H COSY

In principle it is possible with many modern spectrometers to carry out correlation experiments using any two NMR-active nuclei, and we shall demonstrate this below by discussing P,C and P,P correlations. 

H COSY spectrum of model compound 1 is shown in Fig. 24. In fact you can see a total of three spectra the central square which is the actual 2D spectrum and two proton 1D spectra at the top and on the left. The computer software generates this combination of spectra automatically using a previously recorded ID proton spectrum. 

A glance at the proton spectra shows that the OH proton is missing, and when we look at the numbers along the axes we can see that in fact only the range from about 1.2 to 7.2 ppm is covered. This is a principle of 2D only record the part of the spectrum which contains useful information Since we want to find out which nucleus couples with which, we do not need to record the OH signal as we already know that it is a singlet. 

The previous experiment (COSY) demonstrated the interactions (J coupling) between protons via the bonding electrons. The NOE effect which we described in Section 1.1.6 functions because of the through-space interactions between protons, and we used the NOE difference and selective NOE experiments to demonstrate it. 

NOE effects can naturally also be investigated by 2D experiments these are known as NOESY and ROESY. 

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Figure Bl.11.12. H- H COSY-45 2D NMR spectrum of methyl-a-gliicopyranose (structure shown). The coupling links and the approximate couplings can be deduced by inspection.

Section 13 19 2D NMR techniques are enhancements that are sometimes useful m gam mg additional structural information A H H COSY spectrum reveals which protons are spin coupled to other protons which helps m deter mining connectivity A HETCOR spectrum shows the C—H connections by correlating C and H chemical shifts... 

Figure 3.10 Effect of different window functions (apodization functions) on the appearance of COSY plot (magnitude mode), (a) Sine-bell squared and (b) sine-bell. The spectrum is a portion of an unsymmetrized matrix of a H-COSY I.R experiment (400 MHz in CDCl, at 303 K) of vasicinone. (c) Shifted sine-bell squared with r/4. (d) Shifted sine-bell squared with w/8. (a) and (b) are virtually identical in the case of delayed COSY, whereas sine-bell squared multiplication gives noticeably better suppression of the stronger dispersion-mode components observed when no delay is used. A difference in the effective resolution in the two axes is apparent, with Fi having better resolution than F. The spectrum in (c) has a significant amount of dispersion-mode line shape.

Figure 7.17 Pulse sequence for soft H,H-COSY with two selective pulses exciting the / multiplet and the second mixing pulse exciting the li multiplet of a three-spin system (/, /,)). (Reprinted from Mag. Reson. Chem. 29, H. Kessler et al., 527,...

The important experiments for our purposes are the correlation experiments, where both axes are chemical shift axes. Certainly the most useful of these is the proton-proton correlation experiment, initially known as COSY (for Correlated SpectroscopY) and now, to make things more precise, as H,H COSY. This experiment is important, as it provides direct information on which proton nuclei couple with which. 

Fig. 24 H,H COSY spectrum of compound 1 in CDC13, measurement time 3.5 min...

P,H COSY with Varying Mixing Times for the Coupling... 

The stopped-flow technique also allows us to obtain spectra which require relatively long measuring times as an example we show the H,H-COSY spectrum (Fig. 36) of peak 8 (retention time 3 min). 

FIGURE 4.10 Stopped-flow H H-COSY NMR spectrum of (all- ) lycopene. (From Albert, K., On-Line LC-NMR and Related Techniques, John Wiley Sons Ltd., 131, 2002. With permission.)... 

The configurations of bis-aminals 68 were determined by analysis of 13C NMR data <2002T5733>. One-, and two-dimensional homo-, and heteronuclear studies ( H, 13C, H- H COSY, HMQC, and HMBC) were conducted for the first time to determine the structures of three stereoisomeric 2-methylperhydro-93-azaphenalcnc alkaloids 45 <1999MRC60>. Complete assignment of H and 13C NMR spectra of compound 86, which is a derivative of 3, has been reported <2002T5733>. The 13C NMR spectrum of compound 98 is consistent with a Cz symmetry <1996JOC4125>. 

Using a variety of NMR 2-D techniques, such as H-H COSY, C-H COSY, DEPT, HMBC, and NOESY, an accurate assignment of the signals of 18 a-(5-substituted-2-hydroxyaryl)-7V-aryl nitrones has been made (159). 

The transfer of magnetization is not restricted to protons as in the H- H COSY experiment, but can also be applied between other nuclei (i.e., H-13C-correlation or 31P-31P correlation experiments). 

Hirota and coworkers41 reported a planar structure of new polyene macrolide antibiotic YS-822A (65), which they isolated. XH and 13C NMR spectra of 65 showed a number of broad and overlapping signals, but the 1H-1H and 13C- H COSY spectra implied the existence of a mycosamine moiety and several other partial structures. The connectivity of these partial structures was established by extensive 2D NMR experiments, including homonuclear Hartmann-Hahn and heteronuclear multiple-bond connectivity measurements, which led to the determination of the gross planar structure of 65. 

Although ID XH and 13C NMR spectra of 65 in DMSO-dg showed a number of broad and overlapping signals, the 13C- H COSY spectrum afforded the assignment... 

FIGURE 14. H- H COSY spectrum of YS-822A (65) in DMSO-d6(300 K). Reproduced by permission of Japan Antibiotics Research Association from Reference 41... 

The 13C and XH NMR data are summarized in Table 26. All one-bond 1H-13C connectivities were determined by a 13C- H COSY experiment. 1H-1H COSY, NOESY and long-range 13C-XH COSY experiments indicated a partial structure of C13H21NO containing an amide as depicted in Figure 25. The geometry of the double bond (2, 3 ) was established as E by measurement of the 3/(CH) value (8.3 Hz) between Cl and H3 in a nondecoupled 13C NMR spectrum. 

FIGURE 27. Partial structures of viridenomycin. (a) Data from H- H COSY experiment (b), (c) The solid line arrows indicate H-13C long-range coupling detected by HMBC... 

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