Raney nickel oximes

Dimethyl ketals and enol ethers are stable to the conditions of oxime formation (hydroxylamine acetate or hydroxylamine hydrochloride-pyridine). Thioketals and hemithioketals are cleaved to the parent ketones by cadmium carbonate and mercuric chloride. Desulfurization of thioketals with Raney nickel leads to the corresponding methylene compounds, while thioenol ethers give the corresponding olefin. In contrast, desulfurization of hemithioketals regenerates the parent ketone. ... 

Two different sets of experimental conditions have been used. Buu-Hoi et al. and Hansen have employed the method introduced by Papa et using Raney nickel alloy directly for the desulfurization in an alkaline medium. Under these conditions most functional groups are removed and this method is most convenient for the preparation of aliphatic acids. The other method uses Raney nickel catalysts of different reactivity in various solvents such as aqueous ammonia, alcohol, ether, or acetone. The solvent and activity of the catalyst can have an appreciable influence on yields and types of compounds formed, but have not yet been investigated in detail. In acetic anhydride, for instance, desulfurization of thiophenes does not occur and these reaction conditions have been employed for reductive acetylation of nitrothiophenes. Even under the mildest conditions, all double bonds are hydrogenated and all halogens removed. Nitro and oxime groups are reduced to amines. 

A solution of 151 grams of 1-(3, 4 -dimethoxyphenyl)-2-propanone oxime in 200 cc of absolute ethanol is treated with 5 grams of Raney nickel catalyst and ammonia in an autoclave at about 25 atm of pressure and at 75 -100°C. The reduction is complete in about one-half hour and the reaction mixture is filtered and fractionated under reduced pressure to recover the a-methylhomoveratrylamine formed by the reduction. a-Methylhomoveratryl-amine thus prepared boiled at 163°-165°C at 18 mm pressure. 

The resulting 4-methylhexanone-2 oxime separates and is dried by any suitable means, such as with a dehydrating agent, for example, sodium sulfate or magnesium sulfate. After drying, 4-methylhexanone-2 oxime is reduced with hydrogen by means of a catalyst, such as Raney nickel, or by reaction of sodium and a primary alcohol, such as ethanol. The resulting 2-amino-4-methylhexane may be purified by distillation, as described in U.S. Patent 2,350,318. 

Heptamide has been prepared by heating heptanoic add with ammonia in a sealed tube 2 at 230°, by treating heptanoic anhydride with ammonia,3 by passing ammonia through heptanoic acid4 at 125-190°, by the rearrangement of heptaldehyde oxime in the presence of Raney nickel in a quartz tube at 150° for 5 minutes,6 by the Will-gerodt reaction with 2-, 3-, or 4-heptanone or heptanal,6-7 and by the action of ammonia on heptanoyl chloride.8... 

A number of organic species, including amides, oximes, and nitriles, undergo reductive amination, a variety of reduction reactions that produce cimines. In general, these processes involve imines, R=N-R, or related species. Reduction processes include hydrogenation using Raney nickel as the catalyst (for nitriles), the reaction with sodium/EtOH (for oximes), and the use of lithium aluminum hydride, LiAlH (for amides or nitriles). Figure 13-16 illustrates the preparation of amphetamine by reductive amination. 

Other hydrogenation methods are less chemoselective. Use of Raney nickel provides hydroxylamines in low yield °. Hydrogenation of 1-acetonaphthone oxime over rhodium-chiral phosphine catalysts was found to proceed under harsh conditions and provided low... 

Nitro compounds in presence of carbonyl group are selectively reduced to amines in the presence of Raney nickel catalyst. Hydrazine reduces nitrdes yielding hydrazones. Under controlled reaction conditions other functional groups, including nitroso and oxime, may be reduced. Many partially hydrogenated derivatives, such as azo-, hydrazo-, and azoxy compounds may be obtained by partial reduction with hydrazine. Reaction with chlorobenzene yields benzene. 

An excellent review of the problems of the enantioselective heterocatalytic hydrogenation of prochiral double bonds, covering the literature up to 1970, has been compiled by Izumi57). Raney nickel catalysts modified with chiral amino acids or dipeptides gave only very moderate enantiomeric excesses of between 0 and 10% in the hydrogenation of olefins, carbonyl compounds or oximes 57). Only Raney nickel modified with (S)-tyrosine furnished a higher enantiomeric excess in the products58). 

