Understanding Mass Spectra: A Basic Approach

387 Pages·2004·3.116 MB·English

by  R. Martin Smith

UNDERSTANDING
MASS SPECTRA
Second Edition
UNDERSTANDING
MASS SPECTRA:
A Basic Approach
SECOND EDITION
R. Martin Smith
A JOHN WILEY & SONS, INC., PUBLICATION
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LibraryofCongressCataloging-in-PublicationData:
Smith,R.Martin.
Understandingmassspectra:abasicapproach.–2nded./R.MartinSmith.
p. cm.
Includesbibliographicalreferencesandindex.
ISBN0-471-42949-X(acid-freepaper)
1.MassSpectrometry. I.Title.
QD96.M3S65 2005
5430.0873–dc22 2004003683
PrintedintheUnitedStatesofAmerica
10 9 8 7 6 5 4 3 2 1
CONTENTS
Preface to the Second Edition xi
Acknowledgments xv
Abbreviations and Notations Used in This Book xvii
1 Instrumentation 1
1.1. Introduction / 1
1.1.1. Overview / 1
1.1.2. Sample Introduction / 3
1.2. Ionization Source / 4
1.2.1. Electron Ionization Source / 5
1.2.2. Chemical Ionization / 8
1.2.3. Other Ionization Methods / 9
1.2.3.1. Electrospray Ionization / 9
1.2.3.2. Desorption Ionization / 12
1.3. m/z Analysis / 13
1.3.1. Time-of-Flight (TOF) / 13
1.3.2. Magnetic Sector / 15
1.3.3. Transmission Quadrupole / 17
1.3.3.1. Selected Ion Monitoring (SIM) / 21
1.3.4. Quadrupole Ion Trap (QIT) / 22
1.3.5. Other Types of Mass Analysis / 24
1.3.5.1. Mass Spectrometry/Mass
Spectrometry(MS/MS) / 24
1.3.5.2. Accurate m=z Analysis / 26
1.3.6. Spectral Skewing / 26
1.4. Ion Detection / 30
1.4.1. Electron Multiplier / 32
1.4.2. Photomultiplier Detector / 33
v
vi CONTENTS
1.5. Data System / 33
1.5.1. Instrument Tuning and Calibration / 33
1.5.2. The Mass Spectrum / 37
1.5.2.1. Production of the Mass Spectrum / 37
1.5.2.2. Terminology: Ions vs. Peaks / 41
1.5.3. Library Searches / 41
1.5.4. Using the Data System to Analyze GC/MS Data / 45
1.6. Criteria for Good-Quality Spectra / 50
Additional Problems / 51
Mass Spectrometric Resources on the Internet / 52
References and Suggested Reading / 53
2 Elemental Composition from Peak Intensities 56
2.1. Natural Isotopic Abundances / 56
2.1.1. Atomic and Molecular Mass / 59
2.1.2. Calculated Exact Masses and Mass Defects / 60
2.2. Determining Elemental Composition from Isotope
Peak Intensities / 64
2.2.1. One or More Atoms of a Single Element / 64
2.2.1.1. Chlorine and Bromine / 64
2.2.1.2. Ion Designation and Nomenclature / 70
2.2.1.3. Probability Considerations with Multiple
Numbers of Atoms / 71
2.2.1.4. Isotope Peak Intensity Ratios for Carbon-Containing
Ions—The Xþ1 Peak / 74
2.2.1.5. A, Aþ1, and Aþ2 Elements / 77
2.2.1.6. Isotope Peak Intensity Ratios for Carbon-Containing
Ions—The Xþ2 Peak / 78
2.2.1.7. Overlapping Peak Clusters—Contributions from
13C Only / 80
2.2.1.8. Silicon / 82
2.2.2. Complex Isotope Clusters / 83
2.2.2.1. Sulfur Dioxide / 83
2.2.2.2. Diazepam / 86
2.3. Obtaining Elemental Compositions from Isotope
Peak Intensities / 89
Examples / 91
Additional Problems / 96
References / 98
CONTENTS vii
3 Ionization, Fragmentation, and Electron Accounting 99
3.1. A Brief Review of Orbitals and Bonding / 99
3.2. Even- and Odd-Electron Species / 101
3.3. Site of Initial Ionization / 103
3.4. Types of Fragmentation / 107
3.5. The Nitrogen Rule / 109
3.6. Energy Considerations in Fragmentation Processes / 110
3.6.1. Fragmentation Rates / 110
3.6.2. Metastable Ions / 112
3.6.3. Energy Diagrams / 113
3.6.4. Stevenson’s Rule / 116
Additional Examples / 117
Problems / 119
References / 120
4 Neutral Losses and Ion Series 121
4.1. Neutral Losses / 121
4.1.1. Losses from the Molecular Ion / 121
4.1.2. Loss of Small Molecules from Aromatic Ions / 126
4.2. Low-Mass Ion Series / 131
4.2.1. n-Alkane Spectra / 132
4.2.2. Effect of Chain Branching on the Spectra of
Aliphatic Hydrocarbons / 134
4.2.3. Ion Series for Nonaromatic Compounds / 136
4.2.4. Aromatic Ion Series / 142
4.2.5. Use of Ion Series: Mass Chromatograms / 145
Additional Problems / 148
References / 148
5 A Rational Approach to Mass Spectral Problem Solving 150
5.1. Guidelines for Solving Mass Spectral Problems / 150
Examples / 153
Problems / 161
Reference / 163
6 a-Cleavage and Related Fragmentations 164
6.1. Introduction / 164
6.2. Benzylic Cleavage / 166
viii CONTENTS
6.3. Cleavage Next to Aliphatic Nitrogen / 170
6.3.1. Structural Relationships: a-Cleavage in
1-Phenyl-2-aminopropanes / 171
