Deuterium carbon oxides

The carcinogenicity of dimethylnitrosamine and 4-nitrosomorpholine was reduced by deuterium substitution for hydrogen on carbon atoms alpha to the amino nitrogen.81 82 Consistent with the hypothesis that alpha-carbon oxidation is required for reactive metabolite formation from nitrosamines, there is a substantial primary deuterium isotope effect (ku/kg = 3.8) on the rate of dimethylnitrosamine N-demethylation. 3 Specific deuteration of 3-methylcholanthrene, a potent polycyclic hydrocarbon carcinogen, showed that oxidation of the 1-carbon atom is critical in the tumor-initiating process in mouse skin. ... 

Substitution of deuterium for hydrogen at the a carbon atom of an aldehyde or a ketone is a convenient way to introduce an isotopic label into a molecule and is readily carried out by treating the carbonyl compound with deuterium oxide (D2O) and base... 

The oxidation of norhomadiene by i-butyl perbenzoate and Cu(I) leads to 1-t-butoxynorbomadiene. Similarly, oxidation with dibenzoyl peroxide and CuBr leads to 7-benzyloxynorbomadiene. In both cases, when a 2-monodeuterated sample of norbomadiene is used, the deuterium is found distributed at all seven carbons in the product. Provide a mechanism which could account for this result. In what w s does this mechanism differ from the general mechanism discussed on pp. 724-725 ... 

Dimethyl sulfate (16 g) is added to a mixture of dimethyl carbonate (400 g) and deuterium oxide (1(X) g) in a 1 liter flask. Two reflux condensers and a drying tube are attached in series (initial rapid evolution of carbon dioxide may entrain some liquid), and the reaction mixture is heated under reflux for 72 hr. The methanol-OD is distilled directly from the reaction flask through a 30 cm Vigreux column. Redistillation from a small amount of sodium yields 275 g of pure methanol-OD bp 66-66.5° isotopic purity, 98.6%. ... 

Ethanol-OD can also be prepared by hydrolyzing diethyl carbonate in the presence of deuterium oxide and diethyl sulfate in a similar way as described in section IX-A-2. 

Trimethylsulfoxonium iodide (38 g) is dissolved in deuterium oxide (170 ml) at 80-100° and anhydrous potassium carbonate (50 mg) is added. The mixture is heated on a steam bath for 1 hr, then cooled to 0° for 2 hr before filtering. The recovered solid is re-equilibrated twice more by the same procedure using fresh deuterium oxide. Yield = 33.4 g (88 %). 

Even isotopes qualify as different substituents at a chirality center. The stereochemistry of biological oxidation of a derivative of ethane that is chrial because of deuterium (D = H) and tritium (T = H) atoms at carbon, has been studied and shown to... 

Still has also carried out mechanistic experiments9 3 from which he could deduce that the major reduction pathway is by attack of hydride ion at the sulphur atom. This conclusion was deduced from the fact that reduction with sodium borodeuteride-aluminium oxide gave a sulphoxide that had only incorporated about 25% mole equivalent of deuterium on to a methyl carbon atom bound to the sulphur atom. The mechanistic pathway for direct reduction is outlined in equation (38), whereas the pathway whereby deuterium could be incorporated is portrayed in equation (39). These reactions support the proposed mechanism for the hydride reduction of sulphones as outlined in Section III.A.l, namely that attack at sulphur by hydride ions may occur, but will be competitive with proton abstraction in cases when the attack at sulphur is not facilitated. 

The oxidation by Cr(VI) of aliphatic hydrocarbons containing a tertiary carbon atom has been studied by several groups of workers. Sager and Bradley showed that oxidation of triethylmethane yields triethylcarbinol as the primary product with a primary kinetic isotope effect of about 1.6 (later corrected by Wiberg and Foster to 3.1) for deuterium substitution at the tertiary C-H bond. Oxidations... 

The dominant factors reversing the conventional ds-hydroboration to the trans-hydroboration are the use of alkyne in excess of catecholborane or pinacolborane and the presence of more than 1 equiv. of EtsN. The P-hydrogen in the ris-product unexpectedly does not derive from the borane reagents because a deuterium label at the terminal carbon selectively migrates to the P-carbon (Scheme 1-5). A vinylidene complex (17) [45] generated by the oxidative addition of the terminal C-H bond to the catalyst is proposed as a key intermediate of the formal trans-hydroboration. 

Recently, the mechanism of 6-nitro-BaP ring hydroxylation has been elucidated by using 3-deutero-6-nitro-BaP (144). When incubated with 3-methylcholanthrene-induced rat liver microsomes, this deuterated analogue yielded the same metabolite profile previously observed with 6-nitro-BaP. Spectroscopic analysis of 3-hydroxy-6-nitro-BaP and 6-nitro-BaP-3,9-hydroquinone indicated that 30% of the deuterium label had migrated to carbon 2, presumably via an NIH shift. Therefore, it appears that 6-nitro-BaP-2,3-oxide is a common intermediate for these two metabolites. 

The authors have also synthesized134 fatty acids labelled with deuterium and carbon-11 in order to investigate if kinetic isotope effects related to fatty acid metabolism can be observed in vivo by pet133,135-137. In vitro, the large kinetic deuterium isotope effects are observed in the oxidation of deuteriated aliphatic carboxylic acids with alkaline permanganate and manganate135-139. 

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