Industrial homogeneous processes

Hydrogenation

Homogeneous hydrogenation is one of the earliest developed industrial homogeneous processes. The most effective homogeneous hydrogenation catalyst is Wilkinson's catalyst having composition RhCl (PPh₃)₃ where PPh₃ is tridentate phosphine ligand. Both monomeric and dimmers [Rh₂Cl₂(PPh₃)₄] forms are active catalyst. Since Rh can exist in two oxidation states, it readily catalyzes oxidative addition and reductive eliminations. The functional groups attached to the phosphine ligands also affect the catalytic activity significantly. Activity is increased significantly by adding methoxy group to the phosphine ligands.

In hydrogenation process the first step is dissociation of one ligand L, which is replaced by a solvent molecule. After ligand dissociation, oxidative addition reaction of H₂ takes place. This is followed by migration of hydride from metal to ethene forming the ethyl group. Finally reductive elimination of ethane completes the cycle. The general reaction sequence can be represented as follows :

Here L=tri-arylphosphines ; S= solvent (ethanol , toluene)

In general, homogeneous hydrogenation processes are industrially of less importance compared to heterogeneous hydrogenation process. However, interest is growing in homogeneous hydrogenation processes particularly in the area of asymmetric hydrogenation. In pharmaceutical industry asymmetric hydrogenation is used to produce enantiomerically pure compounds having desirable clinical properties. The main advantage of this process is the high selectivity which eliminate the production of non-desired enantiomer which is non active or can cause undesirable side effects.

Example of asymmetric hydrogenation

1. Synthesis of L-dopa:

The asymmetric hydrogenation of cinnamic acid derivatives involves synthesis of L-Dopa. L-Dopa is a drug for treating Parkinson disease. It is one of the recently developed industrial processes. L-Dopa structure is shown below. The C atom bonded to the NH₂ group is the chiral center. The enantiomer D-Dopa is ineffective form.

The reaction is carried out in the presence of rhodium complex having asymmetric diphosphine ligand which induces enantio-selectivity. The hydrogenation reaction is carried out with a substituted cinnamic acid. The main step in L-Dopa synthesis, the hydrogenation of prochiral alkene to a specific optical isomer is shown below.

Fig. 1: Critical step in hydrogenation of prochiral alkene to specific enantiomer.

Catalyst is prepared by reacting Rh salt with an alkene chloride, such as hexadiene chloride or cyclooctadiene chloride , producing a cationic Rh species.

In the first step, alkene co-ordinates to rhodium species. The next step is hydrogenation involving oxidative addition of hydrogen to the alkene complex. The oxidative addition of hydrogen is irreversible and determines the enantioselectivity. Migration of hydride locks the configuration of the enantiomeric center. In this system, the same hydrogenation step determines the rate as well as selectivity.

The difference between this catalytic step and step involving Wilkinson catalyst lies in the sequence of the oxidative addition and the alkene complexation. For rhodium complex catalysts , the intermediate alkene complex has been spectroscopically observed. Subsequently, oxidative addition of H₂ and insertion of the alkene occurs, followed by reductive elimination of the hydrogenation product.