Hydrogenation oxime reduction

Hydrogenation of oximes to primary amines usually can be made to proceed smoothly despite the potential complications cited earlier. Many of the same considerations applicable to control of nitrile reductions hold for oxime reductions as well. Oximes, unlike nitriles, can be reduced to hydroxylamines. 

Open-chain alkanes, alkyl halide reduction, 29-31 Organosilicon hydrides bond strengths, 5-6 hypervalent silicon species, 9-11 ionic hydrogenation, 5 trivalent silicon species, 7-9 Orthoesters, reduction of, 97-99 Oxime reduction, 102... 

Reduction of isatin-3-oximes to the corresponding 3-aminooxindole has been carried out using stannous chloride in acetic acid51 or in hydrochloric acid.92 3-Aminooxindole has also been obtained by electrochemical reduction288 and catalytic hydrogenation.169 Reduction... 

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. 

An alternative synthesis of ( )-a- and ( )--y-lycoranes (57 and 93) commenced with the 2-oxocyclohexyl acetic acid derivative 114 obtained by the alkylation of the enamine derived from 113 (Scheme 10) (116). Refluxing the oxime of 114 with zinc dust in glacial acetic acid afforded a mixture of the lactams 115, 116, and 117 in an approximate ratio of 4 6 3. The structure of 115 was verified by catalytic hydrogenation to give the lactam 118, which had previously been converted to ( )-a-lycorane (57). When the lactam 116 was subjected to sequential catalytic hydrogenation, hydride reduction, and Pictet-Spengler cyclization, ( )-y-lycorane (93) was obtained. A more efficient route to ( )-a-lycorane (57) involved refluxing the ketone 114 first with benzylamine in xylene and then with 87% formic acid to furnish the unsaturated lactam 119. 

Toward this end, the process team envisioned that the oxime reduction and subsequent cyclization to form pyrrole 27 could be effected using hydrogenative conditions, which would avoid the problems associated with stoichimetric zinc salts and therefore greatly simplify the workup and isolation of the product. This strategy was successfully realized by stirring a solution of oxime 12 and P-ketoamide 26 in acetic acid under 45 psi of H2 in the presence of 10% palladium on carbon. The desired product 27 could then be isolated in 77% yield after filtration to remove the catalyst, pH adjustment to 11-13, and subsequent extraction into CH2C12. 

An interesting and unusual synthesis of racemic leucine (Leu, L) was carried out as shown in Scheme 12.34 and reported early in the twentieth century. As shown, 2-methyl-l-propanol was converted to the corresponding iodide with hydrogen iodide (HI) and the primary alkyl iodide reacted with sodium salt derived from methyl acetoacetate to yield 5-methyl-3-carboxymethyl-2-hexanone. This, treated with nitrosyl sulfate (0=N-0S03H), yields the decarbonylated methyl 5-methyl-pentanoate-2-oxime. Reduction of the latter produced racemic leucine (Leu, L). 

Thebainone (Schopf), CigHjjOgN. This substance, which must be distinguished from Pschorr s thebainone (metothebainone of Schopf (see p. 248) ), is formed, along with the latter in the reduction of thebaine by stannous chloride in hydrochloric acid, and was isolated by Schopf and Hirsch. Its prior isolation by Pschorr, as confirmed by Morris and Small, has been referred to already. It crystallises with 0-5 HjO, has m.p. 151-2°, yields a hydriodide, m.p. 258-9°, methiodide, m.p. 223°, and an oxime, m.p. 185-6°. On catalytic hydrogenation it yields dihydrothebainone (LI), and can be degraded to 3 4 6-triacetoxyphenanthrene, m.p. 165-7°. On this basis formula (XLIX) is assigned to it. The mechanism of the formation of codeinone, thebainone and mefathebainone from thebaine is discussed by Schopf and Hirsch. ... 

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. 

Reductive alkylations have been carried out successfully with compounds that are not carbonyls or amines, but which are transformed during the hydrogenation to suitable functions. Azides, azo, hydrazo, nitro and nitroso compounds, oximes, pyridines, and hydroxylamines serve as amines phenols, acetals, ketals, or hydrazones serve as carbonyls 6,7,8,9,12,17,24,41,42,58). Alkylations using masked functions have been successful at times when use of unmasked functions have failed (2). In a synthesis leading to methoxatin, a key... 

Aromatic nitro compounds are hydrogenated very easily aliphatic nitro compounds considerably more slowly. Hydrogenations have been carried out successfully under a wide range of conditions including vapor phase (S9). Usually the goal of reduction is the amine, but at times the reduction is arrested at the intermediate hydroxylamine or oxime stage nitroso compounds never accumulate, although their transient presence may appreciably influence the course of reaction. In practice, nitro compounds often contain other reducible functions that are to be either maintained or reduced as well. 

C-Nitroso compounds with an a-hydrogen atom rearrange readily to the corresponding oxime (/7y) and perhaps to the unsaturated hydroxylamine 145). Reduction of these is discussed in the chapter on oximes. 

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