In reductive alkylation

Plaiinum was more efficient lhan rhodium in ihese experimenis. These catalysts give excellent yields of tertiary amines in reductive alkylation of aliphatic secondary amines with ketones ( 6). 

Alkylation lo yield a leriiary amine may occur easily if the formation involves cyclization (ii). Catalysts may have a marked influence. In reductive alkylation of ammonia wilh cyclohexanones, more primary amine was formed over Ru and Rh and more secondary amine over Pd and Pt. Reduction of the ketone to an alcohol is an important side reaction over ruthenium. 

Nickel, rhodium, palladium, platinum, and Raney cobalt (43) have all been used successfully in reductive alkylations. Platinum is the most used by far (J6). With small carbonyl molecules, such as acetone, palladium is about as effective as platinum, but as the molecular weight increases, platinum is apt to be more effective (SO). 

Platinum and rhodium sulfided catalysts are very effective for reductive alkylation. They are more resistant to poisoning than are nonsulfided catalysts, have little tendency to reduce the carbonyl to an alcohol, and are effective for avoidance of dehydrohalogenation in reductive alkylation of chloronitroaromatics and chloroanilines (14,15). Sulfided catalysts are very much less active than nonsulfided and require, for economical use, elevated temperatures and pressures (300-2(KX) psig, 50-l80 C). Most industrial reductive alkylations, regardless of catalyst, are used at elevated temperatures and pressures to maximize space-time yields and for most economical use of catalysts. 

Platinum oxide may show induction periods (13) in reductive alkylation and prereduction has been recommended (37,47), but it is not always necessary (19). 

A variety of solvents have been used in reductive alkylations. In industrial practice, excess carbonyl compound is often used as both reactant and solvent. 

This common technique, and many others, failed in reductive alkylation of 13 by 12 to 14, and, in an unusual variation, Campbell and Lavagnino 10) obtained satisfactory results only with an excess of aniline serving as both reactant and solvent. Normal procedures were satisfactory when the more basic cyclohexylamine was the reactant. 

In this study we examine the generalities in reductive alkylation however, since the subject is vast, we limited ourselves to the interaction of aromatic and aliphatic primary amines and diamines with ketones. The ketones examined include the cyclic ketone, cyclohexanone, and aliphatic ketones such as acetone, and methyl isobutyl ketone (MIBK). We limited our study to sulfided and unsulfided Pt and Pd catalysts supported on activated carbon that were commercially available from Evonik Degussa Corporation. 

In the same vein, reduction of tropilidene (1) in the presence of butyl chloride results in reductive alkylation (equation 3). The reaction was employed in a synthesis of fi-thujaplicin10. 

The effect of using different sized substituents on the carbonyl compound in reductive alkylations has received some attention recently... 

Refluxing of 2,6-bis(te/ t-butyl)-4-methoxyphenyl 1-nitrocyclopropanecarboxylate in tetrahy-drofuran containing methylmagnesium bromide resulted in reductive alkylation and formation of 2,6-bis-(/er/-butyl)-4-methoxyphenyl l-[hydroxy(methyl)amino]cyclopropanecarboxylate in 66% yield. 

With a primary amine such as n-octylamine, we observe at low conversion (8 %) high selectivity for the N-monoalkylated product whereas 90 % N,N-dimethylated amine are formed at high conversion (94 %). In reductive alkylation, it is even more difficult to obtain the monomethylated product selectively. For example, in the Eschweiler Clarke procedure [17], only the dimethylated amine is formed, even with an amine-to-formaldehyde ratio of 1. In the Hofmann-type reaction, a mixture of mono- and dimethylamine with the corresponding trimethylammonium salt is generally produced. 

In reductive alkylation of aromatic amines the water formed is often removed by azeotropic distillation before the hydrogenation or a preformed Schiff base may be reduced (cf. page 554). These procedures are particularly suitable for reductive alkylation of ketones886,1006 in order to counter reduction of the ketone to the secondary alcohol. Here too formation of the alcohol can be repressed by adding a catalytic amount of ammonium chloride or acetic acid to the ketone-amine mixture (cf. page 521). 

Secondary Amines.- Selective monoalkylation of primary amines is a goal still actively pursued. Modified borohydride reagents applied in reductive alkylations have been particularly successful in achieving this aim. Sodium cyanoborohydride was used in an effi-cient synthesis of alkylated amino-sugars and also in the synthesis of the imino-carbohydrates 1-deoxynojirimycin and 1-deoxymannojirimycin, in which the reductive alkylation occurred in... 

Synthesis of Vinylsilanes. The title compound can be used in reductive alkylation sequences for the synthesis of functionalized vinylsilanes with high isomeric purity (eq 2). One sequence consists of a regioselective cA-hydroboration, transmetalation. 

---