C-Methyl groups

The acidic character of the hydrogen atoms of C-methyl groups linked to the pyrazolium ring (Figure 22 Section 4.04.2.1.1(11)) facilitates a number of reactions difficult to carry out with neutral pyrazoles. Since efficient methods of dealkylation have been described (Section 4.04.2.3.lO(ii)), the synthesis via the pyrazolium salt is a useful alternative. The same behaviour is observed for indazolium salts, for example, nucleophilic addition to aromatic aldehydes (78JOC1233). 

The mass spectra of primary mono- and diaminoquinoxalines (with or without additional C-methyl groups) have been measured and analyzed. The role of N-pyridinyl-A -(quinoxalinylethyl)thiourea derivatives as HIV-1 (human immunodeficiency 1) reverse transcriptase inhibitors has been discussed in detail. 

C-methyl group or 4 -C-azido group in nucleoside analogues targeting the hepatitis C virus (HCV) RNA polymerase NS5B. 

Considerable deuteriation occurs at the C-methyl group when the salt (107) is treated with methan[2H]ol-sodium methoxide, indicating that the resonance-stabilized anion (108) is formed as well as the ylide (109),... 

In the apparatus described above C-methyl groups can also be... 

Fig.4 Comparison of background levels in [ C, H]-HSQC spectra of bacterial samples grown on C-methyl group labeled methionine without over-expression (A) and with over-expression of calmodulin (B). The spectrum in C was measured with a smaller spectral width as the spectrum in B. Only the free methionine and the nine methionine resonances of calmodulin are visible. Reprinted with permission from Serber et al., 2004...

It is perhaps worth mentioning that substitution of other groups for the C-methyl group in amidinium ions has an effect on their pA a-values, which is best correlated with Hammett s -constants (p = —1T98), and the same is true of C-substituted N-phenylami-dinium ions (p = —12-08) (Charton, 1965). This is in line with the suggestion made on page 286, that -constants are a measure of the inductive and mesomeric interactions of groups with a carbon in the sp state of hybridization. 

The kinetically controlled protonation method may also be applied to the determination of the conformational free energy of C-methyl groups in piperidines. For example, protonation of 1,5-dimethylpiperidine (in which 13C is located in the /V-CH3 group) in dodecane and estimation of the ions produced by 13C-NMR spectroscopy gives AG20° of 1.5 0.1 kcal mol-1 for the 3-methyl group.169... 

The conformational free energies of C-methyl groups in piperidine and yV-methylpiperidine have been estimated183 by low temperature ( — 80 to... 

Martin B. Neuworth The Kuhn-Roth method has a number of limitations. These were discussed by Brandenberger et al. (Anal. Chem. 33, 453 (1961)). The normal method for estimating C-methyl groups is based on a determination of total acidity calculated as acetic acid. Brandenberger has shown that other acids can be produced during the oxidation—e.g., benzoic acid, and these acids steam distil with the acetic acid. Therefore, when the classical Kuhn-Roth procedure is applied to a substance like coal, it would lead to methyl group values of questionable significance. 

Variable temperature 13C NMR spectroscopy has shown that the 1,2,3,4,5,6-hexamethyl-hexahydro-l,2,4,5-tetrazine (57) is the trans isomer with the two C-methyl groups equatorial and the N-methyl groups symmetrically diaxial and diequatorial. The observed dynamic 13C NMR effects are consistent with (57a) and (57b) as the major conformation and probably (57c) as the minor one. The first coalescence represents the freezing out of (57c) while the (57a) (57b) interconversion remains fast. The nitrogen inversion barrier was found to be 32.2 kJ moF1 <79JCS(P2)98l). The He(I) photoelectron spectrum of (57) confirmed the NMR data (80JCS(P2)9l). 

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