Hydrogenation of oximes

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. 

Both base and noble-metal catalysts have been used with success in the hydrogenation of oximes. Base metals, such as nickel 1,13,50,76) or cobalt 26,63), are used at elevated temp>eratures and pressures ( 80-l00 "C, 100 atm), and under these conditions runaway reactions have occurred with easily reduced compounds. Due caution must be exercised by limiting the catalyst or hydrogen or by sufficient dilution with solvent 22). 

Solvents influence the hydrogenation of oximes in much the same way as they do hydrogenation of nitriles. Acidic solvents prevent the formation of secondary amines through salt formation with the initially formed primary amine. A variety of acids have been used for this purpose (66 ), but acids cannot always be used interchangeably (43). Primary amines can be trapped also as amides by use of an anhydride solvent (2,/5,57). Ammonia prevents secondary amine formation through competition of ammonia with the primary amine in reaction with the intermediate imine. Unless the ammonia is anhydrous hydrolysis reactions may also occur. 

Oximes undergo hydrogenation to hydroxylamines and/or amines depending on reaction conditions. Platinum oxide is the most frequently used catalyst for selective hydrogenation of oximes to hydroxylamines. Reduction of chiral oxime 96 over palladium catalyst (equation 66) proceeds in high yield and stereoselectivity. High stereoselectivity was observed in catalytic hydrogenation of a-alkoxyoximes . 

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. 

There has been no new information on the hydrogenation of oximes in recent years. A detailed summary of this field was published in 1985446. 

Attempted catalytic hydrogenation of oxime E,Z-25 ended up with significant amounts of ring-opened compounds hampering distillative purification of the desired compound rac-26. 

TABLE 8.1 Hydrogenation of Oximes over Raney Ni and Raney Co0" ... 

There are some reports on the asymmetric catalytic hydrogenation of C=N double bonds. Rhodium phosphine complexes do not have high activity, and the stereoselectivity is low. - Homogeneous hydrogenation of oximes, Schiff s bases and cyclic imines " have been reported. A cyano cobalt complex has been used for the homogeneous catalytic hydrogenation of oximes and Schiff s bases but the degree of asymmetric induction is unknown. 

Raney cobalt is useful for the hydrogenation of oximes and nitriles to primary amines. 

Catalytic hydrogenation of oximes to amines requires conditions resembling those for catalytic hydrogenation of nitro compounds and nitriles.20d The catalyst should be as active as possible, e.g., Raney nickel101 (if necessary, platinized), platinum oxide,102 palladium-charcoal,103 palladium-barium sulfate,104 or rhodium-alumina.105 This rhodium catalyst also serves for reduction of an amidoxime to the amidine.106 Hydrogenation may be effected under pressure, but the temperature should be kept as low as possible to avoid formation of secondary amines. 

Comparatively with these metals, ruthenium is less investigated, even some data about the asymmetric hydrogenation of oximes, allytic alcohols or p-keto esters using BINAP, DIOP or BIPHEM... 

Transfer hydrogenation of oxime 158 derived from salicylaldehyde with ammonium formate produced the dialkylamine in good yield instead of the primary amine, but primary amines were produced from other substrates under identical reaction conditions. Thus, m-chlorobenzylamine was produced in 74% yield and, more surprising, the nitro group in 162 was slower to reduce than the oxime to give m-nitrobenzylamine in good yield (Schenre 35). ... 

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