1¹⁹F NMR

¹⁹F NMR is a powerful tool for the structural determination of fluorinated molecules and the monitoring of processes involving fluorinated species.

A ¹⁹F spectrum spreads its signals over a very wide range. Almost every proton in a ¹H spectrum falls within about 12 ppm, whereas fluorine signals cover roughly 700 ppm across the compounds in the table below. The reason is the electrons closest to the nucleus. They partly screen it from the instrument's magnetic field, so the field it experiences is slightly weaker than the one applied. This screening is called shielding, and the more of it a nucleus has, the further to the right its signal lies. A proton has only its single bonding electron, and the shielding this provides barely changes from one environment to another, so proton signals crowd together. Fluorine surrounds its nucleus with three lone pairs, and these outer electrons are much more sensitive to the surrounding chemistry: a change in a neighbouring group, or even a change of solvent, alters the shielding — and so the position of the signal — far more for fluorine than for a proton. As a result, fluorines in different environments are usually well separated, and can be distinguished even where the corresponding protons would overlap.

A fluorine signal is often a group of lines rather than a single one — a separate effect from the shielding that sets its position. A neighbouring nucleus that is itself magnetic, usually a hydrogen, carries its own small magnetic field, which points one way or the other; that small contribution adds to or subtracts from the total field the fluorine feels, so the fluorine experiences slightly different fields depending on the neighbour's orientation, and its signal splits accordingly. Each set of n equivalent neighbours splits it into n+1 lines — the same rule as in ¹H — so the number of lines tells you how many neighbours there are. The size of the splitting, measured in hertz, is the coupling constant, and it is as informative as the number of lines: a given pair of nuclei separated by a given number of bonds and geometry gives a characteristic value, reproducible from one molecule to the next, so the measured constants serve as a fingerprint for assigning a structure. A one-bond C–F coupling of around 250 Hz, for instance, is recognisably that and little else. This splitting, called spin–spin coupling, is carried through the bonds, and in fluorine it reaches unusually far: a fluorine couples not only to atoms one bond away but to those two, three, even four bonds distant, so one signal reports on a whole region of the structure. In a para-substituted fluorobenzene, for example, the fluorine is split by the four ring hydrogens into a “triplet of triplets” — the two nearer hydrogens giving one splitting, the two further ones a smaller one. The same effect appears from the carbon side: each carbon within a few bonds of the fluorine is split in its ¹³C signal, the splitting shrinking with every additional bond.

Because a ¹⁹F spectrum shows only the compound of interest, on a clean baseline, it can be used to measure how much of a species is present — a yield or a purity — and not only to identify it: as in ¹H NMR, the integrated area of a signal is proportional to the number of nuclei producing it, whether that signal is a single line or a split multiplet. This holds only when the spectrum is properly acquired. Fluorine relaxes slowly — its T₁ is long — so the signal needs time to recover between successive scans; at least five times T₁ must be allowed, which in practice means a relaxation delay (d1) of 30 seconds or more. If the d1 is not long enough, a yield determined from the integration of ¹⁹F signals can vary by 20–30 % from one sample to the next, and even from one spectrometer to another.

A measurement NorrChemica runs shows this in use. The active fluoride content of a tetramethylammonium fluoride–methanol adduct (TMAF·MeOH) — the fraction of its fluoride that is chemically available — is determined by ¹⁹F and ¹H NMR together. The fluoride gives a single ¹⁹F signal and the tetramethylammonium cation a single ¹H signal; both spectra are recorded on the same solution against 1,3,5-trifluorobenzene, a reference that appears in each and cancels between them, so the two integrals return the amount of fluoride per cation directly. Acquired with a 30-second relaxation delay, the adduct returned 0.91 fluoride per cation — against an ideal of one — with 0.92 and 0.86 for two commercial batches measured the same way.

Reference — ¹⁹F shift map (CFCl₃ = 0)

2³¹P NMR

³¹P NMR is a powerful tool for the structural determination of phosphorus-containing compounds and the monitoring of reactions involving them.

Phosphorus has a single natural isotope, ³¹P, at 100 % abundance, and it is spin-½, so its signals are sharp. A phosphorus spectrum is usually recorded with the protons decoupled — written ³¹P{¹H} — which removes the splitting caused by nearby hydrogens and leaves a sharp signal for each distinct phosphorus environment. Because phosphorus is far less common in a sample than hydrogen, the baseline is clean and uncrowded: counting the signals shows how many phosphorus environments are present, and their positions — their shifts — begin to identify them.

