Deuterated compounds Deuterium oxide

During the course of these mechanistic studies a wide range of possible applications of this reaction have been revealed. When the reduction is carried out with lithium aluminum deuteride and the anion complex decomposed with water, a monodeuterio compound (95) is obtained in which 70% of the deuterium is in the 3a-position. Reduction with lithium aluminum hydride followed by hydrolysis with deuterium oxide yields mainly (70 %) the 3j5-di-epimer (96), while for the preparation of dideuterio compounds (94) both steps have to be carried out with deuterated reagents. ... 

The aforementioned deuterated derivatives were prepared by way of reduction of a ketone, aldehyde, or ester with sodium borodeu-teride, or by deuteroboration of an alkene. An interesting reaction, perhaps eventually applicable to direct deuteration of polysaccharides, was reported by Koch and Stuart413 and by them and their coworkers,41b who found that treatment of methyl a-D-glucopyranoside with Raney nickel catalyst in deuterium oxide results in exchange of protons attached to C-2, C-3, C-4, and C-6. In other compounds, some protons of CHOH groups are not replaced, but the spectra may nevertheless be interpreted with the aid of a- and /3-deuterium effects. 

A halo atom may be replaced by deuterium by the action of deuterium oxide on the Grignard reagent,83 87 121 or by reduction of the bromo compound with zinc and deuterated acetic acid.89 It has been shown that the first method does not give completely specific deuteration.87... 

As a consequence, benzylic protons in a- and y-alkyl groups (but not in p-positions) are acidic and in water are in equilibrium with the corresponding methylenepyrans water at pH <5. Because the symmetric y-methylenepyrans (y-anhydrobases) are more stable than a-methylenepyrans [57], the isotopic exchange with deuterium oxide proceeds about ten times faster in y than in a, and this allows the synthesis of regiospecifically deuterated alkylpyrylium salts, which can then be converted into other deuterated compounds because the reaction with nucleophiles takes place even faster [58, 59],... 

Palladium deuteride 1 may act as an activator of C-H bonds at allylic positions and may form Jt-allyl palladium. Via the equilibrium between Jt-allyl palladium and alkene, H-D exchange will occur by C=C double bond migration. As shown in Scheme 5, cyclododecene was converted into the fully deuterated compound by treatment with hydrothermal deuterium oxide in the presence of Pd/C catalyst. Without Pd/C, no deuteration was observed under these reaction conditions [16]. 

When 3-deoxy-3-hydrazino-1,2 5,6-di-O-isopropylidene-a-D-gIuco-furanose (13) is oxidized47 in alkaline deuterium oxide, the corresponding deuterated 3-deoxy compound (14) is formed with 94%... 

Reaction with deuterium oxide, O-deuterated alcohols or acids is commonly used to provide evidence for the formation of organomagnesium compounds (e.g. see Ref. [3]). Although the presence of water normally inhibits the reaction of organic halides with magnesium, it is noteworthy that under appropriate conditions a Barbier procedure was successful [4] ... 

Deuterium oxide is available in ton quantities. It is used in certain nuclear reactions, to synthesize deuterated compounds as nmr solvents, and for labelled compounds in reaction mechanism and spectroscopic studies. 

Infrared spectroscopy has not very often been used to check the deuterium purity of alkynes, with the exception of the case of compounds with the C=CD group. For these compounds a quantitative method, analogous to the one used to determine the deuterium content of deuterium oxide by n.m.r., has been described . Known quantities of the non-deuterated hydrocarbon RC=CH are successively added to the corresponding RC=CD compound of unknown deuterium purity, and the transmittance of the v(=CH) or K=CD) band is followed i>s. the added amounts of RC CH. The method is long but it does not require precise knowledge of the coefficient of molar extinction, e, of the v(=CH) band. Its main advantage is the elimination of errors due to molecular associations. It is not applicable to volatile compounds. 

Dideuteriodiimide. Berson et al generated dideuteriodiimide (N2D.2) from potassium azodicarboxylate and acetic acid-O-d in the solvent methanol O-d. The labeled acetic acid was prepared from acetic anhydride and deuterium oxide. The methanol-O-d was prepared by the method of Streitwieser et al.3 Berson et al. used the reagent for deuteration of double bonds and found that no scrambling occurred. Generally there is some 10-15% of starting olefin which has not reacted, but the unsaturated compound can be washed out using aqueous silver nitrate solution. 

Very often lithium enolates, e.g., those produced with lithium diisopropylamide, yield only low levels of deuterated carbonyl compounds when treated with deuterium oxide or deuterated alcohols (see table below). This is due to the fact that the secondary amine formed becomes involved in the protonation162. Deuterated acids, e.g., diisopropyl (2/ ,3/ )-2,3-dihydroxy-<72-butanedioate behave in a similar way, however, the observed enantioselectivities are somewhat higher. The complex from which a deuteron (or proton) is transferred probably contains lithium enolate, amine and the proton source (see also Section 2.1.6.1.2.). 

In accordance with the constitution LV, the mild (70°) treatment of macralstonidine with deuterium chloride in deuterium oxide gives a mixture of the nonadeutero ketone (XXXIc), 9,11,12-trideutero-ilIa-methylsarpagine, and 9,10,11,12,18,18,18,20,11, 12 -decadeutero-macralstonidine (LV-dio)- The first of these products was unequivocally identified with the fission product obtained from macralstonine under similar reaction conditions (see above). The deuterium substitution pattern in the trideutero-V,j-methylsarpagine becomes clear from its mass spectrum since all fragment ions which contain the intact benzene ring (e.g., LVIII) are observed three mass units higher than in the un-deuterated compound. 

Deuterated compounds may be needed for mechanistic or physical studies and a very high purity (i.e., preferably at least 97% of the product should consist of the compound having the D-atom on the desired place) is often necessary. A general method consists in treating the alkali-metal derivative with deuterium oxide or deuteriomethanol or -ethanol. The presence of undeuterated compound may be due to incomplete metallation, therefore this reaction is carried out with an excess of the basic reagent. This involves, however, some risk of introduction of more than one D-atom, especially when the quench operation is not conducted in the proper way ... 

According to the proposed mechanism, the electrophilic arylpaUadium iodide 326, formed by an oxidative addition of Ar-1 to a Pd(0) species, was proposed to activate the central carbon-carbon double bond in the cyclic cumulene intermediate 317b to form the complex 327. A subsequent attack by the Zr-C(sp ) nucleophilic center produces the aUcenylpalladium intermediate 325, which upon reductive elimination furnishes the corresponding alkenylzirconium species 324. Hydrolysis of the latter finally produces the 3-methylenecyclopentene 319. To support the mechanistic hypothesis, deuterolysis was carried out to provide the deuterated compound 319-D in 60% yield with a high level of deuterium incorporation [87]. 

In the H-NMR study, it was found that in D2O the C-11 methylene protons in (1) easily exchange with deuterium atoms even at near neutral pH (37). In the deuterated compound (20), the signals for the C-10 methylene protons appear as a clear AB pattern (Table 2). Oxidation of the dideuterated compound (20) afforded oc-dideuterated guanidopropionic acid (17). 

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