Deuterated compounds Pyridine

The deuterium nucleus is an excellent probe of anisotropic motion, since one can readily monitor the stereochemical dependence of relaxation times and then deduce the reorientational parameters (1,2,12). The use of H NMR to detect segmental motions was described above. In another study relaxation times (Tj ) were measured for a large number of deuterated compounds (12) and analyzed in terms of isotropic or anisotropic motions. Pyridine-d5, for example, exhibited equality in Ti values for all positions (1.2 0.1 s), which was taken to be indicative of r id isotropic molecular reorientation. In the case of [2,4,6- H3]benzaldehyde, the relative Tj values, para position less than ortho positions, indicated anisotropic motion with rotation about an axis through the para C- H bond being more rapid than that about the other two orthogonal axes (12). 

Katritzky et al.509 have also made a kinetic study of the deuteration of substituted pyridine-l-oxides (Table 147). For the 2,4,6-trimethyl compound, the rate-acidity profile shows the conjugate acid to be reacting. The slope of the plot, however, was less (0.33) than that (0.56) obtained for 2,4,6-trimethylpyridine... 

Kinetic studies of base-catalysed hydrogen exchange of heterocyclic compounds have been carried out. Paudler and Helmick515 measured second-order rate coefficients for deuteration of derivatives of imidazo[l,2-a]pyridine(XXXIII), imidazo[l,2-a]pyrimidine(XXXIV), and 1,2,4-triazolo[1,5-a]pyrimidine(XXXV)... 

The divalent Co(salen) complex (69a) is one of the most versatile and well-studied Co coordination compounds. It has a long and well-documented history and we shall not restate this here. Recent applications of (69a) as both a synthetic oxygen carrier and as a catalyst for organic transformations are described in Sections 6.1.3.1.2 and 6.1.4.1 respectively. Isotropic shifts in the HNMR spectrum of low-spin Co(salphn) (69b) were investigated in deuterated chloroform, DMF, DMSO, and pyridine.319 Solvent-dependent isotropic shifts indicate that the single unpaired electron, delocalized over the tetradentate 7r-electron system in CHCI3, is an intrinsic property of the planar four-coordinate complex. The high-spin/low-spin equilibrium of the... 

The pyridine-catalyzed aromatic proton exchange with deuterium provides a simple indication of the ability of a phenol to participate in chromene formation. Only those phenols which undergo exchange react with the unsaturated carbonyl compound, the attack occurring at the positions of deuteration (64JA2084). 

Separation of five compounds (DL, 6-OH-DL, 3-OH-DL, 7V-OH-DL, and 1-pyridine-/V-oxide-DL) was achieved using an Alliance HPLC system (Waters Corp., Milford, CA) equipped with a 2690 model pump, an autoinjector, a Polaris Cl8-A guard column (Varian Inc., Lake Forest, CA), and a Luna Phenyl-Hexyl analytical column (Phenomenex, Inc., Torrance, CA) maintained at 40°C. For robust characterization of each isomeric compound, an online HDX LC-MS method was developed. The composition of regular and deuterated mobile phases is summarized below ... 

None of the LC-MS experiments, under deuterated or nondeuterated conditions, provided a means for distinguishing hydroxylamine A-OH-DL from 1-pyridine-A-oxide-DL, and therefore these compounds were further investigated by LC-MS/MS. 

To demonstrate that the proposed methods are suitable for structural elucidation of isomeric metabolites and derivatives in biological matrices, human plasma was spiked with the mixture of DL, 6-OH-DL, 3-OH-DL, /V-OH-DL, and 1-pyridine-/V-oxide-DL. The resulting sample was extracted and analyzed by LC-MS and LC-MS/MS in ESI and APCI modes as described above. HDX was successfully performed online when the extract was injected directly onto the HPLC column without drying and reconstituting the sample in a deuterated solvent. In general, there were no differences between the results obtained for the spiked plasma extract and for the mixture of the standard compounds, which indicates that the LC-MS methods with HDX described here are applicable for the analysis drug-derived material in plasma or other biological matrices. 

The results for the deuteration of 2-, 3-, and 4-picolines are summarized in Table IX. With 2-picoline, specific deuteration in the a-position only is observed on cobalt, whereas platinum is catalytically active for all positions,105 as is nickel chloride which catalyzes deuteration of the methyl group in particular. As with pyridine, borohydride-reduced oxide catalysts are more active than self-activated preparations. The much higher reactivity in 2-picoline compared with pyridine in selfactivation indicates that the methyl group compensates for deactivation from the nitrogen lone pair. Hydrogen for self-activation in the former compound originates predominantly from the methyl group. 

Compound (8), under Vilsmeier formylation and nitration (nitric acid-acetic anhydride) conditions, proceeded as might have been expected for electrophilic substitution reactions to give the 1-substituted products (142) and (143). Reduction of (143) gave predominantly the imidazopyridine (144) with a small amount of the tetrahydro derivative (145) (81JCS(P1)78). Heating (8) in D2O led to the 1-deutero derivative (78HCA1755) via deuter-ation-deprotonation or via the tautomeric 2-(diazomethyI)pyridine tautomer of (8). 

Pilotti et al. carried out studies on the identification of tobacco alkaloids, their mammalian metabolites and related compounds by gas chromatography-mass spectrometry using packed columns (SE-30, SE-52 and Carbowax 20 M + KOH) and capillary columns (33 m - Emulphor 0 and 9.6 m - 0V-101). Various pyridine compounds, either identified or implied as intermediates in the manmalian metabolism of nicotine present in tobacco or tobacco smoke, were studied by GC-MS. Preliminary GC-MS experiments on the determination of nicotine using capillary columns in combination with multiple ion detection (MID) employing deuterated nicotine as internal standard were reported. The gas chromatographic data of the compounds investigated... 

The most widely used solvent is deuterated chloroform (CDCI3) which is sufficiently polar to dissolve the majority of organic compounds. Also used are acetone-d5(C3DgO), methanol-d4(CD30D, pyridine-d5(C5D5N) or heavy water (D2O). 

The structures of most benzophenones have been determined by 1D ( H, l3C, and DEPT) and 2D (COSY, HSQC, HMBC, and NOESY) NMR experiments. The majority of benzophenone NMR spectra have been recorded in CDCI3 and CD3OD. Benzene-c4, mixtures of benzene-<4 and CDCI3 [75], or pyridine-ds have also been used [88,93]. The aforementioned solvents were used to resolve overlapping signals of studied compounds. Deuterated TFA (0.1%) has also been used to increase the rate of keto-enol interconversion in benzophenones. We now turn our attention to the structural elucidation of xanthochymol (138). 

Most NMR experiments with resveratrol oligomers are performed in deuterated acetone. This solvent has proven itself ideal for this class of compounds due to the high degree of solubility of the resveratrol oligomers and the lack of overlap between the solvent and analyte peaks. The second most commonly employed solvent is deuterated methanol, with deuterated dimethyl sulfoxide and pyridine used only occasionally. In some cases the NMR spectra of some O-methyl and O-acetyl resveratrol oligomer derivatives have been collected in deuterated chloroform [51,57,93,103]. 

---