When a phosphorus atom is bound to a metal, the ³¹P spectrum shows it directly, through coupling. The standard illustration is Wilkinson's catalyst, Rh(PPh₃)₃Cl — a rhodium centre carrying three triphenylphosphine (PPh₃) ligands. Rhodium's only isotope, ¹⁰³Rh, is magnetic (spin-½) and 100 % abundant, so a phosphorus bound to it is split into a doublet — two lines of equal height — by the rhodium–phosphorus coupling; a free, uncoordinated PPh₃ has no magnetic neighbour and stays a single line. The doublet is therefore direct evidence that the phosphorus is attached to the metal.

The size of the splitting carries more. When the catalyst reacts with hydrogen the rhodium changes oxidation state, and the rhodium–phosphorus coupling constant changes with it: the rhodium(I) phosphines split by about 143–171 Hz, the rhodium(III) species by around 101 Hz. Measuring the splitting therefore tells you not only that the phosphorus sits on the metal, but which oxidation state the metal is in.

Phosphorus NMR can also follow processes that take place in solution. If a molecule interconverts between forms, or ligands move between positions on a metal, the spectrum reflects how fast this happens: while the process is fast the affected signals merge into a single, averaged one, and as it is slowed — usually by cooling the sample — the separate environments emerge, to be counted and measured. Wilkinson's catalyst shows this: at room temperature its phosphines exchange too quickly for the fine detail to appear, and only on cooling does the full coupling pattern resolve.

The immediate surroundings of a phosphorus can also be read from its coupling to hydrogens. The clean ³¹P{¹H} spectrum deliberately removes this coupling; recording the spectrum with the hydrogens left coupled brings it back, and the multiplicity that then appears reports the hydrogens near the phosphorus — one bonded directly to it produces a large splitting, while the smaller splittings from hydrogens a few bonds away are characteristic of groups such as phosphites and phosphonates. Whether or not to decouple is therefore a choice between a simpler spectrum and this added structural detail.

Reference — ³¹P shift map (85% H₃PO₄ = 0)

3¹¹B NMR

¹¹B NMR can be a very useful analytical tool for the structural determination of boron-containing compounds and, in particular, for establishing how the boron is coordinated.

Boron's more abundant isotope, ¹¹B, makes up about 80 % of natural boron. Unlike ¹⁹F and ³¹P, which are spin-½, ¹¹B has a higher spin — it is a quadrupolar nucleus — and such nuclei relax quickly. Fast relaxation broadens the lines, so a ¹¹B signal is broad rather than sharp. This costs some resolution, but the position of the signal — its chemical shift — still carries the information that matters most for boron. Shifts are quoted against boron trifluoride etherate (BF₃·OEt₂) at 0.

The ¹¹B shift reads the boron's coordination number — the number of groups attached to it. Three-coordinate boron, trigonal, with three attachments, resonates downfield; four-coordinate boron, tetrahedral, with a fourth group added, resonates upfield, towards and below zero. The position of the signal therefore identifies the coordination geometry.

A single molecule that can adopt both forms shows this directly. A neutral diazaborine, its boron three-coordinate through a B–OH group, resonates at δ 28.5; the same boron as its four-coordinate difluoroborate, with a fourth bond to fluorine, resonates at δ 3.0. The two are far enough apart that the shift alone establishes the geometry.

Boron moves readily between three- and four-coordinate forms as conditions change, which makes ¹¹B NMR fundamental to understanding how these boron species behave in solution.

The same fast relaxation that broadens boron's own signal also affects the atoms bonded to it. A carbon attached to boron is broadened in the ¹³C spectrum, often so much that it is not seen at all — so a quaternary carbon missing from an otherwise complete ¹³C spectrum is itself a sign of a carbon–boron bond. For the same reason, coupling to boron is usually not resolved: in the difluoroborate above, the two boron–fluorine bonds produce no visible splitting, the ¹⁹F and the ¹¹B each appearing as a single broad signal.

Reference — ¹¹B shift map (BF₃·OEt₂ = 0)