Deuterium labeled compounds

The method using GC/MS with selected ion monitoring (SIM) in the electron ionization (El) mode can determine concentrations of alachlor, acetochlor, and metolachlor and other major corn herbicides in raw and finished surface water and groundwater samples. This GC/MS method eliminates interferences and provides similar sensitivity and superior specificity compared with conventional methods such as GC/ECD or GC/NPD, eliminating the need for a confirmatory method by collection of data on numerous ions simultaneously. If there are interferences with the quantitation ion, a confirmation ion is substituted for quantitation purposes. Deuterated analogs of each analyte may be used as internal standards, which compensate for matrix effects and allow for the correction of losses that occur during the analytical procedure. A known amount of the deuterium-labeled compound, which is an ideal internal standard because its chemical and physical properties are essentially identical with those of the unlabeled compound, is carried through the analytical procedure. SPE is required to concentrate the water samples before analysis to determine concentrations reliably at or below 0.05 qg (ppb) and to recover/extract the various analytes from the water samples into a suitable solvent for GC analysis. 

It is interesting to remark that classical hydrogenation is a method used to prepare deuterium-labeled compounds by aromatic dehalogenation, but the usual reaction conditions suffer from several limitations. A microwave-enhanced catalytic dehalogenation procedure for rapid and specific deuterium labeling of N-4-picolyl-4-halogenobenzamide 68, by use of deuterated formate, [41] was recently reported (Scheme 8.25). 

The use of deuterated organosilicon hydrides in conjunction with proton acids permits the synthesis of site-specific deuterium-labeled compounds.59 126 221 Under such conditions, the deuterium atom in the final product is located at the charge center of the ultimate carbocation intermediate (Eq. 62). With the proper choice of a deuterated acid and organosilicon hydride, it may be possible to use ionic hydrogenation in a versatile manner to give products with a single deuterium at either carbon of the original double bond, or with deuterium atoms at both carbon centers.127... 

Table 6. Determination of the Absolute Configuration of Deuterium-Labeled Compounds by Neutron Diffraction...

Because of its low acidity, hydrogen cyanide seldom adds to nonactivated multiple bonds. Catalytic processes, however, may be applied to achieve such additions. Metal catalysts, mainly nickel and palladium complexes, and [Co(CO)4]2 are used to catalyze the addition of HCN to alkenes known as hydrocyanation.l67 l74 Most studies usually apply nickel triarylphosphites with a Lewis acid promoter. The mechanism involves the insertion of the alkene into the Ni—H bond of a hydrido nickel cyanide complex to form a cr-alkylnickel complex173-176 (Scheme 6.3). The addition of DCN to deuterium-labeled compound 17 was shown to take place... 

A 20% polyethylene glycol succinate on Kieselguhr column (1.2 m, 443 K, 50 ml min helium carrier gas) was used for GC analyses. Deuterium-labelled compounds were analysed by NMR spectroscopy (JEOL C 60-HL equipment) after separation with a Carlo Erba Mod P preparative GC. Mass spectrometric analyses of the reaction mixtures were carried out with a Hewlett Packard 5890A GC instrument (25 m HP-20M column, 353-473 K) coupled with a 5970 MSD quadrupole mass spectrometer (El source, 70 eV, 1-s scans, HP 59970 MS ChemStation data system). 

Complex H-NMR spectra of a-adducts can often be simplified by use of specifically deuterium-labeled compounds. By comparison of the un-deuterated with the deuterated covalent amino fT-adducts, in many cases the H-NMR peaks can be easily assigned. 

When compounds V (R = ethyl, isopropyl, cyclopentyl, n-butyl, or tert-butyl) have been heated 30-50°C above their melting points, VIII and the corresponding olefins have been obtained by (3 elimination (87,94). The course of the reaction has been controlled by the use of the deuterium-labeled compound V (R = CD2Me). It has been shown that all of the deuterium occurred in the ethylene formed by thermolysis (94). When R is methyl or phenyl, the thermolysis of V results in formation of IX. The styryl derivatives of V (R = cis-CH=CHPh and trans-CH=CHPh) have also been synthesized from VI and the corresponding Grignard reagents (94). Interestingly, thermolysis of these deriva-... 

Denterinm is invariably prepared from heavy water, which itself is mannfactnred by the electrolytic emichment of water, and is available for use as a moderator in nuclear reactors. D2O is useful as a source of deuterium in deuterium-labeled compounds. Deuterium compounds such as heavy water have been extensively studied. In Table 3, a number of physical properties of normal water and heavy water are compared. 

