Hydrogen/deuterium oxide exchange

The slightly different physical properties of deuterium allow its concentration in ordinary hydrogen (or the concentration of a deuterium-containing compound in a hydrogen compound) to be determined. Exchange of deuterium and hydrogen occurs and can be used to elucidate the mechanism of reactions (i.e. the deuterium is a non-radioactive tracer). Methanol exchanges with deuterium oxide thus ... 

In pyridazine, base-catalyzed hydrogen-deuterium exchange takes place at positions 4 and 5 more easily than at positions 3 or 6. Deuteration of pyridazine 1-oxide in NaOD/DiO... 

In pyridazin-3(2//)-one only the hydrogen at position 6 is replaced at 180 °C, while in 3-hydroxypyridazine 1-oxide the deuterium exchange takes place first at position 6 and then at position 4 at 140 °C. 5-Hydroxy- and 5-methoxy-pyridazine 1-oxide exchange only the hydrogen at position 6 at 150 °C. 

Pyridine, 3-(dimethylamino)-amination, 2, 236 methylation, 2, 342 nitration, 2, 192 iV-oxide synthesis, 2, 342 Pyridine, 4-(dimethylamino)-in acylation, 2, 180 alkyl derivatives pK, 2, 171 amination, 2, 234 Arrhenius parameters, 2, 172 as base catalysts, 1, 475 hydrogen-deuterium exchange, 2, 286 ionization constants, 2, 172 methylation, 2, 342 nitration, 2, 192 iV-oxide synthesis, 2, 342... 

Beyer synthesis, 2, 474 electrolytic oxidation, 2, 325 7r-electron density calculations, 2, 316 1-electron reduction, 2, 282, 283 electrophilic halogenation, 2, 49 electrophilic substitution, 2, 49 Emmert reaction, 2, 276 food preservative, 1,411 free radical acylation, 2, 298 free radical alkylation, 2, 45, 295 free radical amidation, 2, 299 free radical arylation, 2, 295 Friedel-Crafts reactions, 2, 208 Friedlander synthesis, 2, 70, 443 fluorination, 2, 199 halogenation, 2, 40 hydrogenation, 2, 45, 284-285, 327 hydrogen-deuterium exchange, 2, 196, 286 hydroxylation, 2, 325 iodination, 2, 202, 320 ionization constants, 2, 172 IR spectra, 2, 18 lithiation, 2, 267... 

A solution of estradiol (38, 15 mg) in methanol-OD (4 ml) and one drop of 10% deuteriosulfuric acid in deuterium oxide is heated under reflux for 5 days. After cooling the reaction mixture is diluted with ether, washed with dilute sodium bicarbonate solution and water, then dried over anhydrous sodium sulfate. Evaporation of the ether gives crystalline 2,4-d2-estradiol (39, 15 mg, 99%), mp 173-175° (ether-hexane), exhibiting 82% isotopic purity and only one aromatic hydrogen by NMR. (For an experimental procedure describing the exchange of aromatic protons under Clemmensen conditions, see section III-D.)... 

The earliest attempts to prepare deuterated steroids were carried out by exchange reactions of aliphatic hydrogens with deuterium in the presence of a surface catalyst. Cholesterol, for example, has been treated with platinum in a mixture of deuterium oxide and acetic acid-OD, and was found to yield... 

The first term was found to correspond to the rate of enolisation (measured by an NMR study of hydrogen-deuterium exchange at the methylene group). The second term predominates at [Cu(II)] > 10 M and is characterised by a primary kinetic isotope effect of 7.4 (25 °C) and a p value of 1.24. Addition of 2,2 -bipridyl (bipy) caused an increase in 2 up to a bipy Cu(II) ratio of 1 1 but at ratios greater than this 2 fell gradually until the enolisation term dominated. The oxidation of a-methoxyacetophenone is much slower but gives a similar rate... 

The catalytic activity in relation to a given reaction occurring on the surface is characterized by the rate g of this reaction, i.e., by the amount of reaction products formed under the given external conditions per unit time on unit surface area. An expression for g has different forms for different reactions. For the reactions of hydrogen-deuterium exchange, oxidation of CO, and synthesis of H2O2, this expression will be derived in Sections III, IV, and V, respectively. 

Thus, Kohn and Taylor (40) point out that the y irradiation of zinc oxide which speeds up the reaction of hydrogen-deuterium exchange lowers the magnitude of the effect when a donor impurity is introduced into the specimen. 

Freund (44) studied the influence of ultraviolet light on the catalytic activity of zinc oxide in relation to the reaction of hydrogen-deuterium exchange. The author noted that the photocatalytic effect was positive and that it decreased with rising temperature. 

The introduction of an impurity into a specimen (accompanied by a change in tv and es ) will transfer us from one point to another in Fig. 9. Suppose that when a donor impurity is introduced into the specimen (decrease in v and e8 ), we are transferred from the point A to the point B. This involves a decrease in K, as can be seen from Fig. 9. Such a decrease in the photocatalytic effect caused by the addition of donor impurities has been observed by Kohn and Taylor (40) who studied the photoreaction of hydrogen-deuterium exchange on zinc oxide exposed to y radiation. 

Let us now turn to a comparison of theory with experiment. Comparing (95), (84), and (68), we find that the dependence of the photocatalytic effect K on the position of the Fermi level at the surface s and in the bulk cv of an unexcited sample for the oxidation of water is the same as for the oxidation of CO or for the hydrogen-deuterium exchange reaction. For this reason, such factors as the introduction of impurities into a specimen, the adsorption of gases on the surface of the specimen, and the preliminary treatment of the specimen will exert the same influence on the photocatalytic effect in all the three reactions indicated above. The dependence of K on the intensity I of the exciting light must also be the same in all the three cases. 

Apart from the preparation of radiotracers, microwave-assisted transformations have also been utilized to carry out simple hydrogen-deuterium exchange reactions. In the case of acetophenone, for example, simple treatment with deuterium oxide as solvent in the presence of molecular sieves at 180 °C for 30 min led to complete... 

Masjedizadeh and coworkers have recently described similar microwave-promoted hydrogen-deuterium exchange reactions in a series of heterocydes using mixtures of deuterium oxide and deuteriomethanol (Scheme 6.173 b) [328], The rapid exchange method was applied to the deuteration of the anti-tumor antibiotic bleomycin A under catalyst-free conditions [328],... 

---