Organic Spectroscopy Mass Spectrometry

General The mass spectrum is a plot of ion abundance versus m/e ratio (mass/charge ratio). The most abundant ion formed in the ionization chamber gives to rise the tallest peak in the mass spectrum, called the base peak. By using one of the many ionization methods, the simple removal of an electron from a molecule yields a positively charged radical cation, known as the molecular ion and symbolized as [M]+. After formation of molecular Ion in the ionization chamber, excess energy causes further fragmentation of the molecular ion. Various positively charged masses (and/or positively charged radical cations) show up in the spectrum. The mass of the molecular ion can be determined to an accuracy of ± 0.0001 of a mass unit, which yields a high resolution (hi-res) mass spectrum. Ionization Methods The most common method of ionization involves Electron impact (EI) in which molecule is bombarded with high-energy electrons. This is the strongest ionization method which usually causes further fragmentation. Since the molecular ion gets fragmented, the molecular ion usually produces a small peak with this method.

Mass Spectrum of Isobutyrophenone 105 (base peak) C6H5CO+ molecular weight = 148 77 C6H5+ molecular ion, M (148) M+1

Facts Concerning the Molecular Ion Peak The peak must correspond to the ion of highest mass excluding the usually much smaller isotopic peaks that occur at M+1, M+2, etc. To be a molecular ion, the ion must contain an odd number of electrons. One electron is lost, forming a radical-cation. To determine this, calculate the IHD. It must be a whole number. Consider an ion at m/z = 112. A possible molecular formula is C6H8O2. The IHD = 3 (a whole number), so this could be the molecular ion. However, an ion at 105 could correspond to a molecular formula of C7H5O. The IHD is 5.5 (not a whole number), so this can’t be the molecular ion. The ion must be capable of producing smaller, fragment ions by loss of neutral fragments of predictable structure.

The Lifetimes of Various Molecular Ions Aromatics > conjugated alkenes > alicyclic compounds> organic sulfides > unbranched hydrocarbons > mercaptans > ketones > amines > esters > ethers > carboxylic acids > branched hydrocarbons > alcohols Therefore, alcohols produce small or non-existent molecular ions because their lifetimes are too short. They fragment before they can be detected. CH3CH2CH2CH2OH MW = 74 No M visible

The Nitrogen Rule The nitrogen rule states that an odd number of nitrogen atoms will form a molecular ion with an odd mass number. An even number of nitrogen atoms (or none at all) will produce a molecular ion with an even mass number. This occurs because nitrogen has an odd-numbered valence. Examples: C6H5CH2NH2 MW = 107 H2NCH2CH2NH2 MW = 60

Determining Possible Molecular Formulas from the Molecular Ion: Rule of 13 Rule of Thirteen: Based upon the assumption that CnHn and its mass of 13 is present in most organic compounds. Divide the molecular ion by 13. This gives a value for n and any remainder (R) = additional H’s. For a M+ = 106, n = 8(106/13) with a R of 2. A possible molecular formula for this ion is C8H8+2 = C8H10 For each CH there are heteroatom equivalents.

Rule of 13 Heteroatom Equivalents Element CH Equivalent 1H12 C 31P C2H7 16O CH4 32S C2H8 14N CH2 16O32S C4 16O14N C2H6 35Cl C2H11 19F CH7 79Br C6H7 28Si C2H4 127I C10H7

Candidate molecular formulas for M+. = 108 108/13 = 8, R = 4  C8H12 O = CH4; therefore, C8H12 – CH4 + O = C7H8O or C8H12 – 2(CH4) + 2O = C6H4O2 or C8H12 – C6H7 + Br = C2H5Br Calculate three candidate molecular formulas for C10H18.

When an odd amu M+. is seen, suspect one nitrogen or an odd multiple. Candidate molecular formulas for a M+. = 121 are: 121/13 = 9, R = 4  C9H13; IHD = 3.5 so it can’t be M+. O = CH4; N = CH2 or C9H13 – CH2 + N = C8H11N; IHD = 3, so it may be M+. or C9H13 – 2(CH2) + 2N = C7H9N2; IHD = 4.5 so it can’t be M+. or C9H13 – 3(CH2) + 3N = C6H7N3; IHD = 5, so it may be M+. or C9H13 – (CH2) – (CH4) + N + O = C7H7NO IHD = 5, so it may be M+.

Determining the Molecular Formula from the Molecular Ion: Isotope Ratio Data In this method, the relative intensities of the peaks due to the molecular ion and related isotopic peaks are examined. Advantage: Does not require an expensive high-res MS instrument. Disadvantages: Isotopic peaks may be difficult to locate. Useless when the molecular ion peak is very weak or does not appear. 3-pentanone

Relative Abundances of Common Elements and Their isotopes Carbon 12C 100 13C 1.08   Hydrogen 1H 2H 0.016 Nitrogen 14N 15N 0.38 Oxygen 16O 17O 0.04 18O 0.20 Sulfur 32S 33S 0.78 34S 4.40 Chlorine 35Cl  37Cl 32.5 Bromine 79Br 81Br 98.0

Example: 3-pentanone, C5H10O %(M + 1) = 100 (M + 1)/M = 1.08 x # C atoms + 0.016 x # H atoms + 0.04 x # O atoms = 1.08 x 5 + 0.016 x 10 + 0.04 x 1= 5.60 Actual spectrum: [1% (M +1)/17.4% (M)] x 100 = 5.75

