University:
Rutgers University Newark
Course:
CHEM 335 | Organic Chemistry
Academic year:

2024
Views:

21

Pages:

58
Author:

Mahitab S.

CHAPTER 14 MASS SPECTROMETRY ©2018 Cengage Learning. All Rights Reserved. Lecture Outline • Definitions in Mass Spectrometry • Interpretation of Mass Spectra ©2018 Cengage Learning. All Rights Reserved. Mass Spectrometry (MS) • Analytical technique for measuring the mass-to-charge ratio (m/z) of ions • Most valuable analytical tool today for determining accurate molecular masses • Information about molecular formula and structure of a compound can be obtained by analyzing its mass spectrum (fragmentation patterns) • Allows sequencing of proteins to determine their structures on a virtually single-cell scale ©2018 Cengage Learning. All Rights Reserved. Mass Spectrometer • Designed to do the following things: • (1) Convert neutral atoms or molecules into a beam of positive or negative ions • (2) Separate the ions on the basis of their mass-to-charge (m/ z) ratio • (3) Measure the relative abundance of each type of ion ©2018 Cengage Learning. All Rights Reserved. Mass Spectrometer • Vaporized sample is bombarded with high-energy electrons in an evacuated ionization chamber • Causes the stripping of electrons from sample molecules to form positively charged ions that are accelerated by a series of negatively charged accelerator plates • Ions move into an analyzing chamber inside a magnetic field that causes the ion beam to curve • Magnetic field is perpendicular to the direction of the ion beam • Radius of curvature of each ion depends on the charge on the ion (z), its mass (m), the accelerating voltage, and the strength of the magnetic field • Electron ionization mass spectrometry (EI-MS) ©2018 Cengage Learning. All Rights Reserved. Introducing Samples into the Ionization Chamber • Samples of less volatile liquids and solids may be placed on the tip of a heated probe and then inserted directly into the ionization chamber • One can link a gas chromatograph (GC) or liquid chromatograph (LC) directly to the mass spectrometer (GC-MS or LC-MS) • GC and LC can separate complex mixtures into pure fractions that can enter the ionization chamber of the mass spectrometer directly (analytical tool) • Enables mass determination of individual components ©2018 Cengage Learning. All Rights Reserved. Molecular Ion • Molecular ion is the species formed by removal of a single electron from a parent molecule in a mass . + spectrometer (radical cation, R ) • Radical cation: Species formed when a neutral molecule loses one electron (R – electron) • Example: When methane is bombarded with high-energy electrons, an electron is dislodged from a molecule to give a molecular ion at m/z 16 ©2018 Cengage Learning. All Rights Reserved. Molecular Ion • Electron lost in forming the molecular ion is determined by the ionization potential of the atom or molecule • Ionization potentials for most organic molecules are between 8 and 15 eV • Radical cation is delocalized throughout the molecule • Molecular formula of the parent molecule is written in brackets with a plus sign to show that it is a cation and a dot to show that it has an odd number of electrons • At times, it is useful to depict the radical cation at a certain position in order to better understand its reactions ©2018 Cengage Learning. All Rights Reserved. Mass Spectrum • Mass spectrum is a plot of the relative abundance of ions vs. their mass-to-charge (m/z) ratio • Cations with larger values of m/z are deflected less than those with smaller m/z values • Base peak: Results from the most abundant cation • Assigned an arbitrary intensity of 100 • Relative abundances of all other cations are reported as percentages of the base peak ©2018 Cengage Learning. All Rights Reserved. Figure 14.2 - Partial Mass Spectrum of Dopamine Showing Peaks with Intensity Equal to or Greater Than 0.5% of the Base Peak ©2018 Cengage Learning. All Rights Reserved. Partial Mass Spectrum of Dopamine • Number of peaks recorded in the mass spectrum depends on the detector sensitivity ©2018 Cengage Learning. All Rights Reserved. Mass Spectrometry Techniques • Electron ionization mass spectrometry (EI-MS) • Fast-atom bombardment mass spectrometry (FAB) • Matrix-assisted laser desorption ionization mass spectrometry (MALDI) • Chemical ionization mass spectrometry (CI) • Electrospray ionization mass spectrometry (ESI-MS) ©2018 Cengage Learning. All Rights Reserved. Example • In mass spectrometry, what is the term used to describe the ion that results from the ejection of one electron from a molecule? 