Mass Spectrometry: Fragmentation and High Resolution

Mass Spectrometry: Fragmentation and High Resolution

Mass spectrometry (MS) is an analytical technique used to determine the relative molecular mass, molecular formula, and structural information of a compound by measuring the mass-to-charge ratio (m/z) of ions.

How a Mass Spectrometer Works

1. Vaporisation — the sample is vaporised (converted to gas phase)

2. Ionisation — gaseous molecules are ionised, typically by electron impact (a beam of high-energy electrons knocks an electron off the molecule):

M(g) → M⁺·(g) + e⁻

The ion formed is a molecular ion (also called the parent ion), denoted M⁺· — it is a radical cation (has both a positive charge and an unpaired electron)

3. Acceleration — ions are accelerated by an electric field

4. Deflection — ions are deflected by a magnetic field; lighter ions and more highly charged ions are deflected more

5. Detection — ions reach the detector, which records the m/z ratio and abundance

The Mass Spectrum

A mass spectrum is a plot of relative abundance (y-axis) against m/z (x-axis, where z is usually 1, so m/z ≈ relative mass).

Key features:

• The molecular ion peak (M⁺) — the peak at the highest m/z value (excluding the M+1 isotope peak) gives the relative molecular mass of the compound
• The base peak — the most abundant peak (tallest), assigned a relative abundance of 100%
• Fragment peaks — peaks at lower m/z values caused by fragmentation of the molecular ion

Fragmentation

The molecular ion is unstable (high energy) and breaks apart into fragments. Only the positively charged fragments are detected. A neutral fragment (radical or molecule) is lost and not detected.

M⁺· → A⁺ + B· (a cation and a radical)

or

M⁺· → A· + B⁺ (a radical and a cation)

Common Fragmentation Losses

The difference between the M⁺ peak and a fragment peak tells you what has been lost:

Loss (m/z units)	Fragment lost	Structural feature
15	CH₃·	Methyl group
17	OH·	Hydroxyl group (alcohol)
18	H₂O	Alcohol (dehydration)
28	CO or CH₂=CH₂	Carbonyl or ethyl
29	CHO· or C₂H₅·	Aldehyde or ethyl group
31	CH₃O· or CH₂OH·	Methoxy or hydroxymethyl
43	CH₃CO· or C₃H₇·	Acetyl (from ketones/esters) or propyl
44	CO₂	Ester or carboxylic acid
45	OC₂H₅·	Ethoxy (from ethyl esters)
77	C₆H₅·	Phenyl group

Worked Example: Mass Spectrum of Butanone (CH₃COCH₂CH₃, Mr = 72)

• M⁺ peak at m/z = 72 (molecular ion)
• m/z = 57: loss of 15 (CH₃·) → CH₃COCH₂⁺ or COCH₂CH₃⁺
• m/z = 43: loss of 29 (C₂H₅·) → CH₃CO⁺ (the acylium ion — very stable, often the base peak in ketone spectra)
• m/z = 29: the C₂H₅⁺ or CHO⁺ fragment

The base peak at m/z = 43 is characteristic of methyl ketones (CH₃CO⁺ is particularly stable).

The M+1 Peak and Molecular Formula

The M+1 peak (one mass unit above M⁺) arises because approximately 1.1% of carbon atoms are ¹³C (instead of ¹²C). The ratio of the M+1 peak to the M⁺ peak can indicate the number of carbon atoms:

Number of C atoms ≈ (M+1 abundance / M⁺ abundance) × 100 / 1.1

For example, if M+1 / M⁺ = 4.4%, then C atoms ≈ 4.4 / 1.1 = 4.

High-Resolution Mass Spectrometry (HRMS)

At low resolution, many compounds share the same integer molecular mass (e.g. CO, N₂, and C₂H₄ all have Mr = 28). High-resolution MS measures m/z to four or more decimal places, allowing the exact molecular formula to be determined.

Exact atomic masses:

• ¹H = 1.00782
• ¹²C = 12.00000 (by definition)
• ¹⁴N = 14.00307
• ¹⁶O = 15.99491

Example: A compound has a molecular ion at m/z = 28.0313.

• CO: 12.0000 + 15.9949 = 27.9949
• N₂: 2 × 14.0031 = 28.0061
• C₂H₄: 2(12.0000) + 4(1.0078) = 28.0313 ✓

The measured mass matches C₂H₄.

Isotope Patterns

Some elements have distinctive isotope patterns that are visible in the mass spectrum:

Bromine: ⁷⁹Br and ⁸¹Br exist in approximately 1:1 ratio. A bromine-containing compound shows two peaks of roughly equal intensity separated by 2 units at the M⁺ region.

Chlorine: ³⁵Cl and ³⁷Cl exist in approximately 3:1 ratio. A chlorine-containing compound shows peaks at M and M+2 in a 3:1 ratio.

Two chlorine atoms (e.g. CH₂Cl₂) show peaks at M, M+2, and M+4 in a 9:6:1 ratio.

Combining MS with Other Techniques

Mass spectrometry is often combined with gas chromatography (GC-MS):

1. GC separates the components of a mixture by their retention times

2. Each component enters the mass spectrometer as it elutes

3. This gives both the identity and quantity of each component

Exam Tips

• The molecular ion peak gives Mr — always look for the highest m/z value (ignore tiny isotope peaks above it)
• Calculate losses from M⁺ to identify structural features: M⁺ − fragment = mass lost
• The base peak (m/z = 43 for methyl ketones, m/z = 77 for phenyl compounds) often identifies the compound class
• In high-resolution questions, calculate exact masses to 4 decimal places to distinguish possible formulae
• For halogen-containing compounds, look for the characteristic isotope pattern at M⁺