Coupling constants three-bond couplings

Eor a macromolecule such as a large protein, the steps in characterization involve, first, identification of the spin systems present, using correlated spectroscopy, and identification of neighboring amino acids. The long range noes are then assigned, and three bond coupling constants ate deterrnined. 

Following a detailed NMR study of the 3-substituted thietane dioxides 188 it was concluded that the three-bond coupling constants can be safely used for stereochemical assignments in this series in particular the 7rih4<4Hz (Table 7, R =H, X = C) is consistent with an equatorial-equatorial interaction. This indicates an axial preference for the 3-substituent R (i.e. 188b) in both liquid and solid phases, and also suggests that the ring is puckered . 

Elucidation of the stereostructure - configuration and conformation - is the next step in structural analysis. Three main parameters are used to elucidate the stereochemistry. Scalar coupling constants (mainly vicinal couplings) provide informa-hon about dihedral bond angles within a structure. Another way to obtain this information is the use of cross-correlated relaxation (CCR), but this is rarely used for drug or drug-like molecules. 

Three-bond coupling constants present even more problems concerning the question of solvent dependence than do the two-bond coupling constants. 

The observed ya-SCS(X) values in 7-exo-substituted norcaranes 97 (225) and those of M(CH3)3 (M = Si, Ge, Sn, or Pb) in cyclohexyl and bicy-clo[2.2. l]heptane derivatives (133) were later interpreted on the same basis. The back-lobe-overlap treatment was further supported by interpretations of H and 13C contact shifts of aliphatic amine signals in the presence of nickel acetyl-acetonate and by INDO calculations (226,227). Additional support came from extensive investigations of the structure dependence of three-bond coupling constants 3JCX (X = H, C, or F) (228,229), although the interpretation of these data has been subjected to criticism (230). 

The fluorine NMR spectrum of 3,3,3-trifluoropropene (Figure 5.14) provides a good example of the doublet observed for the trifluoromethyl group in such compounds, in this case at 69.9 ppm, with a three-bond coupling constant of only 4 Hz. 

As resolution increases, small couplings beyond three bonds often become noticeable as line broadening of the benzylic CH2 and CH3 peaks in Figure 3.34 and Problem 7.2, respectively (see Appendix F for coupling constants). 

The three-bond coupling constants, Vc H, between H(l) and the carbon a to C(2) for the E,Z pairs of trisubstituted enamines (viz 45-46) also allow the distinction between the E and Z isomers8. In line with that observed13 in vicinally disubstituted olefins, in the -isomers, having the 2-Me and H(l) in /raws-disposition, the coupling (Jtrans 6.9-7.1 Hz) is always larger than in the Z-isomers with the 2-Me and H(l) cis (Jcis 5.8-6.0 Hz). 

Si-N Bond Lengths (A), Bond and Dihedral Angles (deg.), and Corresponding Two-and Three-Bond Coupling Constants in Hexacoordinate Fluoro-Complexes50... 

Proton NMR spectra in organic molecules can be interpreted without regard to the structural carbon framework because the predominant 12C has no nuclear spin. However, 13C has a spin of V2, which not only permits its direct observation but also provides features in the H spectrum from the 13C that is present at a natural abundance of 1.1%. As we saw in Chapter 5, J(13C-H) is normally 100—200 Hz, whereas two- and three-bond coupling constants often run 5-10 Hz. Hence a resonance line from a proton attached to a 12C atom is accompanied by weak 13C satellites separated by 1J(13C-H) and placed almost symmetrically about the main line. (The departure from precisely symmetrical disposition arises from the 13C/12C isotope effect on the 1H chemical shift, as described in Section 4.8.) For example, the proton resonance of chloroform in Fig. 6.14a shows 13C satellites. 

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