Hydrogen-isotope exchange

With the development of liquid scintillation counters which permit tracer levels of tritium to be measured accurately, isotope exchange reactions are now usually carried out with tritium rather than deuterium. Frequently, however, it is useful to compare rates of exchange for all three isotopes and deuterium exchange may be followed using, for example, mass spectrometry [22]. An example of the application of isotope exchange to proton transfer from carbon is shown in eqns. (8) and (9) for the hydroxide ion catalysed exchange of phenylacetylene in aqueous solution [23], viz. 

Since the reaction is carried out in a pH range where phenylacetylene will be negligibly dissociated (for example, at pH 8 assuming a p/f value of 21 for phenylacetylene [24] ca. 1 part in 101 3 will be dissociated) the intermediate carbanion reaches only steady state concentrations. Since the tritium label is present in tracer quantities it is also assumed that k k-i where fe-i and k2 are written as first-order rate coefficients 

In some cases, particularly in solvents of low dielectric constant where ion pair formation is important, the assumption that k2 k, is not always valid. The intermediate formed by reaction between carbon acid (RCT) and base (B) may return to reactants at a rate comparable with the rate at which it goes on to products (11), viz. 

The reaction is then said to involve internal return [25]. In this case the rate expression is given by 

The reaction does not involve internal return and the rate of exchange, as discussed above, refers to a proton transfer step. This mechanism applies to most carbon acids in aqueous solution and the expected general base catalysis is observed, (ii) k2 fe t, feobs = kxk2/k- - The observed rate coefficient is composite and the rate of exchange does not refer to a simple proton transfer step. It has been argued that the reaction will then show catalysis by hydroxide ion only and not by general bases when carried out in aqueous solution [26]. This arises because the rate of reaction depends upon the equilibrium concentration of intermediate in eqn. (11) which will depend upon the concentration and basicity of B. It 

The choice of solvent can also be beneficial in another respect. This possibility was highlighted by the findings of Cioffi on the Raney Nickel catalyzed hydrogen-deuterium exchange of a model carbohydrate (l-O-methyl-jS-o-galactopyranoside), but under ultrasonic irradiation (Table 18.2) [47]. Extensive deuteriation at the C-4 position occurred for a series of etheral solvents, the C-3 position was deuterated by seven solvent systems and the C-2 position deuterated less extensively, also by seven solvent systems. For l,4-dioxane-D20 no labeling at the C-2 position occurred and for l,2-dimethoxyethane-D20 no C-3 labeling was observed. 

The benefits of using ionic compounds in microwave-enhanced reactions (see Chapter 7 in this book) led us to explore the possibility of using ionic solvents i.e. ionic liquids, as donors for both deuterium and tritium. Whilst D2O is now relatively inexpensive and available at high isotopic enrichment, tritiated water is usually employed, for safety reasons, at low isotopic incorporation (we typically use 

HTO at 5 or 50 Ci specific activity corresponding to 0.2-2% isotopic incorporation). This is a serious limitation when there is a need to provide compounds at high specific activity. 

Ease of separation of tritiated products from a reaction medium is an important feature in the choice of labeling procedure. Sometime ago we used polymer-supported acid and base catalysts [12, 13] to good effect and vith the current interest in Green Chemistry one can expect to see more studies vhere the rate accelerations observed under micro vave-enhanced conditions are combined vith the use of solid catalysts such as Nafion, or zeolites. 

Selective C-2(H)deuteriation of a number of heterocyclic compounds (imidazole, 

---

A more detailed study of the nitration of quinolinium (l) in 80-05 % sulphuric acid at 25 °C, using isotopic dilution analysis, has shown that 3-) 5-) 6-, 7- and 8-nitroquinoline are formed (table 10.3). Combining these results with the kinetic ones, and assuming that no 2- and 4-nitration occurs, gives the partial rate factors listed in table 10.4. Isoquinolinium is 14 times more reactive than quinolinium. The strong deactivation of the 3-position is in accord with an estimated partial rate factor of io for hydrogen isotope exchange at the 3-position in the pyridinium ion. It has been estimated that the reactivity of this ion is at least 10 less than that of the quinolinium ion. Based on this estimate, the partial rate factor for 3-nitration of the pyridinium ion would be less than 5 x io . 

Pyridinium sulfate, bis-l,2,4,6-tetramethyl-hydrogen isotope exchange reactions, 2, 194 Pyridinium-1 -sulfonates reactions, 2, 34... 

In this chapter it is clearly impossible to do more than sample the extensive literature on the carbon acidity of sulfinyl and sulfonyl compounds, as it illuminates the electronic effects of these groups, particularly in connection with linear free-energy relationships. There are three main areas to cover first, as already indicated, equilibrium acidities (pKa values) second, the kinetics of ionization, usually studied through hydrogen isotopic exchange and finally, the kinetics of other reactions proceeding via carbanionic intermediates. 

Bottinga, Y. 1969 Calculated fractionation factors for carbon and hydrogen isotope exchange in the system calcite-carbon dioxide-graphite-methane-hydrogen-water vapour. Geochimica et CosmochimicaActa 33 49-64. 

M-Values Observed for the Hydrogen Isotope Exchange in Benzene... 

Fig. 4. Hydrogen isotope exchange between C6H and C6D6. Correlation of randomisation rate constant kF, with percentage d-character of the metallic bonds (4). 

S. P., Wilkinson, D. J., Parallel chemistry investigations of ortho-directed hydrogen isotope exchange between substituted aromatics and isotopic water novel catalysis by cyclooctadienyliridium( I) pentan-1,3-dionates, Tetrahedron Lett. 2000, 41, 2705-2708. 

The tritiation procedures given in Tab. 13.1 all have serious limitations/disadvan-tages. Thus for all three hydrogen isotope exchange reactions HTO is used as the do-... 

We chose the microwave-enhanced Raney Nickel catalyzed hydrogen isotope exchange of indole and N-methylindole as our substrates and D20, CD3COCD3, CD3OD and CDC13 as the solvents. The thermal reaction had already been the subject of a recent study [44], The microwave-enhanced method was some 500-fold faster than the corresponding thermal reaction (at 40 °C). Furthermore the pattern of labeling (Scheme 13.3) varied with the choice of solvent. Thus in the case of indole it-... 

Many ionic liquids are based on N,N-dialkylimidazolium cations (BMI) which form salts that exist as liquids at, or below, room temperature. Their properties are also influenced by the nature of the anion e. g. BF T PFg. The C-2(H) in imidazole is fairly labile but the C-4(H) and the C-5(H) are less so. Under microwave-enhanced conditions it is therefore possible to introduce three deuterium atoms (Scheme 13.4). As hydrogen isotope exchange is a reversible reaction this means that the three deuterium atoms can be readily exchanged under microwave irradiation. For storage purpose it might be best to back-exchange the C-2(D) so that the 4,5-[2H2] isotopomer can be safely stored as the solid without any dangers of deuterium loss. The recently... 

Hydrogen isotope exchange reactions of organic compounds in liquid ammonia, 1, 156... 

Gold, V., and F. A. Long Hydrogen Isotope Exchange between Anthracene... 

---