
can be calculated from eqn.
Index = (n) (m/2) (x/2) + (y/2) + 1
Calculate for C
7
H
7
NO
7 3 5 0 5 1 5 7 3.5 + 0.5 + 1 = 5
The index give some idea about the structure of molecular
ion. Even-electron ions give an odd multiple of 0.5, while
dd l t f t i i i t l f th odd electron fragment ions give integer values of the
index.
Sinapinic acid
Nicotinic acid co c ac d
Niacin
Vitamin B3