Reactions deuteration

The incorporation of a chapter on deuteration in a steroid monograph is quite reasonable since development of a number of the most important deuteration reactions have actually had their impetus through steroid research. The field of steroid chemistry offers possibly the largest variety of deuteration reactions of any area of organic chemistry. Many of these deuteration techniques have also been used for tritium labeling, which is especially pertinent in view of the large demand for tritiated steroids as tracers in biological experiments. 

The first reaction yields a mixture of all deuterobenzenes, the second one, the deuteration reaction, a mixture of deuterocyclohexanes, mainly C6H6D6 up to C6Di2. The rates of these reactions can be measured with fair accuracy, and additional information can be derived from the isotopic distributions of the reaction products. Schrage and Burwell 36) already demonstrated the usefulness of exchange reactions for studying the heterogeneity of catalyst surfaces. 

Moreover, there are indications that the edge sites are particularly active, both in the exchange and in the deuteration reaction. No such effect has been found on nickel. 

The application of deuterated ammonium formate as a deuterium source in transfer deuteration reactions of aromatic heterocycles has been reported by Derdau (Scheme 6.173 c) [329]. It was found that the reaction time could be reduced from 12-18 h (50 °C, oil bath) to 20 min at 80 °C by employing microwave irradiation, using deuteriomethanol as solvent and 10% palladium-on-charcoal as a catalyst. 

Yields for reaction with benzophenone and CDjOD (over 90% deuteration) reaction with other electrophiles was unsuccessful. 

Here, the phenyl radical once again attacks the unsamrated bond. However, the steric effect and larger cone of acceptance (the methyl group screens the p carbon atom and makes it less accessible to addition) direct the addition process of the radical center of the phenyl radical to the a carbon atoms of methylacetylene and propylene (the carbon atom holding the acetylenic hydrogen atom). Consequently, crossed beam reactions with complex hydrocarbon molecules can be conducted and valuable information on the reaction pathways can be derived if (partially) deuterated reactions are utilized. 

During deuteration reactions, considerable isotope exchange and a little isomerization are observed. All these properties are characteristic of a catalytic cycle involving a relatively long lived alkyl complex. 

Integration of the differential equation for the rate of change (with time) of the iodine molecule concentration coupled with an iterative procedure for varying the values of k, k jk and kjk furnished a set of rate coefficients [ki,k2, kjkj] which minimized the deviation between a calculated reaction time and the measured reaction time. A similar group of experiments on the D2-I2 system furnished kinetic isotope effects on the rate coefficients as well as k, k and kjks for the deuterated reactions. The resulting Arrhenius parameters are summarized in Table 4. 

A more direct approach is to use sodium deuteroxide in deuterium oxide to remove the aluminum from the Raney alloy. The activity of the resulting catalyst depends on the temperature and duration of the leaching process. Washing the catalyst with deuterium oxide and/or dioxane gives an effective catalyst for deuteration reactions. 

The amounts of the various deutero-benzenes and deutero-cyclohex-anes formed during the course of reaction between benzene and deuterium on a number of evaporated metallic films have been followed by a mass-spectrometric technique. The most extensive results were obtained over platinum and palladium films because both the exchange reaction and the deuteration reaction were found to occur simultaneously on these metals, but some results were also obtained with nickel, tungsten, iron, and silver films. 

In all cases, the total percentage of cyclohexanes increased linearly with time typical results are shown in Fig. 1. This implies that the deuteration reaction is zero order with respect to the pressure of benzene and the values of the rate constant, K, as %/min. 10 mg. of catalyst, were determined. The results for palladium and platinum, plotted as logiofcc against 1/T° K, are shown in Fig. 2. The deuteration on tungsten at —25° was too fast to be measured accurately the reaction was complete in 4 to 5 min. on a film weighing 7.6 mg., corresponding to a rate of at least 30%/ min. 10 mg. On iron, the value at 0° was 1.06 %/min. 10 mg., and no deuteration was observed over silver at 293 or 373°. 

Equations for dissociation pressures of nickel chloride hexahydrate to tetrahydrate and the nickel chloride hexadeuterate to tetradeuterate are presented. The equation for the deuterate reaction is based on the experimental vapour pressures reported in [37BEL]. The equation for the hexahydrate/tetrahydrate equilibrium matches the experimental points from Derby and Yngve [16DER/YNG] so well that it raises the question of whether the reported equation is from a fit to the earlier data [16DER/YNG], rather than based on new experiments. The transition temperature reported in [37BEL] matches that in [16DER/YNG] exactly (within 0.01 K). 

Fig. 10. AOD spectrum of the deuterated reaction center P870 of wild-type Rhodobacter sphaeroides. Note the sharp zero-phonon hole at the laser wavelength 910 A [Data from N. R. S. Reddy, P. A. Lyle, and G. J. Small, Photosymh. Res. 31, 167 (1992)].

Scheme 10.1 Tandem hydrosilylation/deuteration reaction catalyzed by 52.

Incorporating deuterium into organic molecules is highly useful for the detection and identification of metabolites and decomposition products of bioactive molecules. Therefore, deuterating reactions such as H/D exchange have been used for many environmental and pharmaceutical applications [155], Moreover, molecules with C-D bonds are helpful for analyzing transition metal-catalyzed reactions [156, 157]. 

Lyle, P.A., Kolaczkowski, S.V., Small, G.J. Photochemical hole-burned spectra of protonated and deuterated reaction centers of Rhodobacter sphaeroides. J. Phys. Chem. 97, 6924-6933 (1993)... 

Deuterated reaction centers, 69f Difference spectra, 27, 255f, 295 Dimer formation, 377f Dithionite-reduction, 12, 21, 70, 77 Donor-acceptor systems, see Model systems... 

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