6.3.2. Cleavage Next to Electron-Deficient Nitrogen / 176
6.3.3. a-Cleavage in Complex Nitrogenous Ring Systems / 179
6.4. Cleavages of Aliphatic Oxygenated Compounds / 180
6.4.1. a-Cleavage / 180
6.4.2. Bond Cleavage Away from the Ionization Site / 184
6.4.3. Cleavage at Carbonyl Groups / 186
6.5. Elimination Fragmentations in Oxygen and
Nitrogen Compounds / 192
6.5.1. Secondary Elimination from Initial a-Cleavage Ions / 192
6.5.2. Hydride Shifts / 195
6.5.3. Elimination Fragmentations of Some
Aromatic Compounds / 196
6.5.4. Water Elimination in Aliphatic Alcohols / 198
Examples / 200
Additional Problems / 202
References / 206
7 Important Mass Spectral Rearrangements / 207
7.1. Introduction / 207
7.2. g-Hydrogen Rearrangement / 208
7.2.1. McLafferty-Type Rearrangement / 208
7.2.2. g-Hydrogen Rearrangement in Alkylbenzenes / 213
7.2.3. g-Hydrogen Rearrangement Initiated by a
Remote Ionization Site / 217
7.3. Cyclohexanone-Type Rearrangement / 223
7.4. Retro Diels–Alder Fragmentation / 228
7.5. Double-Hydrogen (McLaffertyþ1) Rearrangement / 234
Additional Problems / 236
References / 237
8 Rationalizing Mass Spectral Fragmentations 238
8.1. General Guidelines / 238
8.2. Loss of Small Molecules / 241
8.2.1. Loss of Small Molecules from Aromatic Ions Revisited / 241
8.2.2. g-Butyrolactone / 243
8.3. Ephedrine / 246
8.4. Ortho Effect: The Hydroxybenzoic Acids / 251
CONTENTS ix
Additional Problems / 254
References / 256
9 Structure Determination in Complex Molecules
Using Mass Spectrometry 257
9.1. Introduction / 257
9.2. ‘‘Designer Drugs’’ Related to MDA / 258
9.3. Cocaine and Its Metabolites / 262
9.3.1. Peak Correlations / 263
9.3.2. Proposed Fragmentations / 268
9.3.3. Application / 271
9.4. Phencyclidine and Its Analogs / 274
9.4.1. Fragmentations of Phencyclidine / 274
9.4.2. Phencyclidine Analogs / 282
9.5. A Practical Problem / 284
References / 285
10 Answers to Problems 287
Index 353
PREFACE TO THE
SECOND EDITION
Mass spectrometry (MS) has undergone a profound change over the past decade.
Instrumentation and techniques related to the automated analysis of biomolecules
andnewdrugsnowaccountforalargepercentageoftheresearchandpublications
in this field. In comparison, gas chromatography/mass spectrometry (GC/MS) and
electron ionization (EI) mass spectra of ‘‘small’’ molecules play a less important
role than they once did. But GC/MS is far from dead, and EIMS continues to be
the ionization method of choice for many laboratories that routinely analyzevola-
tilizable low molecular mass compounds such as drugs, flavor and odor compo-
nents, pesticides, and petroleum products. This situation seems unlikely to
change in the near future.
The interpretation of EI mass spectra has always been a challenging subject to
learnandtoteach—especiallytoindividualswhohavenothadthebenefitofagra-
duateeducationinchemistryorwhohavebeenoutofcollegeforseveralyears.The
challenge is compounded by manufacturer-encouraged reliance on library search
results for compound identification. Why learn anything about spectral interpreta-
tionwhenthecomputercandoallthework?Theanswertothisquestionissimple,
as most conscientious users quickly realize. The library search often does not pro-
vide a realistic answer or (worse) may provide an answer that looks correct but is
not.Evensoftwareprogramsthatprofessto‘‘interpret’’unknownspectra can only
provide probable answers. After that, you are left to your own devices.
It was tempting to substantially increase the breadth and depth of the material
thatwascoveredinthefirstedition.However,myexperiencehasbeenthatanency-
clopedic presentation of mass spectral interpretation does not givebeginningmass
spectrometrists what they need, which is a presentation that provides a few funda-
mental concepts in a logical, organized manner, without distracting and unneces-
sary detail. I wrote and revised this book for beginning mass spectrometrists, and
I have retained the simplicity of its approach for that reason.
My own understanding of mass spectral interpretation has developed, and con-
tinuestodevelop,bytrialanderror.Iamadmittedlymostlyself-taught.Myknowl-
edgeofmassspectralliteraturehasbeenlimitedbythenatureofmycareer,whose
primaryfocuswasforensicscience,notmassspectrometry.Somewillseethatasa
xi