SubscribeNext to the "glamorous" homogeneous hydrogenation highlighted by the 2001 Nobel Prize award to Noyori and Knowles for the enantioselective version, the more traditional heterogeneous hydrogenation may seem a bit old-fashioned and thought not to have much of a future.
In this and future contributions, we intend to contradict this pessimistic view and show the potential of modern heterogeneous hydrogenation catalysts for the selective, efficient synthesis and manufacture of complicated, multifunctional target molecules. We will concentrate on three aspects of this technology.
First, we will give an overview with illustrations for important chemo- and stereoselective transformations which offer shorter synthetic routes and lower production costs.
Next we will briefly describe the state-of-the-art of modern, commercially available hydrogenation catalysts. Finally, we will describe Solvias capability to address problems which sometimes occur during process development of a catalytic reaction.
Table 1:
Important catalytic hydrogenation reactions; preferred metal and solvent types.
| Substrate | Reaction | Metal | Solvent |
| azides | RN3 -> RNH2 | Pd, Pt, Ni | polar |
| aromatic nitro groups | ArNO2 -> ArNH2 | Ni, Pd, Pt | various |
| benzyl derivatives(debenzylation) | ArCH2X -> ArCH3 + HX X = OR, NR2 | Pd | protic, acidic or basic |
| alkenes | R2C=CR2 -> R2HC-CHR2 | Pd, Pt, Rh, Ni | various |
| alkynes | RC=CR -> RHC=CHR | Pd/Pb | low polarity |
| aliphatic C=O groups | R2CO -> R2CHOH | Ni, Ru, Pt, Rh | polar |
| aromatic C=O groups | ArCOR -> ArCH(OH)R | Pd, Pt, Cu | polar |
| aryl halides | ArX -> ArH X = Cl, Br, I | Pd | basic |
| nitriles | RCN -> RCH2NH2 | Ni, Ph / Pd, Pt | basic / acidic |
| imines | R2C=NR -> R2CHNHR | Pd, Pt | various |
| Oximes | R2C=NOR R2CHNH2 | Ni / Pt, Pd | basic / acidic |
| (hetero)aromatic rings | Rh, Ru, Pt | various | |
As shown in Table 1, many different functions can be hydrogenated with a few catalytically active metals. However, when dealing with multifunctional molecules, catalytic activity for the desired transformation is not enough, as the catalyst also has to be chemoselective. That is, it should not affect other reducible functional groups.
This is indeed possible with many combinations of reducible functions, and Figure 1 gives an overview of general rules for chemoselective hydrogenations of various substrate types. Of course, depending on the particular combination of functional groups, there are exceptions to these rules. In the following paragraphs, we will illustrate the potential of modern heterogeneous catalysts for several important transformations.
Figure 1: Rules for chemoselective hydrogenation of important functions
routine transformation using standard catalysts with selectivities > 90 %
moderately difficult and/or with modified catalyst, and/or S < 90 %
difficult, and/or only in special cases with modified catalyst, and/or S < 50%
Most heterogeneous hydrogenation catalysts are safe and easy to handle and can be readily separated from the reaction mixture by simple filtration, allowing convenient work-up and isolation of the desired product. The classical and most-used hydrogenation catalysts are the noble metals Pt, Pd, Rh and Ru supported on active carbon, along with Raney nickel and a few supported Ni and Cu catalysts.
Many factors influence the catalytic properties of such catalysts and it is important to realize that even after nearly a century of use, it is not possible to adequately characterize a heterogeneous catalyst at the molecular level. There are quite a number of manufacturers who supply a full range of hydrogenation catalysts, including Degussa, Engelhard, Grace, Heraeus, and Johnson Matthey. Many manufacturers have developed specialized catalysts for the most important and widely used transformations.
Of the numerous parameters of a heterogeneous hydrogenation catalyst that affect its catalytic performance, the following are the most important ones. Type of metal: As already mentioned, Pd, Pt, Rh, Ru, Ni and Cu are most often used. Each metal has its own activity and selectivity profile (see Table 1). Type of catalyst: Noble metals are usually supported on a carrier, sometimes they are used as fine powders (Pd black and Pt black, PtO2), Ni is most often applied as skeletal Raney nickel or supported on silica, Cu as Cu-chromite.
Metal loading: For noble metal catalysts 5% loading is standard. For Ni/SiO2 the loading is 20-50%. The concentration of the metal is usually given in the description of the catalyst, e.g., 5 weight % of palladium metal on an active carbon support is designated as 5% Pd/C (for the calculation, the dry weight of the catalysts is used). Type of support: Charcoal (also called active carbon) is most common; charcoals can adsorb large amounts of water, and for safety reasons, many catalysts are sold with a water content of 50%. Aluminium and silicon oxides as well as CaCO3 and BaSO4 are also used as supports, but usually for special applications.
Figure 2:
Hydrogenation of nitro groups with modified Pt catalysts developed by Solvias, resulting in chemoselectivities >95%
Figure3:
Chemoselective hydrogenation of a nitro group in the presence of an allyl ester
Hydrogenation of Aromatic Nitro Groups
Hydrogenation with heterogeneous catalysts is the method of choice for the conversion of aromatic nitrocompounds to the corresponding anilines. Whereas the hydrogenation of simple nitroarenes poses few selectivity problems and is routinely carried out on a very large scale, the situation is different when other reducible functional groups are present in the molecule.
We have developed two novel catalyst systems capable of the hydrogenation of aromatic nitro groups with selectivities of >90%. The protocols are complementary to each other and allow the selective hydrogenation of aromatic nitro-groups in the presence of almost any other functional group. Fig. 2. shows several examples.
The necessary catalysts are commercially available from Degussa, as well as other catalyst manufacturers, and the technology has been applied on a multi-ton scale for a number of nitro group hydrogenations. The example shown in Figure 3 depicts the hydrogenation of a herbicide nitroarene intermediate without affecting the aryl chloride substituent or the allyl group, which is reduced extremely easily with standard hydrogenation catalysts.
How Solvias Can Support You?
The big question is always how to find the best catalyst for a desired reaction in the shortest possible time and with the best chances of success?
When developing a hydrogenation process, the hierarchy of the variables is generally: metal > reaction medium > type of catalyst support > reaction conditions. As discussed above, in the hydrogenation of multifunctional molecules low catalyst activity is not usually the most difficult problem, but rather the selectivity of the catalyst. The functions to be converted and the functions to be preserved determine which metal has the best chance for high selectivity.
While there exist a number of specialized books and reviews that address this central problem, practical experience plays a very important role. Solvias has this experience having been developing hydrogenation processes for many decades. To date over 33,000 different substrates have been hydrogenated in the laboratories that currently make up Solvias hydrogenation laboratories, with a quite notable success rate.
We have a broad range of homogeneous and heterogeneous catalysts in stock which are commercially available on any scale. From initial screening through development and scale-up, Solvias can assist in all phases of process development according to the specific needs and requirements of our customer, in order to find the optimal catalyst system in the shortest possible time.
In the next edition of Solvias Prospects, we will discuss further applications of chemoselective heterogeneous hydrogenation including hydrogenation of ketones and C=N groups, the selective Rosenmund reduction of acid chlorides, and removal of benzyl protecting groups.