Without question the main application of PGMs in the pharmaceutical industry is catalytic hydrogenation

Without question the main application of PGMs in the pharmaceutical industry is catalytic hydrogenation. Their popularity is largely explained by the rather unique nature of chemical processing operations in this industry. As a consequence of this emphasis on low pressure conditions, platinum and palladium catalysts are the ones most frequently employed because of their outstanding activity in the reduction of a wide range of functional groups at low hydrogen pressure. Other metals, particularly nickel, rhodium and ruthenium, are used to a lesser extent. However, the main reason palladium-catalyzed carbon-carbon bond formation is widely gaining popularity in the production of pharmaceutical intermediates over the past years. Although a variety of palladium catalyzed reactions are known from literature, 3 reactions are dominant in the pharmaceutical production:
• The Heck Reaction
• The Suzuki, Negishi, Kumada reactions
• The Sonogashira reaction
These reactions have in common the formation of a carbon bond to a sp2 carbon atom usually of an aromatic ring catalyzed by homogenous palladium catalysts.
2.2.1 Platinum and Palladium Catalyst uses in the synthesis of:
1. Vitamin A
The key step in the industrial synthesis of vitamin A is the selective reduction of an acetylenic bond to an olefinic bond in a highly unsaturated intermediate, 1,6-dihydroxy-3, 7-dimethyl-9-( 2′,6′,6′-trimethylcyclohexenyl)- zJ7-nonadiene-4-yne(I). This takes place under various different steps, but however for accomplishment of this step, was the development of a special palladium catalyst supported on calcium carbonate and poisoned with lead acetate and quinolone. This can take place at either atmospheric or higher pressures and is highly selective in adding one mole of hydrogen to the acetylenic linkage without attacking the olefinic bonds. The catalyst has proved useful in the selective reduction of quite a number of acetylenic compounds in addition to the one which has just been described.

Also, on another note there two manufacturing routes for manufacturing Vitamin A, which utilize rhodium-catalyzed hydro formylation for the synthesis of an aldehyde intermediate. The process developed at BASF involves hydro formylation of 1,2-diacetoxy-3-butene to give the branched aldehyde. Elimination of acetic acid gives them a b-unsaturated aldehyde which leads to Vitamin A acetate by Wittig reaction. An analogous process was developed by Roche starting from 1,4diacetoxy-2-butene. Hydro formylation gives aldehyde 2b, which eliminates acetic acid to give 3b which is then isomerized to 3a. The only other application of hydro formylation applied to the synthesis of a pharmaceutical intermediate on a commercial scale has recently been reported. The synthesis of (S)-allysine ethylene acetal, an intermediate in the manufacture of angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) inhibitors, using a combination of hydro formylation and enzymatic catalysis. Croton aldehyde ethylene acetyl was hydroformylated to the linear aldehyde using the Rh-biphephos catalyst. For example, researchers at Pharmacia (now Pfizer) reported the hydro formylation of N-Boc-(S)-7-allylcaprolactam on 250-g scale using Rh-biphephos to give aldehyde with 96% linear selectivity.
2. Vitamin B-Riboflavin
An intermediate common to several industrial processes for manufacturing riboflavin is N-Dribityl-3,4-dimethylaniline or its tetra acetate (IV). Most, if not all, of these processes involve a catalytic hydrogenation step in the route to this important intermediate. One such catalytic hydrogenation is the reductive coupling of tetra acetyl-D-ribono nitrile (111) with 3,4dimethylaniline (11). This reaction proceeds in the presence of a palladium catalyst at low pressure. Another published process for preparing the same compound also starts with 3,4- dimethylaniline (11) but employs D-ribono-lactone in place of the more difficultly prepared ribononitrile. The initial reaction gives the ribonamide which is acetylated and then dehydrated and chlorinated with phosphorous pentachloride to form the chloramine (V). The chloramine (V) is next hydrogenated in the presence of a palladium on calcium carbonate catalyst. Still another approach (4) to the same intermediate involves the preparation of 2,3,4,5-tetraacetyl-D-ribose (VII) by means of a Rosenmund reduction of tetraacety1-Dribonyl chloride (VI) with a palladium on barium sulphate catalyst in refluxing xylene at atmospheric pressure:

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