1. 2. 3. 4. 5. Base peak Parent peak Fragment Analyte None of these ©2018 Cengage Learning. All Rights Reserved. Example • What quantity is detected in mass spectrometry? 1. 2. 3. 4. 5. The energy of a molecule The number of electrons ejected from a molecule The number of ions of a particular mass-to-charge ratio The number of electrons needed to ionize a molecule The number of hydrogen atoms in a molecule ©2018 Cengage Learning. All Rights Reserved. Example • Which of the following reasons explains why some peaks are larger than others in a mass spectrum? 1. 2. 3. 4. 5. The larger peaks represent fragments that are more stable The larger peaks represent fragments that are less stable Cations tend to give larger peaks than radical cations Radical cations tend to give larger peaks than cations None of these ©2018 Cengage Learning. All Rights Reserved. Resolution • Measure of how well a mass spectrometer separates ions of different mass • Low-resolution mass spectrometry • Instruments capable of distinguishing among ions of different nominal mass [ions that differ by one or more atomic mass units (amu)] • High-resolution mass spectrometry • Instruments capable of distinguishing among ions that differ in precise mass by as little as 0.0001 amu ©2018 Cengage Learning. All Rights Reserved. Resolution • C3H6O and C3H8O have nominal masses of 58 and 60 and can resolved by low-resolution mass spectrometry • C3H8O and C2H4O2 both have nominal masses of 60 and can be distinguished by high-resolution MS ©2018 Cengage Learning. All Rights Reserved. Presence of Isotopes • Elements common to organic compounds, including H, C, N, O, S, Cl, and Br, are mixtures of isotopes • Exceptions: F, P, and I exclusively as 19F, 31P, 127I • Example: Naturally occurring carbon is 98.90% 12C and 1.10% 13C • There are 1.11 atoms of carbon-13 in nature for every 100 atoms of carbon-12 ©2018 Cengage Learning. All Rights Reserved. Mass Spectrum of Dopamine • The small peak at m/z 154 from an ion 1 amu heavier than the molecular ion of dopamine is the sum of four separate peaks, each of amu 154 • Each peak corresponds to the presence in the ion of a single heavier isotope of H, C, N, or O in dopamine • Called an M + 1 peak as its peak corresponds to an ion 1 amu heavier than the molecular ion ©2018 Cengage Learning. All Rights Reserved. Table 14.2 - Precise Masses and Natural Abundances of Isotopes Relative to 100 Atoms of the Most Abundant Isotope ©2018 Cengage Learning. All Rights Reserved. Example 14.1 - Exact Mass Calculation • Calculate the precise mass of each ion to five significant figures • Unless otherwise indicated, use the mass of the most abundant isotope of each element • Solution a. 12.0000 + 2(1.00783) + 2(34.9689) = 83.953 b. 84.957 c. 85.951 ©2018 Cengage Learning. All Rights Reserved. Relative Abundance of M, M + 2, M + 1 Peaks • Common elements giving rise to significant M + 2 peaks are chlorine, bromine, and oxygen • Oxygen makes the major contribution to the M + 2 peak in compounds containing only C, H, N, and O • Sulfur is the only other element common to organic compounds that gives a significant M + 2 peak • Sulfur in nature is 95.02% 32S and 4.21% 34S ©2018 Cengage Learning. All Rights Reserved. Figure 14.3 - Mass Spectrum of Chloroethane • Chlorine in nature is 75.77% 35Cl and 24.23% 37Cl • Ratio of M to M + 2 peaks of approximately 3:1 indicates the presence of a single chlorine in chloroethane, as seen in the figure below ©2018 Cengage Learning. All Rights Reserved. Figure 14.4 - Mass Spectrum of 1-Bromopropane • Bromine in nature is 50.5% 79Br and 49.5% 81Br • Ratio of M to M + 2 peaks of approximately 1:1 indicates the presence of a single bromine atom in 1-bromopropane, as seen in the figure below ©2018 Cengage Learning. All Rights Reserved. Comparison of M + 2 and M + 1 Peaks • M + 1 peaks are not useful for accurate determinations of molecular formulas • Relatively low in intensity compared to the molecular ion peak and are difficult to measure with any precision • M + 2 peaks can be useful for getting a rough idea of the number of carbons, oxygens, sulfurs, and halogens ©2018 Cengage Learning. All Rights Reserved. Fragmentation of Molecular Ions • Electrons with energies of 70 eV [approximately 6750 kJ (1600 kcal)/mol] are commonly used in EI to: • Attain high efficiency of molecular ion formation • Give reproducible mass spectra • 70 eV energy is sufficient to dislodge one or more electrons from a molecule and cause