If unlabeled precursors are added the investigation of pathways is mainly based on quantitative data and requires significant increases of metabolites. The use of deuterium labeled compounds offers the possibility to follow conversions of precursors with lower metaboli-zation rates, because the formed products can be detected based on their content of deuterium by using the more sensitive method of capillary gas chromatography-mass spectrometry. This technique revealed that two independent pathways starting from different precursors contribute to the formation of S-octalactone in pineapple. 

Photorearrangement of the homobenzobarrelene (58) yields products (59) and (60) by direct or sensitized irradiation. By using deuterium labelled compounds and n.m.r. analysis of the product it was concluded that the rearrangement to (60) is regioselective and follows path a 4.4 times more often than path b (Scheme 3). The influence of methyl substitution was also investigated. 

Norcarene (92) is photochemically reactive by both direct and triplet-sensitized irradiation. Direct irradiation at 214 nm affords the products shown in Scheme 6, and the reaction path was studied in detail by the use of deuterium-labelled compounds. Under sensitized conditions, two products were formed (Scheme 7). The authors reason that it is difficult to differentiate between concerted and biradical paths for product formation, owing to the... 

One reaction, mentioned in this section, combines some features of the meth-ylenecyclopropane rearrangement and the vinylcyclopropane rearrangement (Section III.C) it is the pyrolysis of 2-vinyl methylenecyclopropane. Here, too, studies with deuterium-labeled compounds have been valuable in helping to unravel the various mechanistic pathways involved. 

Analytes may be quantitated using an internal standard or by the method of standard addition. An internal standard is a structural analog (e.g. deuterium-labeled compound), a known amount of which is added to specimens prior to any preparatory steps such as extraction or hydrolysis. Ideally, the internal standard should be as chemically similar to the analyte of interest as possible, so that throughout the analytical procedure (e.g. extraction, chromatographic separation and ionization processes) and under the specified conditions (e.g. derivatization), its recovery will be similar to the analyte s. The concentration of analyte can then be determined from the ratio of the analyte response to the internal standard response. 

Deuterium isotope effects are studied most often, because deuterium is relatively cheap, the synthesis of deuterium-labelled compounds is frequently straightforward and the effects are large and thus easy to measure with sufficient accuracy. Kinetic isotope effects can be attributed largely to the difference in the zero-point energies of the C—H and C—D stretching vibrations in the reactant, E0 = hvl2. The vibrational... 

Mass spectral data played a relatively minor role in the structural elucidation of securinine (Section II, A, 1). Somewhat later Audier and Parello carried out a detailed analysis of the mass spectral fragmentation of securinine, dihydrosecurinine, and tetrahydrosecurinine using deuterium-labeled compounds (36). This investigation has intrinsic... 

Since 1913 scientists had accepted the existence of isotopes, but conventional wisdom claimed that isotopes of a given element could not be differentiated or separated by a chemical process. Urey challenged and overturned this thinking in 1932 by showing that deuterium (D2) could be concentrated in the form of deuterium oxide, or heavy water (D2O), and then converted back into pure deuterium by electrolysis of the D2O. Deuterium and deuterium oxide are convenient sources of deuterium-labeled compounds that today are used routinely in medicine and science. 

Another application of pulse chromatographic methods is in studies of the kinetics of isotope-exchange reactions [75]. A deuterium-labelled compound was formed as a pulse of a volatile compound (reagent) passed through a column packed with Gas-Chrom A with 10% of Carbowax 6000 and 10% of KO H applied on its surface. The isotope exchange rate is a characteristic of the nature of the substance under investigation and is of... 

The labeling of organic compounds with stable or radioactive isotopes now constitutes an extremely important area of preparative chemistry. The number of publications in that field has grown to such an extent that it is almost impossible to find them all. This alone indicates the ever growing importance of labeled compounds in diverse branches of science moreover, the work reactivates the experimental demands on preparative chemists because an extraordinarily large number of compounds of different isotopic composition are open to synthesis. For instance, even such a relatively simple molecule as propane can afford no less than twenty-nine different deuterium-labeled compounds with eight different molecular formulae. 

Considerations of this kind do not apply to labeling with deuterium, which is available cheaply as the almost pure isotope and is not dangerous. Deuterium-labeled compounds are, for instance, used in analysis, in studies of reaction mechanism, for investigation of isotope effects, and for research on the metabolism of biochemically important substances. They are of particular value for the determination of the structure of chemical substances both by means of chemical reactions and by means of mass spectroscopy or IR or NMR spectroscopy. Moreover, the perdeuterated compounds are important solvents for use in these physical measurements. 

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