Proton chemical shift data

Proton chemical shift data from nuclear magnetic resonance has historically not been very informative because the methylene groups in the hydrocarbon chain are not easily differentiated. However, this can be turned to advantage if a polar group is present on the side chain causing the shift of adjacent hydrogens downfteld. High resolution C-nmr has been able to determine position and stereochemistry of double bonds in the fatty acid chain (62). Broad band nmr has also been shown useful for determination of soHd fat content. 

Most of the multifluoro-substituted pyridines were prepared more than 30 years ago in the Birmingham fluorine group using CoF3 technology. Scheme 6.34 provides the multitude of fluorine and proton chemical shift data that were accumulated at that time. It will be seen that, all other things being equal, fluorines at the 2-position are most deshielded and fluorines at the 3-position are the most shielded. Scheme 6.35 provides a few examples of substituted tetrafluoropyridines. 

Table XIII summarizes proton chemical shift data for the three carbonium ion salts (Via, b, and c) and for the alcohols from which they were prepared by treatment with concentrated sulfuric acid or trifluoroacetic...

Figure 8. Graphical Comparison of Proton Chemical Shift Data for Model bis-Acetates 11a-l and the Peracetate Derivatives of Uvaricin (12), Rolliniastatin I (14), and Asimicin (15).

In that early work we relied much more on proton than carbon chemical shift trends. This was, in part, driven by the limited quantities of some of the twelve pure, synthetic, model compounds. However, the proton shift trends were also more meaningful than the carbon for this particular set of model compounds. It is our contention that proton chemical shift data should be used more frequently for this purpose and that this underutilization is largely a bias of technological origin. From the advent of C NMR spectroscopy chemical shift trends were recognized to be of primary importance. Relatively large field dispersion and the routine lack of coupling data predisposed... 

FIGURE 9 On-flow HPLC-UV chromatogram (229 nm) and H NMR detection of a I mg sample of ranitidine HCI spiked with its related substances A-C. UV absorbance data are presented on the y-axis, and proton chemical shift data are presented on the x-axis. 

Figure 8.22. Proton chemical shift data for furan, tetrahydrofuran, and two dihydrofurans showing the downfield shift, presnmably associated with a ring current, for the protons aronnd the periphery of the ring.

The proton chemical shifts of the protons directly attached to the basic three carbon skeleton are found between 5.0 and 6.8 ppm. The J(H,H) between these protons is about -5 Hz. The shift region is similar to the region for similarly substituted alkenes, although the spread in shifts is smaller and the allene proton resonances are slightly upfield from the alkene resonances. We could not establish a reliable additivity rule for the allene proton shifts as we could for the shifts (vide infra) and therefore we found the proton shifts much less valuable for the structural analysis of the allene moiety than the NMR data on the basic three-carbon system. 

The NMR spectra of heterocyclic compounds with seven or more ring members are as diverse as the shape, size and degree of unsaturation of the compounds. NMR is perhaps the most important physical method to ascertain the structure, especially the conformational statics and dynamics, of large heterocycles. Proton-proton coupling constants provide a wealth of data on the shape of the molecules, while chemical shift data, heteroatom-proton coupling constants and heteronuclear spectra give information of the electronic structure. Details are found in Chapters 5.16-5.22. Some data on seven-membered rings are included in Table 10. 

NMR chemical shift data from die protons ortho or para to the electron-withdrawing group can be used to determine the reactivity of the monomer indirecdy.58 Carbon-13 and 19F NMR can be used to probe the chemical shift at the actual site of nucleophilic reaction. In general, lower chemical shifts correlate widi lower monomer reactivity. Carter reported that a compound might be appropriate for nucleophilic displacement if the 13 C chemical shift of an activated Buoride ranges from 164.5 to 166.2 ppm in CDC1359. 

The only physical property which has been studied for substituted vinylidene sets is the nmr chemical shift of the vinylidene proton in substituted ethylenes and in tra s-l,2-disubstituted ethylenes. The first attempt at correlating chemical shift data for substituted ethylenes with the Hammett equation appears to be the work of Banwell and Sheppard (53), who reported a correlation of A2 values with the or constants, the A2 values being defined by the equation... 

H NMR data has been reported for the ethylzinc complex, Zn(TPP—NMe)Et, formed from the reaction of free-base N-methyl porphyrin H(TPP—NMe) with ZnEti. The ethyl proton chemical shifts are observed upheld, evidence that the ethyl group is coordinated to zinc near the center of the porphyrin. The complex is stable under N2 in the dark, but decomposed by a radical mechanism in visible light.The complex reacted with hindered phenols (HOAr) when irradiated with visible light to give ethane and the aryloxo complexes Zn(TPP—NMe)OAr. The reaction of Zn(TPP—NMe)Et, a secondary amine (HNEt2) and CO2 gave zinc carbamate complexes, for example Zn(TPP—NMclOiCNEti."" ... 

Larger solvent effects can be observed for proton spectra, particularly when using benzene- - As can be seen from the data in Table 2.4, proton chemical shifts in the other solvents, particularly CDC13 and acetone-, are reasonably consistent. 

Although the spectra of fluorine containing compounds are non-exceptional, other than for the F—H coupling, and are highly predicable, typical proton chemical shift and coupling constant data will be provided within each chapter for each class of fluoroorganic compound. 

Characteristic 1H and 13C NMR Data. The examples in Scheme 3.7 provide relevant proton and carbon chemical shift data. 

Some typical proton and carbon chemical shift and coupling constant data for allylic and benzylic systems are given in Scheme 3.54. An alkenyl substituent or a phenyl substituent on either a CH2F or a —CHF- group has virtually no effect upon that carbon s chemical shift, and they also only affect the proton chemical shift by about 0.5 ppm. 

Carbon and Proton NMR Data. Some typical carbon and proton chemical shift and coupling constant data for fluorothiophenes are given in Scheme 3.70. Note that the two-, three-, and four-bond F—C... 

Typical proton and carbon chemical shift data for heterocycles bearing a CF2H group and, in the case of pyridine, a CF2R group are provided in Scheme 4.59. 

Unfortunately, it is impossible to cover all the potential pitfalls that wait for the unwary. Many more will come to light in the following chapters but for now we will concentrate on supplying you with useful proton NMR chemical shift data... We have done this by collating various types of protons into convenient groups, but first, let s clear the wood from the trees and deal with commonly encountered solvents and impurities in the regularly used NMR solvents. 

Figure 5. Dependence of corrected proton chemical shifts on charge density. See Table 1 for data and references.

Figure 9. Charge dependence of proton chemical shifts of methyl groups on ions. See Table 2 for data and references, o Raw data corrected for ring current coirected for ring current and. ...

Figure 10. Correlation of proton chemical shifts of methyl groups in carbonium ions with carbon-13 shifts of the adjacent trigonal carbon atoms. See Table 3 for data and references, o Aryldimethylcarbonium ions cycloalkcnyl cations a phenylmethyl-carbonium ions.

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