Protons, carbon-attached, chemical shift

HETCOR (Section 13 19) A 2D NMR technique that correlates the H chemical shift of a proton to the chemical shift of the carbon to which it is attached HETCOR stands for heteronuclear chemical shift correlation Heteroatom (Section 1 7) An atom in an organic molecule that IS neither carbon nor hydrogen Heterocyclic compound (Section 3 15) Cyclic compound in which one or more of the atoms in the nng are elements other than carbon Heterocyclic compounds may or may not be aromatic... 

Proton and Carbon-13 Chemical Shifts for Methyl Groups Attached to Carbonium Ion Centres... 

Multinuclear NMR data for homologous senes of fluoromethylated malo-nates [72] and trimethylsilanes [97] are compiled in Table 11. In both senes, fluoromethyl attachment is to a quaternary site These compounds are readily synthesized using fluorohalomethanes to incorporate the final fluoromethyl moiety All the malonates, except diethyl methyltnfluoromethylmalonate (4) [93], are isopropyl-substituted diethyl esters [72]. The silane data, with the exception of trimethyltrifluoromethylsilane (5) [95], are from reference 97 Chemical shift data are very comparable, with the malonates having higher proton and fluorine chemical shifts but slightly lower carbon values. The magnitudes of cf and 2J jp coupling are similar for both sets of compounds. 

For protons attached to atoms other than carbon the chemical shifts of protons attached to oxygen increase with increasing acidity of the O-H group thus 5=1—6 ppm for alcohols, 4-12 ppm for phenols and 10-14 ppm for carboxylic acids. Hydrogens bound to nitrogen (1° and 2° amines) are found at 5 = 3—8 ppm. The approximate chemical shift regions are shown in Fig. 29.5. 

Two-dimensional NMR resulted naturally from pulse programming concepts [20]. The basic idea is that a second dimension could be simulated by acquiring a series of spectra in which a delay period in the pulse sequence was incrementally increased. In what seemed at first like pure magic, it became possible, for example, to correlate a carbon s chemical shift in one dimension with the proton chemical shift of its attached proton in a second dimension. Again, the ingenuity for designing pulse programs to tease out the data of interest was boundless, and development of new experiments has continued unabated until the present. 

HETCOR A 2D NMR technique that correlates the chemical shift of a proton to the chemical shift of the carbon to which it is attached. HETCOR stands for heteronuclear chemical shift correlation. 

The heteronuclear shift correlated 2D-NMR spectrum of a cyclic peptide, cyclo(Pro-Phe-Gly-Phe-Gly), is presented in Figure 5.53. The proton chemical shifts (0-5 ppm) are on the horizontal axis while the chemical shifts (20-70 ppm) are on the vertical axis. The cross peaks establish the interconnection between the chemical shifts of protons and the chemical shifts of carbon atoms to which those protons are attached. 

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 induced field of a carbonyl group (C=0) deshields protons in much Ihe same way lhal a carbon-carbon double bond does and Ihe presence of oxygen makes il even more eleclron wilhdrawmg Thus protons attached to C=0 m aldehydes are Ihe leasl shielded of any protons bonded to carbon They have chemical shifts m Ihe range 8 9-10... 

A second 2D NMR method called HETCOR (heteronuclear chemical shift correlation) is a type of COSY in which the two frequency axes are the chemical shifts for different nuclei usually H and With HETCOR it is possible to relate a peak m a C spectrum to the H signal of the protons attached to that carbon As we did with COSY we 11 use 2 hexanone to illustrate the technique... 

A nitrogen atom at X results in a variable downfield shift of the a carbons, depending in its extent on what else is attached to the nitrogen. In piperidine (45 X = NH) the a carbon signal is shifted by about 20 p.p.m., to ca. S 47.7, while in A-methylpiperidine (45 X = Me) it appears at S 56.7. Quaternization at nitrogen produces further effects similar to replacement of NH by A-alkyl, but simple protonation has only a small effect. A-Acylpiperidines show two distinct a carbon atoms, because of restricted rotation about the amide bond. The chemical shift separation is about 6 p.p.m., and the mean shift is close to that of the unsubstituted amine (45 X=NH). The nitroso compound (45 X = N—NO) is similar, but the shift separation of the two a carbons is somewhat greater (ca. 12 p.p.m.). The (3 and y carbon atoms of piperidines. A- acylpiperidines and piperidinium salts are all upfield of the cyclohexane resonance, by 0-7 p.p.m. 

Substituent effects (substituent increments) tabulated in more detail in the literature demonstrate that C chemical shifts of individual carbon nuclei in alkenes and aromatic as well as heteroaromatic compounds can be predicted approximately by means of mesomeric effects (resonance effects). Thus, an electron donor substituent D [D = OC//j, SC//j, N(C//j)2] attached to a C=C double bond shields the (l-C atom and the -proton (+M effect, smaller shift), whereas the a-position is deshielded (larger shift) as a result of substituent electronegativity (-/ effect). 

Most 13C spectra are run on Fourier-transform NMR (FT-NMR) spectrometers using broadband decoupling of proton spins so that each chemically distinct carbon shows a single unsplit resonance line. As with NMR, the chemical shift of each 13C signal provides information about a carbon s chemical environment in the sample. In addition, the number of protons attached to each carbon can be determined using the DEPT-NMR technique. 

One disadvantage of the APT experiment is that it does not readily allow us to disdnguish between carbon signals with the same phases, i.e., between CH3 and CH carbons or between CH2 and quaternary carbons, although the chemical shifts may provide some discriminatory information. The signal strengths also provide some useful information, since CH3 carbons tend to be more intense than CH carbons, and the CH2 carbons are usually more intense than quaternary carbons due to the greater nuclear Overhauser enhancements on account of the attached protons. 

The heteronuclear multiple-quantum coherence (HMQC) spectrum, H-NMR chemical shift assignments, and C-NMR data of podophyllo-toxin are shown. Determine the chemical shifts of various carbons and connected protons. The HMQC spectra provide information about the one-bond correlations of protons and attached carbons. These spectra are fairly straightforward to interpret The correlations are made by noting the position of each crossf)eak and identifying the corresponding 8h and 8c values. Based on this technique, interpret the following spectrum. 

The HMQC spectrum of podophyllotoxin shows heteronuclear crosspeaks for all 13 protonated carbons. Each cross-peak represents a one-bond correlation between the C nucleus and the attached proton. It also allows us to identify the pairs of geminally coupled protons, since both protons display cross-peaks with the same carbon. For instance, peaks A and B represent the one-bond correlations between protons at 8 4.10 and 4.50 with the carbon at 8 71.0 and thus represent a methylene group (C-15). Cross-peak D is due to the heteronuclear correlation between the C-4 proton at 8 4.70 and the carbon at 8 72.0, assignable to the oxygen-bearing benzylic C-4. Heteronuclear shift correlations between the aromatic protons and carbons are easily distinguishable as cross-peaks J-L, while I represents C/H interactions between the methylenedioxy protons (8 5.90) and the carbon at 8 101.5. The C-NMR and H-NMR chemical shift assignments based on the HMQC cross-peaks are summarized on the structure. 

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