Fluorine and phosphorus NMR

Fluorine and phosphorus are the two heteroatoms in organic chemistry most frequently studied by NMR after hydrogen and carbon. 

Phosphorus ( P,/= 1/2) another common monoisotopic element, has been studied since the beginnings of NMR. It has a great sensitivity and it is an important element in the composition of numerous biological compounds. 

CHAPTER 15 - NUCLEAR MAGNEHC RESONANCE SPECTROSCOPY CFCI3 

Scale given In ppm with respect to the reference compounds 

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The principle behind NMR is that, when a molecule is placed in a strong external magnetic field, certain nuclei of atoms within the molecule, such as H, 13C, 15N, 19F and 31P, will resonate as they absorb energy at specific frequencies that are characteristics of their electronic environment. Because most drug and protein molecules are composed of hydrogen, carbon, nitrogen, fluorine and phosphorus, NMR is ideally suited to unravel structural information of drugs and proteins. 

The identity of RN(PF2)2 compounds can be confirmed by their quantitative reaction with hydrogen chloride (237) and by their characteristic fluorine and phosphorus NMR spectra (239) (Section XI). 

The identity of phosphinodifluorophosphine was confirmed by proton, fluorine, and phosphorus NMR studies (Section XI) and by observation of the parent ion in the mass spectrum 275). 

As we have already pointed out in the section dealing with heteronuclear coupling that it is not always necessary to confirm the presence of a particular hetero atom by acquiring the NMR spectrum of that nucleus. More often than not, the hetero atom will have a clear signature in the proton or carbon spectrum. Fluorine and phosphorus are both examples of nuclei that couple to protons over two, three, four and even more bonds. 

Gonen, O., Murphy-Boesch, J., Li, C. W., et al. (1997) Simultaneous 3D NMR spectroscopy of proton-decoupled fluorine and phosphorus in human liver during 5-fluorouracil chemotherapy. Magnetic Resonance in Medicine, 37, 164-169. 

Azo dyestuffs derived from sulphonated 1- and 2-naphthols have been studied by means of l3C NMR spectroscopy.95 100 In azo dyes containing fluorine and phosphorus and in 15N-labelled compounds the appropriate y(X,13C) coupling constants have been found. Typical values of these constants are shown in Tables 7, 10, 11 and 14. 

Figure 15.27 Positions of some NMR signals due to fluorine and phosphorus.

The most commonly studied atom is hydrogen ( H-NMR). Other atoms that can be studied are carbon, fluorine and phosphorus. A NMR spectrum consists of absorption peaks from which information on functional groups and relative number of hydrogen atoms can be retrieved. 

NMR is an extremely powerful method for observing the environment of an atom of interest. The element most commonly studied is hydrogen bonded to another element, usually carbon, and is referred to as NMR spectroscopy (sometimes called HNMR, H NMR, P NMR, or proton NMR). The second most commonly studied element is carbon, specifically 13C, bonded to other carbon atoms and to hydrogen atoms. Other elements commonly measured include fluorine, nitrogen, and phosphorus. 

NMR is a valuable technique in the analysis of lipid phases. More specifically, proton, deuterium, carbon-13, fluorine-19, and phosphorus-31 NMR have been utilized for analysis of the dynamic and motional properties of lipids, lipid diffusion, ordering properties, head-group hydration, lipid asymmetry, quantitation of lipid composition, and head-group conformation and dynamics. Cullis et al. and Gruner et al. have shown the importance of P-31 NMR as a tool in the determination of phase properties and lipid asymmetry and the identification of bilayer, hexagonal, and isotropic phases. 

Now that the principles of NMR spectroscopy have been introduced, we will see how NMR spectra of the two most common nuclei—hydrogen and carbon-13—are obtained. The principles described for carbon-13 are applicable to many other spin- /2 nuclei, such as nitrogen-15, fluorine-19, silicon-29, and phosphorus-31. Topics to be discussed include the components of a typical NMR spectrometer, preparation of a sample, signal optimization techniques, spectral acquisition, selection of processing parameters, spectral presentation, and calibration of the spectrometer. 

The NMR spectrum of the recently synthesized 1,3-ditertiary-butyl-2,4-difluorodiazadiphosphetidine (which is an XAA X spin system X = fluorine, A = phosphorus) has been analysed and the trans-annular phosphorus-phosphorus coupling constant found to be 92.5 Hz 260a). 

The outer P atoms show a doublet at -10 ppm, the inner P atom is represented by a triplet at -25 ppm. The large coupling constant (864 Hz) between the fluorine and the phosphorus nucleus (Figure 3-49) is worth mentioning, which is of course found in the P NMR spectrum as well as in the NMR spectrum. 

For ligands with suitable proton, fluorine, or phosphorus atoms, low-temperature NMR studies are informative and reveal either the 3 2 or 4 1 ratio. 

Determination of the ratio of end-groups to monomeric units in systems of another type must be mentioned. Suppose that the end-group contains an element readily detected by NMR, such as fluorine or phosphorus, and that the bodies of the macromolecules are free from that element. Clearly, determination of, say, the fluorine content of the whole polymer could lead to a value of the required ratio. It is necessary to use as a standard a properly... 

Other nuclei besides hydrogen ( H) that have a spin of i or greater, and are used in NMR studies, include deuterium ( H), fluorine ( F), carbon-13 ( C), nitrogen-14 and -15 ( N and N), and phosphorus-31 ( P). Much higher resolutions are often possible with these nuclei, aUowing exact sequences of structures to be determined along the chain. 

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