Deuterium oxide mixtures with

Eujen and coworkers6-8 prepared trifluoromethylgermane-d3 for an infrared and Raman study, by treating trifluoromethyltriiodogermane with sodium borodeuteride in a phosphoric acid-d3-deuterium oxide mixture at room temperature (equation 7). 

Bakke, Bethell and Parker also found that diphenyldiazomethane decomposed by a cation mechanism when the reaction was carried out by anodic oxidation in acetonitrile-water (deuterium oxide) mixtures. The primary hydrogen-deuterium kinetic isotope effect of 3.3 at 17 °C found in this reaction was identical to that found for the acid catalysed reaction above, and confirmed that proton transfer to the diazo carbon occurs in the ratedetermining step of the reaction. This is obviously consistent with the formation of a carbocation intermediate see equation 31. The rate-determining proton transfer reaction has been confirmed by the observation that the reaction ceases when 2,6-lutidine is added. 

A solution of 5a-pregn-9-en-12-one (36, 29 mg) in methanol-OD (5 ml) is saturated with 20% sodium deuterioxide in deuterium oxide and heated under reflux for 3 days. After cooling, the reaction mixture is diluted with ether... 

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... 

A solution of the ketone (10 mg) in dry dioxane (5 ml) is placed in the cathode compartment of the cell. Then 10% deuteriosulfuric acid in deuterium oxide (5 ml) is added slowly with stirring. A small additional quantity of dioxane may be necessary to maintain a homogeneous solution. The anode compartment is filled with an identical solvent mixture and the electrode inserted. The current is adjusted to 1(X) milliamps and the electrolysis is continued for 6-10 hr with rapid stirring. The progress of the reaction is... 

Displacement of aromatic halogen in 2,4-diiodo-estradiol with tritiated Raney nickel yields 2,4-ditritiated estradiol. Aromatic halogen can also be replaced by heating the substrate with zinc in acetic acid-OD or by deuteration with palladium-on-charcoal in a mixture of dioxane-deuterium oxide-triethylamine, but examples are lacking for the application of these reactions in the steroid field. Deuteration of the bridge-head position in norbornane is readily accomplished in high isotopic purity by treatment of the... 

Tri-isopropyl borate (94 g) is placed into a 250 ml round bottom flask (oven dried) and deuterium oxide (30 ml) is added with stirring. Boric acid begins to precipitate immediately. There action mixture is stirred and heated under... 

Bromine (7 ml) is added dropwise to a mixture of white sand (14 g) and red phosphorus (3 g, dried at 165° under vacuum) moistened with 5 ml of deuterium oxide. The apparatus is fitted with an exit tube to allow the liberated deuteriobromic acid to pass through two U-tubes and into a receiving flask. The first trap contains glass beads and is cooled in an ice-salt slurry. The second contains glass beads and red phosphorus moistened with deuterium oxide. The deuterium bromide gas is collected in the appropriate solvent at ice bath temperature. A small amount of phosphorus pentoxide should be added to remove any deuterium oxide if anhydrous reagent is required. 

Malhotra and Johnson (70) have further shown that 2-methylcyclo-hexanone on treatment with 1 equivalent of pyrrolidine and 1.5 equivalents of 50% deuterioacetic acid-deuterium oxide in diglyme solution for 1 hr gave a mixture of 6c-deuterated and 6,6 -dideuterated ketones. The formation of these deuterated species was explained by the mechanistic sequence outlined in Scheme 2. 

Surfactant mixtures were used as obtained and are listed with their properties in Table II. Sodium chloride and calcium chloride were Fisher reagent grade. Deuterium oxide was Aldrich Gold Label and had a surface tension of 70.4 mN/m at 23°C measured with a W iI heImy pi ate tens i ometer. 

The stereochemistry of dienes has been found to have a pronounced effect in the concerted cyclo-additions with benzyne 64>65h A concerted disrotatory cyclo-addition of tetrafluorobenzyne, leading for example with trans- (3-methylstyrene to (63, R = Me), is likely and in accord with the conservation of orbital symmetry 68>. However while the electro-cyclic rearrangement of (63, R = H) to (65, R = H) is not allowed, base catalysed prototropic rearrangement is possible. A carbanion (64, R = H) cannot have more than a transient existence in the reaction of tetrafluorobenzyne with styrene because no deuterium incorporation in (65) was detected when either the reaction mixture was quenched with deuterium oxide or when the reaction was conducted in the presence of a ten molar excess of deuteriopentafluorobenzene. 

When we allowed pentafluorophenyl-lithium to decompose in ether in the presence of an excess of N, ZV-dimethy laniline we obtained the compounds (92) 70, X = F), (94), the latter as the major compound, and a product which was shown to be (97). That this latter compound did not arise by metallation of 2V,lV-dimethylaniline followed by addition to tetrafluorobenzyne was shown by quenching the reaction mixture with deuterium oxide. No deuterium incorporation was detected. The compound (97) provides a rare example of a product derived by a Stevens rearrangement in which aryl migration has occurred b>. 

The NMR spectrum shown in Figure 5 was obtained by dissolving hydralazine hydrochloride in deuterium oxide containing 3-(trimethylsilyl)-1-propane-sulfonic acid sodium salt (DSS). The series of peaks at 0, 0.6, 1.8, and 3 ppm are all due to the DSS. The peak at 4.8 ppm is due to HDO which forms on exchange with the solvent and the peaks at 8.01 and 8.61 ppm are due to the aromatic protons. The NMR spectrum of the base (Figure 6) was obtained in a 1 1 mixture of dimethylsulfoxide-d,- deuterochloroform. 

Comparison with Experiment. DEUTERIUM OXIDE AND WATER MIXTURES. For a solute showing no preferential solvation (K = 1, AGps0, = 0), then dp = xp from Equation 65, and a plot of 5 against xp is a straight line. Such behavior has been found for the fluoride ion in D2O-H2O mixtures (24). The free energy of transfer from Equation 67 for an ion which shows no preferential solvation will be given by... 

After the solution has been cooled in an ice bath, 120 ml. of the ethereal solution containing 0.039 mole of diazomethane is added, the flask is stoppered loosely with a cork, and the reaction mixture is stirred vigorously at 0° for one hour. The lower deuterium oxide layer is removed with a pipette and a fresh 11-ml. portion of the sodium deuteroxide solution is added. This mixture is then stirred for one hour at 0°, and the process is repeated until a total of four exchanges have been performed. The ethereal diazomethane solution is then decanted into a clean, dry 250-ml. Erlenmeyer flask and dried over 10 g. of anhydrous sodium carbonate. The resulting solution (approximately 110 ml.) contains (spectrophotometric analysis, Note 4, or titration with benzoic acid, Note 3) 0.020-0.022 mole (51-56%) of dideuteriodiazomethane which is 98-99% deuter-ated (Note 6). 

The deuterium content can be determined by reaction of the deuterated diazomethane with benzoic acid-O d in anhydrous ether followed by analysis of methyl benzoate for deuterium content either by n.m.r. spectrometry or by mass spectrometry. The benzoic acid-O-d is prepared by heating a mixture of 48.6 g. (0.216 mole) of benzoic anhydride (obtained from Aldrich Chemical Company, Inc.), 0.10 g. (0.0009 mole) of anhydrous sodium carbonate, and 7.0 g. (0.35 mole) of deuterium oxide to 90° for 2 hours. The resulting mixture is distilled at atmospheric pressure in a short-path still fitted with a receiver protected from atmospheric moisture by a drying tube. After removal of a forerun, b.p. 100-101°, the benzoic... 

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