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Short answer
Mass spectroscopy fragmentation rules are the patterns that tell you which bonds break when a molecular ion falls apart, so you can predict the peaks in a spectrum or work backwards from them to a structure. The ones worth knowing first are the nitrogen rule, alpha cleavage, loss of water (M−18) from alcohols, the McLafferty rearrangement, the halogen isotope pattern and the even-electron rule. They work well for simple molecules and lose reliability for complex ones.
Definition and scope
In a mass spectrum the molecular ion (M+) is the intact ionised molecule, and the base peak is the most intense peak, set to 100%. Fragmentation rules explain the other peaks: each one is a charged piece of the molecule, and the gap between M+ and a fragment is the mass of what was lost. The worked examples below follow the examples in the OpenStax Organic Chemistry chapter on mass spectrometry of common functional groups.
The rules in practice
Nitrogen rule
A compound with an odd number of nitrogen atoms has an odd-numbered molecular weight (OpenStax). An odd-numbered molecular ion usually means one or three nitrogen atoms, and an even-numbered one usually means zero or two. It is a quick first check on the molecular ion before you interpret fragments.
Alpha cleavage
Alcohols and aliphatic amines break the C–C bond nearest the heteroatom. In ketones and aldehydes the bond between the carbonyl carbon and the adjacent alpha carbon breaks, giving a neutral radical and a resonance-stabilised acyl cation. In triethylamine, alpha cleavage supplies the base peak (see the table below).
Dehydration of alcohols (M−18)
Alcohols have a second pathway, loss of water, which produces an ion 18 mass units below M+. It can be weak or absent, so a missing M−18 peak does not by itself rule out an alcohol.
McLafferty rearrangement
A carbonyl compound with a hydrogen on the gamma carbon (three atoms from the carbonyl) can transfer that hydrogen to the carbonyl oxygen. The bond between the alpha and beta carbons then breaks and a neutral alkene is lost. The rearrangement ion is a separate peak from the alpha-cleavage ions.
Halogen isotope patterns
Chlorine occurs as 35Cl and 37Cl in roughly a 3:1 ratio, so a chlorine-containing ion shows an M and M+2 pair at about 3:1. Bromine (79Br and 81Br) gives an M and M+2 pair at about 1:1. A fragment peak without a partner two units higher has lost the halogen.
Even-electron rule
When cleavage occurs from an even-electron ion, it is normal for the fragment ion to be even-electron too (Nakata, 2019). The paper notes that some single-electron cleavages violate the rule.
Worked examples: predict, then check
Each row uses the molecular weight or peak values from the OpenStax chapter. Work out the expected peak from the rule, then compare it with the observed spectrum.
| Compound | M+ (m/z) | Rule applied | Predicted or observed peak |
|---|---|---|---|
| 2-Pentanol | 88 | Alpha cleavage (alcohol) | Alpha cleavage is the pathway shown in the spectrum; only a small dehydration peak (M−18) is observed |
| Triethylamine | 101 | Alpha cleavage (amine); odd M+ fits one nitrogen | Base peak at 86, loss of a methyl group |
| Butyrophenone | 148 | Alpha cleavage versus McLafferty | Alpha cleavage loses C3H7 (43) to give 105; McLafferty loses C2H4 (28) to give 120 |
| 2-Methyl-3-pentanol | 102 | Two alpha cleavages plus possible dehydration | Expected 73, 59 and 84; both alpha-cleavage peaks observed (73 and 59), no 84 peak |
| Chloroethane | 64 | Chlorine isotopes | M+2 at 66, about 3:1 |
| 1-Bromohexane | 164 | Bromine isotopes | M+2 at 166, about 1:1; fragments at 135/137 keep the bromine, m/z 85 has no 87 partner so it does not |
The 2-methyl-3-pentanol row is the useful one: dehydration is a real alcohol pathway, yet the spectrum shows no peak at 84. A rule tells you what is possible, and the spectrum tells you which pathway wins. The butyrophenone row shows two rules competing in one molecule, which is why you test each candidate peak against both.
Where the rules stop working
Nakata (2019) states that fragmentation rules can be quite useful for interpreting mass spectra of simple compounds, but that interpretation is harder for structurally complex molecules containing multiple heteroatoms, because it is unclear where the charge and unpaired electron sit. The even-electron rule also does not necessarily hold when the precursor receives a large amount of energy from collisional activation.
In practice, that means rules of thumb are a starting hypothesis for small molecules, while for complex analytes you compare against reference spectra. The NIST Chemistry WebBook hosts reference spectra from the NIST Mass Spectrometry Data Center, and our guide to NIST library match factors covers reading a library match. For fragmentation that happens inside the instrument rather than on paper, see electrospray ionization source parameters and MRM transitions. For GC-MS work, derivatization changes the analyte and therefore the fragments you will see; the GC-MS versus LC-MS comparison and the LC-MS overview place these techniques side by side.
Common misunderstandings
- An expected peak is always present. In 2-methyl-3-pentanol the predicted M−18 peak at 84 was not observed.
- One rule explains the whole spectrum. Butyrophenone shows alpha cleavage (105) and McLafferty (120) side by side.
- Any fragment from a bromine or chlorine compound shows the isotope pair. Only fragments that still contain the halogen do; m/z 85 in 1-bromohexane has no partner.
- The rules hold for every ion type. The even-electron rule has documented exceptions, especially at high collisional activation.
FAQ
What is the nitrogen rule in mass spectrometry?
A compound with an odd number of nitrogen atoms has an odd-numbered molecular weight, so an odd M+ suggests an odd number of nitrogens.
What is a McLafferty rearrangement?
A gamma hydrogen transfers to the carbonyl oxygen, the alpha–beta carbon bond breaks, and a neutral alkene is lost. In butyrophenone this loses C2H4 and gives m/z 120.
How do I tell whether a fragment still contains chlorine or bromine?
Look for the M/M+2 pair: about 3:1 for chlorine and about 1:1 for bromine. A fragment with no partner two units higher has lost the halogen.
Sources
All sources checked 2026-10-29.
- OpenStax, Organic Chemistry, section 12.3 Mass Spectrometry of Some Common Functional Groups: https://openstax.org/books/organic-chemistry/pages/12-3-mass-spectrometry-of-some-common-functional-groups
- Nakata H. Structure and m/z of Singly Charged Even-Electron Fragment Ions in Organic Mass Spectrometry: “A Rule of Mass Shift” Revisited. Mass Spectrometry (Tokyo) 2019;8(1):A0074: https://pmc.ncbi.nlm.nih.gov/articles/PMC6920629
- NIST Chemistry WebBook, NIST Mass Spectrometry Data Center reference spectra: https://webbook.nist.gov/chemistry/
