Catalysis, tritiate

For exchange of non-labile organic hydrogen atoms, acid-base catalysis (or some other catalytic hydrogen-transfer agent such as palladium or platinum) is required. The method routinely gives tritiated products having a specific activity almost 1000 times that obtained by the Wilzbach method shorter times are required (2-12h) and subsequent purification is easier. 

The standard work of Evans [2] as well as a survey of the papers produced in the Journal of Labeled Compounds and Radiopharmaceuticals over the last 20 years shows that the main tritiation routes are as given in Tab. 13.1. One can immediately see that unlike most 14C-labeling routes they consist of one step and frequently involve a catalyst, which can be either homogeneous or heterogeneous. One should therefore be able to exploit the tremendous developments that have been made in catalysis in recent years to benefit tritiation procedures. Chirally catalyzed hydrogenation reactions (Knowles and Noyori were recently awarded the Nobel prize for chemistry for their work in this area, sharing it with Sharpless for his work on the equivalent oxidation reactions) immediately come to mind. Already optically active compounds such as tritiated 1-alanine, 1-tyrosine, 1-dopa, etc. have been prepared in this way. 

This involves rate-determining proton transfer, equation (37) in principle it should show general acid catalysis, but in practice this usually cannot be seen as the catalyzing acid is simply H30+ . A typical example would be aromatic hydrogen exchange, such as the detritiation of tritiated benzene shown in equation (38) 147... 

Gaseous carbonium ions from the decay of tritiated molecules, 8, 79 General base and nucleophilic catalysis of ester hydrolysis and related reactions, 5, The Gomberg Century Free Radicals 1900-2000, 36, 1 Gomberg and the Nobel Prize, 36, 59... 

The Pd technology is particularly appropriate for the Livermore site because the water table is fairly far below the surface (20-30 m deep), which makes trenching (e.g. for iron wall barriers) difficult. In addition, the rapid reaction rates and small reactors afforded by Pd catalysis permit the system to be contained within a well bore, which keeps the tritiated water at the site largely below the ground surface. The facility at the Livermore field site consists of two packed bed reactors, place in series in a well-bore. The flow rate is 4 L/min, which yields a residence time of five minutes in the first column and six minutes in the second column. A membrane is used to diffuse hydrogen gas into the influent stream prior to the first reactor. The... 

Heterogeneous metal catalysis is the most useful general method for the deuteration and/or tritiation of heterocyclic compounds.57 It involves exchange between the organic substrate and isotopic hydrogen (as water, usually, or gas) in the presence of a Group VIII transition metal catalyst at temperatures up to 180° [Eq. (18)]. 

This sort of problem underlines the need for an unequivocal determination of microscopic ionization constants. As already mentioned, the rate-limiting step in catalysis is controlled by an ionization with a pKa of 7. Cruickshank and Kaplan (30) used a-chymotrypsin as a test enzyme and estimated the pKa of its two histidine residues from the pH dependence of their reaction with trace amounts of tritiated l-fluoro-2,4-dinitro-benzene. From their data, a pKa of 6.8 was assigned to His-57 and 6.7 to His-40, which is not involved in catalysis. This data is consistent with deprotonation of His-57 being the critical ionization for catalysis. 

Elegant isotope labelling studies by Rose and coworkers (Rieder and Rose, 1959 Rose, 1962) established the general mechanistic features of the TIM reaction. Proton transfer is mediated by a single enzymatic base, and the reaction proceeds via an intermediate that is either a cis enediol phosphate (Figure 2) or one of the tvo possible symmetrical enediolates. The evidence for enzyme-mediated proton transfer is the catalysis by the enzyme of loss of radioactive label from substrate to solvent water, or of exchange-in of label from deuterated or tritiated water to... 

Heterogeneous catalysis (Pd) in tritiation of l,4-dien-3-ones leads mainly to l) -tritiation (ca. 76%). Tritium distribution studies indicate that the reaction is probably a 1,4-addition of tritium onto the more exposed p-face of the dienone, which is tilted downwards with respect to ring b (211). Homogeneous catalysis with tris(triphenylphosphine)rhodium chloride, however, is known to favour la-tritiation. Similarly, homogeneous hydrogenation of the less reactive... 

Because tritium is radioactive, the number of laboratories that are set up to use this radionuclide in the study of catalysis is very small. This is unfortunate because the radioactivity can be put to good advantage, e.g., in following the rates of very slow reactions in a relatively short time. Nevertheless, proper radiochemical facilities and appropriate experience is required prior to embarking on research using tritiated compounds. 

Before the war, using one of the earliest samples of tritium from the Radiation Laboratory c.t Berkeley, he found the rate of isomerization of n-butane to isobutane, over aluminum chloride promoted with water, was proportional to the rate of exchange of hydrogens between the hydrocarbon and a catalyst promoted with tritiated water. This observation may have been part of the stimulus for the more detailed studies with isotopic tracers of acid catalysis after the war. 

Cyclohepta-amylose has been converted into the phosphates (21)—(23), which were examined as catalysts for the hydrolysis of 4-nitrophenyl tetrahydropyranyl ether at low pH and for the exchange of 4-t-butylphenacyl alcohol (tritiated in the a-methylene group) at high pH. All three isomers, as the phosphate dianions, were effective catalysts for the latter reaction in which the functional group assists enolization of the bound ketone. Only the 3-phosphate (22) showed net catalysis of the hydrolysis of the ether, which was bound and hydrolysed with the assistance of a monoanionic phosphoric acid group. 

Estradiol-17 8 slows the inactivation and excess /J-mercaptoethanol stops it. When tritiated 16a-bromoacetoxyestradiol 3-raethyl ether is used, subsequent hydrolysis and amino acid analyses indicate dicarboxy-methylation of a histidyl residue at the site of enzyme catalysis. The histidyl residue labeled by this procedure must certainly be different... 

It is obviously of importance for these studies to have a variety of means available for the incorporation of tritium into organic molecules. This is done using catalytic systems and is where the subject takes on a particular interest to the organometallic chemist. Indeed, the high sensitivity of H NMR makes it an ideal tool for the study of surface catalysis, an area of research which has already been reviewed, " or for the mechanistic study of metal catalyzed reactions. Tritiation can be carried out with... 

Phase transfer catalysis has been exploited with beneficial effect in isotope exchange reactions. Chemically sensitive compounds that would not survive under the conventional base catalysis conditions can be labeled successfully. For example 23 was tritiated in benzene solution using HHO/NaOH/n-Bu4NBr, with a recovery of 80%, and the base-sensitive steroids 2A and were tritiated without double bond isomerization (location of tritium not reported) (Figure 3.11) ... 

Figure 3.20 Compounds labeled from tritiated water by palladium(O) catalysis...

One report describes a study of HNaY zeolite for the catalysis of tritium exchange into simple aromatic compounds. In analogy with the use of the water-sensitive EtAlCl2 (Section 3.1.2), the anhydrous active centers of the thermally activated zeolite were exposed to small quantities of tritiated water, and subsequent heating to 175 °C with substrate induced the exchange-labeling of the latter. Success was limited to aromatic compounds without bulky substituents or electron-withdrawing substituents, and the pattern of label incorporation was that of electrophilic substitution. 

Figure 3.22 Substrate labeled from tritiated water by alumina catalysis 3.3 Heterogeneous Catalysis in Solution with Tritium Gas...

Homogeneous Catalysis in Solution with Tritiated Water... 

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