An environmentally bening technology: selective liquid-phase catalytic hydrogenation Antal Tungler Department of Chemical Technology BUTE 2004
E fa c tor Comparison of atom utilisation Topics of the presentation : Types of selectivity Methods of improving selectivity Asymmetric catalysis New substrates and modifiers in enantioselective hydrogenations Diastereoselective hydrogenations Perspectives of the preparation of optically active compounds with hydrogenation Results from our laboratory are highlighted! PhNO 2 + 3H 2 = PhNH 2 + 2H 2 O A U = 93/129 = 72 % PhNO 2 + 2Fe +H 2 O = PhNH 2 + Fe 2 O 3 A U = 93/253 = 36,8 % PhCOCH 3 + H 2 PhCH(OH)CH 3 A U = 120/120 = 100 % 4 PhCOCH 3 + NaBH 4 + 4 H 2 O 4 PhCH(OH)CH 3 + NaB(OH) 4 A U = 122/147,5 = 82,7 % Reduction Catalytic Stoichiometric
Catalytic asymmetric syntheses A further possibility to increase effectiveness! Every step with 100% stereoselectivity halves the amount of required starting materials!
metal catalyzed reactions with chiral ligands
Heterogeneous catalytic reactions, with chiral synthons or with chiral modifiers, primarily liquid-phase hydrogenations
The most important properties of catalysts: activity, stability, selectivity
Types of selectivity in hydrogenations:
Enantioselectivity β -ketoester hydrogenation with tartaric acid modified Raney-nickel catalyst Hydrogenation of the C=C bond of isophorone with Pd in the presence of (S)-proline Tungler and his co-workers, 1989 Best ee > 60%
Chronology of asymmetric catalysis
First attempt: 1966 Cu II catalyzed addition of diazoaceticacid ester to styrene, ~ 10% ee
First good enantioselectivity: 1972, with DIOP ligand
First (published) large scale industrial application: 1991 Takasago menthol process
First attempt: 1922 bromine addition on cinnamic acid by ZnO/fructose Erlenmeyer
First good enantioselectivity: 1960 beta-ketoester hydrogenation with tartaric acid modified Raney-nickel
Best system: 1976 alpha-ketoester hydrogenation with cinchonidine modified Pt-on-alumina catalyst
This is nearly the ideal process! Development took more than 20 years!
Comparison of homogeneous and heterogeneous catalysts Comparison of homogeneous and heterogeneous asymmetric catalysts Uniform active sites: zeolites, better characterisation Improve separation: two-phase systems, heterogenisation, encapsulation, increase productivity What to do? Difficult preparation, poorly defined, transport limitations Sensitivity, small stability and activity, difficult separation Disadvantages Activity, separation, stability, recovery Selectivity, scope, variability, well defined Advantages Heterogeneous Homogeneous Characteristics Uniform active sites: zeolite support, better characterisation Improve separation: two-phase systems, heterogenisation, encapsulation, increase productivity What to do? Poorly defined, usually small ee, only on low temperature, up till now only metal catalysts Sensitivity, small activity, difficult separation, complicated ligand synthesis Disadvantages Activity, separation Selectivity, broad scope, variability, high ee Advantages
How can be infuenced selectivity? Change the solvent Replace the catalyst
Modification of the catalyst with alloying of the active metal The preparation of aromatic aldehydes with the hydrogenation of the corresponding acid chlorides with SELCAT RA Pd-Cu/C catalyst
With poisoning of the catalyst Both aniones and cationes can influence the catalytic activity and selectivity! With adjusting of pH the stereoselectivity of the hydrogenation of ketones can be influenced (see menthol!) Trans-acetylamino cyclohexanol, 80% stereoselectivity
The intermediate of the hydrogenation is the cyclohexanone derivative, in basic medium the equatorial alcohol is formed in excess.
Influencing the selectivity with the mode of preparation, metal deposition aliphatic tetralol aromatic tetralol 80% regioselectivity with the SELCAT Q catalyst
Extend the scope : new substrates in Pt/cinchona mediated reactions 96.5
Hydrogenation of isophorone in the presence of ( S )-proline as a chiral auxiliary A. Tungler, M. Kajtár, T. Máthé, G. Tóth, E. Fogassy, J. Petró: Catalysis Today, 5, 159-171, (1989). A. Tungler, T. Máthé, J. Petró, T. Tarnai: J. of Molecular Catal. 61 , 259-267, (1990).
Search for new catalysts, modifiers and substrates
Perspectives of different hydrogenation methods for the preparation of optically active compounds hopeful no limited promising good Industrial application broad narrow increasing increasing broad Scope acceptable poor good good excellent Chemical yield poor excellent good good excellent good excellent good excellent Optical purity Schiff’s bases Picolinic acid amide Pd/C Isophorone Pd-(S)-proline Ethyl pyruvate Pt/cinchonidine Dehydroamino acid DIPAMP/PTA Al 2 O 3 Metolachlor/ Josiphos Examples Diastereo- selective hydrogenation Use of chiral auxiliaries in the reaction mixture Chiral modification of heterogeneous catalysts Anchored homogeneous catalysis Homogeneous transition metal complex catalysis Methods
The author gratefully acknowledge the financial support of the Commission of European Communities, COST PECO 12382 and the support of the Hungarian OTKA Foundation, I am grateful to Gedeon Richter Co. for supplying vinpocetin.
Prof. Roger Sheldon, Dir. Pierre Gallezot, Michel Besson Dr. for co-operation