Aliphatic nitro compounds are reduced to various products, in all the published examples, only C-F bonds at a-positions are reduced, while the nitro group can be reduced in two steps. Catalytic hydrogenation of primary nitro compounds over palladium transforms them to the corresponding isonitroso compounds, i. e. oximes, while secondary nitro groups are converted into amines (Table 4). The reduction with Raney nickel alloy converts all types of nitro compounds into the corresponding amines, e. g. formation of 14.136... 

Heterogeneous hydrogenation of the C=N bond is a very widely used synthetic process with application to small and large-scale reactions. Many of the catalysts described in other sections may also be employed, for example those based on supported rhodium, palladium etc, and Raney Nickel. This area has been reviewed extensively recently192. Hydrogenation of oximes and hydrazones results in formation of amines. Milder conditions can be used for oxime reduction if the ethylaminocarbonyl derivative is prepared in situ prior to reduction276. 

By means of this reaction Caldwell and Jones (103) obtained citronell-amide in 50% yield when 20 g. of citronellaldoxime and 3 g. of Raney nickel were heated at 100-105° for 2 hours, and, after dilution with ether, the catalyst was removed by filtration through activated alumina. The oxime of tetrahydrocitral, when heated for 2 hours at 110-120° with Raney nickel, gave a 70 % yield of the amide of 2,6-dimethyloctanoic acid. 

Nitrile oxide 75, generated in situ from oxime 74, gives intramolecular 1,3-dipolar cycloaddition affording a mixture of inseparable oxocane 76 and oxonane 77 in a ratio of 1 1.4 (Scheme 11). Hydrogenation of these isoxazolines with Raney nickel leads to keto alcohols 78 and 79, which can be separated by chromatography <2006SL1205>. 

Reduction of nitroalkenes. Vinyl nitro compounds are reduced to saturated ketones or aldehydes by Raney nickel and an aqueous solution of sodium hypophosphite. Ester groups, C=C bonds, and aryl NO, and halo groups are not reduced. Under these conditions nitroalkanes arc reduced to amines, and oximes are converted into carbonyl compounds in high yield. 

Reduction of oximes to ketones. Ketoximes can be converted to ketones by hydrogenation catalyzed by Raney nickel (deactivated with acetone) in THF/CH,OH/H,0 or in CHiOH/H,0 containing boric acid to facilitate hydrolysis of the intermediate imine... 

Aldoximes are rearranged to amides at 100-150° under the catalytic influence of Raney nickel. The yields of amides from the oximes of acetaldehyde, heptaldehyde, benzaldehyde, and furfural are good (75 96%)> although the reactions are carried out on a small scale only. 

Reduction of oximes to primary amines proceeds readily and can be accomplished with hydrogen and Raney nickel catalyst with or without high pressures (50-90%)." Primary amines formed from... 

Raney nickel) of the potassium salt of D-xy/o-5-hexulosonic acid oxime produces a mixture of 5-amino-5-deoxy-L-idonic and -D-glu-conic acid in the ratio of 2 1, which is converted into the methyl ester hydrochloride. Upon treatment with alkali, spontaneous cyclization to the pair of 1,5-lactams occurs. 5-Amino-5-deoxy-L-idono-l,5-lactam and 5-amino-5-deoxy-D-glucono-l,5-lactam were separated by recrystallization. The optical rotatory dispersion curves of both compounds were discussed. A new type of lactam, namely, 2-enamino-N,N -bis[(p-methoxycarbonyl)phenyl]-4-(D-gaiacfo-penta-acetoxypentyl)-4-butanelactam was prepared by tbe reaction of 5,6,7,8,9-penta-0-acetyl-3,4-dideoxy-D-ga/ocfo-nonulos- rcns-3-en-l-onic acid with methyl p-aminobenzoate. 

Catalytic hydrogenation of 8-chloro-6-phenyl-l,3-dihydro-2//-4,1,5-benzoxadiazocin-2-one oxime in the presence of Raney nickel affords 6-chloro-2-(hydroxymethyl)-4-phenylquinazoline in 49% yield. 

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