Raney-nickel catalyst utilization

Enolate Amination. Amination likewise can be effected using Di-t-butyl Azodicarboxylate (DBAD). Despite the excellent yields and diastereoselectivity obtained using this methodology (eq 24), the harsh conditions required for further transformation of the resultant hy drazide adducts (Triftuoroacetic Acid and hydrogenation at 500 psi over Raney Nickel catalyst) limit its synthetic utility. 

A number of different types of classic Raney nickel catalysts with varying activities have been prepared by the addition of the commercially available alloy to sodium hydroxide solutions. These catalysts have been designated as Wl, W2, W3, W4, W5, W6, W7 and W8. The procedures utilized to prepare these catalysts differ in the amount of sodium hydroxide used, the temperature at which the alloy is added to the basic solution, the temperature and duration of alloy digestion after addition to the base and the method used to wash the catalyst free from the sodium aliuninate and the excess base. These differences are listed in Table 12.1. 

Acylhydrazones, particularly those embodying an electron-deficient acyl group (e.g., 4-trifluoromethylbenzoyl ), condense with silyl ketene acetals in the presence of Sc(OTf)j. The efficiency can be judged by a quantitative reaction utilizing 5 mol% of ScjOTf), versus the second best reaction (42%) which requires 100 mol% of the Lewis acid BFj OEtj. Since the N-N bond of the products is easily cleaved by hydrogenation (Raney nickel catalyst), a convenient route to 3-amino esters is developed. 

Hoffmann-LaRoche has developed a process that utilizes R,R-tartaric acid/ NaBr modified Raney nickel catalyst in the asymmetric hydrogenation of 60 to give 61 in 100% yield and 90-92% ee (6-100-kg scale) for the synthesis of the intermediate of tetrahydrolipstatin (62), a pancreatic lipase inhibitor (Scheme 22) [5]. 

Obviously the contribution of the pore walls—according to the current density distribution—to cathodic hydrogen evolution becomes negligible beyond 10 fim pore depth so that for a perfect, undivided Raney-nickel coating of 100 fim thickness, only 7 to 8% utilization is anticipated. This is the reason why the fissures and cracks, the so-called tertiary structure of the catalyst, formed in Raney-nickel coatings by the leaching process are so important for improving its utilization. 

According to the different exchange current densities, i0, for hydrogen oxidation and hydrogen evolution on Ni and Pt, the catalytic activity of platinum is by a factor of several hundred to a thousand higher than that of nickel. Therefore, if the utilization of Raney-nickel particles below 10 jum size approaches 100%, it is clear that Pt-activated porous soot particles must be by a factor of from 10 to 30 smaller than Raney-nickel particles to achieve full utilization, that is, vanishing fuel starvation of the catalyst. This happens to be the case with soot agglomerates that are by their very nature of correct size (dv < 0.1 /im) (150, 151). 

Selective reduction to hydroxylamine can be achieved in a variety of ways the most widely applicable systems utilize zinc and ammonium chloride in an aqueous or alcoholic medium. The overreduction to amines can be prevented by using a two-phase solvent system. Hydroxylamines have also been obtained from nitro compounds using molecular hydrogen and iridium catalysts. A rapid metal-catalyzed transfer reduction of aromatic nitroarenes to N-substituted hydroxylamines has also been developed the method employs palladium and rhodium on charcoal as catalyst and a variety of hydrogen donors such as cyclohexene, hydrazine, formic acid and phosphinic acid. The reduction of nitroarenes to arylhydroxyl-amines can also be achieved using hydrazine in the presence of Raney nickel or iron(III) oxide. ... 

This preparative method is one having the most general utility. It utilizes in situ reduction of suitable vicinal trans-nzido sulfonates to intermediary amino sulfonates, which undergo base-induced cyclization to epimines. Elevated temperatures are often required to complete the cyclization. The reduction by hydrazine with Raney nickel originally used was later largely replaced by lithium aluminum hydride reduction in tetrahydrofuran or diethyl ether. Re-duction by sodium borohydride, hydrogenation over Adams catalyst, and reduction by tributyltin hydride have also been reported on occasion. Reductive cyclization by LiAlH4, which is now the method of choice, proceeds... 

The direct attachment of a thiol to a side-chain requires a post-ligation desulfurization step for its removal. This approach was first reported by Yan and Dawson, who extended hydrogenolytic desulfurization of cysteine to the chemical synthesis of proteins by NCL, utilizing Ala as a new ligation junction (Scheme 7) [134]. In the same study, they also noted that not only Raney nickel but also palladium could be used as the catalyst. In addition, the application was expanded to other residues such as Leu, Val, and Be. A subsequent refinement of this method... 

A recent modification in the use of Raney nickel may greatly enhance its utility. Industrial use of the standard procedure has been limited by the necessity to use such large quantities of the very expensive Raney nickel. It now appears that the use of the nickel-aluminium alloy itself in formic acid leads to very efficient desulphurizations with Ni/S ratios of only 0 2. High proportions of the aluminium seem to give the best results, apparently because of the ability of the aluminium to regenerate the active nickel catalyst. Similar results were obtained using nickel or cobalt salts in the presence of auxiliary metals such as aluminium or iron. 

We have utilized this reaction path with some modifications (scheme 3). The diketene addition to 4-chloro-2-nitroaniline occurred spontaneously at room temperature with traces of 4-dimethylaminopyridine. Cyclisation and reduction were then completed in a one-pot procedure in a mixture of isopropanol and water. This allow the use of only 2.2 equivalents of sodium hydroxide instead of 5 to 6 in water and to control the temperature of the cyclisation at "65 C. Various catalysts, particularly Raney nickel or palladium on charcoal (8) were known to be efficient for the hydrogenation of the N-oxide. Eventual overreduction to the 3,4-dihydro-2(lH)-quinoxalinone could be smoothly compensated by reoxidising with hydrogen peroxide or air (9). 

Sulphurated borohydrides can reduce oximes to amines the intermediate hydroxylamines are isolable. Sodium borohydride reduces nitriles to amines in high yield in the presence of Raney nickel as catalyst. The titanocene-promoted fixation-reduction of molecular nitrogen has been utilized in the conversion of ketones into amides and acid chlorides into nitriles in an overall reductive deoxygenation, as exemplified in Scheme 109. 

The MA method can be used for making new Raney catalysts from spent and deactivated ones in industrial processes. Utilization and regeneration of the latter is an Important problem in economy and ecology which has not been settled as yet. There are big difficulties in the remelting of powders wlch is associated with their easy oxidizability leading to big losses (up to 40%) of metallic nickel (ref.12). 

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