Halogen M M + 2 M + 4 M + 6 Br 100 97.7 Br2 195.0 95.4 Br3 293.0 286.0 Relative Intensities of Isotope Peaks for Bromine and Chlorine Halogen M M + 2 M + 4 M + 6 Br 100 97.7 Br2 195.0 95.4 Br3 293.0 286.0 93.4 Cl 32.6 Cl2 65.3 10.6 Cl3 97.8 31.9 3.47 BrCl 130.0 Br2Cl 228.0 159.0 31.2 Cl2Br 163.0 74.4 10.4

156 158

236 234 238

112 114

192 190 194

Determining the Molecular Formula from the Molecular Ion: High Resolution MS (HRMS) Using low resolution (LR) MS, you could not distinguish between the following molecular formulas, each of which has a mass of 60: C3H8O = (3 x 12) + (8 x 1) + 16 = 60 C2H8N2 = (2 x 12) + (8 x 1) + (2 x 14) = 60 C2H4O2 = (2 x 12) + (4 x 1) + (2 x 16) = 60 CH4N2O = 12 + (4 x 1) + (2 x 14) + 16 = 60 However, they can be distinguished using HRMS.

Precise Masses of Some Common Elements Atomic Weight Isotope Mass Hydrogen 1.0097 1H 1.00783 2H 2.01410 Carbon 12.01115 12C 12.0000 13C 13.00336 Nitrogen 14.0067 14N 14.0031 15N 15.0001 Oxygen 15.9994 16O 15.9949 17O 16.9991 18O 17.9992 Fluorine 18.9984 19F Silicon 28.086 28Si 27.9769 29Si 28.9765 30Si 29.9738 Phosphorus 30.974 31P 30.9738 Sulfur 32.064 32S 31.9721 33S 32.9715 34S 33.9679 Chlorine 35.453 35Cl 34.9689 37Cl 36.9659 Bromine 79.909 79Br 78.9183 81Br 80.9163 Iodine 126.904 127I 126.9045 Using precise masses: C3H8O = 60.05754 C2H8N2 = 60.06884 C2H4O2 = 60.02112 CH4N2O = 60.03242

Fragmentation Patterns Most common: one-bond cleavage to produce an odd-electron neutral fragment, (radical, which is not detected) and an even-electron carbocation. Ease of frag- mentation to form cations follows the scheme below: CH3+ < RCH2+ < R2CH+ < R3C+ < CH2=CH-CH2+ < C6H5-CH2+ Difficult Easy Radical (not detected)

Fragmentation Patterns (cont.) Two-bond cleavage: The odd-electron molecular ion produces an odd-electron fragment ion and an even-electron neutral fragment (not detected). Not detected McLafferty Rearrangement

Cleavage at branch points MW = 86 57 71

-cleavage to hetero atoms MW = 102 cleavage  to hetero atoms CH3-CH=OH+ 43 87

-cleavage to aromatic ring MW = 134 91 92 (from McLafferty Rearrangement)

Cleavage  to carbonyl groups MW = 86 43

McLafferty rearrangement carboxylic acids 60

McLafferty rearrangement esters MW = 102 74

Hexane C6H14 MW = 86.18 Molecular ion peaks are present, possibly with low intensity.  The fragmentation pattern contains clusters of peaks 14 mass units apart (which represent loss of (CH2)nCH3).

3-Pentanol C5H12O MW = 88.15 An alcohol's molecular ion is small or non-existent.  Cleavage of the C-C bond next to the oxygen usually occurs.  A loss of H2O may occur as in the spectrum below.

3-Phenyl-2-propenal C9H8O MW = 132.16 Cleavage of bonds next to the carboxyl group results in the loss of hydrogen (molecular ion less 1) or the loss of CHO (molecular ion less 29).

3-Methylbutyramide C5H11NO MW = 101.15 Primary amides show a base peak due to the McLafferty rearrangement.

n-Butylamine C4H11N MW = 73.13 Molecular ion peak is an odd number. Alpha-cleavage dominates aliphatic amines.

n-Methylbenzylamine C8H11N MW = 121.18 Another example is a secondary amine shown below.  Again, the molecular ion peak is an odd number.  The base peak is from the C-C cleavage adjacent to the C-N bond.

Molecular ion peaks are strong due to the stable structure. Naphthalene C10H8 MW = 128.17 Molecular ion peaks are strong due to the stable structure.

2-Butenoic acid C4H6O2 MW = 86.09 In short chain acids, peaks due to the loss of OH (molecular ion less 17) and COOH (molecular ion less 45) are prominent due to cleavage of bonds next to C=O.

Fragments appear due to bond cleavage next to C=O (alkoxy group loss, -OR) and hydrogen rearrangements.                                                  Ethyl acetate C4H8O2 MW = 88.11

Ethyl methyl ether C3H8O MW = 60.10 Fragmentation tends to occur alpha to the oxygen atom (C-C bond next to the oxygen).

1-Bromopropane C3H7Br MW = 123.00 The presence of chlorine or bromine atoms is usually recognizable from isotopic peaks.

4-Heptanone C7H14O MW = 114.19 Major fragmentation peaks result from cleavage of the C-C bonds adjacent to the carbonyl.

Which structure supports the following mass spectrum?

Which structure supports the following mass spectrum?

Which structure supports the following mass spectrum?

An unknown compound has the mass spectrum shown below. The IR spectrum shows peaks in the 3100-3030 and the 2979-2879 cm-1 ranges and a strong absorption at 1688 cm-1. Suggest a structure consistent with this data.

An unknown compound has the mass spectrum shown below An unknown compound has the mass spectrum shown below. The IR spectrum shows peaks in the 2963-2861 cm-1 range and a strong absorption at 1718 cm-1. Suggest a structure consistent with this data.