Reductive alkylation, heterogeneous hydrogenation

The synthesis of an N-alkylarylamine by the reductive alkylation of an aromatic primary amine with a ketone is used in the preparation of antioxidants for polymers and rubber. The alkylation of an amine with a ketone is typically carried out in the liquid phase using heterogeneous catalysts such as Pd, Pt, Rh, or Ru supported on carbon (1,2). The reaction of ADPA with MIBK yields an imine, which then is hydrogenated over a Pt or sulfur promoted-Pt catalyst to yield 6-PPD. 

When an aldehyde or a ketone is treated with ammonia or a primary or secondary amine in the presence of hydrogen and a hydrogenation catalyst (heterogeneous or homogeneous), reductive alkylation of ammonia or the amine (or reductive amination of the carbonyl compound) takes place.165 The reaction can formally be regarded as occurring in the following manner (shown for a primary amine), which probably does correspond to the actual sequence of steps 166... 

CO into a metal-hydrogen bond, apparently analogous to the common insertion of CO into a metal-alkyl bond (6). Step (c) is the reductive elimination of an acyl group and a hydride, observed in catalytic decarbonylation of aldehydes (7,8). Steps (d-f) correspond to catalytic hydrogenation of an organic carbonyl compound to an alcohol that can be achieved by several mononuclear complexes (9JO). Schemes similar to this one have been proposed for the mechanism of CO reduction by heterogeneous catalysts, the latter considered to consist of effectively separate, one-metal atom centers (11,12). As noted earlier, however, this may not be a reasonable model. 

Hydrogenation of a mixture of amines and aldehydes or ketones results in the formation of unsymme-trical secondary amines. The hydrogenation of the intermediate aldimine or ketimine can be carried out by heterogeneous catalytic hydrogenation over metal catalysts such as platinum, palladium, nickel or Raney nickel. The overall reaction can be regarded as an alkylation of the amino compounds, and also as a reductive amination of the aldehyde or ketone (Scheme 3). 

The mechanism of homogeneous catalysis invoives the same steps as heterogeneous catalysis. An initial tt complex is formed with the reactant. Metal-hydride bonds then react with the complexed alkene to form a C-H bond and a bond between the metal and alkyl group. There can be variation in the timing of formation of the M—H bonds. The metal carbon bond can be broken by either reductive elimination or protonolysis. Note that reductive elimination changes the metal oxidation state, whereas protonolysis does not. The catalytic cycle proceeds by addition of alkene and hydrogen. 

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