Tritium hydride

The introduction of tritium into molecules is most commonly achieved by reductive methods, including catalytic reduction by tritium gas, PH2], of olefins, catalytic reductive replacement of halogen (Cl, Br, or I) by H2, and metal pH] hydride reduction of carbonyl compounds, eg, ketones (qv) and some esters, to tritium-labeled alcohols (5). The use of tritium-labeled building blocks, eg, pH] methyl iodide and pH]-acetic anhydride, is an alternative route to the preparation of high specific activity, tritium-labeled compounds. The use of these techniques for the synthesis of radiolabeled receptor ligands, ie, dmgs and dmg analogues, has been described ia detail ia the Hterature (6,7). 

Additionally, it has been noted that Tetralin operates via hydride transfer, at least in its reduction of quinones. Thus it has been shown that Tetralin readily donates hydrogen to electron-poor systems, such as quinones at 50°-160°C. The reaction is accelerated by electron-withdrawing substituents on the H-acceptor and polar solvents, and is unaffected by free radical initiators (6). These observations are consistent with hydride transfer, as is the more recent finding of a tritium isotope effect for the reaction (7). 

Two important classes of reactions use labelled tin compounds to prepare labelled compounds for mechanistic and analytical purposes. In the first type of reaction, labelled trialkyl- or triaryl tin hydrides (stannanes) are used to reduce (replace) several different groups such as halogen, —N02, —N=C, —N=C=Se, —COOR, —SR or an acetal group with a deuterium or a tritium atom. 

The first type of reaction uses a deuterated or tritiated tin hydride (R3Sn—L) to reduce (replace) a group (LG) with deuterium or tritium, respectively (equation 56),... 

In addition, Kozuka and Lewis measured the tritium isotope effect for the reaction between the n -hexyl, the 2-hexyl and the 2-methy 1-2-pentyl radicals with triphenyltin hydride and triphenyltin hydride-t see the last three entries in Table 11. The isotope effect of 2.55 found for the triphenyltin hydride-w-hexyl radical reaction was slightly smaller... 

TABLE 11. The primary hydrogen-tritium kinetic isotope effects found in the reactions between various alkyl radicals and tributyltin hydride and tributyltin hydride-t... 

M. W. Lee, Tritium separation using metal hydrides , htlD //sti.srs.gov/fulltest/dpms861 l/dpms8611/odf (1986). 

D-xylose was converted into 2-furaldehyde in acidified, tritiated water, no carbon-bound isotope was detected. This suggested that the 1,2-enediol (2) reacted immediately, as otherwise, tritium would have been detected at the aldehydic carbon atom of 2-furaldehyde, as a result of aldose-ketose interconversion.An acidic dehydration performed with d-[2- H]xylose showed that an intramolecular C-2-C-1 hydrogen transfer had actually occurred. Thus, these data indicated that an intramolecular hydride shift is more probable than the previously accepted step involving a 1,2-enediol intermediate. 

Before we turn to other investigations of the stabilized ion it is interesting briefly to compare the rates of hydride shifts found in the strong acid systems with rates obtained under solvolytic conditions. Collins and Lietzke (1967) and Berson et al. (1967) have deduced the rates of 3,2- and 6,2-hydrogen migration relative to the rate of solvent capture for norbornyl ions in acetic acid, formic acid and other common solvents from elaborate C scrambling studies due to Roberts and Lee (1951) and Roberts et al., (1954) and tritium labelling studies of Lee and Lam (1966). From the ratio of these... 

Hydrides. Replacement of hydrogen by deuterium or tritium in VH2 or (V, NbjHj results in a more stable compound, the inverse of the normal effect of isotopic substitution. ... 

Isotope effects have also been applied extensively to studies of NAD+/NADP+-linked dehydrogenases. We typically treat these enzymes as systems whose catalytic rates are limited by product release. Nonetheless, Palm clearly demonstrated a primary tritium kinetic isotope effect on lactate dehydrogenase catalysis, a finding that indicated that the hydride transfer step is rate-contributing. Plapp s laboratory later demonstrated that liver alcohol dehydrogenase has an intrinsic /ch//cd isotope effect of 5.2 with ethanol and an intrinsic /ch//cd isotope effect of 3-6-4.3 with benzyl alcohol. Moreover, Klin-man reported the following intrinsic isotope effects in the reduction of p-substituted benzaldehydes by yeast alcohol dehydrogenase kn/ko for p-Br-benzaldehyde = 3.5 kulki) for p-Cl-benzaldehyde = 3.3 kulk for p-H-benzaldehyde = 3.0 kulk for p-CHs-benzaldehyde = 5.4 and kn/ko for p-CHsO-benzaldehyde = 3.4. 

Although the pure titanium-hydrogen system exhibits the normal isotope effect, many titanium alloys show the inverse effect. The exchange of pro-tium-tritium mixture with the hydrided phase of these alloys has demonstrated an inverse protium-tritium isotope effect in Ti-V, Ti-Mo, Ti-Cr, Ti-Mn, and the ternary alloy TiCrMn (1). On the other hand, Ti-Co, Ti-Fe, and Ti-Ni systems exhibit the normal isotope effect. Clearly much can be learned from a study of these systems. 

Hydrogen-Tritium Exchange Studies. Isotope exchange experiments were conducted as described previously for the 7-phase hydrides (except TiMo2, that does not form the 7-phase). The results of the isotope separation determinations are shown in Table VI, where the parameter a is defined as ... 

Budding. J.V.. RJ. Hemley. arid H.K, Mao -High-Pressure Chemistry ol Hydrogen in Metals In Sim Sindy of Ivon Hydride" Santee. 421 (July 26. 19911. Crawloril. M "Accelerator Hye- tor Warhead Tritium. Srieme, 469 iJanuary 2". 9K9, ... 

By Reduction of Unsaturated Precursors The method of choice for labeling with tritium is the reduction of a suitable unsaturated precursor (containing a double bond, carbonyl group, etc.) with carrier-free tritium gas or tritiated metal hydrides. The major limitation of this method is the availability of a suitable unsaturated precursor of the desired compound. It is essential to carry out the synthesis in a non-hydroxylic solvent (dioxane, ethyl acetate, etc.). Reductions carried out in alcohol or water will lead to almost complete exchange of the tritium gas with the solvent. 

The tumor-promoting 145, activating a broad number of cells by inhibition of endoplasmic calcium ATPase136,137, has been tritium labelled138 (equation 71) by butanoylation of debutanoylthapsigargin, 146, prepared by stereoselective reduction of ketene 147 with sodium boro[3H]hydride. The fluorescent derivative 148 of 145 has also been synthesized... 

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