Deuterium production methods

Since some authors did not report information on the above cited side reactions, we carried out some catalytic deuterations of methyl dimorphecolate (methyl 9-hydroxy-octadeca-trara-lO, tra s-12-dienoate), an optically pure precursor of (9/ )-9-HSA. We used an in situ deuterium production method, and we report the new results obtained in section 4 of this Chapter. 

Two significant results of that investigation were that deuterium incorporation was found to vary with product fraction and that preferential incorporation of deuterium was found in benzylic structural positions. The purpose of this research is to extend the use of the deuterium tracer method to donor solvent reactions. 

Enantioselective cyclization was also successful in the rhodium-catalyzed hydrosilylation of silyl ethers 44 derived from allylic alcohols. High enantioselec-tivity (up to 97% ee) was observed in the reaction of silyl ethers containing a bulky group on the silicon atom in the presence of a rhodium-BINAP catalyst (Scheme 18) [53]. The cyclization products 45 were readily converted to the 1,3-diols 46 by the oxidation. During studies on this asymmetric hydrosilylation, a silyl-rhodation pathway in the catalytic cycle was demonstrated by a deuterium scrambling method [54]. 

The use of deuterium oxide and sodium deuterium oxide in the preparation of Raney nickel leads to the formation of deutero Raney nickel suitable for replacing dithioacetals with deuterium The method suffers from some scrambling of the isotope often leading to products of low isotopic purity. Deuteration of (25R)-5a-spirostan-12-one (II) by this... 

D and 0-H of the alcohol can be transferred selectively to become P-C-D and Y-H in the product, respectively [49, 50]. Since this process is the same with the direct hydrogen transfer (Scheme 6) and TM-free MPV-O (Scheme 40, vide infra) routes, the deuterium labeling method cannot be used to distinguish them. 

Laser photolysis of a precursor may also be used to generate a reagent. In a crossed-beam study of the D + FI2 reaction [24], a hypertliennal beam of deuterium atoms (0.5 to 1 eV translational energy) was prepared by 248 mn photolysis of DI. This preparation method has been widely used for the preparation of molecular free radicals, both in beams and in experiments in a cell, with laser detection of the products. Laser photolysis as a method to prepare reagents in experiments in which the products are optically detected is fiirtlier discussed below. 

Dissolved Minerals. The most significant source of minerals for sustainable recovery may be ocean waters which contain nearly all the known elements in some degree of solution. Production of dissolved minerals from seawater is limited to fresh water, magnesium, magnesium compounds (qv), salt, bromine, and heavy water, ie, deuterium oxide. Considerable development of techniques for recovery of copper, gold, and uranium by solution or bacterial methods has been carried out in several countries for appHcation onshore. These methods are expected to be fully transferable to the marine environment (5). The potential for extraction of dissolved materials from naturally enriched sources, such as hydrothermal vents, may be high. 

Two serious drawbacks of this method are the extensive deuterium scrambling around the reaction site and the occasional formation of olefinic side products, which are hard to separate by conventional means. The extent of olefin formation may depend on the nature of the Raney nickel since it is known that desulfurization with deactivated Raney nickel can yield olefins. Best results are obtained when the deuterated Raney nickel is prepared very rapidly and used immediately after preparation. 

Deuterioboration of 5a-cholest-2-ene (171), followed by oxidation of the alkylborane intermediate with hydrogen peroxide in the presence of sodium hydroxide, illustrates the application of this method for the preparation of c/5-deuterium labeled alcohols.(For the preparation of tra 5 -deuterium labeled alcohols see section VII-A.) The predominant reaction product is 2a-di-5a-cholestan-3a-ol (172, 1.03 D/mole) which is accompanied by 3a-di-5a-cholestan-2a-ol (173) and other minor products." ... 

A process involving water electrolysis is the production of heavy water. During cathodic polarization the relative rates of deuterium discharge and evolution are lower than those of the normal hydrogen isotope. Hence, during electrolysis the solution is enriched in heavy water. When the process is performed repeatedly, water with a D2O content of up to 99.7% can be produced. Electrochemical methods are also used widely in the manufacture of a variety of other inorganic and organic substances. 

By using a mixture of ethyl acetate and D2O as solvent for hydrogenation, up to 75% deuterium is incorporated in the reduced product.13 This result indicates that the role of water here is not only as a solvent. Research on asymmetric hydrogenation in an aqueous medium is still actively being pursued. The method has been applied extensively in the synthesis of various amino acid derivatives.14... 

Electrolysis continued to be used for primary enrichment in countries with abundant electric power, such as Iceland and Norway, where the H2 is used in ammonia manufacture [9]. Molecular deuterium, D2, is produced in Norway by the electrolysis of DzO. For heavy water production, the method has, for the most part, been replaced by steam-H2S exchange columns for heavy water enrichment ... 

Use of deuterated silane and/or acid with this method leads to site-specific deuterium incorporation in the reduced products. Thus, treatment of 2-methyl-l-pentene with one equivalent of deuterated triethylsilane and two equivalents of trifluoroacetic acid at 50° for 24 hours gives 2-rnethylpentane-2-(7l in 90% yield (Eq. 73) 221 In the same way, isopropenylcyclopropane gives an 80% yield of deuterated isopropylcyclopropane after 30 minutes at —10° (Eq. 74).221... 

However, the 13C NMR method is not quantitative and the products were therefore also analysed by the quantitative 2H 1H NMR spectra. Typical spectra are shown in Figure 3 and results are summarised in Table I. It can be seen that solvolysis of (XX), L pyridine, in the absence of added pyridine gives largely the 1—D2 isomer but that, when sufficient pyridine is added, the selectivity is reversed and the product is largely the 3-D2 isomer. In no case is there evidence for deuterium at either the 1- or 4-position. Solvolysis of (XX), L2 2,2 -bipyridyl gives largely the 3-D2 isomer. These results are interpreted in terms of the mechanism shown in Scheme IV. 

Deuterium, 8 456—485 13 759. See also Canadian Deuterium Uranium (CANDU) reactors analytical methods, 8 467-468 economic aspects, 8 467 health and safety factors, 8 461-462 physical properties, 8 457-462, 459t production of heavy water, 8 459t, 462-467... 

Remote double labelling techniques have been used successfully in the determination of enzyme KIEs (Kiick, 1991). A variant of this technique was applied to a nonenzymatic reaction by Matsson and co-workers (Axelsson et al., 1990). They determined the primary carbon and secondary deuterium KIEs for the SN2 reaction between methyl iodide and hydroxide ion in 50% dioxane-water at 25°C. The a-carbon KIE was determined by the UC method (Axelsson et al. 1987,1991). In this method, a mixture of substrate molecules labelled with UC (tm = 20.4 min) and 14C is used. The reactants and products... 

The reduction of thiocarbonyl derivatives by EtsSiH can be described as a chain process under forced conditions (Reaction 4.50) [89,90]. Indeed, in Reaction (4.51) for example, the reduction of phenyl thiocarbonate in EtsSiD as the solvent needed 1 equiv of dibenzoyl peroxide as initiator at 110 °C, and afforded the desired product in 91 % yield, where the deuterium incorporation was only 48% [90]. Nevertheless, there are some interesting applications for these less reactive silanes in radical chain reactions. For example, this method was used as an efficient deoxygenation step (Reaction 4.52) in the synthesis of 4,4-difluoroglutamine [91]. 1,2-Diols can also be transformed into olefins using the Barton-McCombie methodology. Reaction (4.53) shows the olefination procedure of a bis-xanthate using EtsSiH [89]. 

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