Raney deuterated

Two techniques, electrochemical reduction (section IIl-C) and Clem-mensen reduction (section ITI-D), have previously been recommended for the direct reduction of isolated ketones to hydrocarbons. Since the applicability of these methods is limited to compounds which can withstand strongly acidic reaction conditions or to cases where isotope scrambling is not a problem, it is desirable to provide milder alternative procedures. Two of the methods discussed in this section, desulfurization of mercaptal derivatives with deuterated Raney nickel (section IV-A) and metal deuteride reduction of tosylhydrazone derivatives (section IV-B), permit the replacement of a carbonyl oxygen by deuterium under neutral or alkaline conditions. 

The preparation of 7,7-d2-cholesterol in 1950 was the first example of deuterium incorporation into steroids via desulfurization of mercaptals with deuterated Raney nickel. A substantially modified version of this reaction subsequently became the first widely used method for site-specific insertion of two deuteriums in place of a carbonyl oxygen. This conversion consists of the preparation of a mercapto derivative (84 85), which usually... 

Two serious drawbacks of this method are the extensive deuterium scrambling around the reaction site and the occasional formation of olefinic side products, which are hard to separate by conventional means. The extent of olefin formation may depend on the nature of the Raney nickel since it is known that desulfurization with deactivated Raney nickel can yield olefins. Best results are obtained when the deuterated Raney nickel is prepared very rapidly and used immediately after preparation. 

Deuteration at C-12 by Desulfurization of a 12-Thioketa with Raney Nickel... 

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... 

Deuteration at C-12 by desulfurization of 12-thioketals with Raney Nickel preparation of the ethylene thioketal, 172 desulfurization of the mercaptal, 173... 

By the use of Raney nickel alloy in D2O and NaOD, richly deuter-ated aliphatic acids have been prepared. " ... 

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-0-methyl-/l-D-galactopyranoside] but under ultrasonic irradiation (Tab. 13.2) [43], Extensive deuteration at C-4 position occurred for a series of ethereal 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 aforementioned deuterated derivatives were prepared by way of reduction of a ketone, aldehyde, or ester with sodium borodeu-teride, or by deuteroboration of an alkene. An interesting reaction, perhaps eventually applicable to direct deuteration of polysaccharides, was reported by Koch and Stuart413 and by them and their coworkers,41b who found that treatment of methyl a-D-glucopyranoside with Raney nickel catalyst in deuterium oxide results in exchange of protons attached to C-2, C-3, C-4, and C-6. In other compounds, some protons of CHOH groups are not replaced, but the spectra may nevertheless be interpreted with the aid of a- and /3-deuterium effects. 

Hydrodesulfurization of certain hydroxy-437 and methoxy-sub-stituted615 alkybenzo[6]thiophenes is a useful means of preparing some otherwise inaccessible alkyl-substituted phenols [e.g., Eq. (15)].015 Various p-methoxyphenylbenzo[6]thiophenes have been employed similarly to prepare the corresponding hydroxydiphenyl-alkanes.464 Catalytic hydrodesulfurization of a-alkyl-/ -(3-benzo[6]-thienyl)propionic acids affords a convenient method of preparing a,y-disubstituted y-phenylbutyric acids.636 Treatment of / -(3-benzo[6]thienyl)acrylic acid with Raney nickel alloy, sodium meth-oxide, and deuterium oxide affords the deuterated acid (366).667... 

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 reaction of 1-hexene with deuterium over nickel-silica at 105° yields hexanes distributed as shown in Table VI (49) no observations on isomerization or exchange were made. The hexanes become progressively more deuterated as the D /hexene ratio is raised. Isomerization of n-hexenes has been observed during their hydrogenation over Raney nickel (50). 

The usual conditions of catalytic hydrogenation can be applied, with certain modifications, for the saturation of carbon-carbon double and triple bonds. Platinum and Raney nickel are the usual catalysts described. It is important that catalysts used for deuteration shall be pretreated with deuterium noble-... 

D2]-9-Octadecene A solution of 9-octadecyne (5 g) in purified dioxan (125 ml) is deuterated in the presence of pretreated Raney nickel. The very selective reaction ceases after absorption of one equivalent of deuterium. The catalyst is then filtered off, the solution is evaporated, and the crude residue is dissolved in sufficient ether to give an approximately 10% solution. After cooling to ca. —45° for 2 h, the resulting crystals are removed further cooling to ca. —50° gives a second fraction. On distillation of the two fractions at 2-3 mm the product of m.p. 140-142° is obtained. 

Phenyl vs. carbomethoxy group effect on selectivity during hydrogenation and exchange of a, 3-unsaturated esters over modified and unmodified deuterated Raney nickel... 

To improve understanding of mechanistic aspects of Raney nickel s selectivity and activity, a series of seven variously substituted a, 3-unsaturated methyl esters were hydrogenated either under deuterium (deuteriumated) or under nitrogen over deuterated Raney nickel. For comparison, some of the molecules were deuteriumated over Pd/C, and in some instances the Raney nickel was modified with L-glutamic acid. 

Dioxane, used as the washing agent for catalyst preparation and also as a reaction media, was spectrograde quality (Matheson, Coleman Bell), In initial experiments no precautions were taken to exclude water from dioxane but this led to water contamination. In later experiments dioxane was stored over a molecular sieve, Linde Type 3A (Matheson, Coleman Bell). Deuterium gas was obtained from Liquid Carbonic Corporation and had an isotope purity of 99.7%. The 99.8% heavy water (DgO), used for preparations of deuterated Raney nickel and as a washing agent, was from Isotopes and Stotler Isotopes Company. 

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