Hydrogenolysis Raney nickel

Chemoselective catalytic hydrogenolysis (10 % Pd/C) of the glycosidic benzyl group of a 2-amino-2-deoxy-D-glucosederivative that carries another benzyl group protecting a 3-hydroxytetradecanoyl substituent at 0-3 has been applied in an efficient synthesis of lipid Y [215]. Benzyl ether is cleaved selectively in the presence of p-methoxy-benzyl ether by Raney nickel hydrogenolysis [216]. 

Crystalline aldehydo-D-ribose tetraacetate (XXXII) has been prepared through the Rosenmund reduction of tetraacetyl-D-ribonyl chloride (XXXI),101 through the selective hydrolysis of tetraacetyl-D-ribose diethyl thioacetal (XXX)109 and through the Raney nickel hydrogenolysis of ethyl thiol-D-ribonate tetraacetate (XXXIII).103-104 The substance has been used in the synthesis of 2,3,4,5-tetraacetyl-D-ribitoll0B and in the synthesis of ribitylaminobenzenes.108... 

Single-bond cleavage with molecular hydrogen is termed hydrogenolysis. Palladium is the best catalyst for this purpose, platinum is not useful. Desulfurizations are most efficiently per-formed with Raney nickel (with or without hydrogen G.R. Pettit, 1962 A or with alkali metals in liquid ammonia or amines. The scheme below summarizes some classes of compounds most susceptible to hydrogenolysis. 

Another mode of reductive ring cleavage is observed for 4-phenylazetidin-2-ones. These undergo N(l)—C(4) bond fission on hydrogenolysis in the presence of Raney nickel to yield the corresponding 3-phenylpropanamides (75S547 p. 583). 

Esters and amides are quite resistant to hydrogenation under almost all conditions so their presence is not expected to cause difficulties. Alkyl ethers and ketals are generally resistant to hydrogenolysis but benzyl ethers are readily cleaved, particularly over palladium or Raney nickel catalysts. ... 

A number of pentacyclic quaternary j8-carbolinium derivatives undergo reactions in which the hetero ring is cleaved. Thus semper-virine (286) is converted in poor yield into the indole derivative 287 on catalytic hydrogenolysis with Raney nickel. Alstonine and serpentine yield the analogous product on treatment with selenium. 

Another group of reactions with the predominant cleavage of the ring comprises catalytic hydrogenation of isoxazole derivatives and has been investigated only recently. The most commonly used catalyst has been Raney nickel,but use has sometimes been made of platinum catalysts. Hydrogenolysis of the 0—N bond (172—>173) occurs in isoxazole, its homologs,and their functional derivatives, for example, isoxazole carboxylic acids- and 5-aminoisoxazoles. ... 

Ruthenium is excellent for hydrogenation of aliphatic carbonyl compounds (92), and it, as well as nickel, is used industrially for conversion of glucose to sorbitol (14,15,29,75,100). Nickel usually requires vigorous conditions unless large amounts of catalyst are used (11,20,27,37,60), or the catalyst is very active, such as W-6 Raney nickel (6). Copper chromite is always used at elevated temperatures and pressures and may be useful if aromatic-ring saturation is to be avoided. Rhodium has given excellent results under mild conditions when other catalysts have failed (4,5,66). It is useful in reduction of aliphatic carbonyls in molecules susceptible to hydrogenolysis. 

Nickel in the presence of ammonia is often used for reduction of nitriles to primary amines. The reaction is done at elevated temperatures and pressures ( 100 C, 1000 psig) unless massive amounts of nickel are used. Cobalt is used similarly but mainly under even more vigorous conditions. Nitriles containing a benzylamine can be reduced over Raney nickel to an amine without hydrogenolysis of the benzyl group (7). A solution of butoxycarbonyl)-3-aminopropyl]-N-<3-cyanopropyl)benzylamine (13.6 g) in 100 ml of ethanol containing 4 g. NaOH was reduced over 3.0 g Raney nickel at 40 psig for 28 h. The yield of A/ -benzyl-Air -(f-butoxycarbonyl)s >ermidine was 95% (7). 

Aziridines, like oxiranes, undergo hydrogenolysis easily with or without inversion of configuration, depending on the catalyst, reaction parameters, and various additives 65aJ08). For example, hydrogenolysis of 2-methyl-2-phenylaziridine in ethanol occurs mainly with inversion over palladium but with retention over platinum, Raney nickel, or Raney cobalt. Benzene solvent or alkali favor retention over palladium as well. 

Hydrogenolysis of cxo-2-phenyl-9-oxabicyclo[3.3, l]nonan-2-ol proceeds exclusively with retention over Raney nickel and with inversion over palladium. No reduction with palladium occurred at all until a drop of perchloric acid was added (36). 

Benzylamines tend to undergo hydrogenolysis with inversion over both Raney nickel and palladium, unlike benzyl-oxygen compounds I2Ia,I67o). 

Hydrazones can be reduced to the hydrazine, and, if continued, hydrogenolysis of the nitrogen-nitrogen bond ensues. Raney nickel (14,15,31,133,134, 178,185), platinum (42,52,139,155,167), and rhodium (130) have each been... 

Carbonyl groups can be converted to methylene groups by desulfurization of thioketals. The cyclic thioketal from ethanedithiol is commonly used. Reaction with excess Raney nickel causes hydrogenolysis of both C—S bonds. 

V-( 1,1 -dimcthylbut-3-cnyl)-hydroxylamine followed by intramolecular 1,3-dipolar cycloaddition, was easily converted into the polyhydroxylated quinolizidine 192 by removal of the isopropylidene group and hydrogenolysis of the N-O bond in the presence of Raney-nickel accompanied by intramolecular reductive amination (Scheme 35) <2001CC915>. 

The hydrogenolysis of the carbon-sulfur bond by Raney nickel con-... 

Reductive desulfurization with Raney nickel of the mercaptolysis products of streptomycin has supplied one of the keys to the elucidation of the structure and configuration of that antibiotic. Since the chemistry of streptomycin has recently been reviewed37 the reactions discussed here will be considered solely as examples of hydrogenolysis and their bearing upon the problem of the structure and configuration of streptomycin will be ignored. 

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