Carbon nonequivalence

Rotation about the carbon-nitrogen bond is slow in amides The methyl groups of NJ dimethylformamide are nonequivalent because one is cis to oxygen the other cis to hydrogen... 

An E-Z discrimination between isomeric oxaziridines (27) was made by NMR data (69JCS(C)2650). The methyl groups of the isopropyl side chains in the compounds (27) are nonequivalent due to the neighboring carbon and nitrogen centres of asymmetry and possibly due to restricted rotation around the exocyclic C—N bond in the case of the Z isomer. The chemical shift of a methyl group in (Z)-(27) appears at extraordinarily high field, an effect probably due to the anisotropic effect of the p-nitrophenyl group in the isomer believed to be Z. 

Consider a nucleus that can partition between two magnetically nonequivalent sites. Examples would be protons or carbon atoms involved in cis-trans isomerization, rotation about the carbon—nitrogen atom in amides, proton exchange between solute and solvent or between two conjugate acid-base pairs, or molecular complex formation. In the NMR context the nucleus is said to undergo chemical exchange between the sites. Chemical exchange is a relaxation mechanism, because it is a means by which the nucleus in one site (state) is enabled to leave that state. 

Consequently rotation about the carbon-nitrogen bond constitutes exchange of the methyl protons between nonequivalent sites, analogous to cis-trans isomerization ... 

When two resonance forms are nonequivalent, the actual structure of the resonance hybrid is closer to the more stable form than to the less stable form. I bus, we might expect the true structure of the acetone anion to be closer to the resonance form that places the negative charge on an electronegative oxygen atom than to the form that places the charge on a carbon atom. 

The information derived from 13C NMR spectroscopy is extraordinarily useful foT structure determination. Not only can we count the number of nonequivalent carbon atoms in a molecule, we can also get information about the electronic environment of each carbon and can even find how many protons each is attached to. As a result, we can answer many structural questions that go unanswered by TR spectroscopy or mass spectrometry. 

How many electronically nonequivalent kinds of protons and how many kinds of carbons are present in the following compound Don t forget that cyclohexane rings can ring-flip. 

Strategy Start with the straight-chain structure, stringing all five carbon atoms one after the other. Then work with structures containing four carbon atoms in a chain with one branch find all the nonequivalent structures of this type. Continue this process using a three-caibon chain, which is the shortest one that can be drawn for C5H12. 

The nonequivalent n orbital extension or the higher electron density in the exo face pyramidizes the unsaturated carbons The -H bonds are bent in the endo face. 

After the introduction of C-labels into the protein or glycoprotein molecule, the ability to assign the resonances to specific carbon atoms is essential. In the case of glycophorin (see Fig. 1), it may readily be seen that 5 lysine residues and 1 N-terminal amino acid (per species) can be reduc-tively di[ C]methylated. This could theoretically lead to 6 resonances (or possibly more, if chemical-shift nonequivalence is observed for the dimethyl species) in the C spectrum of methylated glycophorin A. However, in most cases, the N, N -di[ C]methyllysine resonances all occur near, or at, the same frequency. It is then necessary to be able at least to assign, or... 

The HETCOR spectrum of a naturally occurring isoprenylcoumarin is shown in Fig. 5.41. The spectrum displays one-bond heteronuclear correlations of all protonated carbons. These correlations can easily be determined by drawing vertical and horizontal lines starting from each peak. For example, peak A represents the correlation between a proton resonating at 8 1.9 and the carbon at 8 18.0. Similarly, cross-peaks E and F show that the protons at 8 4.9 and 5.1 are coupled to the same carbon, which resonates at 8 114.4 i.e., these are the nonequivalent protons of an exomethylenic... 

NMR provides one of the most powerful techniques for identification of unknown compounds based on high-resolution proton spectra (chemical shift type integration relative numbers) or 13C information (number of nonequivalent carbon atoms types of carbon number of protons at each C atom). Structural information may be obtained in subsequent steps from chemical shifts in single-pulse NMR experiments, homo- and heteronuclear spin-spin connectivities and corresponding coupling constants, from relaxation data such as NOEs, 7) s 7is, or from even more sophisticated 2D techniques. In most cases the presence of a NOE enhancement is all that is required to establish the stereochemistry at a particular centre [167]. For a proper description of the microstructure of a macromolecule NMR spectroscopy has now overtaken IR spectroscopy as the analytical tool in general use. 

This pattern of chemical-shift nonequivalence is also manifested by the nonanomeric carbon atoms. 

These new derivatives were isolated in good yields (60-94%) as high boiling liquids and were fully characterized by NMR spectroscopy (1H, 13C, and 11B) and elemental analysis. The proton NMR of the starting material 1 shows a well-resolved multiplet and quintet for the trimethylene bridge. Upon monosubstitution, however, three complex multiplets are observed, indicative of the unsymmetrical structures of these derivatives. Also, the nonequivalence of the N-C carbon atoms is clearly apparent in the 13C NMR spectra of 2-4. 

In the reactions mentioned in the preceding sections, several "stereoselective processes have been involved. Various examples have verified that the extension of singly-occupied MO determines the favorable spatial direction of interaction with other species. If there are two such nonequivalent directions in the molecule, the reaction will become stereoselective. Two or more hydrogen atoms attached to the same carbon atom are in some cases nonequivalent. Such a nonequivalence becomes a cause of stereoselectivity and has been explained theoretically. Also several cases have been mentioned in which some nucleophiles selectively attack the molecule from a certain spatial direction. 

Another common situation that can lead to second order spectra is an open chain system such as meso-l,2-difluoro-l,2-phenylethane whose magnetically nonequivalent spin system and resultant second order fluorine NMR spectrum (Fig. 2.7) can only be understood by examination of the contributing conformations about its fluorine bearing carbons.10... 

For 4,6-disubstituted dioxaboraphosphorinanes an increase in the share of the conformation with nonequivalent substituents at the carbon atoms is observed (C form). A comparison of the equilibria A+ C and B C indicates the C form to be more stable than form B, but less stable than... 

Both the 1 1 and the 1 2 bonded alkenes should show structural isomers, with, for the ethylene adduct, nonequivalence of the two protons bonded to the carbon. For substituted olefins, it is often possible to detect the presence of both isomeric forms, especially with the osmium derivatives. However, all these molecules are fluxional and the flux-... 

If there are at least three bonds between X and the observed carbon (C C8,. . . ), the geometric relation between the two atoms is no longer defined by bond lengths (/) and bond angles (4>) alone. In this situation relevant carbon atoms may be in stereochemically nonequivalent positions merely because of different torsional angles (t) between the X-C and the Cp-C7 bonds (e.g., Scheme 6). ... 

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