extensive fragmentation • Fragments may be unstable as well and, in turn, break apart to even smaller fragments ©2018 Cengage Learning. All Rights Reserved. Fragmentation of Molecular Ions • Under a given set of ionizing conditions, fragmentation pattern and relative abundances of ions are unique for each compound and are characteristic of that compound • Fragmentation patterns provide valuable information about molecular structure ©2018 Cengage Learning. All Rights Reserved. Fragmentation of Molecular Ions • Chemistry of ion fragmentation can be understood in terms of the formation and relative stabilities of carbocations in solution • Where fragmentation occurs to form new carbocations, the mode that gives the most stable carbocation is favored • Thus, the probability of fragmentation to form new carbocations increases in the following order: ©2018 Cengage Learning. All Rights Reserved. Example • High-resolution mass spectrometry allows one to determine the molecular formula of a molecule 1. True 2. False ©2018 Cengage Learning. All Rights Reserved. Example • High-resolution mass spectrometry would allow one to distinguish between the following two molecules 1. 2. True False ©2018 Cengage Learning. All Rights Reserved. Interpreting a Mass Spectrum • If no large M + 2 peak is present, the elements 18O, 34S, 37Cl, and 81Br are absent • These are the only elements to give significant M + 2 peaks • Find if the mass of the molecular ion is odd or even using the nitrogen rule • Nitrogen rule: If a compound has an: • Even number (including zero) of nitrogen atoms, its molecular ion will appear at an even m/z value • Odd number of nitrogen atoms, its molecular ion will appear at an odd m/z value ©2018 Cengage Learning. All Rights Reserved. Mass Spectra of Alkanes • Rules for interpreting mass spectra of alkanes: • Fragmentation tends to occur toward the middle of unbranched chains rather than at the ends • Differences in energy among allylic, benzylic, 3°, 2°, 1°, and methyl carbocations in gas phase are much greater than the differences among comparable radicals • Where alternative modes of fragmentation are possible, the more stable carbocation tends to form in preference to the more stable radical • Unbranched alkanes fragment to form a series of cations differing by 14 amu (a CH2 group), with each fragment formed by a one-bond cleavage having an odd mass number ©2018 Cengage Learning. All Rights Reserved. Figure 14.5 - Mass Spectrum of Octane ©2018 Cengage Learning. All Rights Reserved. Figure 14.6 - Mass Spectrum of 2,2,4-Trimethylpentane ©2018 Cengage Learning. All Rights Reserved. Figure 14.7 - Mass Spectrum of Methylcyclopentane ©2018 Cengage Learning. All Rights Reserved. Example 14.2 - Predicting Structure from Mass Spectra • The base peak at m/z 56 in the mass spectrum of methylcyclopentane corresponds to loss of ethylene to give a radical cation with the molecular formula C4H8+· • Propose a structural formula for this radical cation and show how it might be formed ©2018 Cengage Learning. All Rights Reserved. Example 14.2 - Predicting Structure from Mass Spectra • Following is a structural formula for a molecular ion that might be formed in the ionizing chamber • A single electron has been dislodged from a carbon-carbon single bond to give a 1° radical and a 2° carbocation • Rearrangement of bonding electrons in this radical cation gives ethylene and a new radical cation ©2018 Cengage Learning. All Rights Reserved. Mass Spectra of Alkenes • Alkenes show a strong molecular ion peak and cleave readily to form resonance-stabilized allylic cations • Cyclohexenes undergo fragmentation to give a 1,3diene and an alkene in a process that is the reverse of a Diels-Alder reaction (Ch. 20) ©2018 Cengage Learning. All Rights Reserved. Figure 14.8 - Mass Spectrum of 1-Butene ©2018 Cengage Learning. All Rights Reserved. Mass Spectra of Alkynes • Alkynes show a strong molecular ion peak, and one of the most prominent peaks is from the delocalization-stabilized 3propynyl (propargyl) cation (m/z 39) or a substituted propargyl cation Mass Spectrum of 1-Pentyne ©2018 Cengage Learning. All Rights Reserved. Mass Spectra of Alcohols • Common fragmentation patterns: • Loss of H2O to give a peak that corresponds to M – 18 • Loss of an alkyl group from the carbon bearing the —OH to give a delocalization stabilized oxonium ion and an alkyl radical • Oxonium ion is stable because of delocalization of charge ©2018 Cengage Learning. All Rights Reserved. Figure 14.10 - Mass Spectrum of 1-Butanol ©2018 Cengage Learning. All Rights Reserved. Example 14.3 - Mass Spectrum of 2-Methyl-2-butanol • A low-resolution mass spectrum of 2-methyl-2-butanol (MW 88) shows 16 peaks, molecular ion is absent. Account for the formation of peaks at m/z 73, 70, 59, and 55 and propose a structural formula for each cation Solution (next slide) • The peak at m/z 73 (M – 15) corresponds to loss of a methyl radical from the molecular ion • The peak at m/z 59 (M – 29) corresponds to loss of an ethyl radical • Loss of water as a neutral molecule from the molecular ion gives an alkene at m/z 70 (M – 18) as a radical cation • Loss of methyl from this radical cation gives an allylic carbocation at m/z 55 ©2018 Cengage Learning. All Rights Reserved. Example 14.3 - Mass Spectrum of 2-Methyl-2-butanol • A low-resolution mass spectrum of 2-methyl-2-butanol (MW 88) shows 16 peaks, molecular ion is absent. Account for the formation of peaks at m/z 73, 70, 59, and 55 and propose a structural formula for each cation ©2018 Cengage Learning. All Rights Reserved. Mass Spectra of Aldehydes and Ketones • Characteristic pattern of aliphatic aldehydes and ketones is cleavage of a bond next to the carbonyl group (α-cleavage) • α-Cleavage of the aldehyde proton gives an M – 1 peak, which helps distinguish an aldehyde from a ketone • McLafferty rearrangement - Fragmentation shown by aldehydes and ketones with a sufficiently long carbon chain ©2018 Cengage Learning. All Rights Reserved. McLafferty Rearrangement of a Ketone • Reaction occurs through a six-membered ring transition state • Example: McLafferty rearrangement of 2-octanone gives 1pentene and a radical cation at m/z 58, which in this case is the enol of acetone (spectrum next slide) ©2018 Cengage Learning. All Rights Reserved. Figure 14.11 - Mass Spectrum of 2-Octanone ©2018 Cengage Learning. All Rights Reserved. Mass Spectra of Carboxylic Acids • Characteristic fragmentation pattern: α-Cleavage of the carboxyl group to give the ion [COOH]+ at m/z 45 • McLafferty rearrangement: Base peak is often the result of the McLafferty rearrangement product ©2018 Cengage Learning. All Rights Reserved. Figure 14.12 - Mass Spectrum of Butanoic Acid • m/z 88 - Molecular ion • m/z 45 - [COOH]+ • m/z 60 - McLafferty rearrangement product ©2018 Cengage Learning. All Rights Reserved. Mass Spectra of Esters • Characteristic fragmentation pattern: α-Cleavage • McLafferty rearrangement ©2018 Cengage Learning. All Rights Reserved. Figure 14.13 - Mass Spectrum of Methyl Butanoate • m/z 102 - Molecular ion • m/z 74 - McLafferty rearrangement • m/z 71 and 59 - Result of α-cleavage ©2018 Cengage Learning. All Rights Reserved. Mass Spectra of Aromatic Hydrocarbons • Most of them show an intense molecular ion peak • Toluene and most alkylbenzenes show a fragment ion at m/z 91 ©2018 Cengage Learning. All Rights Reserved. Mass Spectra of Amines • Fragmentation pattern for 1°, 2°, and 3° amines is β-cleavage ©2018 Cengage Learning. All Rights Reserved. Example • Which of the following C6H12O isomers would be expected to produce an m/z peak at M+−18? 1. 2. 3. 4. ©2018 Cengage Learning. All Rights Reserved. Example • Which of the following compounds is most likely to undergo a McLafferty rearrangement? 1. 2. 4. 3. 5. ©2018 Cengage Learning. All Rights Reserved. Applications of Mass Spectrometry • Routine molecule identification in the organic synthesis laboratory in both industrial and academic settings • Uses gas chromatography (GC-MS) and liquid chromatography (LC-MS) as the primary methods • Drug testing of athletes and advanced forensic science • Use GC-MS to identify traces of pharmaceuticals or illicit drugs in blood samples • Luggage screening devices to identify traces of known explosives ©2018 Cengage Learning. All Rights Reserved. Problem 14.31 - α-cleavage • 2-Methylpentanal and 4-methyl-2-pentanone are constitutional isomers with the molecular formula C6H12O, and each shows a molecular ion peak in its mass spectrum at m/z 100 • Spectrum A shows significant peaks at m/z 85, 58, 57, 43, and 42, and spectrum B shows significant peaks at m/z 71, 58, 57, 43, and 29. Assign each compound its correct spectrum ©2018 Cengage Learning. All Rights Reserved. Problem 14.31 - α-cleavage • The expected α-cleavage and McLafferty rearrangement fragmentations are shown below • The α-cleavage fragments at m/z 85 (spectrum A) and 29 (spectrum B) demonstrate that spectrum A corresponds to 4methyl-2-pentanone, and Spectrum B corresponds to 2methylpentanal ©2018 Cengage Learning. All Rights Reserved.