Methylene carbons, attached proton

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. 

Correlations of Methylene and Methine Protons with Attached Carbons... 

Obviously we cannot however simply correlate the signal intensities with the presence of attached protons. So relaxation must also play a very important role. Relaxation times T, for carbon atoms also depend on whether these are protonated or not, and while T, for methyl or methylene groups may only be a few seconds, it may be as long as around 2 min for quaternary carbons Now the choice of an ideal relaxation delay becomes impossible, and so we have to make compromizes, which result in the large variations in signal intensity. 

In the side chain of cholesteryl chloride C atoms with the same number of attached protons are found to behave similarly [166] the methyl carbon atoms C-26 and C-27 relax more slowly than C-21, the methylene carbon C-24 slower than C-23, and the methine carbon atom C-25 slower than C-20. The mobility of the side chain thus increases with increasing distance from the steroidal skeleton. 

A second difficulty of fully decoupled 13C NMR spectra is that die connectivity in the molecule is difficult to establish (except by chemical shift correlation) because coupling patterns are absent. This dilemma is partially resolved by die use of a technique called off-resonance decoupling. In off-resonance decoupled 13C spectra, the carbons are coupled only to diose protons directly attached to diem and die coupling is first order. Thus quaternary carbons are singlets, methine carbons are doublets, methylene carbons are triplets, and methyl carbons are quartets. It is possible to use diis information to establish proton-carbon connectivity,... 

The carbons of l,2-epoxy-5-hexene can be assigned from the off-resonance decoupled spectrum (Figure 11.32). In the fully decoupled spectrum it is clear that the olelinic carbons ( 115 and 1385) are distinct from die epoxide carbons ( 47 and 525) and from the methylene carbons ( 30 and 325), but it is not possible to assign which is which. In the off-resonance decoupled spectrum, both the olelinic and epoxide carbons are distinguished by their splitting patterns from the numbers of directly attached protons. The methylene carbons, however, are both triplets and cannot be distinguished. 

The other experiment worth mentioning, which, by the way, is also obsolete, is the attached proton test or APT. This experiment is based on the different magnitudes of Tl—13C coupling for methine, methylene, and methyl groups. By adjusting certain delays in the pulse sequence (not given), quaternary and methylene carbons could be phased up, and methine and methyl carbons could be phased down. Since phase is arbitrary, this order could be reversed. This ability of distinguishing... 

We can begin with either a carbon or a proton resonance and obtain equivalent results. We will use the carbon axis as our starting point because we usually have less overlap there. For example, a line drawn parallel to the proton axis at about 68 ppm on the carbon axis (the carbinol carbon) intersects five cross peaks none of the five correlations corresponds to the attached proton (VCH) at 3.8 ppm. Four of the cross peaks correspond to the two pairs of diastereotopic methylene groups (2.48, 2.22,1.45, and 1.28 ppm) and these represent, 2iCH, or two-bond couplings. The fifth interaction (3/CH) correlates this carbon atom (68 ppm) to the isopropyl methine proton (1.82 ppm), which is bonded to a carbon atom in the /3-position. The other carbon atom in a /3-position has no attached protons so we do not have a correlation to it from the carbinol carbon atom. Thus, we have indirect carbon connectivities to two a-carbons and to one of two /3-carbons. 

Another useful example can be found by drawing a line from the carbon resonance at 41 ppm. This carbon is the C-5 methylene and we first note that correlations to the attached protons at 2.48 and 2.22 ppm are absent. There is only one a-carbon that has one or more attached protons its corresponding correlation is found to the C-4 carbinol methine proton at 3.83 ppm. There are three /3-carbons and they all have attached protons. The C-3 methylene carbon shows indirect correlation through both of its diastereotopic protons at 1.45 and 1.28 ppm. The C-7 olefinic methine proton gives a cross peak at 6.39 ppm as do the protons of the olefinic methylene group attached to C-6 at 5.16 and... 

APT is a technique for -decoupled 13C spectra, which uses the phase (normal or upside down) of the 13C peaks as a way to encode information about the number of protons attached to a carbon Cq (quaternary carbon, no protons), CH (methine, one proton), CH2 (methylene, two), or CH3 (methyl, three). These spectra are called edited because the phase (positive absorptive or negative absorptive) is modified relative to a normal 13C spectrum in order to encode additional information. APT gives all of the information of a normal carbon spectrum with somewhat reduced sensitivity, and it tells you whether the number of attached protons is odd (CH3 or CH) or even (CH2 or quaternary). 

This used to be a common way of distinguishing methyl, methylene and methine carbons. However, as can be seen in the spectrum above, it is not a clean experiment methylene carbons with non-equivalent protons attached often give particularly messy results ( 8.2.2). /-modulated spin-echoes, INEPT or DEPT provide much more reliable ways of determining multiplicities ( 3.3.2 and 8.5). 

Interrupted-Proton-Decoupling Experiments. Interrupted-pro-ton-decoupling experiments were carried out with a 50- xs interruption. This technique selects quaternary carbons (those lacking an attached proton) and rapidly moving methyl carbons. Resonances from methylene and methine carbons are suppressed unless, for some reason, their motion within the solid occurs at a rate similar to that of methyl groups. In essence, the interrupted-proton-decoupling experiment, which has not been previously reported for amber samples, provides an alternative fingerprint for the samples. 

CH2, Jqh - 189 Hz). Thus all three methylene carbons are identical, and the protons attached to each of them are nonequivalent. Equilibrating classical cyclopropylcarbinyl cations can be ruled out not only based on substantially shielded averaged methylene carbon NMR shift, but also due to the presence of nonequivalent geminal protons on each of the methylene carbons. A pentacoordinated nonclassical bicyclobutonium ion can account for the observed results. The proton NMR absorptions at 3 4.64 and 4.21 are assigned to the endo- and exo-methylene hydrogens, respectively, based on the NMR spectra of the stereospeciflcally deuteriated cyclopropylcarbinyl cations The endo-deuteriated cyclopropylcarbinyl cation was prepared from alcohol 5a, whereas a 1 1 mixture of endo- and exo-deuteriated cations were prepared from alcohol 5b (equations 10 and 11). 

NMR experiments, involving iH-lH-COSY, DQC-COSY, 1H- 3C-HETCOR, 1H-13C-COLOC and iR-lH-NOESY techniques, have been used in order to determine unambiguously the swainsonine structure and its 1,2,8-triacetate [162]. Four methylene and four methyne protons are evident in the spectrum of swainsonine in its IH- C-HETCOR NMR spectrum, the most downfield carbon resonance (5 75.23) is the methyne carbon connected to nitrogen (C-8a), and the chemical shift of the attached proton (H-8a) is observed at 5 1.89 (dd, J= 10.4 Hz). H-8a is coupled to H-8 (6 3.77, ddd, J= 11, 10, 4 Hz), as well as to H-1 (8... 

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